TY  - JOUR
AU  - Burgy, O.*
AU  - Lehmann, M.
C1  - 74878
C2  - 57648
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Small packages but big insights: Extracellular vesicles as biomarkers in interstitial lung disease associated with systemic sclerosis.
JO  - Eur. Respir. J.
VL  - 65
IS  - 6
PB  - European Respiratory Soc Journals Ltd
PY  - 2025
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Funk, M.C.
AU  - Nawroth, J.
AU  - Lehmann, M.
C1  - 72674
C2  - 56704
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - A breath of the future: A novel human model for COPD and beyond.
JO  - Eur. Respir. J.
VL  - 64
IS  - 6
PB  - European Respiratory Soc Journals Ltd
PY  - 2024
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Emphysema, the progressive destruction of gas exchange surfaces in the lungs, is a hallmark of chronic obstructive pulmonary disease (COPD) that is presently incurable. This therapeutic gap is largely due to a poor understanding of potential drivers of impaired tissue regeneration, such as abnormal lung epithelial progenitor cells, including alveolar type II (ATII) and airway club cells. We discovered an emphysema-specific sub-population of ATII cells located in enlarged distal alveolar sacs, termed asATII cells. Single cell RNA-seq and in situ localisation revealed that asATII cells co-express the alveolar marker surfactant protein C (SPC) and the club cell marker secretaglobin-3A2 (SCGB3A2). A similar ATII sub-population derived from club cells was also identified in mouse COPD models using lineage labeling. Human and mouse ATII sub-populations formed 80-90% fewer alveolar organoids than healthy controls, indicating reduced progenitor function. Targeting asATII cells or their progenitor club cells could reveal novel COPD treatment strategies.
AU  - Hu, Y.*
AU  - Hu, Q.*
AU  - Ansari, M.
AU  - Riemondy, K.*
AU  - Pineda, R.H.*
AU  - Sembrat, J.*
AU  - Leme, A.S.*
AU  - Ngo, K.*
AU  - Morgenthaler, O.*
AU  - Ha, K.*
AU  - Gao, B.*
AU  - Janssen, W.J.*
AU  - Basil, M.C.*
AU  - Kliment, C.R.*
AU  - Morrisey, E.*
AU  - Lehmann, M.
AU  - Evans, C.M.*
AU  - Schiller, H.
AU  - Königshoff, M.*
C1  - 71489
C2  - 56212
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Airway derived emphysema-specific alveolar type II cells exhibit impaired regenerative potential in COPD.
JO  - Eur. Respir. J.
VL  - 64
IS  - 6
PB  - European Respiratory Soc Journals Ltd
PY  - 2024
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - BACKGROUND: Fibroblast to myofibroblast conversion is a major driver of tissue remodeling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet, their specific activation states and phenotypic trajectories during injury and repair have remained unclear. METHODS: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-seq and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. Our findings were validated in IPF patient tissues in situ as well as in cell differentiation and invasion assays using patient lung fibroblasts. Cell differentiation and invasion assays established a function of SFRP1 in regulating human lung fibroblast invasion in response to TGFβ1. MEASUREMENTS AND MAIN RESULTS: We discovered a transitional fibroblast state characterized by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1+ cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1+ transitional fibroblasts and Cthrc1+ myofibroblasts. TGFβ1 downregulated SFRP1 in non-invasive transitional cells and induced their switch to an invasive CTHRC1+ myofibroblast identity. Finally, using loss of function studies we showed that SFRP1 modulates TGFβ1 induced fibroblast invasion and RHOA pathway activity. CONCLUSIONS: Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies SFRP1 as a modulator of TGFβ1 driven fibroblast phenotypes in fibrogenesis. These findings are relevant in the context of therapeutic interventions that aim at limiting or reversing fibroblast foci formation.
AU  - Mayr, C.
AU  - Sengupta, A.
AU  - Asgharpour, S.
AU  - Ansari, M.
AU  - Pestoni, J.
AU  - Ogar, P.
AU  - Angelidis, I.
AU  - Liontos, A.*
AU  - Rodriguez-Castillo, J.A.*
AU  - Lang, N.J.
AU  - Strunz, M.
AU  - Porras-Gonzalez, D.L.
AU  - Gerckens, M.
AU  - De Sadeleer, L.J.
AU  - Oehrle, B.
AU  - Viteri-Alvarez, V.
AU  - Fernandez, I.E.
AU  - Tallquist, M.*
AU  - Irmler, M.
AU  - Beckers, J.
AU  - Eickelberg, O.*
AU  - Stoleriu, M.G.*
AU  - Behr, J.*
AU  - Kneidinger, N.*
AU  - Wuyts, W.A.*
AU  - Wasnick, R.
AU  - Yildirim, A.Ö.
AU  - Ahlbrecht, K.*
AU  - Morty, R.E.*
AU  - Samakovlis, C.*
AU  - Theis, F.J.
AU  - Burgstaller, G.
AU  - Schiller, H.
C1  - 69760
C2  - 55258
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Sfrp1 inhibits lung fibroblast invasion during transition to injury induced myofibroblasts.
JO  - Eur. Respir. J.
VL  - 63
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2024
SN  - 0903-1936
ER  - 

TY  - CONF
AB  - Our study focuses on the intricate connection between tissue-level organization and ciliated organ function in humans, particularly in understanding the morphological organization of airways and their role in mucociliary clearance. Mucociliary clearance is a key mechanical defense mechanism of human airways, and clearance failure is associated with many respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma. While single-cell transcriptomics have unveiled the cellular complexity of the human airway epithelium, our understanding of the mechanics that link epithelial structure to clearance function mainly stem from animal models. This reliance on animal data limits crucial insights into human airway barrier function and hampers the human-relevant in vitro modeling of airway diseases. This study, for the first time, maps the distribution of ciliated and secretory cell types along the airway tree in both rats and humans, noting species-specific differences in ciliary function and elucidates structural parameters of airway epithelia that predict clearance function in both native and in vitro tissues alike. By uncovering how tissue organization influences ciliary function, we can better understand disruptions in mucociliary clearance, which could have implications for various ciliated organs beyond the airways.
AU  - Roth, D.
AU  - Sahin, A.T.
AU  - Ling, F.
AU  - Senger, C.N.*
AU  - Quiroz, E.J.*
AU  - Calvert, B.A.*
AU  - van der Does, A.M.*
AU  - Güney, T.G.
AU  - Tepho, N.
AU  - Glasl, S.
AU  - van Schadewijk, A.*
AU  - von Schledorn, L.*
AU  - Olmer, R.*
AU  - Kanso, E.*
AU  - Nawroth, J.
AU  - Ryan, A.L.*
C1  - 70708
C2  - 56515
TI  - Structure-function relationships of mucociliary clearance in human airways.
JO  - Eur. Respir. J.
VL  - 64
PY  - 2024
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Yildirim, A.Ö.
AU  - Conlon, T.M.
AU  - Adcock, I.M.*
AU  - Gosens, R.*
AU  - Lehmann, M.
AU  - Kapellos, T.
AU  - Tesfaigzi, Y.*
AU  - Polverino, F.*
AU  - Sauler, M.*
AU  - Wasnick, R.
AU  - Neptune, E.R.*
C1  - 71848
C2  - 56341
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - COPD-iNET: A call to the lung community for action to combat the global epidemic of COPD.
JO  - Eur. Respir. J.
VL  - 64
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2024
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - BACKGROUND: Impulse oscillometry (IOS) allows an effort-independent evaluation of small airway function in asthma. Unfortunately, well-determined minimal clinically important differences (MCID) for IOS-measures are lacking. Here, we provide MCIDs for frequently used IOS-measures, namely frequency dependence of resistance (FDR) and area of reactance (AX) in patients with asthma. METHODS: We performed IOS at baseline and 1 year later in adult patients with mild to severe asthma (n=235). In a two-step approach, we first applied a distribution-based method to statistically determine the MCID. Next, we validated the proposed MCID according to patient-reported outcome measures (PROMs) of Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ) and Asthma Control Test (ACT). We used multivariable analyses to investigate the proposed MCIDs as predictors for improvements in PROMs in comparison to the established MCID of FEV1. RESULTS: The proposed MCID was a decline of≥0.06 kPa·L-1·s-1 and≥0.65 kPa·L-1 for FDR and AX, respectively. Patients who had changes beyond the MCID for both FDR and AX showed greater improvements in all PROMs than those who had not. The mean improvements in PROMs were beyond the established MCID for ACQ and AQLQ and approximated the MCID for ACT score. Multivariable analyses demonstrated the MCID for both FDR and AX as independent predictors for the MCID of all PROMs. The MCID for FDR was a stronger predictor of all PROMs than the MCID for FEV1. CONCLUSION: This study provides MCIDs for IOS-derived measures in adult patients with asthma and emphasizes that small airway function is a distinguished endpoint beyond the conventional measure of FEV1.
AU  - Abdo, M.*
AU  - Kirsten, A.M.*
AU  - von Mutius, E.
AU  - Kopp, M.*
AU  - Hansen, G.*
AU  - Rabe, K.F.*
AU  - Watz, H.*
AU  - Trinkmann, F.*
AU  - Bahmer, T.*
AU  - ALLIANCE study group*
C1  - 67482
C2  - 54147
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Minimal clinically important difference for impulse oscillometry in adults with asthma.
JO  - Eur. Respir. J.
VL  - 61
IS  - 5
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Background Virus infections drive COPD exacerbations and progression. Antiviral immunity centres on the activation of virus-specific CD8+ T-cells by viral epitopes presented on major histocompatibility complex (MHC) class I molecules of infected cells. These epitopes are generated by the immunoproteasome, a specialised intracellular protein degradation machine, which is induced by antiviral cytokines in infected cells. Methods We analysed the effects of cigarette smoke on cytokine-and virus-mediated induction of the immunoproteasome in vitro, ex vivo and in vivo using RNA and Western blot analyses. CD8+ T-cell activation was determined in co-culture assays with cigarette smoke-exposed influenza A virus (IAV)-infected cells. Mass-spectrometry-based analysis of MHC class I-bound peptides uncovered the effects of cigarette smoke on inflammatory antigen presentation in lung cells. IAV-specific CD8+ T-cell numbers were determined in patients peripheral blood using tetramer technology. Results Cigarette smoke impaired the induction of the immunoproteasome by cytokine signalling and viral infection in lung cells in vitro, ex vivo and in vivo. In addition, cigarette smoke altered the peptide repertoire of antigens presented on MHC class I molecules under inflammatory conditions. Importantly, MHC class I-mediated activation of IAV-specific CD8+ T-cells was dampened by cigarette smoke. COPD patients exhibited reduced numbers of circulating IAV-specific CD8+ T-cells compared to healthy controls and asthmatics. Conclusion Our data indicate that cigarette smoke interferes with MHC class I antigen generation and presentation and thereby contributes to impaired activation of CD8+ T-cells upon virus infection. This adds important mechanistic insight on how cigarette smoke mediates increased susceptibility of smokers and COPD patients to viral infections.
AU  - Chen, J.
AU  - Wang, X.
AU  - Schmalen, A.
AU  - Haines, S.
AU  - Wolff, M.*
AU  - Ma, H.*
AU  - Zhang, H.*
AU  - Stoleriu, M.-G.
AU  - Nowak, J.
AU  - Nakayama, M.
AU  - Bueno, M.*
AU  - Brands, J.*
AU  - Mora, A.L.*
AU  - Lee, J.S.*
AU  - Krauss-Etschmann, S.*
AU  - Dmitrieva, A.
AU  - Frankenberger, M.
AU  - Hofer, T.P.
AU  - Nößner, E.
AU  - Moosmann, A.*
AU  - Behr, J.*
AU  - Milger, K.*
AU  - Deeg, C.A.*
AU  - Staab-Weijnitz, C.A.
AU  - Hauck, S.M.
AU  - Adler, H.
AU  - Goldmann, T.*
AU  - Gaede, K.I.*
AU  - Behrends, J.*
AU  - Kammerl, I.E.
AU  - Meiners, S.
C1  - 68374
C2  - 54646
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Antiviral CD8+T-cell immune responses are impaired by cigarette smoke and in COPD.
JO  - Eur. Respir. J.
VL  - 62
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Chen, Y.
AU  - Schniering, J.
AU  - Müller, M.
AU  - Albanese, P.*
AU  - Jankevics, A.*
AU  - Jentzsch, R.C.
AU  - Tata, A.*
AU  - Ansari, M.
AU  - De Sadeleer, L.J.
AU  - Yang, L.
AU  - Heumos, L.
AU  - Agami, A.
AU  - Zhou, S.
AU  - Mayr, C.
AU  - Hatz, R.*
AU  - Schneider, C.P.*
AU  - Behr, J.*
AU  - Hilgendorff, A.
AU  - Yildirim, A.Ö.
AU  - Stoleriu, M.G.*
AU  - Dorfmueller, P.*
AU  - Theis, F.J.
AU  - Tata, P.R.*
AU  - Luecken, M.
AU  - Scheltema, R.A.*
AU  - Schiller, H.
C1  - 69785
C2  - 55065
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - A spatially resolved extracellular matrix proteome atlas of the distal human lung.
JO  - Eur. Respir. J.
VL  - 62
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Conlon, T.M.
AU  - Yildirim, A.Ö.
C1  - 67569
C2  - 54074
TI  - Oxysterol metabolism dictates macrophage influx during SARS-CoV-2 infection.
JO  - Eur. Respir. J.
VL  - 61
IS  - 3
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - De Sadeleer, L.J.
AU  - Chen, Y.
AU  - Jentzsch, R.C.
AU  - Wang, Z.
AU  - Qazi, N.
AU  - Lang, N.J.
AU  - Albanese, P.*
AU  - Jankevics, A.*
AU  - Theis, F.J.
AU  - Scheltema, R.A.*
AU  - Wuyts, W.A.*
AU  - Gote-Schniering, J.*
AU  - Schiller, H.
C1  - 69772
C2  - 55063
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Evolution of epithelial-mesenchymal cell circuits in the progression of pulmonary fibrosis.
JO  - Eur. Respir. J.
VL  - 62
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Gote-Schniering, J.*
AU  - Lehmann, M.*
AU  - Ansari, M.*
AU  - Wiedemann, K.*
AU  - Melo-Narváez, M.C.*
AU  - Steinchen, C.*
AU  - Jentzsch, R.C.
AU  - Mayr, C.*
AU  - Chen, Y.*
AU  - Lang, N.*
AU  - Agami, A.*
AU  - Angelidis, I.*
AU  - Zhou, S.*
AU  - Koenigshoff, M.*
AU  - Theis, F.J.
AU  - Schiller, H.B.*
C1  - 69771
C2  - 55061
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Spatiotemporal analysis of inflammaging and senescence programs in lung fibrosis using time-resolved single-cell transcriptomics and multiplexed immunofluorescence.
JO  - Eur. Respir. J.
VL  - 62
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - RATIONALE: Pulmonary vascular disease (PVD) affects the majority of preterm neonates with bronchopulmonary dysplasia (BPD) and significantly determines long-term mortality through undetected progression into pulmonary hypertension. OBJECTIVES: To associate characteristics of pulmonary artery (PA) flow and cardiac function with BPD-associated PVD near term using advanced magnetic resonance imaging (MRI) for improved risk stratification. METHODS: Preterms <32 weeks postmenstrual age (PMA) with/without BPD were clinically monitored including standard echocardiography and prospectively enrolled for 3TMRI in spontaneous sleep near term (AIRR study). Semi-manual PA flow quantification (phase-contrast MRI, no BPD n=28, mild n=35, moderate/severe n=25) was complemented by cardiac function assessment (cine MRI). MEASUREMENTS AND MAIN RESULTS: We identified abnormalities in PA flow and cardiac function, i.e. increased net forward volume (ratio right-over-left), decreased mean relative area change and pathologic right end-diastolic volume to sensitively detect BPD-associated PVD while correcting for PMA (L1OAUC=0.88/sensitivity=0.80/specificity=0.81). We linked these changes to increased right ventricular (RV) afterload (RV-arterial coupling (p=0.02), PA midsystolic notching (p=0.015(t2)), cardiac index (p=1.67×10-8)) and correlated echocardiographic findings. Identified in moderate/severe BPD, we successfully applied the PA flow model in heterogeneous mild BPD cases, demonstrating strong correlation of PVD probability with indicators of BPD severity, i.e., duration of mechanical ventilation (R=0.62, p=3.7×10-4) and oxygen supplementation (R=0.58, p=9.2×10-4). CONCLUSIONS: Abnormalities in MRI PA flow and cardiac function exhibit significant, synergistic potential to detect BPD-associated PVD, advancing the possibilities of risk-adapted monitoring.
AU  - Häfner, F.
AU  - Kindt, A.S.D.*
AU  - Strobl, K.*
AU  - Forster, K.*
AU  - Heydarian, M.
AU  - Gonzalez-Rodriguez, E.
AU  - Schubert, B.
AU  - Kraus, Y.*
AU  - Robert, D.P.*
AU  - Flemmer, A.W.*
AU  - Ertl-Wagner, B.*
AU  - Dietrich, O.*
AU  - Stoecklein, S.*
AU  - Tello, K.*
AU  - Hilgendorff, A.
C1  - 68611
C2  - 54728
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - MRI pulmonary artery flow detects lung vascular pathology in preterms with lung disease.
JO  - Eur. Respir. J.
VL  - 62
IS  - 6
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - This multi-country study offers crucial evidence on the associations between tropical cyclone exposure and heightened daily respiratory mortality in East Asia. Significant impacts were observed for pneumonia and COPD deaths, rather than asthma. https://bit.ly/42rCIqM
AU  - He, C.
AU  - Chen, R.*
AU  - Kim, H.*
AU  - Hashizume, M.*
AU  - Lee, W.*
AU  - Honda, Y.*
AU  - Kim, S.E.*
AU  - Guo, Y.L.*
AU  - Schneider, A.E.
AU  - Ge, W.*
AU  - Zhu, Y.*
AU  - Zhou, L.*
AU  - Kan, H.*
C1  - 67893
C2  - 54371
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Tropical cyclone and daily respiratory mortality across East Asia: a time series study.
JO  - Eur. Respir. J.
VL  - 62
IS  - 1
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - COPD is a devastating respiratory condition that manifests via persistent inflammation, emphysema development and small airway remodelling. Lung regeneration is defined as the ability of the lung to repair itself after injury by the proliferation and differentiation of progenitor cell populations, and becomes impaired in the COPD lung as a consequence of cell intrinsic epithelial stem cell defects and signals from the micro-environment. Although the loss of structural integrity and lung regenerative capacity are critical for disease progression, our understanding of the cellular players and molecular pathways that hamper regeneration in COPD remains limited. Intriguingly, despite being a key driver of COPD pathogenesis, the role of the immune system in regulating lung regenerative mechanisms is understudied. In this review, we summarise recent evidence on the contribution of immune cells to lung injury and regeneration. We focus on four main axes: 1) the mechanisms via which myeloid cells cause alveolar degradation; 2) the formation of tertiary lymphoid structures and the production of autoreactive antibodies; 3) the consequences of inefficient apoptotic cell removal; and 4) the effects of innate and adaptive immune cell signalling on alveolar epithelial proliferation and differentiation. We finally provide insight on how recent technological advances in omics technologies and human ex vivo lung models can delineate immune cell-epithelium cross-talk and expedite precision pro-regenerative approaches toward reprogramming the alveolar immune niche to treat COPD.
AU  - Kapellos, T.
AU  - Conlon, T.M.
AU  - Yildirim, A.Ö.
AU  - Lehmann, M.
C1  - 68616
C2  - 54757
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - The impact of the immune system on lung injury and regeneration in COPD.
JO  - Eur. Respir. J.
VL  - 62
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Lehmann, M.
AU  - Kolb, M.*
C1  - 67789
C2  - 54267
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Another piece in the pirfenidone puzzle.
JO  - Eur. Respir. J.
VL  - 61
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Turner, M.C.*
AU  - Andersen, Z.J.*
AU  - Neira, M.*
AU  - Krzyzanowski, M.*
AU  - Malmqvist, E.*
AU  - González Ortiz, A.*
AU  - Kiesewetter, G.*
AU  - Katsouyanni, K.*
AU  - Brunekreef, B.*
AU  - Melén, E.*
AU  - Ljungman, P.*
AU  - Tolotto, M.*
AU  - Forastiere, F.*
AU  - Dendale, P.*
AU  - Price, R.*
AU  - Bakke, O.*
AU  - Reichert, S.*
AU  - Hoek, G.*
AU  - Pershagen, G.*
AU  - Peters, A.
AU  - Querol, X.*
AU  - Gerometta, A.*
AU  - Samoli, E.*
AU  - Markevych, I.*
AU  - Basthiste, R.*
AU  - Khreis, H.*
AU  - Pant, P.*
AU  - Nieuwenhuijsen, M.*
AU  - Sacks, J.D.*
AU  - Hansen, K.*
AU  - Lymes, T.*
AU  - Stauffer, A.*
AU  - Fuller, G.W.*
AU  - Boogaard, H.*
AU  - Hoffmann, B.*
C1  - 68662
C2  - 54867
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Clean air in Europe for all! Taking stock of the proposed revision to the ambient air quality directives: a joint ERS, HEI and ISEE workshop report.
JO  - Eur. Respir. J.
VL  - 62
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) with co-existent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. METHODS: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE:non-CPFE: derivation cohort=317:183; replication cohort=358:152), who were subgrouped using 10%, or 15% visual emphysema thresholds, and an unsupervised machine learning model considering emphysema and ILD extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (DLco) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. RESULTS: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline DLco compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year DLco decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations. CONCLUSION: When assessing disease progression in IPF, DLco decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.
AU  - Zhao, A.*
AU  - Gudmundsson, E.*
AU  - Mogulkoc, N.*
AU  - van Moorsel, C.*
AU  - Corte, T.J.*
AU  - Vasudev, P.*
AU  - Romei, C.*
AU  - Chapman, R.*
AU  - Wallis, T.J.M.*
AU  - Denneny, E.*
AU  - Goos, T.*
AU  - Savas, R.*
AU  - Ahmed, A.*
AU  - Brereton, C.J.*
AU  - van Es, H.W.*
AU  - Jo, H.*
AU  - De Liperi, A.*
AU  - Duncan, M.*
AU  - Pontoppidan, K.*
AU  - De Sadeleer, L.J.
AU  - van Beek, F.*
AU  - Barnett, J.*
AU  - Cross, G.*
AU  - Procter, A.*
AU  - Veltkamp, M.*
AU  - Hopkins, P.*
AU  - Moodley, Y.*
AU  - Taliani, A.*
AU  - Taylor, M.*
AU  - Verleden, S.*
AU  - Tavanti, L.*
AU  - Vermant, M.*
AU  - Nair, A.*
AU  - Stewart, I.*
AU  - Janes, S.M.*
AU  - Young, A.L.*
AU  - Barber, D.*
AU  - Alexander, D.C.*
AU  - Porter, J.C.*
AU  - Wells, A.U.*
AU  - Jones, M.G.*
AU  - Wuyts, W.A.*
AU  - Jacob, J.*
C1  - 68770
C2  - 54980
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Mortality surrogates in combined pulmonary fibrosis and emphysema.
JO  - Eur. Respir. J.
VL  - 63
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2023
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Bal, C.*
AU  - Idzko, M.*
AU  - Škrgat, S.*
AU  - Koch, A.
AU  - Milger, K.
AU  - Schulz, C.*
AU  - Zehetmayer, S.*
AU  - Hamelmann, E.*
AU  - Buhl, R.*
AU  - Korn, S.*
C1  - 65358
C2  - 52674
TI  - Fraction of exhaled nitric oxide is associated with disease burden in the German Asthma Net severe asthma cohort.
JO  - Eur. Respir. J.
VL  - 59
IS  - 6
PY  - 2022
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - BACKGROUND: Comprehensive studies investigated the role of T cells in asthma leading to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B cells to this chronic inflammatory disease. In this study, we investigated the contribution of various B cell populations to specific clinical features in asthma. METHODS: In the All Age Asthma Cohort (ALLIANCE) a subgroup of 154 adult asthma patients and 28 healthy controls were included for B cell characterisation by flow cytometry. Questionnaires, lung function measurements, blood differential counts and allergy testing of participants were analysed together with comprehensive data on B cells via association studies and multivariate linear models. RESULTS: Patients with severe asthma showed decreased immature B cell populations while memory B cells were significantly increased compared to both mild-moderate asthma patients and healthy controls. Furthermore, increased frequencies of immunoglobulin A positive (IgA+) memory B cells were associated with impaired lung function and specifically with parameters indicative for augmented resistance in the peripheral airways. Accordingly, asthma patients with small airway dysfunction (SAD) defined by impulse oscillometry showed increased frequencies of IgA+ memory B cells, particularly in patients with mild to moderate asthma. Additionally, IgA+ memory B cells significantly correlated with clinical features of SAD such as exacerbations. CONCLUSIONS: With this study we demonstrate for the first time a significant association of increased IgA+ memory B cells with asthma and SAD, pointing towards future options for B cell-directed strategies in preventing and treating asthma.
AU  - Habener, A.*
AU  - Grychtol, R.*
AU  - Gaedcke, S.*
AU  - Deluca, D.*
AU  - Dittrich, A.M.*
AU  - Happle, C.*
AU  - Abdo, M.*
AU  - Watz, H.*
AU  - Pedersen, F.*
AU  - König, I.R.*
AU  - Thiele, D.*
AU  - Kopp, M.V.*
AU  - von Mutius, E.
AU  - Bahmer, T.*
AU  - Rabe, K.F.*
AU  - Meyer-Bahlburg, A.*
AU  - Hansen, G.*
AU  - ALLIANCE Study Group (Zissler, U.M.
AU  - Maison, N.
AU  - Illi, S.
AU  - Marzi, C.
AU  - Schmidt-Weber, C.B.)
C1  - 65078
C2  - 52138
TI  - IgA+ memory B cells are significantly increased in patients with asthma and small airways dysfunction.
JO  - Eur. Respir. J.
VL  - 60
IS  - 5
PY  - 2022
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Heinzelmann, K.
AU  - Hu, Q.
AU  - Hu, Y.*
AU  - Dobrinskikh, E.*
AU  - Ansari, M.
AU  - Melo-Narváez, C.
AU  - Ulke, H.M.
AU  - Leavitt, C.*
AU  - Mirita, C.*
AU  - Trudeau, T.*
AU  - Saal, M.L.*
AU  - Rice, P.*
AU  - Gao, B.*
AU  - Janssen, W.J.*
AU  - Yang, I.V.*
AU  - Schiller, H. B.
AU  - Vladar, E.K.*
AU  - Lehmann, M.
AU  - Königshoff, M.*
C1  - 65071
C2  - 52139
TI  - Single cell RNA sequencing identifies G-protein coupled receptor 87 as a basal cell marker expressed in distal honeycomb cysts in idiopathic pulmonary fibrosis.
JO  - Eur. Respir. J.
VL  - 59
IS  - 6
PY  - 2022
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The Human Cell Atlas (HCA) consortium aims to establish an atlas of all organs in the healthy human body at single-cell resolution to increase our understanding of basic biological processes that govern development, physiology and anatomy, and to accelerate diagnosis and treatment of disease. The lung biological network of the HCA aims to generate the Human Lung Cell Atlas as a reference for the cellular repertoire, molecular cell states and phenotypes, and the cell-cell interactions that characterise normal lung homeostasis in healthy lung tissue. Such a reference atlas of the healthy human lung will facilitate mapping the changes in the cellular landscape in disease. The discovAIR project is one of six pilot actions for the HCA funded by the European Commission in the context of the H2020 framework program. DiscovAIR aims to establish the first draft of an integrated Human Lung Cell Atlas, combining single-cell transcriptional and epigenetic profiling with spatially resolving techniques on matched tissue samples, as well as including a number of chronic and infectious diseases of the lung. The integrated Lung Cell Atlas will be available as a resource for the wider respiratory community, including basic and translational scientists, clinical medicine, and the private sector, as well as for patients with lung disease and the interested lay public. We anticipate that the Lung Cell Atlas will be the founding stone for a more detailed understanding of the pathogenesis of lung diseases, guiding the design of novel diagnostics and preventive or curative interventions.
AU  - Luecken, M.
AU  - Zaragosi, L.E.*
AU  - Madissoon, E.*
AU  - Sikkema, L.
AU  - Firsova, A.B.*
AU  - De Domenico, E.*
AU  - Kuemmerle, L.
AU  - Saglam, A.*
AU  - Berg, M.*
AU  - Gay, A.C.A.*
AU  - Schniering, J.
AU  - Mayr, C.
AU  - Abalo, X.M.*
AU  - Larsson, L.*
AU  - Sountoulidis, A.*
AU  - Teichmann, S.*
AU  - van Eunen, K.*
AU  - Koppelman, G.H.*
AU  - Saeb-Parsy, K.*
AU  - Leroy, S.*
AU  - Powell, P.*
AU  - Sarkans, U.*
AU  - Timens, W.*
AU  - Lundeberg, J.*
AU  - van den Berge, M.*
AU  - Nilsson, M.*
AU  - Horváth, P.*
AU  - Denning, J.*
AU  - Papatheodorou, I.*
AU  - Schultze, J.L.*
AU  - Schiller, H. B.
AU  - Barbry, P.*
AU  - Petoukhov, I.*
AU  - Misharin, A.V.*
AU  - Adcock, I.*
AU  - von Papen, M.*
AU  - Theis, F.J.
AU  - Samakovlis, C.*
AU  - Meyer, K.B.*
AU  - Nawijn, M.C.*
C1  - 64264
C2  - 51827
TI  - The discovAIR project: A roadmap towards the Human Lung Cell Atlas.
JO  - Eur. Respir. J.
VL  - 59
IS  - 3
PY  - 2022
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - RATIONALE: In adults, personalised asthma treatment targets patients with T2-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children. OBJECTIVES: To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages. METHODS: In the multicenter clinical ALL Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years (1 year in adults). Extensive clinical characterisation (questionnaires, blood differential count, allergy testing, lung function and sputum induction (in adults) was performed at baseline and follow-ups. Interleukin (IL)-4, IL-5 and IL-13 were measured after stimulation of whole blood with LPS or anti-CD3/CD28. MEASUREMENTS AND MAIN RESULTS: Based on blood eosinophil counts and allergen-specific serum IgE antibodies (sIgE), patients were categorised into four mutually exclusive phenotypes: "Atopy-only", "Eosinophils-only", "T2-high" (eosinophilia+atopy) and "T2-low" (neither eosinophilia nor atopy). The T2-high phenotype was found across all ages, even in very young children in whom it persisted to a large degree even after 2 years of follow-up. T2-high asthma in adults was associated with childhood onset suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterised by excessive production of specific IgE to allergens (p<0.0001) and, from school age onwards, by increased production of IL-5 after anti-CD3/CD28 stimulation of whole blood. CONCLUSIONS: Using easily accessible biomarkers, patients with T2-high asthma can be identified across all ages delineating a distinct phenotype. These patients may benefit from therapy with biologicals even at younger age.
AU  - Maison, N.
AU  - Omony, J.
AU  - Illi, S.
AU  - Thiele, D.*
AU  - Skevaki, C.*
AU  - Dittrich, A.M.*
AU  - Bahmer, T.*
AU  - Rabe, K.F.*
AU  - Weckmann, M.*
AU  - Happle, C.*
AU  - Schaub, B.*
AU  - Meier, M.*
AU  - Foth, S.*
AU  - Rietschel, E.*
AU  - Renz, H.*
AU  - Hansen, G.*
AU  - Kopp, M.V.*
AU  - von Mutius, E.
AU  - Grychtol, R.*
AU  - ALLIANCE Study Group (Marzi, C.
AU  - Zissler, U.M.
AU  - Schmidt-Weber, C.B.)
C1  - 64547
C2  - 51938
TI  - T-high asthma phenotypes across life span.
JO  - Eur. Respir. J.
VL  - 60
IS  - 3
PY  - 2022
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Schniering, J.
AU  - Maciukiewicz, M.*
AU  - Tanadini-Lang, S.*
AU  - Maurer, B.*
C1  - 65070
C2  - 52141
TI  - Reply to: The potential and challenges of radiomics in uncovering prognostic and molecular differences in interstitial lung disease associated with systemic sclerosis.
JO  - Eur. Respir. J.
VL  - 59
IS  - 6
PY  - 2022
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - RATIONALE: Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of regulated cell death (including apoptosis and necroptosis) and inflammation, both drivers of chronic obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVE: We aimed to define the contribution of RIPK1 kinase-dependent cell death and inflammation in the pathogenesis of COPD. METHODS: We assessed RIPK1 expression in single-cell RNA-sequencing data from human and mouse lungs and validated RIPK1 levels in lung tissue of COPD patients via immunohistochemistry. Next, we assessed the consequences of genetic and pharmacological inhibition of RIPK1 kinase activity in experimental COPD, using Ripk1S25D /S25D kinase deficient mice and the RIPK1 kinase inhibitor GSK'547. MEASUREMENTS AND MAIN RESULTS: RIPK1 expression increased in alveolar type I (AT1), AT2, ciliated and neuroendocrine cells in human COPD. RIPK1 protein levels were significantly increased in airway epithelium of COPD patients, compared to never smokers and smokers without airflow limitation. In mice, exposure to cigarette smoke (CS) increased Ripk1 expression similarly in AT2 cells, and further in alveolar macrophages and T cells. Genetic and/or pharmacological inhibition of RIPK1 kinase activity significantly attenuated airway inflammation upon acute and subacute CS-exposure, as well as airway remodeling, emphysema and apoptotic and necroptotic cell death upon chronic CS-exposure. Similarly, pharmacological RIPK1 kinase inhibition significantly attenuated elastase-induced emphysema and lung function decline. Finally, RNA-sequencing on lung tissue of CS-exposed mice revealed downregulation of cell death and inflammatory pathways upon pharmacological RIPK1 kinase inhibition. CONCLUSIONS: RIPK1 kinase inhibition is protective in experimental models of COPD and may represent a novel promising therapeutic approach.
AU  - Van Eeckhoutte, H.P.*
AU  - Donovan, C.*
AU  - Kim, R.Y.*
AU  - Conlon, T.M.
AU  - Ansari, M.
AU  - Khan, H.*
AU  - Jayaraman, R.*
AU  - Hansbro, N.G.*
AU  - Dondelinger, Y.*
AU  - Delanghe, T.*
AU  - Beal, A.M.*
AU  - Geddes, B.*
AU  - Bertin, J.*
AU  - Berghe, T.V.*
AU  - De Volder, J.*
AU  - Maes, T.*
AU  - Vandenabeele, P.*
AU  - Vanaudenaerde, B.M.*
AU  - Deforce, D.*
AU  - Škevin, S.*
AU  - Van Nieuwerburgh, F.*
AU  - Verhamme, F.M.*
AU  - Joos, G.F.*
AU  - Idrees, S.*
AU  - Schiller, H. B.
AU  - Yildirim, A.Ö.
AU  - Faiz, A.*
AU  - Bertrand, M.J.M.*
AU  - Brusselle, G.G.*
AU  - Hansbro, P.M.*
AU  - Bracke, K.R.*
C1  - 67133
C2  - 53494
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - RIPK1 kinase-dependent inflammation and cell death contribute to the pathogenesis of COPD.
JO  - Eur. Respir. J.
VL  - 61
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2022
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. OBJECTIVE: To examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school-age. METHODS: We used individual-participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75), and asthma at a median age of 7 (range 4 to 15) years. RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75 (Z-score (95% CI): ranging from -0.09 (-0.14, -0.04) to -0.30 (-0.36, -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR (95%CI): ranging from 2.10 (1.98, 2.22) to 6.30 (5.64, 7.04)), and from 1.25 (1.18, 1.32) to 1.55 (1.47, 1.65)), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as proxy for early-life asthma. CONCLUSION: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower upper respiratory tract infections.
AU  - van Meel, E.R.*
AU  - Mensink-Bout, S.M.*
AU  - den Dekker, H.T.*
AU  - Ahluwalia, T.S.*
AU  - Annesi-Maesano, I.*
AU  - Arshad, S.H.*
AU  - Baïz, N.*
AU  - Barros, H.*
AU  - von Berg, A.*
AU  - Bisgaard, H.*
AU  - Bønnelykke, K.*
AU  - Carlsson, C.J.*
AU  - Casas, M.*
AU  - Chatzi, L.*
AU  - Chévrier, C.*
AU  - Dalmeijer, G.*
AU  - Dezateux, C.*
AU  - Duchen, K.*
AU  - Eggesbø, M.*
AU  - van der Ent, C.K.*
AU  - Fantini, M.*
AU  - Flexeder, C.
AU  - Frey, U.*
AU  - Forastiere, F.*
AU  - Gehring, U.*
AU  - Gori, D.*
AU  - Granell, R.*
AU  - Griffiths, L.J.*
AU  - Inskip, H.*
AU  - Jerzyńska, J.*
AU  - Karvonen, A.M.*
AU  - Keil, T.*
AU  - Kelleher, C.*
AU  - Kogevinas, M.*
AU  - Koppen, G.*
AU  - Kuehni, C.E.*
AU  - Lambrechts, N.*
AU  - Lau, S.*
AU  - Lehmann, I.*
AU  - Ludvigsson, J.*
AU  - Magnus, M.C.*
AU  - Melén, E.*
AU  - Mehegan, J.*
AU  - Mommers, M.*
AU  - Andersen, A.N.*
AU  - Nystad, W.*
AU  - Pedersen, E.S.L.*
AU  - Pekkanen, J.*
AU  - Peltola, V.*
AU  - Pike, K.C.*
AU  - de Moira, A.P.*
AU  - Pizzi, C.*
AU  - Polanska, K.*
AU  - Popović, M.*
AU  - Porta, D.*
AU  - Roberts, G.*
AU  - Santos, A.C.*
AU  - Schultz, E.S.*
AU  - Standl, M.
AU  - Sunyer, J.*
AU  - Thijs, C.*
AU  - Toivonen, L.*
AU  - Uphoff, E.*
AU  - Usemann, J.*
AU  - Vafeidi, M.*
AU  - Wright, J.*
AU  - de Jongste, J.C.*
AU  - Jaddoe, V.W.V.*
AU  - Duijts, L.*
C1  - 65034
C2  - 52146
TI  - Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: A meta-analysis of 150 000 European children.
JO  - Eur. Respir. J.
VL  - 60
IS  - 4
PY  - 2022
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - BACKGROUND: Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a 3-strata model to categorise risk as low, intermediate, or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on 4 risk categories with intermediate risk subdivided into intermediate-low and intermediate-high risk. METHODS: We analysed data from COMPERA, a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on functional class (FC), 6 min walking distance (6 MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal fragment of pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed with Kaplan-Meier analyses, log-rank testing, and Cox proportional hazards models. RESULTS: Data from 1,655 patients with PAH were analysed. Using the 3-strata model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined 4-strata risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the 3-strata model and in 49.2% with the 4-strata model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk. CONCLUSIONS: Modified risk stratification using a 4-strata model based on refined cut-off levels for FC, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original 3-strata model.
AU  - Hoeper, M.M.*
AU  - Pausch, C.*
AU  - Olsson, K.M.*
AU  - Huscher, D.*
AU  - Pittrow, D.*
AU  - Grünig, E.*
AU  - Staehler, G.*
AU  - Vizza, C.D.*
AU  - Gall, H.*
AU  - Distler, O.*
AU  - Opitz, C.*
AU  - Gibbs, J.S.R.*
AU  - Delcroix, M.*
AU  - Ghofrani, H.A.*
AU  - Park, D.H.*
AU  - Ewert, R.*
AU  - Kaemmerer, H.*
AU  - Kabitz, H.J.*
AU  - Skowasch, D.*
AU  - Behr, J.
AU  - Milger, K.*
AU  - Halank, M.*
AU  - Wilkens, H.*
AU  - Seyfarth, H.J.*
AU  - Held, M.*
AU  - Dumitrescu, D.*
AU  - Tsangaris, I.*
AU  - Vonk-Noordegraaf, A.*
AU  - Ulrich, S.*
AU  - Klose, H.*
AU  - Claussen, M.*
AU  - Lange, T.J.*
AU  - Rosenkranz, S.*
C1  - 63411
C2  - 51424
TI  - COMPERA 2.0: A refined 4-strata risk assessment model for pulmonary arterial hypertension.
JO  - Eur. Respir. J.
VL  - 60
IS  - 1
PY  - 2021
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Immune cells contain a specialised type of proteasome, i.e. the immunoproteasome, which is required for intracellular protein degradation. Immunoproteasomes are key regulators of immune cell differentiation, inflammatory activation and autoimmunity. Immunoproteasome function in peripheral immune cells might be altered by smoking and in COPD thereby affecting immune cell responses.We here analysed the expression and activity of proteasome complexes in peripheral blood mononuclear cells (PBMC) isolated from healthy male young smokers as well as from patients with severe COPD and compared them to matching controls. Proteasome expression was upregulated in COPD patients as assessed by RT-qPCR and mass spectrometry-based proteomics analysis. Proteasome activity was quantified using activity-based probes and native gel analysis. We observed distinct activation of immunoproteasomes in the peripheral blood cells of young male smokers and severely ill COPD patients. Native gel analysis and linear regression modeling confirmed robust activation and elevated assembly of 20S proteasomes, which correlated significantly with reduced lung function parameters in COPD patients. The immunoproteasome was distinctly activated in COPD patients upon inflammatory cytokine stimulation of PBMCs in vitro Inhibition of the immunoproteasome reduced proinflammatory cytokine expression in COPD-derived blood immune cells.Given the crucial role of chronic inflammatory signalling and the emerging involvement of autoimmune responses in COPD, therapeutic targeting of the immunoproteasome might represent a novel therapeutic concept for COPD.
AU  - Kammerl, I.E.
AU  - Hardy, S.
AU  - Flexeder, C.
AU  - Urmann, A.
AU  - Peierl, J.
AU  - Wang, Y.
AU  - Vosyka, O.
AU  - Frankenberger, M.
AU  - Milger, K.
AU  - Behr, J.
AU  - Koch, A.
AU  - Merl-Pham, J.
AU  - Hauck, S.M.
AU  - Pilette, C.*
AU  - Schulz, H.
AU  - Meiners, S.
C1  - 63113
C2  - 51324
TI  - Activation of immune cell proteasomes in peripheral blood of smokers and COPD patients - implications for therapy.
JO  - Eur. Respir. J.
VL  - 59
IS  - 3
PY  - 2021
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - BACKGROUND: Survival after curative resection of early-stage lung adenocarcinoma (LUAD) varies and prognostic biomarkers are urgently needed. METHODS: Large-format tissue samples from a prospective cohort of 200 patients with resected LUAD were immunophenotyped for cancer hallmarks TP53, NF1, CD45, PD-1, PCNA, TUNEL, and FVIII, and were followed for median (95%CI)=2.34 (1.71-3.49) years. RESULTS: Unsupervised hierarchical clustering revealed two patient subgroups with similar clinicopathologic features and genotype, but with markedly different survival: "proliferative" patients (60%) with elevated TP53, NF1, CD45, and PCNA expression had 50% 5-year overall survival while "apoptotic" patients (40%) with high TUNEL had 70% 5-year survival [HR95%CI=2.23 (1.33-3.80); p=0.0069]. Cox regression and machine learning algorithms including random forests built clinically useful models: a score to predict overall survival and a formula and nomogram to predict tumour phenotype. The distinct LUAD phenotypes were validated in TCGA and KMplotter data and showed prognostic power supplementary to IASLC TNM stage and WHO histologic classification. CONCLUSIONS: Two molecular subtypes of LUAD exist and their identification provides important prognostic information.
AU  - Lamort, A.-S.
AU  - Kaiser, J.C.
AU  - Pepe, M.
AU  - Lilis, I.*
AU  - Ntaliarda, G.*
AU  - Somogyi, K.*
AU  - Spella, M.*
AU  - Behrend, S.J.
AU  - Giotopoulou, G.A.
AU  - Kujawa, W.
AU  - Lindner, M.*
AU  - Koch, I.*
AU  - Hatz, R.A.*
AU  - Behr, J.*
AU  - Sotillo, R.*
AU  - Schamberger, A.C.
AU  - Stathopoulos, G.T.
C1  - 63792
C2  - 51760
TI  - Prognostic phenotypes of early-stage lung adenocarcinoma.
JO  - Eur. Respir. J.
VL  - 60
IS  - 1
PY  - 2021
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - BACKGROUND: Radiomic features calculated from routine medical images show great potential for personalized medicine in cancer. Patients with systemic sclerosis (SSc), a rare, multi-organ autoimmune disorder, have a similarly poor prognosis due to interstitial lung disease (ILD). OBJECTIVES: To explore computed tomography (CT)-based high-dimensional image analysis (radiomics) for disease characterisation, risk stratification, and relaying information on lung pathophysiology in SSc-ILD. METHODS: We investigated two independent, prospectively followed SSc-ILD cohorts (Zurich, derivation cohort, n=90; Oslo, validation cohort, n=66). For every subject, we defined 1'355 robust radiomic features from standard-of-care CT images. We performed unsupervised clustering to identify and characterize imaging-based patient clusters. A clinically applicable prognostic quantitative radiomic risk score (qRISSc) for progression-free survival was derived from radiomic profiles using supervised analysis. The biological basis of qRISSc was assessed in a cross-species approach by correlation with lung proteomics, histological and gene expression data derived from mice with bleomycin-induced lung fibrosis. RESULTS: Radiomic profiling identified two clinically and prognostically distinct SSc-ILD patient clusters. To evaluate the clinical applicability, we derived and externally validated a binary, quantitative radiomic risk score composed of 26 features, qRISSc, that accurately predicted progression-free survival and significantly improved upon clinical risk stratification parameters in multivariable Cox regression analyses in the pooled cohorts. A high qRISSc score, which identifies patients at risk for progression, was reverse translatable from human to experimental ILD and correlated with fibrotic pathway activation. CONCLUSIONS: Radiomics-based risk stratification using routine CT images provides complementary phenotypic, clinical and prognostic information significantly impacting clinical decision-making in SSc-ILD.
AU  - Schniering, J.
AU  - Maciukiewicz, M.*
AU  - Gabryś, H.S.*
AU  - Brunner, M.*
AU  - Blüthgen, C.*
AU  - Meier, C.*
AU  - Braga-Lagache, S.*
AU  - Uldry, A.C.*
AU  - Heller, M.*
AU  - Guckenberger, M.*
AU  - Fretheim, H.*
AU  - Nakas, C.T.*
AU  - Hoffmann-Vold, A.M.*
AU  - Distler, O.*
AU  - Frauenfelder, T.*
AU  - Tanadini-Lang, S.*
AU  - Maurer, B.*
C1  - 63265
C2  - 51315
TI  - Computed tomography-based radiomics decodes prognostic and molecular differences in interstitial lung disease related to systemic sclerosis.
JO  - Eur. Respir. J.
VL  - 59
IS  - 5
PY  - 2021
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Background The effectiveness of the Munich Breathlessness Service (MBS), integrating palliative care, respiratory medicine and physiotherapy, was tested in the BreathEase trial in patients with chronic breathlessness in advanced disease and their carers.Methods BreathEase was a single-blinded randomised controlled fast-track trial. The MBS was attended for 5-6 weeks; the control group started the MBS after 8 weeks of standard care. Randomisation was stratified by cancer and the presence of a carer. Primary outcomes were patients' mastery of breathlessness (Chronic Respiratory Disease Questionnaire (CRQ) Mastery), quality of life (CRQ QoL), symptom burden (Integrated Palliative care Outcome Scale (IPOS)) and carer burden (Zarit Burden Interview (ZBI)). Intention-to-treat (ITT) analyses were conducted with hierarchical testing. Effectiveness was investigated by linear regression on change scores, adjusting for baseline scores and stratification variables. Missing values were handled with multiple imputation.Results 92 patients were randomised to the intervention group and 91 patients were randomised to the control group. Before the follow-up assessment after 8 weeks (T1), 17 and five patients dropped out from the intervention and control groups, respectively. Significant improvements in CRQ Mastery of 0.367 (95% CI 0.065-0.669) and CRQ QoL of 0.226 (95% CI 0.012-0.440) score units at Ti in favour of the intervention group were seen in the ITT analyses (n=183), but not in IPOS. Exploratory testing showed nonsignificant improvements in 21311.Conclusions These findings demonstrate positive effects of the MBS in reducing burden caused by chronic breathlessness in advanced illness across a wide range of patients. Further evaluation in subgroups of patients and with a longitudinal perspective is needed.
AU  - Schunk, M.*
AU  - Le, L.*
AU  - Syunyaeva, Z.*
AU  - Haberland, B.*
AU  - Tänzler, S.*
AU  - Mansmann, U.*
AU  - Schwarzkopf, L.
AU  - Seidl, H.
AU  - Streitwieser, S.*
AU  - Hofmann, M.*
AU  - Müller, T.*
AU  - Weiß, T.*
AU  - Morawietz, P.*
AU  - Rehfuess, E.A.*
AU  - Huber, R.M.*
AU  - Berger, U.*
AU  - Bausewein, C.*
C1  - 61201
C2  - 50087
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Effectiveness of a specialised breathlessness service for patients with advanced disease in Germany: A pragmatic fast track randomised controlled trial (BreathEase).
JO  - Eur. Respir. J.
VL  - 58
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2021
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - BACKGROUND: Asthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3). OBJECTIVE: To delineate the degradation of COL4A3 in allergic airway inflammation and evaluate the resultant product as a biomarker for anti-IgE therapy response. METHODS: The serological COL4A3 degradation marker C4Ma3 (Nordic Bioscience, Denmark) and serum cytokines were measured in the ALLIANCE cohort (pediatric cases/controls: 134/35; adult cases/controls: 149/31). Exacerbation of allergic airway disease in mice was induced by sensitising to OVA, challenge with OVA aerosol and instillation of poly(cytidylic-inosinic). Fulacimstat (chymase inhibitor, Bayer) was used to determine the role of mast cell chymase in COL4A3 degradation. Patients with cystic fibrosis (CF, n=14) and CF with allergic broncho-pulmonary aspergillosis (ABPA, n=9) as well as severe allergic, uncontrolled asthmatics (n=19) were tested for COL4A3 degradation. Omalizumab (anti-IgE) treatment was assessed by the Asthma Control Test. RESULTS: Serum levels of C4Ma3 were increased in asthma in adults and children alike and linked to a more severe, exacerbating allergic asthma phenotype. In an experimental asthma mouse model, C4Ma3 was dependent on mast cell chymase. Serum C4Ma3 was significantly elevated in CF plus ABPA and at baseline predicted the success of the anti-IgE therapy in allergic, uncontrolled asthmatics (diagnostic odds ratio 31.5). CONCLUSION: C4Ma3 level depend on lung mast cell chymase and are increased in a severe, exacerbating allergic asthma phenotype. C4Ma3 may serve as a novel biomarker to predict anti-IgE therapy response.
AU  - Weckmann, M.*
AU  - Bahmer, T.*
AU  - Bülow Sand, J.M.*
AU  - Rank Rønnow, S.*
AU  - Pech, M.*
AU  - Vermeulen, C.*
AU  - Faiz, A.*
AU  - Leeming, D.J.*
AU  - Karsdal, M.A.*
AU  - Lunding, L.*
AU  - Oliver, B.G.G.*
AU  - Wegmann, M.*
AU  - Ulrich-Merzenich, G.*
AU  - Juergens, U.R.*
AU  - Duhn, J.*
AU  - Laumonnier, Y.*
AU  - Danov, O.*
AU  - Sewald, K.*
AU  - Zissler, U.M.
AU  - Jonker, M.A.*
AU  - König, I.*
AU  - Hansen, G.*
AU  - Mutius, E. von*
AU  - Fuchs, O.*
AU  - Dittrich, A.M.*
AU  - Schaub, B.*
AU  - Happle, C.*
AU  - Rabe, K.F.*
AU  - van de Berge, M.*
AU  - Burgess, J.K.*
AU  - Kopp, M.V.*
C1  - 62777
C2  - 51058
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - COL4A3 is degraded in allergic asthma and degradation predicts response to anti-IgE therapy.
JO  - Eur. Respir. J.
VL  - 58
IS  - 6
PB  - European Respiratory Soc Journals Ltd
PY  - 2021
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Objective: There is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions.Methods: We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy.Results: Among the 588 patients suitable for analysis, the mean +/- so age was 69.8 +/- 9.1 years, and 81.0% were male. The mean +/- so duration of disease since diagnosis was 1.8 +/- 3.4 years. The mean +/- SD value at baseline for forced vital capacity (FVC) and diffusion capacity (D-LCO) were 68.6 +/- 18.8% predicted and 37.8 +/- 18.5% predicted, respectively. During a mean +/- so follow-up of 1.2 +/- 0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% versus 46% and 62% versus 21%, respectively, for patients with versus without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and D-LCO was slow and did not differ significantly between patients with or without antifibrotic therapy.Conclusions: Survival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This su vests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and D-LCO.
AU  - Behr, J.
AU  - Prasse, A.*
AU  - Wirtz, H.*
AU  - Koschel, D.*
AU  - Pittrow, D.*
AU  - Held, M.*
AU  - Klotsche, J.*
AU  - Andreas, S.*
AU  - Claussen, M.*
AU  - Grohe, C.*
AU  - Wilkens, H.*
AU  - Hagmeyer, L.*
AU  - Skowasch, D.*
AU  - Meyer, J.F.*
AU  - Kirschner, J.*
AU  - Glaeser, S.*
AU  - Kahn, N.*
AU  - Welte, T.*
AU  - Neurohr, C.*
AU  - Schwaiblmair, M.*
AU  - Bahmer, T.*
AU  - Oqueka, T.*
AU  - Frankenberger, M.
AU  - Kreuter, M.*
C1  - 60403
C2  - 49232
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: Long-term results of the INSIGHTS-IPF registry.
JO  - Eur. Respir. J.
VL  - 56
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2020
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Circulating immune cell populations have been shown to contribute to interstitial lung disease (ILD). In this study, we analysed circulating and lung resident monocyte populations, and assessed their phenotype and recruitment from the blood to the lung in ILD. Flow cytometry analysis of blood samples for quantifying circulating monocytes was performed in 105 subjects: 83 with ILD (n=36, n=28 and n=19 for nonspecific interstitial pneumonia, hypersensitivity pneumonitis and connective-tissue disease-associated ILD, respectively), as well as 22 controls. Monocyte localisation and abundance were assessed using immunofluorescence and flow cytometry of lung tissue. Monocyte populations were cultured either alone or with endothelial cells to assess fractalkine-dependent transmigration pattern. We show that circulating classical monocytes (CM) were increased in ILD compared with controls, while nonclassical monocytes (NCM) were decreased. CM abundance correlated inversely with lung function, while NCM abundance correlated positively. Both CCL2 and CX3CL1 concentrations were increased in plasma and lungs of ILD patients. Fractalkine co-localised with ciliated bronchial epithelial cells, thereby creating a chemoattractant gradient towards the lung. Fractalkine enhanced endothelial transmigration of NCM in ILD samples only. Immunofluorescence, as well as flow cytometry, showed an increased presence of NCM in fibrotic niches in ILD lungs. Moreover, NCM in the ILD lungs expressed increased CX3CR1, M2-like and phagocytic markers. Taken together, our data support that in ILD, fractalkine drives the migration of CX3CR1(+) NCM to the lungs, thereby perpetuating the local fibrotic process.
AU  - Greiffo, F.R.
AU  - Viteri-Alvarez, V.
AU  - Frankenberger, M.
AU  - Dietel, D.
AU  - Ortega-Gomez, A.*
AU  - Lee, J.S.*
AU  - Hilgendorff, A.
AU  - Behr, J.*
AU  - Soehnlein, O.*
AU  - Eickelberg, O.
AU  - Fernandez, I.E.
C1  - 57374
C2  - 47782
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - CX3CR1-fractalkine axis drives kinetic changes of monocytes in fibrotic interstitial lung diseases.
JO  - Eur. Respir. J.
VL  - 55
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2020
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Kaiser, J.C.
AU  - Stathopoulos, G.T.
C1  - 60143
C2  - 49693
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Socioeconomic correlates of SARS-CoV-2 and influenza H1N1 outbreaks.
JO  - Eur. Respir. J.
VL  - 56
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2020
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Bronchiolitis obliterans syndrome (BOS) is a major complication after lung transplantation (LTx). BOS is characterised by massive peribronchial fibrosis, leading to air trapping induced pulmonary dysfunction. Cathepsin B, a lysosomal cysteine-protease, was shown to enforce fibrotic pathways in several diseases. However, the relevance of Cathepsin B in BOS progression has not yet been addressed. The aim of the study was to elucidate the function of Cathepsin B in BOS pathogenesis.We determined Cathepsin B levels in BAL fluid and lung tissue from healthy donors (HD) and BOS LTx patients. Furthermore, Cathepsin B activity was assessed via a FRET-based assay and protein expression was determined using Western blotting, ELISA, and immunostaining. To investigate the impact of Cathepsin B in the pathophysiology of BOS, we used an in-vivo orthotopic left-LTx mouse model. Mechanistic studies were performed in-vitro using macrophage and fibroblast cell lines.We found a significant increase of Cathepsin B activity in BALF and lung tissue from BOS patients, as well as in our murine model of lymphocytic bronchiolitis (LB). Moreover, Cathepsin B activity was associated with an increased biosynthesis of collagen, and negatively affected lung function. Interestingly, we observed that Cathepsin B was mainly expressed in macrophages that infiltrated areas characterised by a massive accumulation of collagen deposition. Mechanistically, macrophage-derived Cathepsin B contributed to TGF-β1-dependent activation of fibroblasts, and its inhibition reversed the phenotype.Infiltrating macrophages release active Cathepsin B promoting fibroblast-activation and subsequent collagen deposition, driving BOS. Cathepsin B represents a promising therapeutic target to prevent the progression of BOS.
AU  - Morrone, C.
AU  - Smirnova, N.F.*
AU  - Jeridi, A.
AU  - Kneidinger, N.*
AU  - Hollauer, C.
AU  - Schupp, J.C.*
AU  - Kaminski, N.*
AU  - Jenne, D.
AU  - Eickelberg, O.*
AU  - Yildirim, A.Ö.
C1  - 60762
C2  - 49536
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Cathepsin B promotes collagen biosynthesis driving Bronchiolitis Obliterans Syndrome.
JO  - Eur. Respir. J.
VL  - 57
IS  - 5
PB  - European Respiratory Soc Journals Ltd
PY  - 2020
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Bahmer, T.*
AU  - Krauss-Etschmann, S.*
AU  - Buschmann, D.*
AU  - Behrends, J.*
AU  - Watz, H.*
AU  - Kirsten, A.*
AU  - Pedersen, F.*
AU  - Waschki, B.*
AU  - Fuchs, O.*
AU  - Pfaffl, M.*
AU  - von Mutius, E.
AU  - Rabe, K.F.*
AU  - Hansen, G.*
AU  - Kopp, M.*
AU  - Koenig, I.R.*
AU  - Bartel, S.*
C1  - 58075
C2  - 48055
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - miR-122-5p and miR-191-5p are increased in plasma small extracellular vesicles in asthma.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Bedard, A.*
AU  - Accordini, S.*
AU  - Carsin, A.*
AU  - Dharmage, S.*
AU  - Fuertes, E.*
AU  - Garcia-Larsen, V.*
AU  - Heinrich, J.
AU  - Janson, C.*
AU  - Jarvis, D.*
AU  - Johannessen, A.*
AU  - Leynaert, B.*
AU  - Maldonado Perez, J.A.*
AU  - Prado Peralta, G.*
AU  - Pin, I.*
AU  - Squillacioti, G.*
AU  - Weyler, J.*
AU  - Garcia-Aymerich, J.*
C1  - 58076
C2  - 48054
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Is the association between physical activity and lung function due to reverse causation? Application of exploratory and causal approaches.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Behr, J.*
AU  - Wirtz, H.*
AU  - Pittrow, D.*
AU  - Prasse, A.*
AU  - Koschel, D.*
AU  - Geier, S.*
AU  - Klotsche, J.*
AU  - Andreas, S.*
AU  - Claussen, M.*
AU  - Grohe, C.*
AU  - Wilkens, H.*
AU  - Hagmeyer, L.*
AU  - Skowasch, D.*
AU  - Meyer, J.F.*
AU  - Kirschner, J.*
AU  - Glaeser, S.*
AU  - Kahn, N.*
AU  - Welte, T.*
AU  - Neurohr, C.*
AU  - Schwaiblmair, M.*
AU  - Held, M.*
AU  - Bahmer, T.*
AU  - Oqueka, T.*
AU  - Frankenberger, M.
AU  - Kreuter, M.*
C1  - 58083
C2  - 48038
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Late Breaking Abstract - Survival and course of lung function in patients with idiopathic pulmonary fibrosis with or without antifibrotic treatment: Long-term results of the INSIGHTS-IPF registry.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Chen, J.
AU  - Brands, J.*
AU  - Bueno, M.*
AU  - Adler, H.
AU  - Mora, A.*
AU  - Meiners, S.
AU  - Kammerl, I.E.
C1  - 58065
C2  - 48051
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - LSC-2019-Effect of cigarette smoke on immunoproteasome function during virus infection.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Fuertes, E.*
AU  - Markevych, I.
AU  - Boyd, A.*
AU  - Mahmoud, O.*
AU  - Thomas, R.*
AU  - Heinrich, J.
AU  - Aymerich, J.G.*
AU  - Roda, C.*
AU  - Henderson, J.*
AU  - Jarvis, D.*
C1  - 58059
C2  - 48036
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Lung function up to adolescence and residential greenspace.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Gonzalez, E.
AU  - Zhang, X.
AU  - Oak, P.
AU  - Markmann, M.*
AU  - Hilgendorff, A.*
C1  - 58060
C2  - 48052
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Hyperoxia exposure induces age-dependent changes in gene expression in healthy mouse lung.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Hardy, S.
AU  - Schneider, A.
AU  - Frankenberger, M.
AU  - Koch, A.
AU  - Milger, K.
AU  - Moulin, C.*
AU  - Fievez, M.*
AU  - Pilette, C.*
AU  - Meiners, S.
AU  - Kammerl, I.E.
C1  - 58064
C2  - 48053
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - LSC-2019-Validating immunoproteasome activity as a potential biomarker in non-invasive samples from COPD patients.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Heinrich, J.
AU  - Thiering, E.
AU  - Jörres, R.A.*
AU  - Schulz, H.
AU  - Kühnisch, J.*
AU  - Standl, M.
C1  - 54855
C2  - 45932
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Lung function and oral health in adolescents.
JO  - Eur. Respir. J.
VL  - 53
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Previous reports link differential DNA methylation (DNAme) to environmental exposures which are associated with lung function. Direct evidence on lung function DNAme is however limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, six-to-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical-bias adjusted residuals of a regression of the normalised absolute beta-values on control-probe-derived principle components were regressed on level and change of FEV1, FEV1/FVC and FVC in covariate-adjusted discovery EWAS. Inverse-variance weighted meta-analyses were performed on results from discovery and replication samples in all participants and never smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: Pdiscovery=3.96×10-21 and Pcombined=7.22×10-50). A score combining ten DNAme markers previously reported to mediate the smoking effect on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function associated methylation signals in adults are predominantly smoking-related and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time points are needed to identify lung function DNAme in never smokers and in children.
AU  - Imboden, M.*
AU  - Wielscher, M.*
AU  - Rezwan, F.I.*
AU  - Amaral, A.F.S.*
AU  - Schaffner, E.*
AU  - Jeong, A.*
AU  - Beckmeyer-Borowko, A.*
AU  - Harris, S.E.*
AU  - Starr, J.M.*
AU  - Deary, I.J.*
AU  - Flexeder, C.
AU  - Waldenberger, M.
AU  - Peters, A.
AU  - Schulz, H.
AU  - Chen, S.*
AU  - Sunny, S.K.*
AU  - Karmaus, W.J.J.*
AU  - Jiang, Y.*
AU  - Erhart, G.*
AU  - Kronenberg, F.*
AU  - Arathimos, R.*
AU  - Sharp, G.C.*
AU  - Henderson, A.J.*
AU  - Fu, Y.*
AU  - Piirilä, P.L.*
AU  - Pietiläinen, K.H.*
AU  - Ollikainen, M.*
AU  - Johansson, A.*
AU  - Gyllensten, U.*
AU  - de Vries, M.*
AU  - van der Plaat, D.A.*
AU  - de Jong, K.*
AU  - Boezen, H.M.*
AU  - Hall, I.P.*
AU  - Tobin, M.D.*
AU  - Jarvelin, M.R.*
AU  - Holloway, J.W.*
AU  - Jarvis, D.*
AU  - Probst-Hensch, N.M.*
C1  - 56031
C2  - 46786
SP  - 1-18
TI  - Epigenome-wide association study of lung function level and its change.
JO  - Eur. Respir. J.
VL  - 54
IS  - 1
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Klett-Tammen, C.J.*
AU  - Lingner, H.*
AU  - Kuhlmann, A.*
AU  - Schmidt, T.*
AU  - Lutter, J.
AU  - Von Der Schulenburg, J.M.*
AU  - Kreuter, M.*
AU  - Welte, T.*
C1  - 58067
C2  - 48064
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Quality of life in German GP-Patients with COPD- a longitudinal study.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Korfei, M.*
AU  - Smaida, M.*
AU  - Klymenko, O.*
AU  - Ruppert, C.*
AU  - Henneke, I.*
AU  - Shalashova, I.*
AU  - Huehn, M.*
AU  - Mahavadi, P.*
AU  - Herold, S.*
AU  - Seeger, W.*
AU  - Adler, H.
AU  - Guenther, A.*
C1  - 58072
C2  - 48058
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Increased susceptibility to gammaherpesvirus-induced lung fibrosis of transgenic mice with conditional overexpression of the ER-stress-factor Chop in alveolar epithelium.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Kovacevic, D.*
AU  - Bartel, S.*
AU  - Pfeiffer, S.
AU  - Schloter, M.
AU  - Krauss-Etschmann, S.*
C1  - 58070
C2  - 48061
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - LSC-2019-The influence of cigarette smoke exposure on the lung and gut microbiome composition in mice.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Kreuter, M.*
AU  - Kabitz, H.*
AU  - Hagmeyer, L.*
AU  - Hammerl, P.*
AU  - Esselmann, A.*
AU  - Wiederhold, C.*
AU  - Skowasch, D.*
AU  - Stolpe, C.*
AU  - Joest, M.*
AU  - Veitshans, S.*
AU  - Maqhuzu, P.N.
AU  - Schwarzkopf, L.
AU  - Hellmann, A.*
AU  - Pfeifer, M.*
AU  - Behr, J.*
AU  - Kauschka, D.*
AU  - Günther, A.*
AU  - Herth, F.J.F.*
AU  - Markart, P.*
C1  - 58074
C2  - 48056
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Treatment and survival diversities in different forms of ILD in Germany - EXCITING registry.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Kuiper, I.N.*
AU  - Svanes, C.*
AU  - Markevych, I.
AU  - Heinrich, J.
AU  - Halvorse, T.n.*
AU  - Bertelsen, R.J.*
AU  - Holm, M.*
AU  - Bråbäck, L.*
AU  - Malinovschi, A.*
AU  - Janson, C.*
AU  - Forsberg, B.*
AU  - Torén, K.*
AU  - Accordini, S.*
AU  - Marcon, A.*
AU  - Jarvis, D.*
AU  - Gislason, T.*
AU  - Benediktsdottir, B.*
AU  - Schlünssen, V.*
AU  - Sigsgaard, T.*
AU  - Johannessen, A.*
C1  - 58078
C2  - 48039
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Preconception air pollution exposure and early onset asthma and hay fever in the offspring.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Lehmann, M.
AU  - Mutze, K.
AU  - Hu, Q.
AU  - Königshoff, M.
C1  - 58061
C2  - 48050
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Late Breaking Abstract - WNT/beta-catenin signaling induces cellular senescence in lung alveolar epithelial cells.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Maqhuzu, P.N.
AU  - Schwarzkopf, L.
AU  - Kreuter, M.*
C1  - 58063
C2  - 48065
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Healthcare resource utilization and direct costs of interstitial lung disease management in Germany.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Markevych, I.
AU  - Fuertes, E.*
AU  - Marcon, A.*
AU  - Dadvand, P.*
AU  - Nowak, D.*
AU  - Aymerich, J.G.*
AU  - Vienneau, D.*
AU  - de Hoogh, K.*
AU  - Jarvis, D.*
AU  - Abramson, M.J.*
AU  - Accordini, S.*
AU  - Amaral, A.F.*
AU  - Bentouhami, H.*
AU  - Bertelsen, R.J.*
AU  - Boudier, A.*
AU  - Bono, R.*
AU  - Bowatte, G.*
AU  - Carsin, A.*
AU  - Dharmage, S.C.*
AU  - Forsberg, B.*
AU  - Gislason, T.*
AU  - Gnesi, M.*
AU  - Holm, M.*
AU  - Jacquemin, B.*
AU  - Janson, C.*
AU  - Jõgi, R.*
AU  - Johannessen, A.*
AU  - Keidel, D.*
AU  - Leynaert, B.*
AU  - Perez, J.A.M.*
AU  - Marchetti, P.*
AU  - Migliore, E.*
AU  - Martinez Moratalla, J.*
AU  - Olsson, D.*
AU  - Orru, H.*
AU  - Pin, I.*
AU  - Potts, J.*
AU  - Probst-Hensch, N.*
AU  - Ranzi, A.*
AU  - Luis Sanchez-Ramos, J.*
AU  - Siroux, V.*
AU  - Schindler, C.*
AU  - Soussan, D.*
AU  - Sunyer, J.*
AU  - Svanes, C.*
AU  - Urrutia Landa, I.*
AU  - Villani, S.*
AU  - Weyler, J.*
AU  - Heinrich, J.
C1  - 58077
C2  - 48040
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Residential greenness and lung function in a prospective cohort of European adults: The ECRHS study.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Meul, T.
AU  - Wang, X.
AU  - Angelidis, I.
AU  - Berschneider, K.
AU  - Schmitt, S.
AU  - Zischka, H.
AU  - von Toerne, C.
AU  - Hauck, S.M.
AU  - Schiller, H. B.
AU  - Meiners, S.
C1  - 58058
C2  - 48034
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Mitochondrial dysfunction activates MHC class I adaptive immune responses in lung aging.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Ramsheh, M.Y.*
AU  - Thun, G.A.*
AU  - Codina, A.E.*
AU  - Haldar, K.*
AU  - Barer, M.*
AU  - Gut, I.*
AU  - Ziegler-Heitbrock, L.
AU  - Singh, D.*
AU  - Brightling, C.*
C1  - 58069
C2  - 48062
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Prevotella genera abundance in bronchial brush samples differentiates COPD from health and is associated with gene expression.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Ramsheh, M.Y.*
AU  - Haldar, K.*
AU  - Barer, M.*
AU  - Ziegler-Heitbrock, L.
AU  - Gut, I.*
AU  - Singh, D.*
AU  - Brightling, C.*
C1  - 58071
C2  - 48059
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Association between COPD bronchial brush microbiome-determined ?Proteobacteria:Firmicutes (G:F) ratio and GOLD grade and symptoms.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Schultz, K.*
AU  - Wittmann, M.*
AU  - Lehbert, N.*
AU  - Schwarzkopf, L.
AU  - Szentes, B.L.
AU  - Nowak, D.*
AU  - Faller, H.*
AU  - Schüler, M.*
C1  - 58068
C2  - 48063
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Asthma control (AC) and Quality of life (QoL) one year after Pulmonary Rehabilitation (PR).
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Schwarzkopf, L.
AU  - Witt, S.
AU  - Waelscher, J.*
AU  - Kreuter, M.*
C1  - 58056
C2  - 48030
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Longitudinal cost of care in individuals with different subtypes of interstitial lung diseases.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Szentes, B.L.
AU  - Schwarzkopf, L.
AU  - Kirsch, F.
AU  - Huber, M.B.
AU  - Schramm, A.*
AU  - Leidl, R.
C1  - 58057
C2  - 48035
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Different methods to classify COPD patients into the ABCD severity groups - Preliminary results of the LQ-DMP project.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Szentes, B.L.
AU  - Schwarzkopf, L.
AU  - Schüler, M.*
AU  - Lehbert, N.*
AU  - Nowak, D.*
AU  - Wittmann, M.*
AU  - Faller, H.*
AU  - Schultz, K.*
C1  - 58066
C2  - 48060
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - How does EQ-5D-5L perform in asthma patients?
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Szentes, B.L.
AU  - Maqhuzu, P.N.
AU  - Kreuter, M.*
AU  - Bahmer, T.*
AU  - Claussen, M.*
AU  - Schwarzkopf, L.
C1  - 58084
C2  - 48037
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Health-related quality of life development in IPF versus other ILD - the HILDA study.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Wolff, M.*
AU  - El-Merhie, N.*
AU  - Reuter, S.*
AU  - Goldmann, T.*
AU  - Yildirim, A.Ö.
AU  - Fehrenbach, H.*
AU  - Krauss-Etschmann, S.*
C1  - 58073
C2  - 48057
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - LSC-2019-Relevant murine model to study the development of COPD pathogenesis in smokers with viral infections.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Zhang, X.
AU  - Rodriguez, E.
AU  - Markmann, M.*
AU  - Oak, P.
AU  - Hilgendorff, A.
C1  - 58062
C2  - 48049
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Expression profiling of genes differentially regulated under hyperoxia andmechanical ventilation in mouse model of neonatal chronic lung disease.
JO  - Eur. Respir. J.
VL  - 54
PB  - European Respiratory Soc Journals Ltd
PY  - 2019
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Alter, P.*
AU  - Rabe, K.F.*
AU  - Schulz, H.
AU  - Vogelmeier, C.F.*
AU  - Jörres, R.A.*
C1  - 55386
C2  - 46139
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Influence of body mass on predicted values of static hyperinflation in COPD.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Byng, D.
AU  - Lutter, J.
AU  - Holle, R.
AU  - Joerres, R.A.
AU  - Karch, A.*
AU  - Karrasch, S.
AU  - Schulz, H.
AU  - Vogelmeier, C.F.*
AU  - Wacker, M.
C1  - 55375
C2  - 46148
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Identifying predictors of healthcare utilization and costs in COPD patients over 18 months: First longitudinal results of the COSYCONET cohort.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood.
AU  - Contreras, Z.A.*
AU  - Chen, Z.*
AU  - Roumeliotaki, T.*
AU  - Annesi-Maesano, I.*
AU  - Baïz, N.*
AU  - von Berg, A.*
AU  - Bergström, A.*
AU  - Crozier, S.*
AU  - Duijts, L.*
AU  - Ekström, S.*
AU  - Eller, E.*
AU  - Fantini, M.P.*
AU  - Kjaer, H.F.*
AU  - Forastiere, F.*
AU  - Gerhard, B.*
AU  - Gori, D.*
AU  - Harskamp-van Ginkel, M.W.*
AU  - Heinrich, J.
AU  - Iñiguez, C.*
AU  - Inskip, H.M.*
AU  - Keil, T.*
AU  - Kogevinas, M.*
AU  - Lau, S.*
AU  - Lehmann, I.*
AU  - Maier, D.*
AU  - van Meel, E.R.*
AU  - Mommers, M.*
AU  - Murcia, M.*
AU  - Porta, D.*
AU  - Smit, H.A.*
AU  - Standl, M.
AU  - Stratakis, N.*
AU  - Sunyer, J.*
AU  - Thijs, C.*
AU  - Torrent, M.*
AU  - Vrijkotte, T.G.*
AU  - Wijga, A.H.*
AU  - Berhane, K.*
AU  - Gilliland, F.*
AU  - Chatzi, L.*
C1  - 54317
C2  - 45488
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts.
JO  - Eur. Respir. J.
VL  - 52
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Costa, R.
AU  - Wagner, D.E.
AU  - De Santis, M.
AU  - Bailey, K.E.*
AU  - Doryab, A.
AU  - Schorpp, K.K.
AU  - Rothenaigner, I.
AU  - Ota, C.
AU  - Baarsma, H.A.
AU  - Campillos, M.J.
AU  - Hadian, K.
AU  - Königshoff, M.*
C1  - 55401
C2  - 46124
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Novel compounds for WNT/beta-catenin induced lung repair in chronic obstructive pulmonary disease.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Chronic respiratory diseases remain a major cause of morbidity and mortality worldwide. The only option at end-stage disease is lung transplantation, but there are not enough donor lungs to meet clinical demand. Alternative options to increase tissue availability for lung transplantation are urgently required to close the gap on this unmet clinical need. A growing number of tissue engineering approaches are exploring the potential to generate lung tissue ex vivo for transplantation. Both biologically derived and manufactured scaffolds seeded with cells and grown ex vivo have been explored in pre-clinical studies, with the eventual goal of generating functional pulmonary tissue for transplantation. Recently, there have been significant efforts to scale-up cell culture methods to generate adequate cell numbers for human-scale bioengineering approaches. Concomitantly, there have been exciting efforts in designing bioreactors that allow for appropriate cell seeding and development of functional lung tissue over time. This review aims to present the current state-of-the-art progress for each of these areas and to discuss promising new ideas within the field of lung bioengineering.
AU  - De Santis, M.
AU  - Bolukbas, D.A.*
AU  - Lindstedt, S.*
AU  - Wagner, D.E.
C1  - 54147
C2  - 45327
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - How to build a lung: Latest advances and emerging themes in lung bioengineering.
JO  - Eur. Respir. J.
VL  - 52
IS  - 1
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - De Santis, M.*
AU  - Ota, C.
AU  - Costa, R.
AU  - Doryab, A.
AU  - Alsafadi, H.N.
AU  - Bolukbas, D.*
AU  - Königshoff, M.*
AU  - Wagner, D.*
C1  - 55373
C2  - 46150
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Development of a hybrid alginate-ECM hydrogel as a potential bioink for 3D bioprinting.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Ehrmann, M.*
AU  - von Mutius, E.
AU  - Hansen, G.*
AU  - Kopp, M.*
AU  - Hohlfeld, J.M.*
AU  - Holz, O.*
AU  - Fuchs, O.*
C1  - 55402
C2  - 46125
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Measurement of volatile organic compounds in exhaled breath of children of the ALL Age Asthma Cohort.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Fernandez, I.E.
AU  - Sun, N.
AU  - Wei, M.
AU  - Witting, M.
AU  - Aichler, M.
AU  - Verleden, S.*
AU  - Schmitt-Kopplin, P.
AU  - Walch, A.K.
AU  - Eickelberg, O.
C1  - 55368
C2  - 46151
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Pharmacometabolic effect of pirfenidone treatment in IPF detected by high resolution MALDI-FTICR imaging.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Fernandez, I.E.
AU  - Greiffo, F.R.
AU  - Roi, R.
AU  - Behr, J.*
AU  - Forrest, A.R.*
AU  - Eickelberg, O.
C1  - 55384
C2  - 46141
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Circulating MDSC modulate IPF progression by orchestrating immunosuppressive and pro-fibrotic networks.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Fuertes, E.*
AU  - Carsin, A.*
AU  - Larsen, V.G.*
AU  - Guerra, S.*
AU  - Pin, I.*
AU  - Leynaert, B.*
AU  - Accordini, S.*
AU  - Martinez-Moratalla, J.*
AU  - Antò, J.M.*
AU  - Urrutia, I.*
AU  - Le Gouellec, A.*
AU  - Heinrich, J.
AU  - Gislason, T.*
AU  - Jõgi, R.*
AU  - Janson, C.*
AU  - Jarvis, D.*
AU  - Garcia-Aymerich, J.*
C1  - 55405
C2  - 46128
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Mediation analysis of CRP on the association of physical activity with FEV1 and FVC: The ECRHS study.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Garcia, A.D.*
AU  - Lidwien, A.M.S.*
AU  - Bossers, A.*
AU  - Inge, M.W.*
AU  - Schmitt, H.*
AU  - Markus, J.E.*
AU  - Depner, M.
AU  - Mueller-Rompa, S.E.*
AU  - Schmaußer-Hechfellner, E.
AU  - Michael, J.C.*
AU  - Cookson, W.*
AU  - Moffatt, M.*
AU  - Von Mutius, E.*
AU  - Dick, J.H.*
C1  - 55381
C2  - 46143
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Indoor airborne microbiota composition associated with asthma and atopy in rural children.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Heinrich, J.*
AU  - Thiering, E.
AU  - Joerres, R.
AU  - Schulz, H.
AU  - Kühnisch, J.
AU  - Standl, M.
C1  - 55378
C2  - 46144
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Lung function and oral health in adolescents.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Jäger, V.
AU  - Thorand, B.
AU  - Huth, C.
AU  - Kahnert, K.*
AU  - Rathmann, W.*
AU  - Peters, A.
AU  - Nowak, D.*
AU  - Joerres, R.A.*
AU  - Schulz, H.
AU  - Karrasch, S.
C1  - 55398
C2  - 46120
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Association between type 2 diabetes, prediabetes and lung function: Results from the KORA cohort.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Johannessen, A.*
AU  - Kuiper, I.N.*
AU  - Accordini, S.*
AU  - Bertelsen, R.J.*
AU  - Forsberg, B.*
AU  - Gislason, T.*
AU  - Heinrich, J.*
AU  - Holm, M.*
AU  - Jogi, R.*
AU  - Kirkeleit, J.*
AU  - Malinovschi, A.*
AU  - Marcon, A.*
AU  - Markevych, I.
AU  - Oudin, A.*
AU  - Schlünssen, V.*
AU  - Sigsgaard, T.*
AU  - Svanes, C.*
AU  - Toren, K.*
AU  - Janson, C.*
C1  - 55395
C2  - 46132
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Long-term air pollution exposure is associated with sick leave 20 years later.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Karvonen, A.M.*
AU  - Kirjavainen, P.V.*
AU  - Täubel, M.*
AU  - Jayaprakash, B.*
AU  - Adams, R.I.*
AU  - Depner, M.
AU  - Hyvärinen, A.*
AU  - Remes, S.*
AU  - von Mutius, E.
AU  - Pekkanen, J.*
C1  - 55389
C2  - 46135
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Indoor microbial diversity and risk of different wheezing phenotypes.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Kindt-Dunjko, A.
AU  - Foerster, K.*
AU  - Flemmer, A.*
AU  - Oak, P.
AU  - Pomschar, A.*
AU  - Ertl-Wagner, B.*
AU  - Krumsiek, J.*
AU  - Hilgendorff, A.
C1  - 55369
C2  - 46152
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Late Breaking Abstract - Protein signature stratifies severity of chronic lung disease in preterms after birth.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Knüppel, L.
AU  - Heinzelmann, K.
AU  - Lindner, M.*
AU  - Hatz, R.*
AU  - Behr, J.*
AU  - Eickelberg, O.*
AU  - Staab-Weijnitz, C.A.
C1  - 55379
C2  - 46145
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - FKBP10 regulates fibroblast migration via synthesis of collagen VI.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Kreuter, M.*
AU  - Kabitz, H.*
AU  - Hagmeyer, L.*
AU  - Hammerl, P.*
AU  - Esselmann, A.*
AU  - Wiederhold, C.*
AU  - Skowasch, D.*
AU  - Stolpe, C.*
AU  - Joest, M.*
AU  - Veitshans, S.*
AU  - Witt, S.
AU  - Leidl, R.
AU  - Hellmann, A.*
AU  - Pfeifer, M.*
AU  - Behr, J.*
AU  - Guenther, A.*
AU  - Kauschka, D.*
AU  - Herth, F.J.F.*
AU  - Markart, P.*
C1  - 55397
C2  - 46129
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Outcome differences between idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILD) - data from the EXCITING registry.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Kuiper, I.N.*
AU  - Svanes, C.*
AU  - Abramson, M.J.*
AU  - Benediktsdottir, B.*
AU  - Bertelsen, R.J.*
AU  - Dennekamp, M.*
AU  - Forsberg, B.*
AU  - Gislason, T.*
AU  - Halvorsen, T.*
AU  - Heinrich, J.
AU  - Holm, M.*
AU  - Janson, C.*
AU  - Jõgi, R.*
AU  - Malinovschi, A.*
AU  - Marcon, A.*
AU  - Markevych, I.
AU  - Moratalla, J.M.*
AU  - Oudin, A.*
AU  - Pearce, J.L.*
AU  - Schlünssen, V.*
AU  - Vega, A.P.*
AU  - Johannessen, A.*
C1  - 55394
C2  - 46131
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Lung health in adulthood after childhood exposure to air pollution and greenness.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Lambert, K.A.*
AU  - Lodge, C.*
AU  - Prendergast, L.A.*
AU  - Bowatte, G.*
AU  - Lowe, A.*
AU  - Wjst, M.
AU  - Abramson, M.J.*
AU  - Dharmage, S.C.*
AU  - Erbas, B.*
C1  - 55385
C2  - 46138
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Associations between early life exposure to pollen and adolescent lung function are modified by residential greenness.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Lamort, A.
AU  - Weiss, S.
AU  - Lillis, I.*
AU  - Armenis, V.*
AU  - Arendt, K.A.M.
AU  - Pepe, M.
AU  - Klotz, L.V.
AU  - Marazioti, A.*
AU  - Spella, M.*
AU  - Giopanou, I.*
AU  - Ntaliarda, G.*
AU  - Giotopoulou, G.A.*
AU  - Lianou, M.*
AU  - Oplopoiou, M.*
AU  - Kauka, K.*
AU  - Jenne, D.
AU  - Stathopoulos, G.T.
C1  - 55380
C2  - 46142
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Tumor-derived granulocyte chemotactic protein 2 cooperates with neutrophil proteinase 3 to drive lung adenocarcinoma.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Lingner, H.*
AU  - Klett-Tammen, C.J.*
AU  - Kuhlmann, A.*
AU  - Schmidt, T.*
AU  - Lutter, J.
AU  - Von Der Schulenburg, J.M.*
AU  - Kreuter, M.*
AU  - Welte, T.*
C1  - 55391
C2  - 46133
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Describing "real world" COPD patients in primary care in Germany - Findings of the BeoNet-Registry.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Both protective and adverse effects of indoor microbial exposure on asthma have been reported, but mostly in children. To date, no study in adults has used non-targeted methods for detection of indoor bacteria followed by quantitative confirmation. A cross-sectional study of 198 asthmatic and 199 controls was conducted within the European Community Respiratory Health Survey (ECRHS) II. DNA was extracted from mattress dust for bacterial analysis using denaturing gradient gel electrophoresis (DGGE). Selected bands were sequenced and associations with asthma confirmed with four quantitative PCR (qPCR) assays. 15 out of 37 bands detected with DGGE, which had at least a suggestive association (p<0.25) with asthma, were sequenced. Of the four targeted qPCRs, Clostridium cluster XI confirmed the protective association with asthma. The association was dose dependent (aOR 0.43 (95% CI 0.22-0.84) for the fourth versus first quartile, p for trend 0.009) and independent of other microbial markers. Few significant associations were observed for the three other qPCRs used. In this large international study, the level of Clostridium cluster XI was independently associated with a lower risk of prevalent asthma. Results suggest the importance of environmental bacteria also in adult asthma, but need to be confirmed in future studies.
AU  - Pekkanen, J.*
AU  - Valkonen, M.*
AU  - Täubel, M.*
AU  - Tischer, C.*
AU  - Leppanen, H.*
AU  - Karkkainen, P.M.*
AU  - Rintala, H.*
AU  - Zock, J.P.*
AU  - Casas, L.*
AU  - Probst-Hensch, N.*
AU  - Forsberg, B.*
AU  - Holm, M.*
AU  - Janson, C.*
AU  - Pin, I.*
AU  - Gislason, T.*
AU  - Jarvis, D.*
AU  - Heinrich, J.
AU  - Hyvärinen, A.*
C1  - 53033
C2  - 44330
CY  - Sheffield
TI  - Indoor bacteria and asthma in adults: A multicentre case-control study within ECRHS II.
JO  - Eur. Respir. J.
VL  - 51
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Pepe, M.
AU  - Pelizza, F.*
AU  - Lamort, A.
AU  - Kanellakis, N.I.*
AU  - Stathopoulos, G.T.
C1  - 55365
C2  - 46153
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Alteration patterns of tobacco carcinogens in lung adenocarcinoma reveal novel KRAS-addicted candidate oncogenes.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Peralta, G.P.*
AU  - Fuertes, E.*
AU  - Carsin, A.*
AU  - Probst-Hensch, N.*
AU  - Marcon, A.*
AU  - Nowak, D.*
AU  - Amaral, A.F.S.*
AU  - Johannessen, A.*
AU  - Janson, C.*
AU  - Dharmage, S.*
AU  - Gislason, T.*
AU  - Garcia-Larsen, V.*
AU  - Abramson, M.J.*
AU  - Sigsgaard, T.*
AU  - Antò, J.M.*
AU  - Weyler, J.*
AU  - Bono, R.*
AU  - Holm, M.*
AU  - Burney, P.*
AU  - Heinrich, J.
AU  - Forsberg, B.*
AU  - Raherison-Semjen, C.*
AU  - Siroux, V.*
AU  - Leynaert, B.*
AU  - Accordini, S.*
AU  - Martinez-Moratalla, J.*
AU  - Sánchez-Ramos, J.L.*
AU  - Jarvis, D.L.*
AU  - Garcia-Aymerich, J.*
C1  - 55387
C2  - 46136
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Body mass index trajectories during adult life and lung function decline.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - There is limited information about potential impact of maternal age on the respiratory health of offspring. We investigated the association of maternal age at delivery with adult offspring’s lung function, respiratory symptoms and asthma, and potential differences according to offspring sex. 10692 adults from 13 countries participating in the European Community Respiratory Health Survey (ECRHS) II responded to standardised interviews and provided lung function measurements and serum for IgE measurements at age 25–55 years. In logistic and linear multilevel mixed models we adjusted for participants’ characteristics (age, education, centre, number of older siblings) and maternal characteristics (smoking in pregnancy, education) while investigating for differential effects by sex. Maternal age was validated in a subsample using data from the Norwegian birth registry. Increasing maternal age was associated with increasing forced expiratory volume in 1 s (2.33 mL per year, 95% CI 0.34–4.32 mL per year), more consistent in females (ptrend 0.025) than in males (ptrend 0.14). Asthma (OR 0.85, 95% CI 0.79–0.92) and respiratory symptoms (OR 0.87, 95% CI 0.82–0.92) decreased with increasing maternal age (per 5 years) in females, but not in males (pinteraction 0.05 and 0.001, respectively). The results were consistent across centres and not explained by confounding factors. Maternal ageing was related to higher adult lung function and less asthma/symptoms in females. Biological characteristics in offspring related to maternal ageing are plausible and need further investigation.
AU  - Real, F.G.*
AU  - Burgess, J.A.*
AU  - Villani, S.*
AU  - Dratva, J.*
AU  - Heinrich, J.
AU  - Janson, C.*
AU  - Jarvis, D.*
AU  - Koplin, J.*
AU  - Leynaert, B.*
AU  - Lodge, C.J.*
AU  - Laerum, B.N.*
AU  - Matheson, M.C.*
AU  - Norbäck, D.*
AU  - Omenaas, E.R.*
AU  - Skulstad, S.M.*
AU  - Sunyer, J.*
AU  - Dharmage, S.C.*
AU  - Svanes, C.*
C1  - 53754
C2  - 44998
CY  - 1752 N St Nw, Washington, Dc 20036-2904 Usa
TI  - Maternal age at delivery, lung function and asthma in offspring: A population-based survey.
JO  - Eur. Respir. J.
VL  - 51
IS  - 6
PB  - Amer Soc Microbiology
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Russell, M.*
AU  - Dharmage, S.*
AU  - Fuertes, E.*
AU  - Jarvis, D.*
AU  - Abramson, M.*
AU  - Heinrich, J.
AU  - Johannessen, A.*
AU  - Lenaert, B.*
AU  - Marcon, A.*
AU  - Probst, N.*
AU  - Raherison, C.*
AU  - Squillacioti, G.*
AU  - Sánchez-Ramos, J.L.*
AU  - Sommar, J.*
AU  - Garcia Aymerich, J.*
C1  - 55400
C2  - 46123
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - The association of vigorous physical activity with 10-year adult asthma incidence.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Schroeder, A.S.*
AU  - Lunding, L.*
AU  - Vock, C.*
AU  - Schaub, B.*
AU  - Zissler, U.M.
AU  - Fehrenbach, H.*
AU  - Wegmann, M.*
C1  - 55370
C2  - 46147
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - IL-37 ameliorates experimental asthma by inhibiting IL-1.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Schultz, K.*
AU  - Wittmann, M.*
AU  - Wagner, R.*
AU  - Lehbert, N.*
AU  - Schwarzkopf, L.
AU  - Szentes, B.L.
AU  - Nowak, D.*
AU  - Faller, H.*
AU  - Schüler, M.*
C1  - 55399
C2  - 46122
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Effectiveness of pulmonary Rrhabilitation for patients with asthma: EPRA-RCT.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Schwarzkopf, L.
AU  - Witt, S.
AU  - Waelscher, J.*
AU  - Polke, M.*
AU  - Kreuter, M.*
C1  - 55404
C2  - 46127
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Associations between comorbidities, their treatment and survival in patients with interstitial lung diseases - a claims data analysis.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Schwarzkopf, L.
AU  - Murawski, M.
C1  - 55406
C2  - 46121
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Survival impact of comorbidity in German Lung Cancer patients - a claims data-based 'Comorbidome'.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Idiopathic pulmonary fibrosis (IPF) is a fatal condition that reduces life expectancy and shows a limited response to available therapies. Pirfenidone has been approved for treatment of IPF, but little is known about the distinct metabolic changes that occur in the lung upon pirfenidone administration.Here, we performed a proof-of-concept study using high-resolution quantitative matrix-assisted laser desorption/ionisation Fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FTICR-MSI) to simultaneously detect, visualise and quantify in situ endogenous and exogenous metabolites in lungs of mice subjected to experimental fibrosis and human patients with IPF, and to assess the effect of pirfenidone treatment on metabolite levels.Metabolic pathway analysis and endogenous metabolite quantification revealed that pirfenidone treatment restores redox imbalance and glycolysis in IPF tissues, and downregulates ascorbate and aldarate metabolism, thereby likely contributing to in situ modulation of collagen processing. As such, we detected specific alterations in metabolite pathways in fibrosis and, importantly, metabolic recalibration following pirfenidone treatment.Together, these results highlight the suitability of high-resolution MALDI-FTICR-MSI for deciphering the therapeutic effects of pirfenidone and provide a preliminary analysis of the metabolic changes that occur during pirfenidone treatment in vivo These data may therefore contribute to improvement of currently available therapies for IPF.
AU  - Sun, N.
AU  - Fernandez, I.E.
AU  - Wei, M.
AU  - Witting, M.
AU  - Aichler, M.
AU  - Feuchtinger, A.
AU  - Burgstaller, G.
AU  - Verleden, S.E.*
AU  - Schmitt-Kopplin, P.
AU  - Eickelberg, O.
AU  - Walch, A.K.
C1  - 54084
C2  - 45345
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Pharmacometabolic response to pirfenidone in pulmonary fibrosis detected by MALDI-FTICR-MSI.
JO  - Eur. Respir. J.
VL  - 52
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Szentes, B.L.
AU  - Schwarzkopf, L.
AU  - Lehbert, N.*
AU  - Wittmann, M.*
AU  - Wagner, R.*
AU  - Nowak, D.*
AU  - Faller, H.*
AU  - Schüler, M.*
AU  - Schultz, K.*
C1  - 55383
C2  - 46140
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Suitable questionnaires to measure quality of life in patients with asthma bronchial undergoing pulmonary rehabilitation.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Walter, J.
AU  - Holle, R.
AU  - Tufman, A.*
AU  - Schwarzkopf, L.
C1  - 55388
C2  - 46137
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Changes in targeted therapy and costs in NSCLC between 2009 and 2013.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Wartenberg, M.*
AU  - Andrault, P.*
AU  - Schamberger, A.C.
AU  - Chazeirat, T.*
AU  - Sizaret, D.*
AU  - Renault, J.*
AU  - Petit, A.*
AU  - Saidi, A.*
AU  - Guyetant, S.*
AU  - Courty, Y.*
AU  - Eickelberg, O.*
AU  - Lalmanach, G.*
AU  - Lecaille, F.*
C1  - 55403
C2  - 46126
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Cigarette smoke induces overexpression of cathepsin S in active smokers with and without COPD.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Welk, V.
AU  - Meul, T.
AU  - Lukas, C.
AU  - Bolukbas, D.*
AU  - Koch, I.*
AU  - Lindner, M.*
AU  - Meiners, S.
C1  - 55374
C2  - 46149
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Analyzing the role of proteasome activator 200 (PA200) in lung cancer.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Witt, S.
AU  - Waelscher, J.*
AU  - Schwarzkopf, L.
AU  - Kreuter, M.*
C1  - 55376
C2  - 46146
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Hospitalisation pattern in Interstitial Lung Diseases: A claims data study.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Witt, S.
AU  - Szentes, B.L.
AU  - Bush, A.*
AU  - Cunningham, S.*
AU  - Kiper, N.*
AU  - Lange, J.*
AU  - Leidl, R.
AU  - Terheggen-Lagro, S.*
AU  - Schwerk, N.*
AU  - Snijders, D.*
AU  - Griese, M.*
AU  - Schwarzkopf, L.
C1  - 55393
C2  - 46134
CY  - 442 Glossop Rd, Sheffield S10 2px, England
TI  - Medication for childhood interstitial lung diseases differs internationally.
JO  - Eur. Respir. J.
VL  - 52
PB  - European Respiratory Soc Journals Ltd
PY  - 2018
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The pulmonary extracellular matrix (ECM) determines the tissue architecture of the lung, and provides mechanical stability and elastic recoil, which are essential for physiological lung function. Biochemical and biomechanical signals initiated by the ECM direct cellular function and differentiation, and thus play a decisive role in lung development, tissue remodelling processes and maintenance of adult homeostasis. Recent proteomic studies have demonstrated that at least 150 different ECM proteins, glycosaminoglycans and modifying enzymes are expressed in the lung, and these assemble into intricate composite biomaterials. These highly insoluble assemblies of interacting ECM proteins and their glycan modifications can act as a solid phase-binding interface for hundreds of secreted proteins, which creates an information-rich signalling template for cell function and differentiation. Dynamic changes within the ECM that occur upon injury or with ageing are associated with several chronic lung diseases. In this review, we summarise the available data about the structure and function of the pulmonary ECM, and highlight changes that occur in idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma and lung cancer. We discuss potential mechanisms of ECM remodelling and modification, which we believe are relevant for future diagnosis and treatment of chronic lung disease.
AU  - Burgstaller, G.
AU  - Oehrle, B.
AU  - Gerckens, M.
AU  - White, E.S.*
AU  - Schiller, H. B.
AU  - Eickelberg, O.*
C1  - 51486
C2  - 43259
CY  - Sheffield
TI  - The instructive extracellular matrix of the lung: Basic composition and alterations in chronic lung disease.
JO  - Eur. Respir. J.
VL  - 50
IS  - 1
PB  - European Respiratory Soc Journals Ltd
PY  - 2017
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Activity-related breathlessness is twice as common among females as males in the general population and is associated with adverse health outcomes. We tested whether this sex difference is explained by the lower absolute forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) in females.This was a cross-sectional analysis of 3250 subjects (51% female) aged 38-67 years across 13 countries in the population-based third European Community Respiratory Health Survey. Activity-related breathlessness was measured using the modified Medical Research Council (mMRC) scale. Associations with mMRC were analysed using ordered logistic regression clustering on centre, adjusting for post-bronchodilator spirometry, body mass index, pack-years smoking, cardiopulmonary diseases, depression and level of exercise.Activity-related breathlessness (mMRC ≥1) was twice as common in females (27%) as in males (14%) (odds ratio (OR) 2.21, 95% CI 1.79-2.72). The sex difference was not reduced when controlling for FEV1 % predicted (OR 2.33), but disappeared when controlling for absolute FEV1 (OR 0.89, 95% CI 0.69-1.14). Absolute FEV1 explained 98-100% of the sex difference adjusting for confounders. The effect was similar within males and females, when using FVC instead of FEV1 and in healthy never-smokers.The markedly more severe activity-related breathlessness among females in the general population is explained by their smaller spirometric lung volumes.
AU  - Ekström, M.*
AU  - Schiöler, L.*
AU  - Grønseth, R.*
AU  - Johannessen, A.*
AU  - Svanes, C.*
AU  - Leynaert, B.*
AU  - Jarvis, D.*
AU  - Gislason, T.*
AU  - Demoly, P.*
AU  - Probst-Hensch, N.*
AU  - Pin, I.*
AU  - Corsico, A.G.*
AU  - Forsberg, B.*
AU  - Heinrich, J.
AU  - Nowak, D.*
AU  - Raherison-Semjen, C.*
AU  - Dharmage, S.C.*
AU  - Trucco, G.*
AU  - Urrutia, I.*
AU  - Martinez-Moratalla Rovira, J.*
AU  - Sánchez-Ramos, J.L.*
AU  - Janson, C.*
AU  - Torén, K.*
C1  - 51199
C2  - 43008
TI  - Absolute values of lung function explain the sex difference in breathlessness in the general population.
JO  - Eur. Respir. J.
VL  - 49
IS  - 5
PY  - 2017
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Vitamin D plays a role in the development of the immune system and the lung, as well as in airway remodelling. Therefore, this study investigated the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and spirometric lung function parameters at age 15 years.In the German birth cohorts GINIplus and LISAplus, lung function testing by spirometry and 25(OH)D measurements were performed during the 15-year follow-up examinations. Valid lung function measurements pre- and/or post-bronchodilation and serum 25(OH)D concentrations, which were adjusted for the date of blood sampling to account for seasonal variability, were available for 2607 adolescents. Associations between 25(OH)D concentrations and spirometric parameters were analysed using generalised additive models adjusted for confounding factors.Serum 25(OH)D concentrations were significantly associated with forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC measured before bronchodilation after adjustment for potential confounders: FEV1 increased by 10 mL (95% CI 2-17), FVC by 20 mL (95% CI 12-28) and FEV1/FVC decreased by 0.177% (95% CI -0.286 to -0.067) per 10 nmol·L(-1) increase in 25(OH)D concentrations. Flow rates (forced expiratory flow rates at 25, 50 and 75% of exhaled FVC (FEF25, FEF50, FEF75) and mean flow rate between 25 and 75% of FVC (FEF25-75)) were not associated with vitamin D. Similar associations were observed for lung function parameters measured after bronchodilation.Vitamin D concentrations are positively associated with volume-related lung function parameters pre- and post-bronchodilation, suggesting structural changes in peripheral airways.
AU  - Flexeder, C.
AU  - Thiering, E.
AU  - Koletzko, S.*
AU  - Berdel, D.*
AU  - Lehmann, I.*
AU  - von Berg, A.*
AU  - Hoffmann, B.*
AU  - Bauer, C.P.*
AU  - Heinrich, J.
AU  - Schulz, H.
C1  - 51010
C2  - 42694
CY  - Sheffield
TI  - Higher serum 25(OH)D concentrations are associated with improved FEV1 and FVC in adolescence.
JO  - Eur. Respir. J.
VL  - 49
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2017
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Identification of disease phenotypes might improve the understanding of patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to assess the impact of pulmonary restriction and air trapping by lung volume measurements at the onset of CLAD.A total of 396 bilateral lung transplant recipients were analysed. At onset, CLAD was further categorised based on plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an increased ratio of residual volume to total lung capacity. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n=95).Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse survival (p<0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were associated with increased mortality when controlling for multiple confounding variables (hazard ratio (HR) 3.57, 95% CI 1.39-9.18; p=0.008; and HR 2.65, 95% CI 1.05-6.68; p=0.039). Furthermore, measurement of lung volumes was useful to identify patients with combined phenotypes.Measurement of lung volumes in the long-term follow-up of lung transplant recipients allows the identification of patients who are at risk for worse outcome and warrant special consideration.
AU  - Kneidinger, N.*
AU  - Milger, K.*
AU  - Janitza, S.*
AU  - Ceelen, F.*
AU  - Leuschner, G.*
AU  - Dinkel, J.*
AU  - Königshoff, M.
AU  - Weig, T.*
AU  - Schramm, R.*
AU  - Winter, H.*
AU  - Behr, J.*
AU  - Neurohr, C.*
C1  - 50925
C2  - 42981
CY  - Sheffield
TI  - Lung volumes predict survival in patients with chronic lung allograft dysfunction.
JO  - Eur. Respir. J.
VL  - 49
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2017
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and the impact of senolytic drugs on senescent lung cells and fibrosis remain unknown. Here we demonstrate that lung epithelial cells exhibit increased P16 and P21 expression as well as senescence-associated β-galactosidase activity in experimental and human lung fibrosis tissue and primary cells.Primary fibrotic mouse alveolar epithelial type (AT)II cells secreted increased amounts of senescence-associated secretory phenotype (SASP) factors in vitro, as analysed using quantitative PCR, mass spectrometry and ELISA. Importantly, pharmacological clearance of senescent cells by induction of apoptosis in fibrotic ATII cells or ex vivo three-dimensional lung tissue cultures reduced SASP factors and extracellular matrix markers, while increasing alveolar epithelial markers.These data indicate that alveolar epithelial cell senescence contributes to lung fibrosis development and that senolytic drugs may be a viable therapeutic option for IPF.
AU  - Lehmann, M.
AU  - Korfei, M.*
AU  - Mutze, K.
AU  - Klee, S.
AU  - Skronska-Wasek, W.
AU  - Alsafadi, H.N.
AU  - Ota, C.
AU  - Costa, R.
AU  - Schiller, H. B.
AU  - Lindner, M.*
AU  - Wagner, A.
AU  - Günther, A.L.*
AU  - Königshoff, M.
C1  - 51676
C2  - 43332
CY  - Sheffield
TI  - Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo.
JO  - Eur. Respir. J.
VL  - 50
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2017
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and it is now evident that proteases are critical pleiotropic actors orchestrating pathophysiological processes. Recent findings evidenced that the net proteolytic activity also relies upon interconnections between different protease and protease inhibitor families in the protease web.In this review, we provide an overview of these novel concepts with a particular focus on pulmonary pathophysiology. We describe the emerging roles of several protease families including cysteine and serine proteases.The complexity of the protease web is exemplified in the light of multidimensional regulation of serine protease activity by matrix metalloproteases through cognate serine protease inhibitor processing. Finally, we will highlight how deregulated protease activity during pulmonary pathogenesis may be exploited for diagnosis/prognosis purposes, and utilised as a therapeutic tool using nanotechnologies.Considering proteases as part of an integrative biology perspective may pave the way for the development of new therapeutic targets to treat pulmonary diseases related to intrinsic protease deregulation.
AU  - Taggart, C.*
AU  - Mall, M.A.*
AU  - Lalmanach, G.*
AU  - Cataldo, D.*
AU  - Ludwig, A.*
AU  - Janciauskiene, S.*
AU  - Heath, N.*
AU  - Meiners, S.
AU  - Overall, C.M.*
AU  - Schultz, C.*
AU  - Turk, B.*
AU  - Borensztajn, K.S.*
C1  - 50652
C2  - 42767
TI  - Protean proteases: At the cutting edge of lung diseases.
JO  - Eur. Respir. J.
VL  - 49
IS  - 2
PY  - 2017
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution.
AU  - Thurston, G.D.*
AU  - Kipen, H.*
AU  - Annesi-Maesano, I.*
AU  - Balmes, J.*
AU  - Brook, R.D.*
AU  - Cromar, K.*
AU  - De Matteis, S.*
AU  - Forastiere, F.*
AU  - Forsberg, B.*
AU  - Frampton, M.W.*
AU  - Grigg, J.*
AU  - Heederik, D.*
AU  - Kelly, F.J.*
AU  - Kuenzli, N.*
AU  - Laumbach, R.*
AU  - Peters, A.
AU  - Rajagopalan, S.*
AU  - Rich, D.*
AU  - Ritz, B.*
AU  - Samet, J.M.*
AU  - Sandström, T.*
AU  - Sigsgaard, T.*
AU  - Sunyer, J.*
AU  - Brunekreef, B.*
C1  - 50369
C2  - 42175
CY  - Sheffield
TI  - A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? An analytical framework.
JO  - Eur. Respir. J.
VL  - 49
IS  - 1
PB  - European Respiratory Soc Journals Ltd
PY  - 2017
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disease with irreversible lung function loss and poor survival. Myeloid-derived suppressor cells (MDSC) are associated with poor prognosis in cancer, facilitating immune evasion. The abundance and function of MDSC in IPF is currently unknown.Fluorescence-activated cell sorting was performed in 170 patients (IPF: n=69; non-IPF interstitial lung disease (ILD): n=56; chronic obstructive pulmonary disease (COPD): n=23; healthy controls: n=22) to quantify blood MDSC and lymphocyte subtypes. MDSC abundance was correlated with lung function, MDSC localisation was performed by immunofluorescence. Peripheral blood mononuclear cell (PBMC) mRNA levels were analysed by qRT-PCR.We detected increased MDSC in IPF and non-IPF ILD compared with controls (30.99±15.61% versus 18.96±8.17%, p≤0.01). Circulating MDSC inversely correlated with maximum vital capacity (r= -0.48, p≤0.0001) in IPF, but not in COPD or non-IPF ILD. MDSC suppressed autologous T-cells. The mRNA levels of co-stimulatory T-cell signals were significantly downregulated in IPF PBMC. Importantly, CD33(+)CD11b(+) cells, suggestive of MDSC, were detected in fibrotic niches of IPF lungs.We identified increased MDSC in IPF and non-IPF ILD, suggesting that elevated MDSC may cause a blunted immune response. MDSC inversely correlate with lung function only in IPF, identifying them as potent biomarkers for disease progression. Controlling expansion and accumulation of MDSC, or blocking their T-cell suppression, represents a promising therapy in IPF.
AU  - Fernandez, I.E.
AU  - Greiffo, F.R.
AU  - Frankenberger, M.
AU  - Bandres, J.
AU  - Heinzelmann, K.
AU  - Neurohr, C.*
AU  - Hatz, R.*
AU  - Hartl, D.*
AU  - Behr, J.*
AU  - Eickelberg, O.
C1  - 49362
C2  - 41775
CY  - Sheffield
SP  - 1171-1183
TI  - Peripheral blood myeloid-derived suppressor cells reflect disease status in idiopathic pulmonary fibrosis.
JO  - Eur. Respir. J.
VL  - 48
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2016
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Neonatal chronic lung disease, i.e. BPD determines long-term pulmonary and neurologic development. Early markers are urgently needed for timely diagnosis and personalized treatment. The prospective study determined structural and functional changes in the preterm lung at the time of diagnosis and identified early disease markers by proteome screening in plasma in the first week of life. 40 infants (27.7±2.09wks, 984±332g) were included for advanced MRI measurements (3-Tesla) and complemented by Infant Lung function testing (ILFT) in spontaneously breathing infants. Plasma samples were processed for proteomic screening by SOMAscan™. Key findings were confirmed in an independent study cohort (n=21 infants). Statistical analysis used penalized and Poisson regression analysis; for protein analysis confounder effects were subtracted by lasso regression. Statistical analysis confirmed a high correlation of MRI and lung function variables and identified a pattern characterizing changes in the lungs of preterm infants by T2- and T1-weighed image analysis and lung volume measurements as well as ILFT. Functional enrichment analysis showed overrepresentation of the GO categories 'immune function', 'extracellular matrix', 'cellular proliferation/migration', 'organ development' and 'angiogenesis' in infants with BPD. One protein was identified as a potential biomarker. We identified a structural pattern characterizing BPD by advanced MRI confirmed by ILFT. The identified protein indicated BPD development in the first week of life enabling personalized treatment strategies.
AU  - Förster, K.
AU  - Sass, S.
AU  - Dietrich, O.*
AU  - Pomschar, A.*
AU  - Nährlich, L.*
AU  - Schulze, A.*
AU  - Flemmer, A.W.*
AU  - Ehrhardt, H.*
AU  - Hübener, C.*
AU  - Eickelberg, O.
AU  - Theis, F.J.
AU  - Ertl-Wagner, B.*
AU  - Hilgendorff, A.
C1  - 53526
C2  - 44607
SP  - PP104
TI  - LSC Abstract – Early biomarkers indicating the development of neonatal chronic lung disease defined by clinical and imaging parameters.
JO  - Eur. Respir. J.
VL  - 48
PY  - 2016
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Lung cancer and pulmonary fibrosis are common, yet distinct, pathological processes that represent urgent unmet medical needs. Striking clinical and mechanistic parallels exist between these distinct disease entities. The goal of this article is to examine lung fibrosis from the perspective of cancer-associated phenotypic hallmarks, to discuss areas of mechanistic overlap and distinction, and to highlight profibrotic mechanisms that contribute to carcinogenesis. Ultimately, we speculate that such comparisons might identify opportunities to leverage our current understanding of the pathobiology of each disease process in order to advance novel therapeutic approaches for both. We anticipate that such "outside the box" concepts could be translated to a more precise and individualised approach to fibrotic diseases of the lung.
AU  - Horowitz, J.C.*
AU  - Osterholzer, J.J.*
AU  - Marazioti, A.*
AU  - Stathopoulos, G.T.
C1  - 48227
C2  - 41017
CY  - Sheffield
SP  - 1842-1854
TI  - "Scar-cinoma": Viewing the fibrotic lung mesenchymal cell in the context of cancer biology.
JO  - Eur. Respir. J.
VL  - 47
IS  - 6
PB  - European Respiratory Soc Journals Ltd
PY  - 2016
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Epidemiological evidence on the associations between exposure to ultrafine particles (UFP), with aerodynamic electrical mobility diameters <100 nm, and health is limited. We gathered data on UFP from five European cities within 2001-2011 to investigate associations between short-term changes in concentrations and respiratory hospitalisations.We applied city-specific Poisson regression models and combined city-specific estimates to obtain pooled estimates. We evaluated the sensitivity of our findings to co-pollutant adjustment and investigated effect modification patterns by period of the year, age at admission and specific diagnoses.Our results for the whole time period do not support an association between UFP and respiratory hospitalisations, although we found suggestive associations among those 0-14 years old. We nevertheless report consistent adverse effect estimates during the warm period of the year, statistically significant after lag 2 when an increase by 10 000 particles per cm(3) was associated with a 4.27% (95% CI 1.68-6.92%) increase in hospitalisations. These effect estimates were robust to particles' mass or gaseous pollutants adjustment.Considering that our findings during the warm period may reflect better exposure assessment and that the main source of non-soluble UFP in urban areas is traffic, our results call for improved regulation of traffic emissions.
AU  - Samoli, E.*
AU  - Andersen, Z.J.*
AU  - Katsouyanni, K.*
AU  - Hennig, F.*
AU  - Kuhlbusch, T.A.J.*
AU  - Bellander, T.*
AU  - Cattani, G.*
AU  - Cyrys, J.
AU  - Forastiere, F.*
AU  - Jacquemin, B.*
AU  - Kulmala, M.*
AU  - Lanki, T.*
AU  - Loft, S.*
AU  - Massling, A.*
AU  - Tobias, A.*
AU  - Stafoggia, M.*
AU  - UF&HEALTH Study Group (*)
C1  - 48885
C2  - 41478
CY  - Sheffield
SP  - 674-682
TI  - Exposure to ultrafine particles and respiratory hospitalisations in five European cities.
JO  - Eur. Respir. J.
VL  - 48
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2016
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - In lung disease, physical activity improves lung function and reduces morbidity. However, healthy populations are not well studied. We estimate the relationship between spirometric indices and accelerometric physical activity in lung-healthy adolescents.895 nonsmoking German adolescents without chronic lung disease (45% male, mean±sdage 15.2±0.26 years) from the GINIplus and LISAplus cohorts completed questionnaires, spirometry, 7-day accelerometry and an activity diary. Physical activity was measured as minutes, quintiles and regularity of daily moderate, vigorous and moderate-to-vigorous physical activity (MVPA), participation in sport and active commuting to school. Primary outcomes were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow at 25-75% of FVC; they were separately correlated with physical activity and adjusted for confounders of respiratory function, including early-life exposures.Adolescents averaged 40 min MVPA per day, typical for European youth. 79% participated in sports and 51% commuted actively. An association was suggested between 3% higher FVC (∼100 mL) and either extreme MVPA quintile or percentage of days with >30 min MVPA (p<0.05). However, after Bonferroni correction all associations between spirometry, active lifestyle and physical activity were nonsignificant.Spirometric indices were not significantly associated with active lifestyle or measures of activity in lung-healthy adolescents after adjustment for confounding and multiple-comparison artefacts.
AU  - Smith, M.
AU  - von Berg, A.*
AU  - Berdel, D.*
AU  - Bauer, C.P.*
AU  - Hoffmann, B.*
AU  - Koletzko, S.*
AU  - Nowak, D.*
AU  - Heinrich, J.
AU  - Schulz, H.
C1  - 48191
C2  - 41055
CY  - Sheffield
SP  - 428-440
TI  - Physical activity is not associated with spirometric indices in lung-healthy German youth.
JO  - Eur. Respir. J.
VL  - 48
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2016
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.
AU  - Subramanian, D.R.*
AU  - Gupta, S.*
AU  - Burggraf, D.
AU  - vom Silberberg, S.
AU  - Heimbeck, I.
AU  - Heiss-Neumann, M.S.
AU  - Haeussinger, K.
AU  - Newby, C.*
AU  - Hargadon, B.*
AU  - Raj, V.*
AU  - Singh, D.*
AU  - Kolsum, U.*
AU  - Hofer, T.P.
AU  - Al-Shair, K.*
AU  - Luetzen, N.*
AU  - Prasse, A.*
AU  - Müller-Quernheim, J.*
AU  - Benea, G.*
AU  - Leprotti, S.*
AU  - Boschetto, P.*
AU  - Gorecka, D.*
AU  - Nowinski, A.*
AU  - Oniszh, K.*
AU  - zu Castell, W.
AU  - Hagen, M.
AU  - Barta, I.*
AU  - Döme, B.*
AU  - Strausz, J.*
AU  - Greulich, T.*
AU  - Vogelmeier, C.*
AU  - Koczulla, A.R.*
AU  - Gut, I.*
AU  - Hohlfeld, J.*
AU  - Welte, T.*
AU  - Lavae-Mokhtari, M.*
AU  - Ziegler-Heitbrock, L.
AU  - Brightling, C.*
AU  - Parr, D.G.*
C1  - 48697
C2  - 41255
CY  - Sheffield
SP  - 92-103
TI  - Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.
JO  - Eur. Respir. J.
VL  - 48
IS  - 1
PB  - European Respiratory Soc Journals Ltd
PY  - 2016
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.
AU  - Vardavas, C.I.*
AU  - Hohmann, C.*
AU  - Patelarou, E.*
AU  - Martinez, D.*
AU  - Henderson, A.J.*
AU  - Granell, R.*
AU  - Sunyer, J.*
AU  - Torrent, M.*
AU  - Fantini, M.P.*
AU  - Gori, D.*
AU  - Annesi-Maesano, I.*
AU  - Slama, R.*
AU  - Duijts, L.*
AU  - de Jongste, J.C.*
AU  - Aurrekoetxea, J.J.*
AU  - Basterrechea, M.*
AU  - Morales, E.*
AU  - Ballester, F.*
AU  - Murcia, M.*
AU  - Thijs, C.*
AU  - Mommers, M.*
AU  - Kuehni, C.E.*
AU  - Gaillard, E.A.*
AU  - Tischer, C.G.
AU  - Heinrich, J.
AU  - Pizzi, C.*
AU  - Zugna, D.*
AU  - Gehring, U.*
AU  - Wijga, A.*
AU  - Chatzi, L.*
AU  - Vassilaki, M.*
AU  - Bergström, A.*
AU  - Eller, E.*
AU  - Lau, S.*
AU  - Keil, T.*
AU  - Nieuwenhuijsen, M.*
AU  - Kogevinas, M.*
C1  - 48091
C2  - 39895
CY  - Sheffield
SP  - 115-124
TI  - The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.
JO  - Eur. Respir. J.
VL  - 48
IS  - 1
PB  - European Respiratory Soc Journals Ltd
PY  - 2016
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The aim of the present study was to analyse the interaction between asthma and smoking in the risk of adult airway obstruction, accounting for atopy. In the European Community Respiratory Health Survey, 15 668 persons aged 20-56 years underwent spirometry in 1991-1993 and 9 years later (n = 8916). Risk of airway obstruction and lung function decline associated with smoking and early-onset (<10 years of age) and late-onset (>10 years of age) asthma were analysed with generalised estimating equation models and random-effect linear models, adjusting for covariates. Interaction of asthma with smoking was expressed as relative excess risk due to interaction (RERI). A 20-fold increase in adult airway obstruction was found among those with early-onset asthma independently of smoking status (never smokers: OR 21.0, 95% CI 12.7-35; current smokers: OR 23.7, 95% CI 13.9-40.6). Late-onset asthma was associated with airway obstruction, with a stronger association among current smokers (OR 25.6, 95% CI 15.6-41.9) than among never-smokers (OR 11.2, 95% CI 6.8-18.6) (RERI 12.02, 95% CI 1.96-22.07). Stratifying by atopy, the association between smoking and asthma was most pronounced among nonatopics. Early- and late-onset asthma were associated with 10-20-fold increased risk of adult airway obstruction. Smoking increased the risk of adult airway obstruction in subjects with asthma onset after age 10 years. Investigation of measures potentially preventive of chronic obstructive pulmonary disease development following asthma is urgently needed.
AU  - Aanerud, M.*
AU  - Carsin, A.E.*
AU  - Sunyer, J.*
AU  - Dratva, J.*
AU  - Gislason, T.*
AU  - Jarvis, D.*
AU  - deMarco, R.*
AU  - Raherison, C.*
AU  - Wjst, M.
AU  - Dharmage, S.C.*
AU  - Svanes, C.*
C1  - 42855
C2  - 35813
CY  - Sheffield
SP  - 635-643
TI  - Interaction between asthma and smoking increases the risk of adult airway obstruction.
JO  - Eur. Respir. J.
VL  - 45
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2015
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO2, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m(-3) increase in NO2 exposure was associated with lower levels of FEV1 (-14.0 mL, 95%CI -25.8- -2.1) and FVC (-14.9 mL, 95% CI -28.7- -1.1). An increase of 10 μg·m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV1 (-44.6 mL, 95% CI -85.4- -3.8) and FVC (-59.0 mL, 95% CI -112.3- -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe.
AU  - Adam, M.*
AU  - Schikowski, T.*
AU  - Carsin, A.E.*
AU  - Cai, Y.*
AU  - Jacquemin, B.*
AU  - Sanchez, M.*
AU  - Vierkötter, A.*
AU  - Marcon, A.*
AU  - Keidel, D.*
AU  - Sugiri, D.*
AU  - Al Kanani, Z.*
AU  - Nadif, R.*
AU  - Siroux, V.*
AU  - Hardy, R.*
AU  - Kuh, D.*
AU  - Rochat, T.*
AU  - Bridevaux, P.O.*
AU  - Eeftens, M.*
AU  - Tsai, M.Y.*
AU  - Villani, S.*
AU  - Phuleria, H.C.*
AU  - Birk, M.
AU  - Cyrys, J.
AU  - Cirach, M.*
AU  - de Nazelle, A.*
AU  - Nieuwenhuijsen, M.J.*
AU  - Forsberg, B.*
AU  - de Hoogh, K.*
AU  - Declerq, C.*
AU  - Bono, R.*
AU  - Piccioni, P.*
AU  - Quass, U.*
AU  - Heinrich, J.
AU  - Jarvis, D.*
AU  - Pin, I.*
AU  - Beelen, R.*
AU  - Hoek, G.*
AU  - Brunekreef, B.*
AU  - Schindler, C.*
AU  - Sunyer, J.*
AU  - Krämer, U.*
AU  - Kauffmann, F.*
AU  - Hansell, A.L.*
AU  - Künzli, N.*
AU  - Probst-Hensch, N.*
C1  - 32110
C2  - 34972
CY  - Sheffield
SP  - 38-50
TI  - Adult lung function and long-term air pollution exposure. ESCAPE: A multicentre cohort study and meta-analysis.
JO  - Eur. Respir. J.
VL  - 45
IS  - 1
PB  - European Respiratory Soc Journals Ltd
PY  - 2015
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - After introduction of the new international guidelines on idiopathic pulmonary fibrosis (IPF) in 2011, we investigated clinical management practices for patients with IPF according to physicians' diagnoses. A prospective, multicenter, noninterventional study with comprehensive quality measures including on-site source data verification was performed in Germany. 502 consecutive patients (171 newly diagnosed, 331 prevalent; mean+-/SD age 68.7+-/9.4 years, 77.9% males) with a mean disease duration of 2.3+-/3.5 years were enrolled. IPF diagnosis was based on clinical assessments and high-resolution computed tomography (HRCT) in 90.2%, and on surgical lung biopsy combined with histology in 34.1% (lavage in 61.8%). The median 6-min walk distance was 320 m (mean 268+-/200 m). The mean forced vital capacity was 72+-/20% pred and diffusing capacity of the lung for carbon monoxide was 35+-/15% pred. No drugs were administered in 17.9%, oral steroids in 23.7%, N-acetylcysteine in 33.7%, pirfenidone in 44.2% and other drugs in 4.6% of patients. Only 2.8% of the cohort was listed for lung transplantation. IPF patients were diagnosed in line with the new guidelines. They had more severe disease than those enrolled in recent randomised controlled trials. In addition to HRCT, the frequency of lung biopsies was surprisingly high. Treatment patterns varied substantially.
AU  - Behr, J.
AU  - Kreuter, M.*
AU  - Hoeper, M.M.*
AU  - Wirtz, H.*
AU  - Klotsche, J.*
AU  - Koschel, D.*
AU  - Andreas, S.*
AU  - Claussen, M.*
AU  - Grohe, C.*
AU  - Wilkens, H.*
AU  - Randerath, W.*
AU  - Skowasch, D.*
AU  - Meyer, F.J.*
AU  - Kirschner, J.*
AU  - Glaeser, S.*
AU  - Herth, F.J.F.*
AU  - Welte, T.*
AU  - Huber, R.M.*
AU  - Neurohr, C.*
AU  - Schwaiblmair, M.*
AU  - Kohlhaeufl, M.*
AU  - Hoeffken, G.*
AU  - Held, M.*
AU  - Koch, A.*
AU  - Bahmer, T.*
AU  - Pittrow, D.*
C1  - 46438
C2  - 37580
CY  - Sheffield
SP  - 186-196
TI  - Management of patients with idiopathic pulmonary fibrosis in clinical practice: The INSIGHTS-IPF registry.
JO  - Eur. Respir. J.
VL  - 46
IS  - 1
PB  - European Respiratory Soc Journals Ltd
PY  - 2015
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - We compared risk factors and clinical characteristics, 9-year lung function change and hospitalisation risk across subjects with the asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), asthma or COPD alone, or none of these diseases.Participants in the European Community Respiratory Health Survey in 1991-1993 (aged 20-44 years) and 1999-2001 were included. Chronic airflow obstruction was defined as pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity
AU  - de Marco, R.*
AU  - Marcon, A.*
AU  - Rossi, A.*
AU  - Antò, J.M.*
AU  - Cerveri, I.*
AU  - Gislason, T.*
AU  - Heinrich, J.
AU  - Janson, C.*
AU  - Jarvis, D.*
AU  - Kuenzli, N.*
AU  - Leynaert, B.*
AU  - Probst-Hensch, N.*
AU  - Svanes, C.*
AU  - Wjst, M.
AU  - Burney, P.*
C1  - 45484
C2  - 37352
SP  - 671-679
TI  - Asthma, COPD and overlap syndrome: A longitudinal study in young European adults.
JO  - Eur. Respir. J.
VL  - 46
IS  - 3
PY  - 2015
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Ageing is the main risk factor for major non-communicable chronic lung diseases, including chronic obstructive pulmonary disease, most forms of lung cancer and idiopathic pulmonary fibrosis. While the prevalence of these diseases continually increases with age, their respective incidence peaks at different times during the lifespan, suggesting specific effects of ageing on the onset and/or pathogenesis of chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis. Recently, the nine hallmarks of ageing have been defined as cell-autonomous and non-autonomous pathways involved in ageing. Here, we review the available evidence for the involvement of each of these hallmarks in the pathogenesis of chronic obstructive pulmonary disease, lung cancer, or idiopathic pulmonary fibrosis. Importantly, we propose an additional hallmark, "dysregulation of the extracellular matrix", which we argue acts as a crucial modifier of cell-autonomous changes and functions, and as a key feature of the above-mentioned lung diseases.
AU  - Meiners, S.
AU  - Eickelberg, O.
AU  - Königshoff, M.
C1  - 43237
C2  - 36349
CY  - Sheffield
SP  - 807-827
TI  - Hallmarks of the ageing lung.
JO  - Eur. Respir. J.
VL  - 45
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2015
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The aim of this study was to determine the effect of six traffic-related air pollution metrics (nitrogen dioxide, nitrogen oxides, particulate matter with an aerodynamic diameter <10 μm (PM10), PM2.5, coarse particulate matter and PM2.5 absorbance) on childhood asthma and wheeze prevalence in five European birth cohorts: MAAS (England, UK), BAMSE (Sweden), PIAMA (the Netherlands), GINI and LISA (both Germany, divided into north and south areas). Land-use regression models were developed for each study area and used to estimate outdoor air pollution exposure at the home address of each child. Information on asthma and current wheeze prevalence at the ages of 4-5 and 8-10 years was collected using validated questionnaires. Multiple logistic regression was used to analyse the association between pollutant exposure and asthma within each cohort. Random-effects meta-analyses were used to combine effect estimates from individual cohorts. The meta-analyses showed no significant association between asthma prevalence and air pollution exposure (e.g. adjusted OR (95%CI) for asthma at age 8-10 years and exposure at the birth address (n = 10377): 1.10 (0.81-1.49) per 10 μg·m(-3) nitrogen dioxide; 0.88 (0.63-1.24) per 10 μg·m(-3) PM10; 1.23 (0.78-1.95) per 5 μg·m(-3) PM2.5). This result was consistently found in initial crude models, adjusted models and further sensitivity analyses. This study found no significant association between air pollution exposure and childhood asthma prevalence in five European birth cohorts.
AU  - Mölter, A.*
AU  - Simpson, A.*
AU  - Berdel, D.*
AU  - Brunekreef, B.*
AU  - Custovic, A.*
AU  - Cyrys, J.
AU  - de Jongste, J.*
AU  - de Vocht, F.*
AU  - Fuertes, E.
AU  - Gehring, U.*
AU  - Gruzieva, O.*
AU  - Heinrich, J.
AU  - Hoek, G.*
AU  - Hoffmann, B.*
AU  - Klümper, C.*
AU  - Korek, M.*
AU  - Kuhlbusch, T.A.J.*
AU  - Lindley, S.*
AU  - Postma, D.*
AU  - Tischer, C.G.
AU  - Wijga, A.*
AU  - Pershagen, G.*
AU  - Agius, R.M.*
C1  - 32585
C2  - 35136
CY  - Sheffield
SP  - 610-624
TI  - A multicentre study of air pollution exposure and childhood asthma prevalence: The ESCAPE project.
JO  - Eur. Respir. J.
VL  - 45
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2015
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Inverse associations have been found between exposure to bio-contaminants and asthma and allergies. The aim of this study was to prospectively assess whether early exposure to bio-contaminants in dust is associated with asthma and allergy later in childhood among children from (sub)-urban areas. In subsets of three European birth cohorts (PIAMA: n = 553; INMA: n = 481; and LISAplus: n = 395), endotoxin, (1,3,)-β-d-glucan and extracellular polysaccharide were measured in dust from living rooms shortly after birth. Current asthma at 6 years and 10 years of age and ever asthma up to 10 years of age were assessed by parental questionnaires. Specific IgE levels at 8 years (PIAMA) and 10 years (LISAplus) were available. Adjusted, cohort-specific logistic regression analyses were performed. Higher endotoxin concentrations were positively associated with current asthma at 6 years of age in PIAMA (adjusted OR 1.96, 95% CI 1.07-3.58), but were inversely related with ever asthma up to 10 years of age in INMA (adjusted OR 0.39, 95% CI 0.16-0.94). No associations with asthma were found for LISAplus. No associations were observed with atopic sensitisation in all cohorts. All associations with (1,3)-β-d-glucan and extracellular polysaccharide were statistically nonsignificant. The suggested immunological mechanisms of early exposure to bio-contaminants with regards to asthma and allergy might be different for children growing up in (sub)-urban environments.
AU  - Tischer, C.G.
AU  - Casas, L.*
AU  - Wouters, I.M.*
AU  - Doekes, G.*
AU  - García-Esteban, R.*
AU  - Gehring, U.*
AU  - Hyvärinen, A.*
AU  - Oldenwening, M.*
AU  - Kerkhof, M.*
AU  - Sunyer, J.*
AU  - Standl, M.
AU  - Thiering, E.
AU  - Torrent, M.*
AU  - Heinrich, J.
AU  - HITEA Study Group (*)
C1  - 32100
C2  - 34963
CY  - Sheffield
SP  - 328-337
TI  - Early exposure to bio-contaminants and asthma up to 10 years of age: Results of the HITEA study.
JO  - Eur. Respir. J.
VL  - 54
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2015
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Animal furs might represent a "proxy" for high and diverse microbial exposures within a critical time window of immune development. We assessed whether sleeping on animal fur shortly after birth is associated with asthma and atopy up to the age of 10 years. LISAplus participants (n=2441) from Munich and Leipzig, Germany, were included in the analysis. Animal fur exposure, cofactors and health outcomes were obtained periodically up to 10 years of age by parental questionnaires. Information on specific IgE to aeroallergens was available at 10 years. Cytokine-producing peripheral T-cells were assessed in a subgroup of children at 2 and 3 years. Confounder-adjusted associations were evaluated using logistic regression analyses. Sleeping on animal fur was very common (55%). In adjusted logistic regression analyses, sleeping on animal fur was inversely associated with recurrent early wheezing at 4 years (adjusted OR 0.75, 95% CI 0.61-0.93) and current asthma at 6 years (adjusted OR 0.56, 95% CI 0.31-1.01). Furthermore, sleeping on animal fur during the first 3 months of life was significantly associated with a persistently stimulated interferon-γ response until the age of 3 years. Animal fur could be an effective measure of creating environments associated with higher microbial exposure.
AU  - Tischer, C.G.
AU  - Standl, M.
AU  - Lehmann, I.*
AU  - Schaaf, B.*
AU  - von Berg, A.*
AU  - Heinrich, J.
C1  - 44110
C2  - 36745
CY  - Sheffield
SP  - 107-114
TI  - Sleeping on animal fur is related to asthma outcomes in later childhood.
JO  - Eur. Respir. J.
VL  - 46
IS  - 1
PB  - European Respiratory Soc Journals Ltd
PY  - 2015
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by a progressive loss of lung tissue. Inducing repair processes within the adult diseased lung is of major interest and Wnt/β-catenin signalling represents a promising target for lung repair. However, the translation of novel therapeutic targets from model systems into clinical use remains a major challenge. We generated murine and patient-derived three-dimensional (3D) ex vivo lung tissue cultures (LTCs), which closely mimic the 3D lung microenvironment in vivo. Using two well-known glycogen synthase kinase-3β inhibitors, lithium chloride (LiCl) and CHIR 99021 (CT), we determined Wnt/β-catenin-driven lung repair processes in high spatiotemporal resolution using quantitative PCR, Western blotting, ELISA, (immuno)histological assessment, and four-dimensional confocal live tissue imaging. Viable 3D-LTCs exhibited preserved lung structure and function for up to 5 days. We demonstrate successful Wnt/β-catenin signal activation in murine and patient-derived 3D-LTCs from COPD patients. Wnt/β-catenin signalling led to increased alveolar epithelial cell marker expression, decreased matrix metalloproteinase-12 expression, as well as altered macrophage activity and elastin remodelling. Importantly, induction of surfactant protein C significantly correlated with disease stage (percent predicted forced expiratory volume in 1 s) in patient-derived 3D-LTCs. Patient-derived 3D-LTCs represent a valuable tool to analyse potential targets and drugs for lung repair. Enhanced Wnt/β-catenin signalling attenuated pathological features of patient-derived COPD 3D-LTCs.
AU  - Uhl, F.
AU  - Vierkotten, S.
AU  - Wagner, D.E.
AU  - Burgstaller, G.
AU  - Costa, R.
AU  - Koch, I.*
AU  - Lindner, M.*
AU  - Meiners, S.
AU  - Eickelberg, O.
AU  - Königshoff, M.
C1  - 44575
C2  - 37009
SP  - 1150-1166
TI  - Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures.
JO  - Eur. Respir. J.
VL  - 46
IS  - 4
PY  - 2015
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Several clinical studies suggest the involvement of premature aging processes in COPD. Using an epidemiological approach we studied whether accelerated aging indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the inter-individual variability of lung function.Our meta-analysis of 14 studies included 934 COPD cases with 15,846 controls defined according to GLI criteria (or 1,189 COPD cases according to GOLD), 2,834 asthma cases with 28,195 controls, and spirometric parameters (FEV1, FVC and FEV1/FVC) of 12,595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex, and smoking status.We observed negative associations between telomere length and asthma (β= -0.0452, p=0.024) as well as COPD (β= -0.0982, p=0.001), with associations being stronger and more significant when using GLI in comparison to GOLD. In both diseases, effects were stronger in females compared to males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10(-7)), FVC (p=2.07×10(-5)), and their ratio FEV1/FVC (p=5.27×10(-3)). The effect was somewhat weaker in apparently healthy subjects compared to COPD or asthma patients.Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma and that lung function may reflect biological aging primarily due to intrinsic processes which are likely to be aggravated in lung diseases.
AU  - Albrecht, E.
AU  - Sillanpää, E.*
AU  - Karrasch, S.
AU  - Alves, A.C.*
AU  - Codd, V.*
AU  - Hovatta, I.*
AU  - Buxton, J.L.*
AU  - Nelson, C.P.*
AU  - Broer, L.*
AU  - Hägg, S.*
AU  - Mangino, M.*
AU  - Willemsen, G.*
AU  - Surakka, I.*
AU  - Ferreira, M.A.*
AU  - Amin, N.*
AU  - Oostra, B.A.*
AU  - Bäckmand, H.M.*
AU  - Peltonen, M.*
AU  - Sarna, S.*
AU  - Rantanen, T.*
AU  - Sipilä, S.*
AU  - Korhonen, T.*
AU  - Madden, P.A.*
AU  - Gieger, C.
AU  - Jörres, R.A.*
AU  - Heinrich, J.
AU  - Behr, J.*
AU  - Huber, R.M.*
AU  - Peters, A.
AU  - Strauch, K.
AU  - Wichmann, H.-E.
AU  - Waldenberger, M.
AU  - Blakemore, A.I.*
AU  - de Geus, E.J.*
AU  - Nyholt, D.R.*
AU  - Henders, A.K.*
AU  - Piirilä, P.L.*
AU  - Rissanen, A.*
AU  - Magnusson, P.K.*
AU  - Viñuela, A.*
AU  - Pietiläinen, K.H.*
AU  - Martin, N.G.*
AU  - Pedersen, N.L.*
AU  - Boomsma, D.I.*
AU  - Spector, T.D.*
AU  - van Duijn, C.M.*
AU  - Kaprio, J.*
AU  - Samani, N.J.*
AU  - Jarvelin, M.R.*
AU  - Schulz, H.
C1  - 28608
C2  - 33480
CY  - Sheffield
SP  - 983-992
TI  - Telomere length in circulating leukocytes is associated with lung function and disease.
JO  - Eur. Respir. J.
VL  - 43
IS  - 4
PB  - European Respiratory Soc. Journals
PY  - 2014
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Bousquet, J.*
AU  - Addis, A.*
AU  - Adcock, I.*
AU  - Agache, I.*
AU  - Agusti, A.*
AU  - Alonso, A.*
AU  - Annesi-Maesano, I.*
AU  - Antò, J.M.*
AU  - Bachert, C.*
AU  - Baena-Cagnani, C.E.*
AU  - Bai, C.*
AU  - Baigenzhin, A.*
AU  - Barbara, C.*
AU  - Barnes, P.J.*
AU  - Bateman, E.D.*
AU  - Beck, L.*
AU  - Bedbrook, A.*
AU  - Bel, E.H.*
AU  - Benezet, O.*
AU  - Bennoor, K.S.*
AU  - Benson, M.*
AU  - Bernabeu-Wittel, M.*
AU  - Bewick, M.*
AU  - Bindslev-Jensen, C.*
AU  - Blain, H.*
AU  - Blasi, F.*
AU  - Bonini, M.*
AU  - Bonini, S.*
AU  - Boulet, L.P.*
AU  - Bourdin, A.*
AU  - Bourret, R.*
AU  - Bousquet, P.J.*
AU  - Brightling, C.E.*
AU  - Briggs, A.*
AU  - Brozek, J.L.*
AU  - Buhl, R.*
AU  - Bush, A.*
AU  - Caimmi, D.*
AU  - Calderon, M.*
AU  - Calverley, P.*
AU  - Camargos, P.A.M.*
AU  - Camuzat, T.*
AU  - Canonica, G.W.*
AU  - Carlsen, K.H.*
AU  - Casale, T.B.*
AU  - Cazzola, M.*
AU  - Cepeda Sarabia, A.M.*
AU  - Cesario, A.*
AU  - Chen, Y.Z.*
AU  - Chkhartishvili, E.*
AU  - Chavannes, N.H.*
AU  - Chiron, R.*
AU  - Chuchalin, A.*
AU  - Chung, K.F.*
AU  - Cox, L.*
AU  - Crooks, G.*
AU  - Crooks, M.G.*
AU  - Cruz, A.A.*
AU  - Custovic, A.*
AU  - Dahl, R.*
AU  - Dahlen, S.E.*
AU  - de Blay, F.*
AU  - Dedeu, T.*
AU  - Deleanu, D.*
AU  - Demoly, P.*
AU  - Devillier, P.*
AU  - Didier, A.*
AU  - Dinh-Xuan, A.T.*
AU  - Djukanovic, R.*
AU  - Dokic, D.*
AU  - Douagui, H.*
AU  - Dubakiene, R.*
AU  - Eglin, S.*
AU  - Elliot, F.*
AU  - Emuzyte, R.*
AU  - Fabbri, L.*
AU  - Fink Wagner, A.*
AU  - Fletcher, M.*
AU  - Fokkens, W.J.*
AU  - Fonseca, J.*
AU  - Franco, A.*
AU  - Frith, P.*
AU  - Furber, A.*
AU  - Gaga, M.*
AU  - Garcés, J.*
AU  - Garcia-Aymerich, J.*
AU  - Gamkrelidze, A.*
AU  - Gonzales-Diaz, S.*
AU  - Gouzi, F.*
AU  - Guzman, M.A.*
AU  - Haahtela, T.*
AU  - Harrison, D.*
AU  - Hayot, M.*
AU  - Heaney, L.G.*
AU  - Heinrich, J.
AU  - Hellings, P.W.*
AU  - Hooper, J.*
AU  - Humbert, M.*
AU  - Hyland, M.*
AU  - Iaccarino, G.*
AU  - Jakovenko, D.*
AU  - Jardim, J.R.*
AU  - Jeandel, C.*
AU  - Jenkins, C.*
AU  - Johnston, S.L.*
AU  - Jonquet, O.*
AU  - Joos, G.*
AU  - Jung, K.S.*
AU  - Kalayci, O.*
AU  - Karunanithi, S.*
AU  - Keil, T.*
AU  - Khaltaev, N.*
AU  - Kolek, V.*
AU  - Kowalski, M.L.*
AU  - Kull, I.*
AU  - Kuna, P.*
AU  - Kvedariene, V.*
AU  - Le, L.T.*
AU  - Lodrup Carlsen, K.C.*
AU  - Louis, R.*
AU  - MacNee, W.*
AU  - Mair, A.*
AU  - Majer, I.*
AU  - Manning, P.*
AU  - de Manuel Keenoy, E.*
AU  - Masjedi, M.R.*
AU  - Melén, E.*
AU  - Melo-Gomes, E.*
AU  - Menzies-Gow, A.*
AU  - Mercier, G.*
AU  - Mercier, J.*
AU  - Michel, J.P.*
AU  - Miculinic, N.*
AU  - Mihaltan, F.*
AU  - Milenkovic, B.*
AU  - Molimard, M.*
AU  - Momas, I.*
AU  - Montilla-Santana, A.*
AU  - Morais-Almeida, M.*
AU  - Morgan, M.*
AU  - N'Diaye, M.*
AU  - Nafti, S.*
AU  - Nekam, K.*
AU  - Neou, A.*
AU  - Nicod, L.P.*
AU  - O'Hehir, R.E.*
AU  - Ohta, K.*
AU  - Paggiaro, P.*
AU  - Palkonen, S.*
AU  - Palmer, S.*
AU  - Papadopoulos, N.G.*
AU  - Papi, A.*
AU  - Passalacqua, G.*
AU  - Pavord, I.D.*
AU  - Pigearias, B.*
AU  - Plavec, D.*
AU  - Postma, D.S.*
AU  - Price, D.*
AU  - Rabe, K.F.*
AU  - Radier Pontal, F.*
AU  - Redon, J.*
AU  - Rennard, S.*
AU  - Roberts, J.*
AU  - Robine, J.M.*
AU  - Roca, J.*
AU  - Roche, N.*
AU  - Rodenas, F.*
AU  - Roggeri, A.*
AU  - Rolland, C.*
AU  - Rosado-Pinto, J.*
AU  - Ryan, D.*
AU  - Samolinski, B.*
AU  - Sanchez-Borges, M.*
AU  - Schünemann, H.J.*
AU  - Sheikh, A.*
AU  - Shields, M.*
AU  - Siafakas, N.M.*
AU  - Sibille, Y.*
AU  - Similowski, T.*
AU  - Small, I.*
AU  - Sola-Morales, O.*
AU  - Sooronbaev, T.*
AU  - Stelmach, R.*
AU  - Sterk, P.J.*
AU  - Stiris, T.*
AU  - Sud, P.*
AU  - Tellier, V.*
AU  - To, T.*
AU  - Todo-Bom, A.*
AU  - Triggiani, M.*
AU  - Valenta, R.*
AU  - Valero, A.L.*
AU  - Valiulis, A.*
AU  - Valovirta, E.*
AU  - van Ganse, E.*
AU  - Vandenplas, O.*
AU  - Vasankari, T.*
AU  - Vestbo, J.*
AU  - Vezzani, G.*
AU  - Viegi, G.*
AU  - Visier, L.*
AU  - Vogelmeier, C.*
AU  - Vontetsianos, T.*
AU  - Wagstaff, R.*
AU  - Wahn, U.*
AU  - Wallaert, B.*
AU  - Whalley, B.*
AU  - Wickman, M.*
AU  - Williams, D.M.*
AU  - Wilson, N.*
AU  - Yawn, B.P.*
AU  - Yiallouros, P.K.*
AU  - Yorgancioglu, A.*
AU  - Yusuf, O.M.*
AU  - Zar, H.J.*
AU  - Zhong, N.*
AU  - Zidarn, M.*
AU  - Zuberbier, T.*
C1  - 31806
C2  - 34774
SP  - 304-323
TI  - Integrated care pathways for airway diseases (AIRWAYS-ICPs).
JO  - Eur. Respir. J.
VL  - 44
IS  - 2
PY  - 2014
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Limited information exists regarding the incidence and predictors of asthma and nasal allergy in adulthood. We determined the incidence rate of asthma and nasal allergy in adults and assessed the predictive value of skin prick tests (SPTs) and radioallergosorbent tests (RASTs) for these two outcomes. Two German centres involved in the European Community Respiratory Health Survey conducted a follow-up assessment in 2012 of the baseline participants (1185 adults aged 21-47 years assessed in 1990). The predictive value of SPTs and RASTs on new-onset asthma and nasal allergy was assessed by Cox regression and by calculating the positive or negative predictive value. During the 20 years between baseline and follow-up, 3.1 and 4.4 per 1000 person-years of new-onset asthma and nasal allergy cases were recorded, respectively. The hazard ratios for SPTs of any specific and of all aeroallergens combined were slightly higher than those of RASTs for asthma and nasal allergy. The negative predictive values of both the SPT and EAST were very high and similar (0.94-0.96), whereas the postive predictive values were low (0.09-0.20). Positive SPT results showed a better association with new onset asthma and nasal allergy than positive EAST either to any specific aeroallergens or to all combined.
AU  - Gallmeier, K.
AU  - Becker, E.
AU  - Kirsten, A.*
AU  - Woelke, G.
AU  - Manuwald, O.*
AU  - Meyer, H.*
AU  - Magnussen, H.*
AU  - Nowak, D.*
AU  - Heinrich, J.
C1  - 29328
C2  - 33713
SP  - 92-102
TI  - Prediction of new-onset asthma and nasal allergy by skin prick test and RAST in a cohort of adults.
JO  - Eur. Respir. J.
VL  - 43
IS  - 1
PB  - European Respiratory Soc Journals
PY  - 2014
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The applicability and interpretation of inert tracer gas washout tests is hampered by the lack of feasible protocols and reproducibility data. We assessed feasibility, variability and reproducibility of a new easy to perform double tracer gas (DTG) single-breath washout (SBW) test and compared this with conventional nitrogen washouts. In 40 healthy nonsmokers and 20 patients with stable chronic obstructive pulmonary disease (COPD), we performed three N2 vital capacity SBWs, three N2 multiple-breath washouts and three tidal DTG-SBW tests. Follow-up was after 1 week, 1 month and 6 months. Main outcomes were the lung clearance index (LCI) (N2 multiple-breath washout), slope of phase III (dN2) (N2 vital capacity SBW) and slope of phase III (SIIIDTG) (DTG-SBW). In healthy subjects, mean±sd LCI at baseline was 6.94±0.61, dN2 0.99±0.42% N2 per litre and SIIIDTG -0.206±0.108 g·mol(-1)·L(-1). In COPD, LCI and dN2 were significantly higher (LCI 12.23±2.67, dN2 7.43±5.38% N2 per litre; p<0.001) and SIIIDTG significantly steeper (-0.653±0.428 g·mol(-1)·L(-1), p<0.001). Reproducibility was high for main outcome parameters: the intraclass correlation coefficient over 6 months was 0.77 (0.86 in COPD) for LCI, 0.82 (0.89) for dN2 and 0.83 (0.93) for SIIIDTG. The tidal DTG-SBW is a reproducible test in healthy and COPD subjects that seems attractive for use in routine clinical settings.
AU  - Husemann, K.*
AU  - Berg, N.*
AU  - Engel, J.*
AU  - Port, J.*
AU  - Joppek, C.*
AU  - Tao, Z.*
AU  - Singer, F.*
AU  - Schulz, H.
AU  - Kohlhäufl, M.*
C1  - 31920
C2  - 34859
SP  - 1210-1222
TI  - Double tracer gas single-breath washout: Reproducibility in healthy subjects and COPD.
JO  - Eur. Respir. J.
VL  - 44
IS  - 5
PY  - 2014
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Königshoff, M.
C1  - 31861
C2  - 34826
CY  - Sheffield
SP  - 297-298
TI  - The new Back to Basics section: Emerging concepts in basic and translational medicine.
JO  - Eur. Respir. J.
VL  - 44
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2014
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Meiners, S.
AU  - Greene, C.M.*
C1  - 32428
C2  - 35089
CY  - Sheffield
SP  - 846-849
TI  - Protein quality control in lung disease: It's all about cloud networking.
JO  - Eur. Respir. J.
VL  - 44
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2014
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The role of air pollution in chronic obstructive pulmonary disease (COPD) remains uncertain.The aim was to assess the impact of chronic exposure to air pollution on COPD in four cohorts using the standardised ESCAPE exposure estimates. Annual average particulate matter (PM), nitrogen oxides (NOx) and road traffic exposure were assigned to home addresses using land-use regression models. COPD was defined by NHANES reference equation (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) less than the lower limit of normal) and the Global Initiative for Chronic Obstructive Lung Disease criterion (FEV1/FVC <0.70) and categorised by severity in non-asthmatics.We included 6550 subjects with assigned NOx and 3692 with PM measures. COPD was not associated with NO2 or PM10 in any individual cohort. In meta-analyses only NO2, NOx, PM10 and the traffic indicators were positively, although not significantly, associated with COPD. The only statistically significant associations were seen in females (COPD prevalence using GOLD: OR 1.57, 95% CI 1.11-2.23; and incidence: OR 1.79, 95% CI 1.21-2.68).None of the principal results were statistically significant, the weak positive associations of exposure with COPD and the significant subgroup findings need to be evaluated in further well standardised cohorts followed up for longer time, and with time-matched exposure assignments.
AU  - Schikowski, T.*
AU  - Adam, M.*
AU  - Marcon, A.*
AU  - Cai, Y.*
AU  - Vierkötter, A.*
AU  - Carsin, A.E.*
AU  - Jacquemin, B.*
AU  - Al Kanani, Z.*
AU  - Beelen, R.*
AU  - Birk, M.
AU  - Bridevaux, P.O.*
AU  - Brunekeef, B.*
AU  - Burney, P.*
AU  - Cirach, M.*
AU  - Cyrys, J.
AU  - de Hoogh, K.*
AU  - de Marco, R.*
AU  - de Nazelle, A.*
AU  - Declercq, C.*
AU  - Forsberg, B.*
AU  - Hardy, R.*
AU  - Heinrich, J.
AU  - Hoek, G.*
AU  - Jarvis, D.*
AU  - Keidel, D.*
AU  - Kuh, D.*
AU  - Kuhlbusch, T.*
AU  - Migliore, E.*
AU  - Mosler, G.*
AU  - Nieuwenhuijsen, M.J.*
AU  - Phuleria, H.*
AU  - Rochat, T.*
AU  - Schindler, C.*
AU  - Villani, S.*
AU  - Tsai, M.Y.*
AU  - Zemp, E.*
AU  - Hansell, A.*
AU  - Kauffmann, F.*
AU  - Sunyer, J.*
AU  - Probst-Hensch, N.*
AU  - Krämer, U.*
AU  - Künzli, N.*
C1  - 30758
C2  - 33836
CY  - Sheffield
SP  - 614-626
TI  - Association of ambient air pollution with the prevalence and incidence of COPD.
JO  - Eur. Respir. J.
VL  - 44
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2014
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The aim was to identify genetic variants associated with refined asthma phenotypes enabling to take into account multiple features of the disease.Latent class analysis (LCA) was applied in 3001 adults ever having asthma recruited in the frame of three epidemiological surveys (ECRHS, SAPALDIA, EGEA). Fourteen personal and phenotypic characteristics from questionnaires and clinical examination were used. A genome wide association study (GWAS) was conducted for each LCA-derived asthma phenotype, compared to subjects without asthma (n=3474).The LCA identified four adult asthma phenotypes, mainly characterized by the activity of the disease, the age of asthma onset and the atopic status. Associations of genome wide significance (<1.25×10-7) were observed between "active adult-onset non-allergic asthma" and rs9851461 flanking CD200 (3q13.2) and between "Inactive/mild non-allergic asthma" and rs2579931 flanking GRIK2 (6q16.3). Borderline significant results (2.5×10(-7).
AU  - Siroux, V.*
AU  - Gonzalez, J.R.*
AU  - Bouzigon, E.*
AU  - Curjuric, I.*
AU  - Boudier, A.*
AU  - Imboden, M.*
AU  - Antò, J.M.*
AU  - Gut, I.*
AU  - Jarvis, D.*
AU  - Lathrop, M*
AU  - Omenaas, E.R.*
AU  - Pin, I.*
AU  - Wjst, M.
AU  - Demenais, F.*
AU  - Probst-Hensch, N.*
AU  - Kogevinas, M.*
AU  - Kauffmann, F.*
C1  - 29062
C2  - 33614
CY  - Sheffield
SP  - 439-452
TI  - Genetic heterogeneity of asthma phenotypes identified by a clustering approach.
JO  - Eur. Respir. J.
VL  - 43
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2014
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Respiratory diseases are an increasing burden for the ageing population. Although our understanding of these diseases has improved significantly over the past decades, diagnostic and therapeutic options for treating lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and lung cancer, remain limited. Multidisciplinary approaches that bridge the gap between medicinal and materials sciences will likely contribute to promising new therapeutic and diagnostic solutions. One such multidisciplinary approach is the use of nanoparticles as carriers for the delivery of drugs. The advantages of using nanoparticles to deliver drugs include: increased drug concentration at the disease site; minimised drug degradation and loss; ease of creating inhalable formulations; and the possibility of specific cell targeting. This article gives a brief overview on the emerging field of nanocarriers as drug delivery vehicles for the treatment of lung diseases.
AU  - van Rijt, S.H.
AU  - Bein, T.*
AU  - Meiners, S.
C1  - 31216
C2  - 34231
CY  - Sheffield
SP  - 765-774
TI  - Medical nanoparticles for next generation drug delivery to the lungs.
JO  - Eur. Respir. J.
VL  - 44
IS  - 3
PB  - European Respiratory Soc Journals Ltd
PY  - 2014
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Baarsma, H.A.
AU  - Koenigshoff, M.
C1  - 47015
C2  - 40492
TI  - WNT5A antagonizes canonical WNT/beta-catenin signaling in lung epithelial cells.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Bartel, S.
AU  - Schulz, N.
AU  - Theis, F.J.
AU  - Alessandrini, F.
AU  - Takenaka, S.
AU  - Eickelberg, O.
AU  - Krauss-Etschmann, S.
C1  - 47019
C2  - 40489
TI  - miRNA-based identification of SEC14L3 deregulation in murine experimental asthma.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Bartmann, J.
AU  - Frankenberger, M.
AU  - Neurohr, C.*
AU  - Eickelberg, O.
AU  - von Wulffen, W.*
C1  - 47011
C2  - 40490
TI  - Prominence of MMP-12 and MMP-13 in dendritic cells and the impact on a murine model of bronchiolitis obliterans.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The airway epithelium forms a physical, chemical and immunological barrier against inhaled environmental substances. In asthma, these barrier properties are thought to be abnormal. In this study, we analysed the effect of grass pollen on the physical and immunological barrier properties of differentiated human primary bronchial epithelial cells. Following exposure to Timothy grass (Phleum pratense) pollen extract, the integrity of the physical barrier was not impaired as monitored by measuring the transepithelial resistance and immunofluorescence staining of tight junction proteins. In contrast, pollen exposure affected the immunological barrier properties by modulating vectorial mediator release. CXC chemokine ligand (CXCL)8/interleukin (IL)-8 showed the greatest increase in response to pollen exposure with preferential release to the apical compartment. Inhibition of the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways selectively blocked apical CXCL8/IL-8 release via a post-transcriptional mechanism. Apical release of CC chemokine ligand (CCL)20/macrophage inflammatory protein-3α, CCL22/monocyte-derived chemokine and tumour necrosis factor-α was significantly increased only in severe asthma cultures, while CCL11/eotaxin-1 and CXCL10/interferon-γ-induced protein-10 were reduced in nonasthmatic cultures. The bronchial epithelial barrier modulates polarised release of mediators in response to pollen without direct effects on its physical barrier properties. The differential response of cells from normal and asthmatic donors suggests the potential for the bronchial epithelium to promote immune dysfunction in asthma.
AU  - Blume, C.*
AU  - Swindle, E.J.*
AU  - Dennison, P.*
AU  - Jayasekera, N.P.*
AU  - Dudley, S.*
AU  - Monk, P.*
AU  - Behrendt, H.
AU  - Schmidt-Weber, C.B.
AU  - Holgate, S.T.*
AU  - Howarth, P.H.*
AU  - Traidl-Hoffmann, C.
AU  - Davies, D.E.*
C1  - 48565
C2  - 41187
SP  - 87-97
TI  - Barrier responses of human bronchial epithelial cells to grass pollen exposure.
JO  - Eur. Respir. J.
VL  - 42
IS  - 1
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - No large study has described the seasonal variation in asthma attacks in population-based asthmatics in whom sensitisation to allergen has been measured. 2637 young adults with asthma living in 15 countries reported the months in which they usually had attacks of asthma and had skin-prick tests performed. Differences in seasonal patterns by sensitisation status were assessed using generalised estimating equations. Most young adults with asthma reported periods of the year when their asthma attacks were more common (range: 47% in Sweden to 86% in Spain). Seasonal variation in asthma was not modified by sensitisation to house dust mite or cat allergens. Asthmatics sensitised to grass, birch and Alternaria allergens had different seasonal patterns to those not sensitised to each allergen, with some geographical variation. In southern Europe, those sensitised to grass allergens were more likely to report attacks occurred in spring or summer than in winter (OR March/April 2.60, 95% CI 1.70-3.97; OR May/June 4.43, 95% CI 2.34-8.39) and smaller later peaks were observed in northern Europe (OR May/June 1.25, 95% CI 0.60-2.64; OR July/August 1.66, 95% CI 0.89-3.10). Asthmatics reporting hay fever but who were not sensitised to grass showed no seasonal variations. Seasonal variations in asthma attacks in young adults are common and are different depending on sensitisation to outdoor, but not indoor, allergens.
AU  - Canova, C.*
AU  - Heinrich, J.
AU  - Antò, J.M.*
AU  - Leynaert, B.*
AU  - Smith, M.*
AU  - Kuenzli, N.*
AU  - Zock, J.P.*
AU  - Janson, C.*
AU  - Cerveri, I.
AU  - de Marco, R.*
AU  - Torén, K.*
AU  - Gislason, T.*
AU  - Nowak, D.*
AU  - Pin, I.*
AU  - Wjst, M.
AU  - Manfreda, J.*
AU  - Svanes, C.*
AU  - Crane, J.*
AU  - Abramson, M.*
AU  - Burr, M.*
AU  - Burney, P.*
AU  - Jarvis, D.*
C1  - 27837
C2  - 32835
SP  - 935-945
TI  - The influence of sensitisation to pollens and moulds on seasonal variations in asthma attacks.
JO  - Eur. Respir. J.
VL  - 42
IS  - 4
PB  - European Respiratory Soc. Journals
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Dehmel, S.
AU  - Nathan, P.
AU  - Milger, K.
AU  - Imker, R.
AU  - Eickelberg, O.
AU  - Krauss-Etschmann, S.
C1  - 47017
C2  - 40491
TI  - Characterization of Tbx21-deficient mice as a model for transgenerational asthma risk propagation.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Fernandez, I.E.
AU  - Amarie, O.V.
AU  - Yildirim, O.
AU  - Koenigshoff, M.
AU  - Eickelberg, O.
C1  - 47012
C2  - 40495
TI  - Novel biomarkers in bleomycin-induced pulmonary fibrosis.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Gimm, T.
AU  - Kossert, M.*
AU  - Alvira, C.M.*
AU  - Ehrhardt, H.*
AU  - Hilgendorff, A.*
C1  - 46998
C2  - 40508
TI  - Role of TNF-a in ventilator-induced lung injury in the developing murine lung.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Gimm, T.
AU  - Hoeland, A.*
AU  - Schwarz, M.*
AU  - Hossain, H.*
AU  - Ehrhardt, H.*
AU  - Gortner, L.*
AU  - Scholz, M.*
AU  - Reicherzer, T.*
AU  - Hauck, S.M.
AU  - Hilgendorff, A.
C1  - 47004
C2  - 40502
TI  - Identification of biomarkers for early diagnosis in BPD.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Hilgendorff, A.*
AU  - Thiel, I.
AU  - Jain, N.
AU  - Koschlig, M.
AU  - Eickelberg, O.
AU  - Schulze, A.*
AU  - Ehrhardt, H.
AU  - Desai, T.*
C1  - 47009
C2  - 40498
TI  - Increased risk for lung injury in PDGF-R alpha deficient newborn mice.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Jia, J.
AU  - Eickelberg, O.
AU  - Yildirim, A.Ö.
C1  - 47002
C2  - 40504
TI  - Cigarette smoke induced Muc5AC is regulated by CARM1 in an ex-vivo airway model.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Keller, I.E.
AU  - Dann, A.
AU  - Fernandez-Buelvaz, I.
AU  - Takenaka, S.
AU  - Guenther, A.*
AU  - Eickelberg, O.
AU  - Meiners, S.
C1  - 47014
C2  - 40493
TI  - Immunoproteasome expression in pulmonary fibrosis.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Chronic lung diseases, including chronic obstructive pulmonary disease, asthma, lung cancer and pulmonary fibrosis, are the second leading cause of death in the world. Currently, only limited therapeutic options exist for chronic lung diseases; in particular, causative therapeutic approaches are missing. Lung transplantation remains the only available therapy for many patients with end-stage lung disease; however, the number of patients listed for lung transplantation by far surpasses the number of suitable donor organs.
AU  - Königshoff, M.
AU  - Saglani, S.*
AU  - Marsland, B.J.*
AU  - Eickelberg, O.
C1  - 23934
C2  - 31298
SP  - 497-499
TI  - Rebuilding a diseased lung: Repair and regeneration.
JO  - Eur. Respir. J.
VL  - 41
IS  - 3
PB  - European Respiratory Soc. Journals
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Korfei, M.*
AU  - Henneke, I.*
AU  - Markart, P.*
AU  - von der Beck, D.*
AU  - Ruppert, C.*
AU  - Mahavadi, P.*
AU  - Klepetko, W.*
AU  - Fink, L.*
AU  - Meiners, S.
AU  - Kraemer, O.*
AU  - Seeger, W.*
AU  - Vancheri, C.*
AU  - Guenther, A.*
C1  - 46999
C2  - 40507
TI  - Comparative proteome analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP).
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Lenz, A.-G.
AU  - Cei, D.
AU  - Schmidmeir, M.
AU  - Pfister, N.
AU  - Burgstaller, G.
AU  - Lentner, B.*
AU  - Eickelberg, O.
AU  - Stöger, T.
AU  - Schmid, O.
AU  - Meiners, S.
C1  - 47008
C2  - 40499
TI  - Fast, efficient and realistic in vitro delivery of inhaled drugs to pulmonary cells: Application to the proteasome inhibitor bortezomib.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Milger, K.
AU  - Eickelberg, O.
AU  - Krauss-Etschmann, S.
AU  - Dehmel, S.
C1  - 47013
C2  - 40494
TI  - MicroRNA based biomarkers for early risk assessment of asthma.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Möller, W.
AU  - Feng, S.*
AU  - Bartenstein, P.*
AU  - Haeussinger, K.*
AU  - Eickelberg, O.
AU  - Schmid, O.
AU  - Tatkov, S.*
C1  - 47000
C2  - 40506
TI  - Nasal high flow clears dead space in healthy volunteers and in an in vitro upper airway model.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Mossina, A.
AU  - Merl, J.
AU  - Vosyka, O.
AU  - Eickelberg, O.
AU  - Hauck, S.M.
AU  - Meiners, S.
C1  - 47001
C2  - 40505
TI  - Proteomic profiling of alveolar epithelial cells exposed to cigarette smoke extract.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Pfister, N.
AU  - Eickelberg, O.
AU  - Meiners, S.
C1  - 47005
C2  - 40501
TI  - Proteasome function in lung fibrosis.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo. Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n=119) or placebo (n=59). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4% of macitentan-treated subjects and 5.1% of placebo recipients. In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group.
AU  - Raghu, G.*
AU  - Million-Rousseau, R.*
AU  - Morganti, A.*
AU  - Perchenet, L.*
AU  - Behr, J.
AU  - MUSIC Study Group (*)
C1  - 44237
C2  - 36859
CY  - Sheffield
SP  - 1622-1632
TI  - Macitentan for the treatment of idiopathic pulmonary fibrosis: The randomised controlled MUSIC trial.
JO  - Eur. Respir. J.
VL  - 42
IS  - 6
PB  - European Respiratory Soc Journals Ltd
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Sarker, R.S.J.
AU  - Bohla, A.
AU  - John, G.
AU  - Kohse, K.
AU  - Amarie, O.V.
AU  - Bedford, M.T.*
AU  - Eickelberg, O.
AU  - Yildirim, A.Ö.
C1  - 47007
C2  - 40500
TI  - Involvement of coactivator associated arginine methyltransferase 1 (CARM1) in development of elastase-induced progressive emphysema.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Schulz, H.
AU  - Sillanpää, E.*
AU  - Karrasch, S.*
AU  - Alves, A.C.*
AU  - Codd, V.*
AU  - Hovatta, I.*
AU  - Buxton, J.L.*
AU  - Nelson, C.P.*
AU  - Broer, L.*
AU  - Hägg, S.*
AU  - Mangino, M.*
AU  - Willemsen, G.*
AU  - Pietiläinen, K.H.*
AU  - Ferreira, M.A.R.*
AU  - Amin, N.*
AU  - Oostra, B.A.*
AU  - Bäckmand, H.M.*
AU  - Peltonen, M.*
AU  - Sarna, S.*
AU  - Rantanen, T.*
AU  - Sipilä, S.*
AU  - Korhonen, T.*
AU  - Madden, P.A.F.*
AU  - Gieger, C.
AU  - Joerres, R.A.*
AU  - Heinrich, J.
AU  - Behr, J.*
AU  - Huber, R.M.*
AU  - Peters, A.
AU  - Strauch, K.
AU  - Wichmann, H.-E.
AU  - Waldenberger, M.
AU  - Blakemore, A.I.F.*
AU  - de Geus, E.J.C.*
AU  - Nyholt, N.*
AU  - Henders, A.K.*
AU  - Piirilä, P.L.*
AU  - Surakka, I.*
AU  - Rissanen, A.*
AU  - Magnusson, P.K.E.*
AU  - Viñuela, A.*
AU  - Martin, N.G.*
AU  - Pedersen, N.L.*
AU  - Boomsma, D.I.*
AU  - Spector, T.D.*
AU  - van Duijn, C.M.*
AU  - Kaprio, J.*
AU  - Samani, N.J.*
AU  - Jarvelin, M.R.*
AU  - Albrecht, E.
C1  - 46997
C2  - 40496
TI  - Telomere length in circulating leukocytes is associated with lung function and disease.
JO  - Eur. Respir. J.
VL  - 42
PY  - 2013
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Annesi-Maesano, I.*
AU  - Heinrich, J.
AU  - Ayres, J.G.*
AU  - Forastiere, F.*
C1  - 8637
C2  - 30238
SP  - 12-13
TI  - Why an ERJ series on air pollution?
JO  - Eur. Respir. J.
VL  - 40
IS  - 1
PB  - European Respiratory Soc.
PY  - 2012
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about the health effects of domestic exposure in adults. Here, we describe the association of respiratory disease, immunoglobulin (Ig)E sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults, and determine whether these associations are modified by polymorphisms in CD14. Endotoxin levels in mattress dust from a population-based sample of 972 adults were measured. Associations were examined using generalised linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed. Mattress endotoxin levels varied from 0.1 to 402.6 EU·mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of forced expiratory volume in 1 s and forced vital capacity with endotoxin was modified by CD14/-260 genotype (p-value for interaction 0.005 and 0.013, respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity were associated with mattress endotoxin levels. In this large epidemiological study of adults, there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14 genotype.
AU  - Bakolis, I.*
AU  - Doekes, G.*
AU  - Heinrich, J.
AU  - Zock, J.P.*
AU  - Heederik, D.*
AU  - Kogevinas, M.*
AU  - Guerra, S.*
AU  - Norbäck, D.*
AU  - Ramasamy, A.*
AU  - Nevalainen, A.*
AU  - Svanes, C.*
AU  - Chen, C.M.
AU  - Verlato, G.*
AU  - Olivieri, M.*
AU  - Castro-Giner, F.*
AU  - Jarvis, D*
AU  - HITEA Study Group (*)
C1  - 7257
C2  - 29617
SP  - 573-581
TI  - Respiratory health and endotoxin: Associations and modification by CD14/-260 genotype.
JO  - Eur. Respir. J.
VL  - 39
IS  - 3
PB  - European Respiratory Soc. Journals Ltd.
PY  - 2012
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Assessment of health-related quality of life in patients with respiratory failure on home ventilation requires appropriate and highly specific measurement tools. We attempt to validate the English version of the Severe Respiratory Insufficiency Questionnaire (SRI). Psychometric properties of the SRI in 152 patients established on home ventilation were assessed. Cronbach's alpha ranged between 0.77 and 0.89 for the seven subscales and and was 0.93 for the summary scale. Principal components analysis revealed a one-factor solution for four and two factors for three subscales. Confirmatory factor analysis revealed a two-factor solution for six subscales, but these factors were dependent on each other. One factor was extracted out of the subscales confirming one summary scale accounting for 70% of the total variance. Correlation analysis between scales of the SRI and the Medical Outcome Study 36-item short-form health survey demonstrated highest correlations between comparable subscales. Chronic obstructive pulmonary disease patients had lower summary scale scores than patients with restrictive chest wall diseases, neuromuscular disorders and obesity hypoventilation syndrome. The English SRI has high internal consistency reliability, clearly established construct and concurrent validity, and is capable of differentiating between different diseases. It is now validated for use in research involving patients receiving home ventilation.
AU  - Ghosh, D.*
AU  - Rzehak, P.
AU  - Elliott, M.W.*
AU  - Windisch, W.*
C1  - 8456
C2  - 30116
SP  - 408-415
TI  - Validation of the English severe respiratory insufficiency questionnaire.
JO  - Eur. Respir. J.
VL  - 40
IS  - 2
PB  - European Respiratory Soc. Journals Ltd.
PY  - 2012
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Although several levels of evidence have suggested an association between systemic inflammation and spirometric lung volumes, data addressing the potential interrelationship between airflow limitation and inflammatory markers are sparse and remain controversial. Potential associations between high-sensitivity C-reactive protein (hsCRP), fibrinogen and lung function were investigated in 1,466 individuals aged 25-85 yrs, representing a general population. Within this cross-sectional population, data on body plethysmography, spirometry, helium dilution and diffusing capacity of the lung for carbon monoxide (D(L,CO)) were analysed. After adjustment for potential confounding factors, such as smoking, obesity and cardiorespiratory fitness, there was an inverse association of hsCRP with forced expiratory and static lung volumes. In neither apparently healthy nor the entire population was inflammation associated with airflow limitation in central airways. In smokers only, higher hsCRP and fibrinogen were associated with an impaired D(L,CO). This study shows that higher levels of hsCRP are associated with decreased lung volumes in a general population over a wide age range. A consistent interrelationship of central airflow limitation and inflammation was not verifiable. Smoking is related to an impaired D(L,CO) in association with an increase in systemic inflammation.
AU  - Gläser, S.*
AU  - Ittermann, T.*
AU  - Koch, B.*
AU  - Völzke, H.*
AU  - Wallaschofski, H.*
AU  - Nauck, M.*
AU  - Warnke, C.*
AU  - Vogelmeier, C.*
AU  - Schulz, H.
AU  - Felix, S.B.*
AU  - Ewert, R.*
AU  - Schäper, C.*
C1  - 7213
C2  - 29550
SP  - 29-37
TI  - Airflow limitation, lung volumes and systemic inflammation in a general population.
JO  - Eur. Respir. J.
VL  - 39
IS  - 1
PB  - European Respiratory Soc. Journal Ltd.
PY  - 2012
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Studies of the impact of long-term exposure to outdoor air pollution on the prevalence of respiratory symptoms and lung function in children have yielded mixed results, partly related to differences in study design, exposure assessment, confounder selection and data analysis. We assembled respiratory health and exposure data for >45,000 children from comparable cross-sectional studies in 12 countries. 11 respiratory symptoms were selected, for which comparable questions were asked. Spirometry was performed in about half of the children. Exposure to air pollution was mainly characterised by annual average concentrations of particulate matter with a 50% cut-off aerodynamic diameter of 10 mu m (PM10) measured at fixed sites within the study areas. Positive associations were found between the average Mho concentration and the prevalence of phlegm (OR per 10 mu g.m(-3) 1.15, 95% CI 1.02-1.30), hay fever (OR 1.20, 95% CI 0.99-1.46), bronchitis (OR 1.08, 95% CI 0.98-1.19), morning cough (OR 1.15, 95% CI 1.02-1.29) and nocturnal cough (OR 1.13, 95% CI 0.98-1.29). There were no associations with diagnosed asthma or asthma symptoms. PM10 was not associated with lung function across all studies combined. Our study adds to the evidence that long-term exposure to outdoor air pollution, characterised by the concentration of PM10, is associated with increased respiratory symptoms.
AU  - Hoek, G.*
AU  - Pattenden, S.*
AU  - Willers, S.*
AU  - Antova, T.*
AU  - Fabianova, E.*
AU  - Braun-Fahrländer, C.*
AU  - Forastiere, F.*
AU  - Gehring, U.
AU  - Luttmann-Gibson, H.*
AU  - Grize, L.*
AU  - Heinrich, J.
AU  - Houthuijs, D.*
AU  - Janssen, N.*
AU  - Katsnelson, B.*
AU  - Kosheleva, A.*
AU  - Moshammer, H.*
AU  - Neuberger, M.*
AU  - Privalova, L.*
AU  - Rudnai, P.*
AU  - Speizer, F.*
AU  - Slachtova, H.*
AU  - Tomaskova, H.*
AU  - Zlotkowska, R.*
AU  - Fletcher, T.*
C1  - 10714
C2  - 30350
SP  - 538-547
TI  - PM10 and children's respiratory symptoms and lung function in the PATY study.
JO  - Eur. Respir. J.
VL  - 40
IS  - 3
PB  - European Respiratory Soc. Journals Ltd.
PY  - 2012
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Cystic fibrosis (CF) lung disease severity is largely independent on the CF transmembrane conductance regulator (CFTR) genotype, indicating the contribution of genetic modifiers. The chemokine receptors CXCR1 and CXCR2 have been found to play essential roles in the pathogenesis of CF lung disease. Here, we determine whether genetic variation of CXCR1 and CXCR2 influences CF lung disease severity. Genomic DNA of CF patients in Germany (n=442) was analysed for common variations in CXCR1 and CXCR2 using a single-nucleotide polymorphism (SNP) tagging approach. Associations of CXCR1 and CXCR2 SNPs and haplotypes with CF lung disease severity, CXCR1 and CXCR2 expression, and neutrophil effector functions were assessed. Four SNPs in CXCR1 and three in CXCR2 strongly correlated with age-adjusted lung function in CF patients. SNPs comprising haplotypes CXCR1_Ha and CXCR2_Ha were in high linkage disequilibrium and patients heterozygous for the CXCR1-2 haplotype cluster (CXCR1-2_Ha) had lower lung function compared with patients with homozygous wild-type alleles (forced expiratory volume in 1 s ≤70% predicted, OR 7.24; p=2.30×10(-5)). CF patients carrying CXCR1-2_Ha showed decreased CXCR1 combined with increased CXCR2 mRNA and protein expression, and displayed disturbed antibacterial effector functions. CXCR1 and CXCR2 genotypes modulate lung function and antibacterial host defence in CF lung disease.
AU  - Kormann, M.S.*
AU  - Hector, A.*
AU  - Marcos, V.*
AU  - Mays, L.E.*
AU  - Kappler, M.*
AU  - Illig, T.
AU  - Klopp, N.
AU  - Zeilinger, S.
AU  - Carevic, M.*
AU  - Rieber, N.*
AU  - Eickmeier, O.*
AU  - Zielen, S.*
AU  - Gaggar, A.*
AU  - Moepps, B.*
AU  - Griese, M.*
AU  - Hartl, D.*
C1  - 7543
C2  - 29791
SP  - 1385-1390
TI  - CXCR1 and CXCR2 haplotypes synergistically modulate cystic fibrosis lung disease.
JO  - Eur. Respir. J.
VL  - 39
IS  - 6
PB  - European Respiratory Society
PY  - 2012
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The proteasome constitutes the main protein waste disposal and recycling system of the cell. Together with the endoplasmatic reticulum (ER) stress and the autophagosome pathway, it also takes centre stage in cellular protein quality control. In lung research, the proteasome is - first of all - a promising therapeutic target to intervene with malignant growth of lung cancer cells. Therapeutic targeting of the proteasome has also been extended to pulmonary fibrosis and asthma, using animal models. Moreover, the proteasome is involved in lung pathogenesis: In cystic fibrosis, rapid proteasomal degradation of mutant cystic fibrosis transmembrane regulator contributes to loss of function of lung epithelial cells. In chronic obstructive pulmonary disease (COPD), pulmonary proteasome expression and activity is downregulated and inversely correlates with lung function. In addition, as the proteasome degrades signaling mediators that have been oxidatively modified in COPD, it contributes to further compromise cellular function. The consequences of proteasomal dysfunction are loss of protein quality control, accumulation of misfolded proteins, and exacerbation of cellular stress, which are also hallmarks of protein quality diseases and premature aging. This suggests that proteasome dysfunction can be regarded as a new pathomechanism for chronic lung diseases, awaiting further therapeutic exploration in the future.
AU  - Meiners, S.
AU  - Eickelberg, O.
C1  - 7477
C2  - 29737
SP  - 1260-1268
TI  - What shall we do with the damaged proteins in lung disease? Ask the proteasome!
JO  - Eur. Respir. J.
VL  - 40
IS  - 5
PB  - European Respiratory Society
PY  - 2012
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The EvA study is an EU funded project (# 200506) under Frame Work Program 7 (FP7), which aims at defining new markers for COPD and its subtypes. The acronym is derived from emphysema versus airway disease, indicating that the project targets these two main phenotypes of the disease. The EvA study is based on the concept that emphysema and airway disease are governed by different pathophysiological processes and these are driven by different genes and a differential gene expression in the lung. To define these genes patients and non-COPD controls are recruited for clinical examination, lung function analysis and computed tomography of the lung. CT scans are used to define the phenotypes based on lung density and airway wall thickness. This is followed by bronchoscopy in order to obtain samples from the airways and the alveoli. These tissue samples along with blood samples are then subjected to genome-wide expression and association analysis and markers linked to the phenotypes are identified. The population of the EvA study is different from other COPD study populations, since patients with current oral glucocorticoid, antibiotics, exacerbations or current smoking are excluded, such that the signals detected in the molecular analysis are due to the distinct inflammatory process of emphysema and airway disease in COPD.
AU  - Ziegler-Heitbrock, L.
AU  - Frankenberger, M.
AU  - Heimbeck, I.
AU  - Burggraf, D.
AU  - Wjst, M.
AU  - Häussinger, K.*
AU  - Brightling, C.*
AU  - Gupta, S.*
AU  - Parr, D.*
AU  - Subramanian, D.*
AU  - Singh, D.*
AU  - Kolsum, U.*
AU  - Boschetto, P.*
AU  - Potena, A.*
AU  - Gorecka, D.*
AU  - Nowinksi, A.*
AU  - Barta, I.*
AU  - Döme, B.*
AU  - Strausz, J.*
AU  - Greulich, T.*
AU  - Vogelmeier, C.*
AU  - Bals, R.*
AU  - Hohlfeld, J.*
AU  - Welte, T.*
AU  - Venge, P.*
AU  - Gut, I.*
AU  - Boland, A.*
AU  - Olaso, R.*
AU  - Hager, J.*
AU  - Hiemstra, P.*
AU  - Rabe, K.F.*
AU  - Unmüßig, M.*
AU  - Müller-Quernheim, J.*
AU  - Prasse, A.*
C1  - 7289
C2  - 29649
SP  - 823-829
TI  - The EvA study: Aims and strategy.
JO  - Eur. Respir. J.
VL  - 40
IS  - 4
PB  - European Respiratory Society
PY  - 2012
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - no Abstract
AU  - European IPF Network (Günther, A.*
AU  - Eickelberg, O.)
AU  - The European IPF Network
C1  - 5787
C2  - 29027
CY  - Sheffield, UK
SP  - 747-748
TI  - The European IPF Network: Towards better care for a dreadful disease.
JO  - Eur. Respir. J.
VL  - 37
IS  - 4
PB  - European Respiratory Soc Journals Ltd
PY  - 2011
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - no Abstract
AU  - Marsland, B.J.*
AU  - Königshoff, M.
AU  - Saglani, S.*
AU  - Eickelberg, O.
C1  - 6643
C2  - 29023
CY  - Switzerland
SP  - 500-501
TI  - Immune system dysregulation in chronic lung disease.
JO  - Eur. Respir. J.
VL  - 38
IS  - 3
PB  - Society and Munksgaard
PY  - 2011
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with unknown pathogenesis. The WNT/β-catenin pathway has recently been reported to be operative in epithelial cells in IPF. Dickkopf (DKK) proteins are known to regulate WNT signalling via interaction with Kremen (KRM) receptors, yet their expression and role in the adult lung and in IPF has not been addressed. We analysed the expression, localisation and function of DKK and KRM proteins in IPF lungs using Western blotting, quantitative RT-PCR, immunohistochemistry, ELISA and functional in vitro studies. Enhanced expression of DKK1 and DKK4 and KRM1 was detected in lung homogenates of IPF patients compared with transplant donors. Immunohistochemistry revealed that DKK1 was predominantly localised in basal bronchial epithelial cells. Furthermore, prominent expression of all proteins was observed in hyperplastic alveolar epithelial cells in IPF. Quantitative measurement of DKK1 revealed enhanced protein expression in the bronchoalveolar lumen of IPF patients. Finally, functional studies using human bronchial and alveolar epithelial cell lines demonstrated that WNT-induced epithelial cell proliferation is regulated by DKK1 in a dose-dependent fashion. In summary, DKK proteins are expressed in the lung epithelium in IPF. DKK proteins influence epithelial cell proliferation and may, therefore, be suitable therapeutic targets for IPF.
AU  - Pfaff, E.-M.*
AU  - Becker, S.*
AU  - Günther, A.*
AU  - Königshoff, M.
C1  - 2092
C2  - 28080
SP  - 79-87
TI  - Dickkopf proteins influence lung epithelial cell proliferation in idiopathic pulmonary fibrosis.
JO  - Eur. Respir. J.
VL  - 37
IS  - 1
PB  - European Respiratory Society
PY  - 2011
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Arg/Arg homozygous for the Gly16Arg polymorphism in ADRB2 have a reduced response to short acting β2-agonists but no effect has been associated with long-acting β2-agonists (LABA). We selected 604 subjects from the European Community Respiratory Health Study with current asthma to evaluate if asthma control and lung function decline were associated with Gly16Arg polymorphism and test if LABA or inhaled corticosteroids (ICS) use modified these effects. There was an increased risk of non-controlled asthma OR=1.33 (1.01-1.75, p=0.046) for each Arg allele. Among nonusers of ICS, the risk of non-controlled asthma among Arg/Arg vs. Gly/Gly subjects was OR=2.73 (1.28-5.82, p=0.009). No increased risk of non-controlled asthma associated to the Arg allele was observed among ICS and/or LABA users. For each Arg allele a decrease of 7.7 mL·year(-1) (SE 2.5) in FEV1 decline was found (p-trend=0.003), irrespective of ICS or LABA use. Arg/Arg subjects vs. Gly/Gly subjects had an increased risk of bronchial hyperresponsiveness with an OR of 2.51 (1.12-5.63, p=0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and bronchial hyperresponsiveness. Absence of genotypic effects on asthma control among ICS users may be due to reversed ADRB2 desensitization.
AU  - Rebordosa, C.*
AU  - Kogevinas, M.*
AU  - Guerra, S.*
AU  - Castro-Giner, F.*
AU  - Jarvis, D.*
AU  - Cazzoletti, L.*
AU  - Pin, I.*
AU  - Siroux, V.*
AU  - Wjst, M.
AU  - Antò, J.M.*
AU  - de, Marco, R.*
AU  - Estivill, X.*
AU  - Corsico, A.G.*
AU  - Nielsen, R.*
AU  - Janson, C.
C1  - 5020
C2  - 28525
SP  - 1029-1035
TI  - ADRB2 Gly16Arg polymorphism, asthma control and lung function decline.
JO  - Eur. Respir. J.
VL  - 38
IS  - 5
PB  - European Respiratory Society
PY  - 2011
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - ATRA is controversially discussed in emphysema therapy. We re-evaluated ATRA in the elastase-model and hypothesized that beneficial effects should be reflected by increased alveolar surface area, elastin expression, and downregulation of inflammatory mediators and matrix metalloproteinases (MMP). Emphysema was induced by porcine pancreatic elastase versus saline in Sprague-Dawley rats. On days 26-37, rats received daily intraperitoneal injections with ATRA (500 μg·kg(-1) b.w.) versus olive-oil. Lungs were removed at day 38. Rat alveolar epithelial L2 cells were incubated with/without elastase followed by ATRA- or vehicle-treatment, respectively. ATRA only partially ameliorated structural defects. Alveolar walls exhibited irregular architecture: increased arithmetic mean thickness, reduction in surface coverage by AEC type II. ATRA only partially restored reduced soluble elastin. It tended to increase the ratio of ED1(+):ED2(+) macrophages. Bronchoalveolar lavage (BAL) cells exhibited a pro-inflammatory state with high expression of IL-1β, CINC-1, TNF-α, NF-ĸB, MMP-2, -9, -12, TIMP-1, and -2 in emphysema with ATRA exerting only little effects. MMP-7 was highly induced by ATRA in healthy but not in emphysematous lungs. ATRA reduced both MMP-2 and TIMP-1 activity in BAL fluid of emphysematous lungs. ATRA-therapy may bear the risk of unwanted side-effects on alveolar septal architecture in emphysematous lungs.
AU  - Seifart, C.*
AU  - Muyal, J.P.*
AU  - Plagens, A.*
AU  - Yildirim, A.Ö.
AU  - Kohse, K.
AU  - Grau, V.*
AU  - Sandu, S.*
AU  - Reinke, C.*
AU  - Tschernig, T.*
AU  - Vogelmeier, C.*
AU  - Fehrenbach, H.
C1  - 5609
C2  - 28594
SP  - 425-439
TI  - ATRA results in irregular repair of septa and fails to inhibit proinflammatory macrophages.
JO  - Eur. Respir. J.
VL  - 38
IS  - 2
PB  - European Respiratory Society
PY  - 2011
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - For a long time, exposure to mould and dampness-derived microbial components was considered a risk factor for the development of respiratory diseases and symptoms. Some recent studies suggested that early childhood exposure to mould components, such as (1,3)-β-D-glucan and extracellular polysaccharides (EPSs), may protect children from developing allergy. We investigated the association of exposure to (1,3)-β-D-glucan, EPS and endotoxin with asthma and allergies in 6-yr-old children. This investigation was the follow-up to a nested case-control study among three European birth cohorts. Children from two ongoing birth cohort studies performed in Germany (n = 358) and one in the Netherlands (n = 338) were selected. Levels of (1,3)-β-D-glucan, EPS and endotoxin were measured in settled house dust sampled from children's mattresses and living-room floors when the children were, on average, 5 yrs of age. At the age of 6 yrs, health outcome information was available for 678 children. In the two German subsets, domestic EPS and endotoxin exposure from children's mattresses were significantly negatively associated with physician-diagnosed asthma (OR per interquartile range increase 0.60 (95% CI 0.39-0.92) and 0.55 (95% CI 0.31-0.97), respectively). In addition, EPS exposure was inversely related to physician-diagnosed allergic rhinitis (OR 0.50, 95% CI 0.31-0.81). For the Dutch population, no associations were observed between exposure to microbial agents and respiratory health outcomes. We found inverse associations between domestic exposure to EPS and endotoxin from children's mattresses, and doctor-diagnosed asthma and rhinitis in German, but not in Dutch, school children. The reasons for the differences between countries are not clear.
AU  - Tischer, C.G.
AU  - Gehring, U.*
AU  - Chen, C.M.
AU  - Kerkhof, M.*
AU  - Koppelman, G.*
AU  - Sausenthaler, S.
AU  - Herbarth, O.*
AU  - Schaaf, B.*
AU  - Lehmann, I.*
AU  - Krämer, U.*
AU  - Berdel, D.*
AU  - von Berg, A.*
AU  - Bauer, .P.*
AU  - Koletzko, S.*
AU  - Wichmann, H.-E.
AU  - Brunekreef, B.*
AU  - Heinrich, J.
C1  - 6196
C2  - 28559
SP  - 1050-1059
TI  - Respiratory health in children, and indoor exposure to (1,3)-β-D-glucan, EPS mould components and endotoxin.
JO  - Eur. Respir. J.
VL  - 37
IS  - 5
PB  - ERS Journal
PY  - 2011
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Critical reviews over the past 10 yrs have found increased respiratory and allergic health outcomes for children living in damp and mouldy environments. However, recent studies have suggested that early childhood exposure to specific mould components may actually protect children from developing allergy. We conducted a systematic review of observational studies published in English from January 1980 to July 2010. This review was conducted according to systematic guidelines for Meta-analyses of Observational Studies in Epidemiology (MOOSE). The literature was searched using a computerised bibliographic database, PubMed. In order to increase the quality of the reviewed studies, meta-analyses of the effects of visible mould exposure on allergic health outcomes were performed and we evaluated the findings according to the Bradford Hill criteria for evidence of causation. The literature search identified 1,398 peer-reviewed scientific publications, and 61 studies that fulfilled the inclusion criteria were included in this review. We observed increased risks of allergic respiratory health outcomes in children exposed to visible mould and mould spores. These findings were confirmed by the results of the meta-analysis and in line with the evaluation criteria according to Bradford Hill. Visible mould was positively associated with asthma (OR 1.49 (95% CI 1.28-1.72)), wheeze (OR 1.68 (95% CI 1.48-1.90)) and allergic rhinitis (OR 1.39 (95% CI 1.28-1.51)). However, there was a tendency of lower risk for allergic health outcomes in children exposed to mould-derived components such as (1,3)-β-d-glucan and extracellular polysaccharides. These findings suggest that home environments with visible mould and mould spore exposure increase the risk of allergic respiratory health outcomes in children. However, further investigations are needed to examine the effects of exposure to mould-derived components as the current literature is inconclusive. In order to disentangle the different effects of overall microbial exposure on children's health, research should focus on specific microbial markers in the home, in combination with new assessment techniques including molecular methods.
AU  - Tischer, C.G.
AU  - Chen, C.-M.
AU  - Heinrich, J.
C1  - 6656
C2  - 29053
CY  - Copenhagen
SP  - 812-824
TI  - Association between domestic mould and mould components, and asthma and allergy in children: A systematic review.
JO  - Eur. Respir. J.
VL  - 38
IS  - 4
PB  - Society and Munksgaard
PY  - 2011
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Brain, J.D.*
AU  - Kreyling, W.G.
AU  - Gehr, P.*
C1  - 1186
C2  - 27268
SP  - 226-227
TI  - Comment on: Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma.
JO  - Eur. Respir. J.
VL  - 35
IS  - 1
PB  - European Respiratory Soc. Journals
PY  - 2010
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Eickelberg, O.
AU  - Laurent, G.*
AU  - Nicod, L.P.*
AU  - Hartl, S.*
AU  - Siafakas, N.M.*
C1  - 6099
C2  - 28076
SP  - 229-230
TI  - European Respiratory Society MD PhD programme in respiratory science.
JO  - Eur. Respir. J.
VL  - 36
IS  - 2
PB  - European Respiratory Soc. Journals Ltd
PY  - 2010
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - nconsistent effects of gas cooking on lung function have been reported. In a previous study from Austria, we demonstrated a significant, though small, reduction of lung function parameters in children living in homes with gas stoves. We used a larger international database to check if this finding can be generalised. To study the relative impact of cooking with gas on lung function parameters of primary school children in a wide range of geographical settings, we analysed flow and volume data of approximately 24,000 children (aged 6-12 yrs) from nine countries in Europe and North America. Exposure information was obtained by comparable questionnaires and spirometry according to an American Thoracic Society/European Respiratory Society protocol. Linear regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytical tools. On average, gas cooking reduced lung function parameters. Overall effects were small (-0.1-0.7%) and only significant for forced vital capacity and forced expiratory volume in 1 s. There was some indication that allergic children were more affected by gas cooking. Under current housing conditions, gas cooking is associated with only small reductions in lung function.
AU  - Moshammer, H.*
AU  - Fletcher, T.*
AU  - Heinrich, J.
AU  - Hoek, G.*
AU  - Hruba, F.*
AU  - Pattenden, S.*
AU  - Rudnai, P.*
AU  - Slachtova, H.*
AU  - Speizer, F.E.*
AU  - Zlotkowska, R.*
AU  - Neuberger, M.*
C1  - 4120
C2  - 27469
SP  - 249-254
TI  - Gas cooking is associated with small reductions in lung function in children.
JO  - Eur. Respir. J.
VL  - 36
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2010
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-alpha (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-alpha (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (Cl) 1.7-3.2; OR for TNFA -308 polymorphism 1.3, 95% Cl 1.1-1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common GIG genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% Cl 2.5-14.4; OR for GIG genotype 1.7, 95% Cl 0.8-3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma.
AU  - Castro-Giner, F.*
AU  - Kogevinas, M.*
AU  - Imboden, M.*
AU  - de Cid, R.*
AU  - Jarvis, D.*
AU  - Mächler, M.*
AU  - Berger, W.*
AU  - Burney, P.*
AU  - Franklin, K.A.*
AU  - Gonzalez, J.R.*
AU  - Heinrich, J.
AU  - Janson, C.*
AU  - Omenaas, E.*
AU  - Pin, I.*
AU  - Rochat, T.*
AU  - Sunyer, J.*
AU  - Wjst, M.
AU  - Antò, J.M.*
AU  - Estivill, X.*
AU  - Probst-Hensch, N.M.*
C1  - 1026
C2  - 26132
SP  - 1003-1009
TI  - Joint effect of obesity and TNFA variability on asthma: Two international cohort studies.
JO  - Eur. Respir. J.
VL  - 33
IS  - 5
PB  - European Respiratory Soc Journals Ltd
PY  - 2009
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Asthma guidelines from the Global Initiative for Asthma (GINA) and from the National Heart, Lung, and Blood Institute provide conflicting definitions of airflow obstruction, suggesting a fixed forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) cut-off point and the lower limit of normality (LLN), respectively. The LLN was recommended by the recent American Thoracic Society/European Respiratory Society guidelines on lung function testing. The problem in using fixed cut-off points is that they are set regardless of age and sex in an attempt to simplify diagnosis at the expense of misclassification. The sensitivity and specificity of fixed FEV1/FVC ratios of 0.70, 0.75 and 0.80 versus the LLN were evaluated in 815 subjects (aged 20-44 yrs) with a diagnosis of asthma within the framework of the European Community Respiratory Health Survey. In males, the 0.70 ratio showed 76.5% sensitivity and 100.0% specificity, the 0.75 ratio 100.0% sensitivity and 92.4% specificity, and the 0.80 ratio 100.0% sensitivity but 58.1% specificity. In females, the 0.70 ratio showed 57.3% sensitivity and 100.0% specificity, the 0.75 ratio 91.5% sensitivity and 95.9% specificity, and the 0.80 ratio 100.0% sensitivity but 72.9% specificity. The fixed cut-off points cause a lot of misidentification of airflow obstruction in young adults, with overestimation with the 0.80 ratio and underestimation with the 0.70 ratio. In conclusion, the GINA guidelines should change their criteria for defining airflow obstruction.
AU  - Cerveri, I.*
AU  - Corsico, A.G.*
AU  - Accordini, S.*
AU  - Cervio, G.*
AU  - Ansaldo, E.*
AU  - Grosso, A.*
AU  - Niniano, R.*
AU  - Tegomo, E.Tsana*
AU  - Antò, J.M.*
AU  - Künzli, N.*
AU  - Janson, C.*
AU  - Sunyer, J.*
AU  - Svanes, C.*
AU  - Heinrich, J.
AU  - Schouten, J.P.*
AU  - Wjst, M.
AU  - Pozzi, E.*
AU  - de Marco, R.*
C1  - 1193
C2  - 26634
CY  - Sheffield
SP  - 568-573
TI  - What defines airflow obstruction in asthma?
JO  - Eur. Respir. J.
VL  - 34
IS  - 3
PB  - European Respiratory Soc Journals
PY  - 2009
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The aim of the present study was to examine the influence of childhood respiratory infections on adult respiratory health. In 1992-1994, the European Community Respiratory Health Survey recruited community based samples of 20-44-yr-old people from 48 centres in 22 countries. Study participants completed questionnaires and underwent lung function testing. On average, 8.9 yrs later, 29 centres re-investigated their samples using similar methods. Mixed effects models comprising an estimate for the random variation between centres were used to evaluate the relevant associations. In total, 9,175 patients participated in both studies, of whom 10.9% reported serious respiratory infections (SRI) before 5 yrs of age and 2.8% reported hospitalisation for lung disease (HLD) before 2 yrs if age. SRI was associated with current wheeze (odds ratio (OR) 1.9, 95% confidence interval (CI) 1.7-2.2), asthma (OR 2.5, 95% CI 2.2-3.1), and lower forced expiratory volume in one second (FEV1; 89 mL; 95% CI 54-126), forced vital capacity (FVC; 49 ml 95% CI 8-90) and FEV1/FVC ratio (-1.2%; 95% CI -1.8- -0.6). Childhood respiratory infections were also associated with new asthma (OR 1.5, 95% CI 1.03-2.0), new wheeze (OR 1.5, 95% cI 1.0-2.4) and persistent wheeze (OR 2.2, 95% CI 1.4-3.6) but not with a decIine in lung function. Similar findings were observed for HDL. These associations were significantly consistent across centres. SRI was associated with lower FEV1 when excIuding ever asthmatics and current wheezers. The impact of early infections was significantly larger in subjects exposed to maternal or active smoking. The impact of childhood respiratory infections on the respiratory system may not only last into adulthood but also influence development and persistence of adult respiratory morbidity.
AU  - Dharmage, S.C.*
AU  - Erbas, B.*
AU  - Jarvis, D.*
AU  - Wjst, M.
AU  - Raherison, C.*
AU  - Norbäck, D.*
AU  - Heinrich, J.
AU  - Sunyer, J.*
AU  - Svanes, C.*
C1  - 1315
C2  - 26235
SP  - 237-244
TI  - Do childhood respiratory infections continue to influence adult respiratory morbidity?
JO  - Eur. Respir. J.
VL  - 33
IS  - 2
PB  - European Respiratory Soc Journals Ltd
PY  - 2009
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Frankenberger, M.
AU  - Heimbeck, I.
AU  - Möller, W.
AU  - Mamidi, S.
AU  - Kaßner, G.
AU  - Pukelsheim, K.
AU  - Wjst, M.
AU  - Neiswirth, M.
AU  - Kroneberg, P.*
AU  - Lomas, D.*
AU  - Halsall, D.*
AU  - Iadarola, P.*
AU  - Fertl, A.
AU  - Häußinger, K.
AU  - Ziegler-Heitbrock, L.
C1  - 494
C2  - 26499
CY  - Lausanne, Schweiz
SP  - 1487-1489
TI  - Inhaled all-trans retinoic acid in an individual with severe emphysema.
JO  - Eur. Respir. J.
VL  - 34
IS  - 6
PB  - European Respiratory Society
PY  - 2009
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The aim of our analysis was to study the association between air pollution and asthma among adults. For this goal, a previously developed "asthma score" was used. Persons aged 25-44 yrs were randomly selected (1991-1993) and followed up (2000-2002) within the European Community Respiratory Health Survey (ECRHS I and II, respectively). The asthma score was defined from 0 to 5, based on the positive answers to the following symptoms reported for the last 12 months: wheeze/breathlessness, chest tightness, dyspnoea at rest, dyspnoea after exercise and woken by dyspnoea. Participants' home addresses were linked to outdoor modelled NO2 estimates for 2001. Negative binomial regression was used to model the asthma score. The score from ECRHS II was positively associated with NO2 (ratio of the mean asthma score (RMS) 1.23, 95% CI 1.09-1.38, for an increase of 10 microg x m(-3)). After excluding participants with asthma and symptoms at baseline, the association remained (RMS 1.25, 95% CI 1.05-1.51), and was particularly high among those reporting a high score in ECRHS II. The latter probably reflects incident cases of asthma. Our results suggest that traffic-related pollution causes asthma symptoms and possibly asthma incidence in adults. The asthma score offers an alternative with which to investigate the course and aetiology of asthma in adults.
AU  - Jacquemin, B.*
AU  - Sunyer, J.*
AU  - Forsberg, B.*
AU  - Aguilera, I.*
AU  - Bouso, L.*
AU  - Briggs, D.*
AU  - de Marco, R.*
AU  - García-Esteban, R.*
AU  - Heinrich, J.
AU  - Jarvis, D.*
AU  - Maldonado, J.A.*
AU  - Payo, F.*
AU  - Rage, E.*
AU  - Vienneau, D.*
AU  - Künzli, N.*
C1  - 838
C2  - 26630
SP  - 834-842
TI  - Association between modelled traffic-related air pollution and asthma score in the ECRHS.
JO  - Eur. Respir. J.
VL  - 34
IS  - 4
PB  - European Respiratory Society
PY  - 2009
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Genetic association studies have related the tumour necrosis factor-alpha gene (TNFA) guanine to adenine substitution of nucleotide -308 (-308G>A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -308G>A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A>G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.
AU  - Castro-Giner, F.*
AU  - Kogevinas, M.*
AU  - Mächler, M.*
AU  - de Cid, R.*
AU  - van Steen, K.*
AU  - Imboden, M.*
AU  - Schindler, C.*
AU  - Berger, W.*
AU  - Gonzalez, J.R.*
AU  - Franklin, K.A.*
AU  - Janson, C.*
AU  - Jarvis, D.*
AU  - Omenaas, E.*
AU  - Burney, P.*
AU  - Rochat, T.*
AU  - Estivill, X.*
AU  - Antò, J.M.*
AU  - Wjst, M.
AU  - Probst-Hensch, N.M.*
C1  - 6412
C2  - 28629
SP  - 350-361
TI  - TNFA -308G>A in two international population-based cohorts and risk of asthma.
JO  - Eur. Respir. J.
VL  - 32
IS  - 2
PB  - European Respiratory Soc Journals LTD
PY  - 2008
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The effect of dog ownership during childhood on the development of allergy has been investigated in few studies with conflicting results. The association between dog contact and indoor endotoxin exposure during infancy and the development of allergic sensitisation and atopic disease up to age 6 yrs was investigated. Two ongoing birth cohorts, the German Infant Nutrition Intervention Programme (GINI; n = 1,962) and the Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA; n = 1,193), were analysed. In both studies, information on children's contact with dogs and their allergic symptoms and doctor-diagnosed allergic disease were collected during follow-up using questionnaires. Specific immunoglobulin E to common aeroallergens was measured at age 6 yrs. House dust samples were collected at age 3 months and the amount of endotoxin was determined. Dog ownership in early childhood was associated with a significantly lower rate of mixed pollen and inhalant sensitisation but not with dog sensitisation or allergic symptoms and diseases up to age 6 yrs. Regular contact with dogs, without ownership, during childhood was not associated with those health outcomes. No associations were found between house dust endotoxin exposure during infancy and sensitisation outcomes. In conclusion, dog ownership in early childhood protects against the development of inhalant sensitisation and this effect cannot be attributed to the simultaneous exposure to endotoxin.
AU  - Chen, C.M.
AU  - Morgenstern, V.
AU  - Bischof, W.*
AU  - Herbarth, O.*
AU  - Borte, M.*
AU  - Behrendt, H.
AU  - Krämer, U.*
AU  - von Berg, A.*
AU  - Berdel, D.*
AU  - Bauer, C.P.*
AU  - Koletzko, S.*
AU  - Wichmann, H.-E.
AU  - Heinrich, J.
AU  - LISAplus Study Group (Wichmann, H.-E.
AU  - Heinrich, J.
AU  - Bolte, G.
AU  - Belcredi, P.
AU  - Jacob, B.
AU  - Schoetzau, A.
AU  - Mosetter, M.
AU  - Schindler, J.
AU  - Höhnke, A.
AU  - Franke, K.
AU  - Laubereau, B.
AU  - Sausenthaler, S.
AU  - Thaqi, A.
AU  - Zirngibl, A.
AU  - Zutavern, A.)
AU  - GINIplus Study Group (Wichmann, H.-E.
AU  - Heinrich, J.
AU  - Schoetzau, A.
AU  - Popescu, M.
AU  - Mosetter, M.
AU  - Schindler, J.
AU  - Franke, K.
AU  - Laubereau, B.
AU  - Sausenthaler, S.
AU  - Thaqi, A.
AU  - Zirngibl, A.
AU  - Zutavern, A.
AU  - Gehring, U.)
C1  - 3660
C2  - 25265
SP  - 963-973
TI  - Dog ownership and contact during childhood and later allergy development.
JO  - Eur. Respir. J.
VL  - 31
IS  - 5
PB  - European Respiratory Society
PY  - 2008
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Allogeneic hematopoietic stem cell transplantation (SCT) has emerged as a curative therapeutic option. However, The role of graft-versus-host disease in lung injury after SCT has still to be determined.In the present study primary bronchial epithelial cells and the bronchial epithelial cell line BEAS-2B were used to investigate immune responses of allogeneic CD8(+) T- cells directed against respiratory epithelial cells.Following stimulation with irradiated bronchial epithelial cells, CD8(+) T-cells produced significant amounts of IFN-gamma, upregulated alloantigen activation markers and proliferated highly compared to T-cells stimulated with IL-2 alone. Furthermore, cytotoxicity assays demonstrated that bronchial epithelial cell specific and Granzyme B-mediated cytolytic activity was induced in CD8(+) T cells. Generation of NK-, NK-like T cells (NKT cells), cytokine-induced killer (CIK) or lymphokine activated killer (LAK) cells could be excluded by phenotyping, culture conditions and neglectable lytic activity following stimulation with IL-2 alone. Inhibition experiments showed that lysis of bronchial epithelial cells was not MHC I restricted but depended on natural killer group 2, member D (NKG2D) signaling, a stimulatory receptor initially shown to be expressed on NK cells.Our data imply that respiratory epithelium has antigen presenting function and directly alloactivates cytotoxic CD8(+) T cells which show nonclassical effector function.
AU  - Kraetzel, K.*
AU  - Stoelcker, B.*
AU  - Eissner, G.*
AU  - Multhoff, G.
AU  - Pfeifer, M.*
AU  - Holler, E.*
AU  - Schulz, C.*
C1  - 1769
C2  - 25405
SP  - 1-8
TI  - NKG2D-dependent effector function of bronchial epithelium activated alloreactive T cells.
JO  - Eur. Respir. J.
VL  - 32
IS  - 3
PB  - European Respiratory Society
PY  - 2008
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Local inflammation in airway diseases is well recognised, but less is known about the association between low-grade systemic inflammatory processes and lung function. The aim of the present study was to assess the association between inflammatory markers and lung function, taking into account polymorphisms in genes coding for inflammatory markers. In 134 post-myocardial infarction patients, six repeated measurements of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen in peripheral blood were assayed using high-sensitivity tests. Spirometry was conducted at baseline. Genotyping of single nucleotide polymorphisms was performed in genes coding for the inflammatory markers. CRP and IL-6 levels were negatively associated with forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC) and mean forced expiratory flow between 25 and 75% of FVC (FEF(25-75%)). In the CRP gene, both the polymorphism rs1205 and the haplotype 2 showed a protective association with FEV(1) and FEF(25-75%), and, to a lesser extent, with FVC. rs1205 and haplotype 2 were both negatively associated with CRP levels in peripheral blood. Analysis with instrumental variables also showed a protective effect between these CRP gene polymorphisms and lung function. Results are very suggestive that heritability of lung function is at least partly controlled by the CRP gene. Applying a Mendelian randomisation approach, the study supports a causal association between low-grade general inflammation and airway diseases.
AU  - Sunyer, J.*
AU  - Pistelli, R.*
AU  - Plana, E.*
AU  - Andreani, M.*
AU  - Baldari, F.*
AU  - Kolz, M.
AU  - Koenig, W.*
AU  - Pekkanen, J.*
AU  - Peters, A.
AU  - Forastiere, F.*
C1  - 3721
C2  - 25561
SP  - 92-97
TI  - Systemic inflammation, genetic susceptibility and lung function.
JO  - Eur. Respir. J.
VL  - 32
IS  - 1
PB  - European Respiratory Society
PY  - 2008
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The relative importance of atopy in the aetiology of rhinitis is largely unknown. The present study investigated the geographical variations in rhinitis in relation to atopy. The cross-sectional study involved 54,178 children (aged 8-12 yrs) from 30 study centres in 22 countries worldwide. Symptoms of rhinoconjunctivitis and rhinitis without conjunctivitis in the last 12 months were reported in parental questionnaires and children were skin-prick tested. The prevalence of rhinoconjunctivitis and rhinitis without conjunctivitis varied widely (1.5-24.5% and 1.4-45.2%, respectively). For rhinoconjunctivitis, the population attributable fraction (PAF) varied 0-71% for a positive skin-prick test to one or more seasonal allergens and 0-41% for perennial allergens. The PAF for sensitisation to seasonal and perennial allergens was higher in affluent countries (36 and 25%, respectively) than nonaffluent countries (1.3 and 12.6%, respectively). For rhinitis without conjunctivitis, the PAF for perennial allergens was 8 and 4% for affluent and nonaffluent countries, respectively. No significant PAF was found for seasonal allergens. Overall, atopy explained only a limited proportion of rhinitis symptoms, suggesting that the importance of other environmental factors has been under emphasised, particularly in less affluent countries. Atopy seems to be only marginally relevant for rhinitis without conjunctivitis, which seems mainly to reflect nonatopic rhinitis.
AU  - Weinmayr, G.*
AU  - Forastiere, F.*
AU  - Weiland, S.K.*
AU  - Rzehak, P.
AU  - Abramidze, T.*
AU  - Annesi-Maesano, I.*
AU  - Björkstén, B.*
AU  - Brunekreef, B.*
AU  - Büchele, G.*
AU  - Cookson, W.O.*
AU  - von Mutius, E.*
AU  - Pistelli, R.*
AU  - Strachan, D.P.*
AU  - ISAAC Phase Two Study Group (*)
C1  - 1472
C2  - 25954
SP  - 1250-1261
TI  - International variation in prevalence of rhinitis and its relationship with sensitisation to perennial and seasonal allergens.
JO  - Eur. Respir. J.
VL  - 32
IS  - 5
PB  - European Respiratory Society
PY  - 2008
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - It has been suggested that early childhood exposure to microbial agents decreases the risk of allergies in children. The current authors studied the association between microbial agents in house dust and allergic sensitisation in children aged 2–4 yrs.Nested case-control studies were performed within ongoing birth cohort studies in Germany, the Netherlands and Sweden and ~180 sensitised and 180 nonsensitised children were selected per country. Levels of bacterial endotoxin, ß(1,3)-glucans and fungal extracellular polysaccharides (EPS) were measured in dust samples from the children’s mattresses and the living-room floors.Combined across countries, higher amounts of mattress dust and higher mattress dust loads of endotoxin, ß(1,3)-glucans and EPS were associated with a significantly decreased risk of sensitisation to inhalant allergens. After mutual adjustment, only the protective effect of the amount of mattress dust remained significant (odds ratio (95% confidence interval) 0.57(0.39–0.84)).Higher amounts of mattress dust may decrease the risk of allergic sensitisation to inhalant allergens. The effect might be partly attributable to endotoxin, ß(1,3)-glucans and extracellular polysaccharides, but could also reflect (additional) protective effects of (microbial) agents other than the ones measured. It is not possible to distinguish with certainty which component relates to the effect, since their levels are highly correlated.
AU  - Gehring, U.
AU  - Heinrich, J.
AU  - Hoek, G.*
AU  - Giovannangelo, M.*
AU  - Nordling, E.*
AU  - Bellander, T.*
AU  - Gerritsen, J.*
AU  - de Jongste, J.C.*
AU  - Smit, H.A.*
AU  - Wichmann, H.-E.
AU  - Wickman, M.*
AU  - Brunekreef, B.*
C1  - 3718
C2  - 24517
SP  - 1144-1153
TI  - Bacteria and mould components in house dust and children's allergic sensitisation.
JO  - Eur. Respir. J.
VL  - 29
IS  - 6
PB  - European Respiratory Society
PY  - 2007
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Childhood farm contact is associated with a lower prevalence of sensitisation and allergic rhinitis. Findings have been contradictory for asthma. The aim of the present study was to investigate the differences between farm and nonfarm subjects using objective measurements. A cross-sectional questionnaire study was performed among rural adults aged 18-44 yrs, of which 37% lived on a farm during the first 3 yrs of life and were thus referred to as "farm subjects". Lung function, bronchial hyperresponsiveness (BHR) to methacholine and sensitisation were measured in a random sample. A total of 1,595 subjects were included in the analyses. Among farm subjects, sensitisation against inhalant allergens (odds ratio (OR) 0.7; 95% confidence interval 0.6-0.9), allergic rhinitis (0.5 (0.4-0.8)) and asthma diagnosis (0.7(0.4-1.1)) were less common than among nonfarm subjects. For BHR and lung function, no statistically significant differences were found between the two groups. Stratifying for sensitisation, farm subjects had a lower OR of asthma diagnosis (0.5 (0.3-1.0)) and a nonsignificantly reduced OR of BHR with sensitisation (0.8 (0.5-1.1)). The present study confirmed, using objective measurements, that farm subjects have a lower prevalence of symptoms and asthma diagnosis, while the prevalence of bronchial hyperresponsiveness does not differ.
AU  - Schulze, A.
AU  - van Strien, R.T.*
AU  - Praml, G.*
AU  - Nowak, D.*
AU  - Radon, K.*
C1  - 2661
C2  - 25252
SP  - 1169-1173
TI  - Characterisation of asthma among adults with and without childhood farm contact.
JO  - Eur. Respir. J.
VL  - 29
IS  - 6
PB  - European Respiratory Society
PY  - 2007
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - High levels of particulate matter in ambient air are associated with increased respiratory and cardiovascular health problems. It has been hypothesised that it is the ultrafine particle fraction (diameter <100 nm) that is largely responsible for these effects. To evaluate the associated mechanisms on a molecular level, the current authors applied an expression profiling approach.
      
      	Healthy mice were exposed to either ultrafine carbon particles (UFCPs; mass concentration 380 µg·m-3) or filtered air for 4 and 24 h. Histology of the lungs did not indicate any pathomorphological changes after inhalation.
      
      	Examination of the bronchoalveolar lavage fluid revealed a small increase in polymorphonuclear cell number (ranging 0.6–1%) after UFCP inhalation, compared with clean air controls, suggesting a minor inflammatory response. However, DNA microarray profile analysis revealed a clearly biphasic response to particle exposure. After 4 h of inhalation, mainly heat shock proteins were induced, whereas after 24 h, different immunomodulatory proteins (osteopontin, galectin-3 and lipocalin-2) were upregulated in alveolar macrophages and septal cells.
      
      	In conclusion, these data indicate that inhalation of ultrafine carbon particles triggers a biphasic pro-inflammatory process in the lung, involving the activation of macrophages and the upregulation of immunomodulatory proteins.
AU  - André, E.
AU  - Stöger, T.
AU  - Takenaka, S.
AU  - Bahnweg, M.*
AU  - Ritter, B.
AU  - Karg, E.W.
AU  - Lentner, B.
AU  - Reinhard, C.
AU  - Schulz, S.
AU  - Wjst, M.
C1  - 2118
C2  - 23800
SP  - 275-285
TI  - Inhalation of ultrafine carbon particles triggers biphasic pro-inflammatory response in the mouse lung.
JO  - Eur. Respir. J.
VL  - 28
IS  - 2
PY  - 2006
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Inequalities in health between socio-economic groups are a major public health concern. The current authors studied associations between parental socio-economic status (SES) and children's respiratory and allergic symptoms in 13 diverse countries, including the Russian Federation, North America (Canada and the USA), and countries across Eastern and Western Europe.
      
      	Data of 57,000 children aged 6–12 yrs, originating from eight cross-sectional studies, were analysed. SES was defined by parental education. Respiratory and allergic symptoms were defined by parental questionnaire reports.
      
      	Multiple logistic regressions showed that low parental education was associated with a decreased risk of inhalant allergy and itchy rash in school children. Furthermore, low parental education was associated with an increased prevalence of wheeze and nocturnal dry cough. No clear association was found between parental education and prevalence of doctor-diagnosed asthma and bronchitis. Part of the difference between socio-economic groups with regard to their children's symptoms was explained by established risk factors, such as parental allergy, smoking during pregnancy, pet ownership, crowding, mould/moisture in the home, use of gas for cooking, and air pollution (particulate matter with a diameter of <10 µm). However, differences remained after adjusting for these variables.
      
      	Children's health was associated with parental education. The association could not fully be explained by established risk factors.
AU  - Gehring, U.
AU  - Pattenden, S.*
AU  - Slachtova, H.*
AU  - Antova, T.*
AU  - Braun-Fahrländer, C.*
AU  - Fabianova, E.*
AU  - Fletcher, T.*
AU  - Galassi, C.*
AU  - Hoek, G.*
AU  - Kuzmin, S.V.*
AU  - Luttmann-Gibson, H.*
AU  - Moshammer, H.*
AU  - Rudnai, P.*
AU  - Zlotkowska, R.*
AU  - Heinrich, J.
C1  - 4709
C2  - 23610
SP  - 95-107
TI  - Parental education and children's respiratory and allergic symptoms in the pollution and the young (PATY) study.
JO  - Eur. Respir. J.
VL  - 27
IS  - 1
PY  - 2006
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The aim of the present investigation was to study changes and determinants for changes in active and passive smoking.
      
      	The present study included 9,053 adults from 14 countries that participated in the European Community Respiratory Health Survey II. The mean follow-up period was 8.8 yrs. Change in the prevalence of active and passive smoking was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. Determinants of change were analysed and the results expressed as adjusted hazard risk ratio (HRR) or odds ratio (OR).
      
      	The prevalence of active smoking declined by 5.9% (5.1–6.8) and exposure to passive smoking in nonsmokers declined by 18.4% (16.8–20.0). Subjects with a lower educational level (HRR: 0.73 (0.54–0.98) and subjects living with a smoker (HRR: 0.45 (0.34–0.59)) or with workplace smoking (HRR: 0.69 (0.50–0.95)) were less likely to quit. Low socio-economic groups were more likely to become exposed (OR: 2.21 (1.61–3.03)) and less likely to cease being exposed to passive smoking (OR: 0.48 (0.37–0.61)).
      
      	In conclusion, the quitting rate was lower and the risk of exposure to passive smoking higher among subjects with lower socio-economic status. Exposure to other peoples smoking decreased quitting rates and increased the risk of starting to smoke.
AU  - Janson, C.*
AU  - Künzli, N.*
AU  - de Marco, R.*
AU  - Chinn, S.*
AU  - Jarvis, D.*
AU  - Svanes, C.*
AU  - Heinrich, J.
AU  - Jõgi, R.*
AU  - Gislason, T.*
AU  - Sunyer, J.*
AU  - Ackermann-Liebrich, U.*
AU  - Antò, J.M.*
AU  - Cerveri, I.*
AU  - Kerhof, M.*
AU  - Leynaert, B.*
AU  - Luczynska, C.*
AU  - Neukirch, F.*
AU  - Vermeire, P.*
AU  - Wjst, M.
AU  - Burney, P.*
C1  - 4714
C2  - 23615
SP  - 517-524
TI  - Changes in active and passive smoking in the European community respiratory health survey.
JO  - Eur. Respir. J.
VL  - 27
IS  - 3
PY  - 2006
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Ambient particles are believed to be a specific health hazard, although the underlying mechanisms are not fully understood. There are data in the literature indicating fast and substantial systemic uptake of particles from the lung. The present authors have developed an improved method to produce ultrafine particles with more stable radiolabelling and defined particle size range. Fifteen subjects inhaled technetium 99m (99mTc)-labelled carbonaceous particles of 100 nm in size. Radioactivity over the lung was followed for 70 h. The clearance of these ultrafine particles from the lungs and specifically translocation to the circulation was tested. Lung retention for all subjects at 46 h was mean+/-sd 99+/-4.6%. Cumulative leaching of 99mTc activity from the particles was 2.6+/-0.96% at 70 h. The 24-h activity leaching in urine was 1.0+/-0.55%. No evidence of a quantitatively important translocation of 100-nm particles to the systemic circulation from the lungs was found. More research is needed to establish if the approximately 1% cleared activity originates from leached activity or insoluble translocated particles, and whether a few per cent of translocated particles is sufficient to cause harmful effects.
AU  - Wiebert, P.*
AU  - Sanchez-Crespo, A.*
AU  - Seitz, J.*
AU  - Falk, R.*
AU  - Philipson, K.*
AU  - Kreyling, W.G.
AU  - Möller, W.
AU  - Sommerer, K.*
AU  - Larsson, S.*
AU  - Svartengren, M.*
C1  - 4098
C2  - 23768
SP  - 286-290
TI  - Negligible clearance of ultrafine particles retained in healthy and affected human lungs.
JO  - Eur. Respir. J.
VL  - 28
IS  - 2
PY  - 2006
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The introduction of genetic approaches in respiratory epidemiology is novel for most epidemiologists, and the post-genome phase poses new challenges. After describing specific questions pertinent to the field of asthma and chronic obstructive pulmonary disease, two main methodological aspects regarding technological and scientific advances are presented in this review. The first one concerns biological aspects in the genome and post-genome phases, i.e. how to study the genome, the transcriptome and the proteome. The second area concerns genetic epidemiology, considering design (case control and family based) and statistical analytical issues. Key aspects are large sample size, good phenotyping and the consideration of environment-by-gene interaction according to windows of opportunity.
      
      	Needs that have been identified include the following. 1) Networking for setting standards in the field and access to sufficiently large samples. 2) Multidisciplinarity; the collaboration of epidemiologists, clinicians, geneticists and specialists in bioinformatics, in addition to specialists in disciplines less familiar to epidemiologists, to be prepared for new phenotypic characterisations based on transcriptome and proteome. 3) Training in genetic analytical techniques for some respiratory epidemiologists, as well as in respiratory epidemiology for some genetic epidemiologists. Implications for research, considering ethical aspects, public health aspects and organisational aspects in the field of genetic and environmental respiratory epidemiology also need to be addressed.
AU  - Kauffmann, F.*
AU  - Post Genome Respiratory Epidemiology Group (Wjst, M.)
C1  - 3084
C2  - 22363
SP  - 471-480
TI  - Post-genome respiratory epidemiology: A multidisciplinary challenge.
JO  - Eur. Respir. J.
VL  - 24
IS  - 3
PY  - 2004
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The aim of the study was to assess the relationship between dietary intake of selected foods and fatty acids with atopic disease prevalence in adults. Data from the European Community Respiratory Health Survey in Erfurt, combined with a 3‐day weighed records dietary survey, was used. Complete data was available from 469 males and 333 females aged 20–64 yrs. Multiple logistic regression was applied comparing the highest with the lowest quartile of dietary exposures and linear trends were tested stratified by sex. In males, margarine intake and a high ratio of omega‐6 to omega‐3 fatty acids were positively associated with hay fever. In females, a high intake of total fat, palmitoleic and oleic acids were positively associated with sensitisation. A high total fat, high monounsaturated fatty acid and high oleic acid consumption were positively associated with hay fever. Whilst an excessive intake of fat or imbalance in fat intake, particular of monounsaturated fatty acids, increased the risk for hay fever and allergic sensitisation in females, mostly no significant associations were found for males. Dietary factors were mostly not related with prevalence rates of bronchial hyperresponsiveness and atopic eczema either in males or in females.
AU  - Trak-Fellermeier, M.A.
AU  - Brasche, S.*
AU  - Winkler, G.*
AU  - Koletzko, B.*
AU  - Heinrich, J.
C1  - 3300
C2  - 21794
SP  - 575-582
TI  - Food and fatty acid intake and atopic disease in adults.
JO  - Eur. Respir. J.
VL  - 23
IS  - 4
PY  - 2004
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Patients with hereditary α1‐proteinase inhibitor (α1‐PI) deficiency are at risk of developing lung emphysema. To prevent the development of this disease, α1‐PI replacement therapy via inhalation may be a more convenient and effective therapy than the intravenous administration of the drug. In order to optimise this treatment approach, lung deposition of inhaled radiolabelled α1‐PI (Prolastin®) was studied using four different commercial inhalation devices (PARI‐LC Star®, HaloLite®, and AKITA® system in combination with LC Star® and Sidestream®) in six patients with α1‐PI deficiency and mild-to-severe chronic obstructive pulmonary disease. The time required to deposit 50 mg of the Prolastin® (5% solution) in the lung periphery was used as a measure for the efficiency of delivery. The time was calculated from measurements of total and peripheral lung deposition of the radiolabelled α1‐PI. This time was shortest for the AKITA® system (18–24 min) and significantly higher for the PARI‐LC Star® (44 min) and the HaloLite® (100 min). The higher efficiency of drug delivery using the AKITA® system is due to the fact that this device controls breathing patterns, which are optimised for each patient individually.
AU  - Brand, P.
AU  - Beckmann, H.*
AU  - Maas Enriquez, M.*
AU  - Meyer, T.*
AU  - Müllinger, B.*
AU  - Sommerer, K.*
AU  - Weber, N.
AU  - Weuthen, T.*
AU  - Scheuch, G.*
C1  - 10184
C2  - 21260
SP  - 263-267
TI  - Peripheral deposition alpha1-protease inhibitor using commercial inhalation devices.
JO  - Eur. Respir. J.
VL  - 22
IS  - 2
PY  - 2003
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The tremendous decline of combustion-derived emissions of traditional air pollutants such as sulphur dioxide (SO2) and total suspended particles (TSP) in Eastern Germany shortly after German reunification in 1990 provided the unique opportunity to study trends of prevalence of respiratory illness along with the improvement of air quality. The present review focused on the results of two repeated surveys of nonallergic respiratory illness in children living in East Germany. The crude prevalence of respiratory illness such as lifetime bronchitis, otitis media, tonsillitis, frequent colds, and frequent cough decreased during the 1990s in East German children. For two surveys the effect estimates showed consistently statistically significant association of TSP with bronchitis. For SO2 statistically significant associations with frequent colds were also consistently found, whereas at least one survey reported higher statistically significant effect estimates for tonsillitis, otitis media, frequent cough and reduced forced vital capacity. The present study concludes that the prevalence of nonallergic respiratory illness in East German children is associated with sulphur dioxide and total suspended particles and that the improvement of air quality has beneficial effects on respiratory health.
AU  - Heinrich, J.
C1  - 10185
C2  - 21619
SP  - 64-69
TI  - Nonallergic respiratory morbidity improved along with a decline of traditional air pollution levels : A review.
JO  - Eur. Respir. J.
VL  - 21
PY  - 2003
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The antioxidant glutathione (GSH) is increased in the epithelial lining fluid (ELF) of chronic smokers. The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), also known as γ‐glutamylcysteine synthetase, consisting of a heavy, catalytic (GCLC) and a light, modulatory (GCLM) subunit. To determine the contribution of bronchoalveolar lavage (BAL) cells to GSH levels in ELF, BAL was performed in eight smokers and eight never-smokers. Intra- and extracellular total glutathione (GSHt) levels and GCL subunit expression were assessed. GSHt was increased in ELF from smokers (1,090.1±163.0 µM versus 559.2±48.2 µM). GSHt content of BAL cells (nmol·mg protein−1) was decreased in smokers without differences reaching statistical significance (8.0±1.4 versus 12.4±2.6). GCLM expression was also reduced in smokers (0.6±0.1 versus 2.8±0.4) and correlated with intracellular GSHt content. There was no significant difference in GCLC expression and in differential cell counts in BAL fluid. The authors conclude that smoking does increase glutathione levels in the epithelial lining fluid but not intracellular levels in bronchoalveolar lavage cells. The data suggest that the intracellular glutathione concentration of bronchoalveolar lavage cells (predominately alveolar macrophages) is regulated by the modulatory glutamate-cysteine ligase subunit rather than the catalytic subunit.
AU  - Neurohr, C.*
AU  - Lenz, A.-G.
AU  - Ding, I.*
AU  - Leuchte, H.*
AU  - Kolbe, T.*
AU  - Behr, J.*
C1  - 10183
C2  - 21245
SP  - 82-87
TI  - Glutamate-cysteine ligase modulatory subunit in BAL alveolar macrophages of healthy smokers.
JO  - Eur. Respir. J.
VL  - 22
IS  - 1
PY  - 2003
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - As part of an international collaborative study on the impact of Traffic-Related Air Pollution on Childhood Asthma (TRAPCA), the health effects associated with long-term exposure to particles with a 50% cut-off aerodynamic diameter of 2.5 microm (PM2.5), PM2.5 absorbance, and nitrogen dioxide (NO2) were analysed. The German part of the TRAPCA study used data from subpopulations of two ongoing birth cohort studies (German Infant Nutrition Intervention Programme (GINI) and Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA)) based in the city of Munich. Geographic information systems (GIS)-based exposure modelling was used to estimate traffic-related air pollutants at the birth addresses of 1,756 infants. Logistic regression was used to analyse possible health effects and potential confounding factors were adjusted for. The ranges in estimated exposures to PM2.5, PM2.5 absorbance, and NO2 were 11.9-21.9 microg m(-3), 1.38-4.39 x 10(-5) m(-1), and 19.5-66.9 microg x m3, respectively. Significant associations between these pollutants and cough without infection (odds ratio (OR) (95% confidence interval (CI)): 1.34 (1.11-1.61), 1.32 (1.10-1.59), and 1.40 (1.12-1.75), respectively) and dry cough at night (OR (95% CI): 1.31 (1.07-1.60), 1.27 (1.04-1.55), and 1.36 (1.07-1.74), respectively) in the first year of life were found. In the second year of life, these effects were attenuated. There was some indication of an association between traffic-related air pollution and symptoms of cough. Due to the very young age of the infants, it was too early to draw definitive conclusions from this for the development of asthma.
AU  - Gehring, U.
AU  - Cyrys, J.
AU  - Sedlmeir, G.*
AU  - Brunekreef, B.*
AU  - Bellander, T.*
AU  - Fischer, P.*
AU  - Bauer, C.P.*
AU  - Reinhardt, D.*
AU  - Wichmann, H.-E.
AU  - Heinrich, J.
C1  - 22091
C2  - 20746
SP  - 690-698
TI  - Traffic-related air pollution and respiratory health during the first 2 yrs of life.
JO  - Eur. Respir. J.
VL  - 19
IS  - 4
PY  - 2002
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Trends in prevalence of atopic diseases and allergic sensitization in children from Eastern Germany during the 1990s were analysed. The study consisted of three regional cross-sectional surveys of a total of 7,632 children (aged 5–14 yrs) in 1992–1993, 1995–1996, and 1998–1999. Information was gathered on atopic diseases and potential predictors by a parental questionnaire. Allergic sensitization for birch, grass, mite, cat, and cladosporium were assessed by radioallergosorbent test (RAST). After adjustment for age, sex and the study area of the participants, prevalence increased between the first and third survey for hay fever, for asthma and for atopic eczema. The adjusted prevalence of allergic sensitization (RAST >0.35 kU·L−1) showed a decrease, whereas the prevalence of strong sensitization (RAST ≥17.5 kU·L−1) increased significantly, specifically in cohorts born after 1989. Further adjustment for possible determinants of these atopic diseases did not change the trend estimates. A clear increase in the prevalence of atopic diseases, with the exception of hay fever, was observed as well as a shift towards a stronger allergic sensitization, which might affect the onset of clinical manifestations of atopic diseases. Differences in the epidemiology of respiratory symptoms, illnesses and allergies between populations living in the former East Germany and those living in the former West Germany have been reported. Among East German children, lower prevalence rates of asthma, and positive skin-prick tests were observed compared to West German children in the early 1990s 1–5. Similarly, among East German adults, lower specific immunoglobulin (Ig) E levels and lower prevalence rates of asthma, wheezing, positive methacholine-challenge tests, allergic rhinitis, and positive skin-prick tests have been reported compared to those of West German adults 6, 7.
AU  - Heinrich, J.
AU  - Hoelscher, B.
AU  - Frye, C.
AU  - Meyer, I.
AU  - Wjst, M.
AU  - Wichmann, H.-E.
C1  - 22065
C2  - 20701
SP  - 1040-1046
TI  - Trends in prevalence of atopic diseases and allergic sensitization in children in Eastern Germany.
JO  - Eur. Respir. J.
VL  - 19
IS  - 6
PY  - 2002
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The current authors examined whether mite and cat allergen and bacterial endotoxin levels in dust of the mothers' mattresses were associated with cord blood immunoglobulin (Ig)E (CB-IgE) levels in newborns. Data from 1,332 term and normal weight neonates, from an ongoing birth cohort study, Influences of life-style related factors on the immune system and the development of allergies in childhood (LISA), with complete information on exposure to biocontaminants in mattress dust and CB-IgE were analysed. Two thirds of CB-IgE were undetectable (<0.35 kU·L−1). Thus, 0.35 and 0.45 kU·L−1 (4th quartile) were chosen as cut-offs. Nonparametric smoothing (generalised additive models) showed statistically significant confounder-adjusted associations between elevated CB-IgE levels (≥0.45 kU·L−1) and log-transformed exposures to cat (linear), mite (inverse u-shaped), and endotoxin (u-shaped). After adjustment for covariables, elevated CB-IgE levels (logistic regression using the 1st–4th quartiles of exposure) were positively associated with high cat-allergen exposure and medium exposure to mite allergen, but were inversely associated with exposure to endotoxin. The associations were similar, but somewhat weaker, when 0.35 kU·L−1 was used as cut-off. These results, showing an association between prenatal allergen and endotoxin exposures and immunoglobulin E production, suggest that the development of foetal immune responses may be affected.
AU  - Heinrich, J.
AU  - Bolte, G.
AU  - Hölscher, B.
AU  - Douwes, J.*
AU  - Lehmann, I.*
AU  - Fahlbusch, B.*
AU  - Bischof, W.*
AU  - Weiss, M.*
AU  - Borte, M.*
AU  - Wichmann, H.-E.
C1  - 22077
C2  - 20724
SP  - 617-623
TI  - Allergens and endotoxin on mothers mattresses and total immunoglobulin E in cord blood neonates.
JO  - Eur. Respir. J.
VL  - 20
IS  - 3
PY  - 2002
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The association between particulate air pollution and asthma medication use and symptoms was assessed in a panel study of 53 adult asthmatics in Erfurt, Germany in winter 1996/1997. Number concentrations of ultrafine particles, 0.01–0.1 µm in diameter (NC0.01–0.1), mean 17,300·cm−3, and mass concentrations of fine particles 0.01–2.5 µm in diameter (MC0.01–2.5), mean 30.3 µg·m−3, were measured concurrently. They were not highly correlated (r=0.45). The associations between ambient particle concentrations and the prevalence of inhaled β2-agonist, corticosteroid use and asthma symptoms, were analysed separately with logistic regression models, adjusting for trend, temperature, weekend, holidays, and first order autocorrelation of the error. Cumulative exposures over 14 days of ultrafine and fine particles were associated with corticosteroid use. β2-agonist use was associated with 5-day mean NC0.01–0.1 and MC0.01–2.5. The prevalence of asthma symptoms was associated with ambient particle concentrations. The results suggest that reported asthma medication use and symptoms increase in association with particulate air pollution and gaseous pollutants such as nitrogen dioxide.
AU  - von Klot, S.
AU  - Wölke, G.
AU  - Tuch, T.*
AU  - Heinrich, J.
AU  - Dockery, D.W.*
AU  - Schwartz, J.*
AU  - Kreyling, W.G.
AU  - Wichmann, H.-E.
AU  - Peters, A.
C1  - 10182
C2  - 20722
SP  - 691-702
TI  - Increased asthma medication use in association with ambient fine and ultrafine particles.
JO  - Eur. Respir. J.
VL  - 20
IS  - 3
PY  - 2002
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The European Community Respiratory Health Survey (ECRHS) was the first study to assess the geographical variation in asthma and allergy in adults using the same instruments and definitions. The database of the ECRHS includes information from approximately 140,000 individuals from 22 countries. The aim of this review is to summarize the results of the ECRHS to date. The ECRHS has shown that there are large geographical differences in the prevalence of asthma, atopy and bronchial responsiveness, with high prevalence rates in English speaking countries and low prevalence rates in the Mediterranean region and Eastern Europe. Analyses of risk factors have highlighted the importance of occupational exposure for asthma in adulthood. The association between sensitization to individual allergens and bronchial responsiveness was strongest for indoor allergens (mite and cat). Analysis of treatment practices has confirmed that the treatment of asthma varies widely between countries and that asthma is often undertreated. In conclusion, the European Community Respiratory Health Survey has shown that the prevalence of asthma varies widely. The fact that the geographical pattern is consistent with the distribution of atopy and bronchial responsiveness supports the conclusion that the geographical variations in the prevalence of asthma are true and most likely due to environmental factors.
AU  - Janson, C.*
AU  - Anto, J.*
AU  - Burney, P.*
AU  - Chinn, S.*
AU  - de Marco, R.*
AU  - Heinrich, J.
AU  - Jarvis, D.*
AU  - Kuenzli, N.*
AU  - Leynaert, B.*
AU  - Luczynska, C.*
AU  - Neukirch, F.*
AU  - Svanes, C.*
AU  - Sunyer, J.*
AU  - Wjst, M.
C1  - 28403
C2  - 33366
SP  - 598-611
TI  - The European Community Respiratory Health Survey: What are the main results so far? European Community Respiratory Health Survey II.
JO  - Eur. Respir. J.
VL  - 18
IS  - 3
PY  - 2001
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - In adults fatal and near-fatal asthma have similar clinical characteristics. Therefore, near-fatal asthma in adults can be used as a model for fatal asthma. A nationwide study on fatal and near-fatal asthma in children <16 yrs was performed in order to assess whether, as in adults, near-fatal asthma can be used as a model for fatal asthma. From 1996 to 1998, all paediatric hospitals and paediatric pulmonologists in Germany were asked to report cases of fatal asthma and near-fatal asthma to a central survey unit (Erhebungseinheit fur seltene padiatrische Erkrankungen in Deutschland (ESPED)) on a monthly basis. All reports were followed by detailed questionnaires. Sixteen fatal and 45 near-fatal asthma cases were analysed. Fatal asthma patients were older than near-fatal asthma patients. Respiratory tract infections were frequently reported only in near-fatal asthma (47 versus 0%). The proportion of cases with rapid-type onset (duration of symptoms < or =1 h) was higher in fatal asthma (53 versus 14%). Long-term regular treatment with short acting beta2-agonists was common in both groups, but the use of concomitant inhaled corticosteroids was significantly lower in fatal asthma cases. A high proportion of poor compliance was observed in both groups. As fatal and near-fatal asthma differ significantly in important clinical aspects, analysis of near-fatal asthma might be of limited value in elucidating the causes of fatal asthma in children.
AU  - Schmitz, T.*
AU  - von Kries, R.*
AU  - Wjst, M.
AU  - Schuster, A.*
C1  - 21635
C2  - 19782
SP  - 845-849
TI  - A nationwide survey in Germany on fatal asthma and near-fatal asthma in children: different entities ?.
JO  - Eur. Respir. J.
VL  - 16
IS  - 5
PY  - 2000
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Oxidative stress in acute respiratory distress syndrome (ARDS) is considered as an important pathophysiological mechanism in acute impairment of lung function. The present study investigated whether a pulmonary oxidant-antioxidant imbalance is indicated by substantial oxidative modification of proteins in bronchoalveolar lavage (BAL) fluid. Oxidatively modified proteins in BAL fluid, as measured by the reduction of protein carbonyl groups with tritiated borohydride, were studied in control subjects, patients with clinically established ARDS, and patients considered at-risk for ARDS because they had had coronary bypass surgery. Subsets of these at-risk patients were pretreated either with methylprednisolone or N-acetylcysteine. The carbonyl content of BAL fluid proteins was greatly increased in ARDS patients (5.0+/-13 nmol carbonyl x mL(-1) BAL fluid; mean+/-SEM; p=0.0004; n=10) and moderately increased in the untreated patients at-risk for ARDS (1.3+/-0.2 nmol x mL(-1); p=0.027; n=19) compared with controls (0.8+/-0.2 nmol x mL(-1); n=12). The two other at-risk groups pretreated either with methylprednisolone or N-acetylcysteine showed carbonyl values that were statistically not different from the controls (1.2+/-0.2 nmol x mL(-1); p=0.13; n=13, and 1.1+/-0.3 nmol x mL(-1); p=0.40; n=8, respectively). These results show that oxidatively modified proteins clearly accumulated in bronchoalveolar lavage fluid of acute respiratory distress syndrome patients, and to a minor extent in untreated at-risk patients. These data suggest a severe oxidant-antioxidant imbalance in acute respiratory distress syndrome.
AU  - Lenz, A.-G.
AU  - Jorens, P.G.*
AU  - Meyer, B.
AU  - de Backer, W.*
AU  - van Overveld, F.*
AU  - Bossaert, L.*
AU  - Maier, K.L.
C1  - 20780
C2  - 18829
SP  - 169-174
TI  - Oxidatively modified proteins in bronchoalveolar lavage fluid of patients with ARDS and patients at-risk for ARDS.
JO  - Eur. Respir. J.
VL  - 13
PY  - 1999
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Oxygen-derived free radicals, released by phagocytic cells, have been postulated to contribute to lung tissue damage. We therefore investigated oxidative damage to proteins from bronchoalveolar lavage fluid (BALF) as an indicator of oxidative stress and to assess antioxidant defences in the lungs. We examined BAL fluids from patients with interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF, nonsmokers (NS) and smokers (S)), sarcoidosis (SARC, nonsmokers), and asbestosis (ASB, ex-smokers (EXS)). The oxidation of BALF proteins is accompanied by the introduction of carbonyl groups into their amino acid side-chains and can be quantitated by labeling these groups with tritiated borohydride. The total lung content of oxidized proteins recovered by bronchoalveolar lavage (BAL) was 0.3 +/- 0.07 nmol carbonyl.mL-1 BALF (mean +/- SEM) in the NS control group (n = 9) and tended to be increased, in the asymptomatic S group (n = 8; 0.59 +/- 0.14 nmol.mL-1). This parameter was significantly elevated both in IPF-NS (n = 14; 0.84 +/- 0.2 nmol carbonyl.mL-1 BALF) and SARC-NS (n = 15; 0.73 +/- 0.16 nmol.mL-1) as compared with the NS control. On the contrary, in smoking patients with IPF (n = 6; 0.41 +/- 0.1 nmol carbonyl.mL-1 BALF) and also in ASB-EXS (n = 6; 0.37 +/- 0.06 nmol.mL-1) it was not different from NS controls. The total amount of oxidized proteins correlated positively with the absolute number of eosinophils (EOS) in IPF-NS, IPF-S and SARC, and also with absolute polymorphonuclear neutrophil (PMN) numbers in IPF-NS and IPF-S. In conclusion, oxidative damage of BALF proteins occurred in nonsmoking patients with IPF and SARC. The amount of oxidized bronchoalveolar lavage fluid protein may provide a quantitative assessment of oxygen burden, a balance between oxidant stress and antioxidant defences.
AU  - Lenz, A.-G.
AU  - Costabel, U.
AU  - Maier, K.L.
C1  - 28746
C2  - 33541
SP  - 307-312
TI  - Oxidized BAL fluid proteins in patients with interstitial lung diseases.
JO  - Eur. Respir. J.
VL  - 9
IS  - 2
PY  - 1996
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - The broadening of inhaled aerosol boluses (aerosol bolus dispersion) during respiration provides a noninvasive measure of convective gas mixing in the lungs. In this study, the sensitivity and specificity of this technique for the diagnosis of early lung impairment due to cigarette smoking was evaluated. Two hundred and sixteen randomly selected subjects (126 smokers and 90 nonsmokers) were investigated with aerosol dispersion in comparison to conventional lung function tests. The cumulative cigarette consumption of the subjects was quantified by 'pack-years' (PY). Smokers were classified into the following groups: 0< PY <10; 10< PY <20; 20< PY <30; and PY >30. Forced expiratory volume in one second (FEV1), maximal expiratory flow at 25, 50 and 75% vital capacity (MEF25, MEF50) and MEF75) decreased significantly with increasing cigarette consumption. In comparison to nonsmokers, FEV1 was significantly reduced in smokers of 10< PY <30, and MEF75 was significantly reduced in smokers of PY >20. Aerosol bolus dispersion increased with increasing PY. For all groups of smokers, even those with PY <10, bolus dispersion was significantly increased in comparison to lifelong nonsmokers, indicating alterations in convective gas mixing in the lungs. Calculation of receiver operating characteristics for the lung function parameters under consideration showed that bolus dispersion has a higher sensitivity and specificity than conventional lung function parameters. Hence, the aerosol bolus dispersion test could be a promising epidemiological tool to study early abnormalities in intrapulmonary gas mixing due to environmental factors.
AU  - Brand, P.
AU  - Tuch, T.H.
AU  - Manuwald, O.
AU  - Bischof, W.
AU  - Heinrich, J.G.
AU  - Wichmann, H.-E.
AU  - Beinert, T.
AU  - Heyder, J.
C1  - 39990
C2  - 38939
SP  - 1830-1838
TI  - Detection of early lung impairment with aerosol bolus dispersion.
JO  - Eur. Respir. J.
VL  - 7
IS  - 10
PY  - 1994
SN  - 0903-1936
ER  - 

TY  - JOUR
AU  - Maier, K.L.
C1  - 40408
C2  - 40064
SP  - 334-336
TI  - How the lung deals with oxidants.
JO  - Eur. Respir. J.
VL  - 6
IS  - 3
PY  - 1993
SN  - 0903-1936
ER  - 

TY  - JOUR
AB  - Phagocytic cells such as alveolar macrophages (AM) or polymorphonuclear neutrophils (PMN) in the bronchoalveolar tract are a potential source of the oxygen-derived free radicals which are presumed to be involved in lung tissue damage. Previous results have shown that the methionine sulphoxide (MET(O)) content of bronchoalveolar lavage fluid (BALF) protein is a reliable parameter to indicate oxidative processes in idiopathic pulmonary fibrosis (IPF). We measured the molar ratio between MET(O) and methionine (MET) in the BALF protein from healthy nonsmokers (control group), healthy smokers and patients with acute or chronic bronchitis (AB or CB). The MET(O)/MET ratio of the nonsmoking group (n = 11) was 0.046 ± 0.008 (mean ± SEM). Healthy smokers (n = 8) had similar values (0.042 ± 0.008), even though they had strongly increased AM counts in BALF. Patients with AB (n = 12) showed an increased MET(O)/MET ratio (0.191 ± 0.031) and had high PMN but normal AM counts in BALF. Patients with CB (n = 13) showed an increase in the MET(O)/MET ratio (0.086 ± 0.010) and moderately increased PMN and markedly increased AM counts. Taking all results together, the MET(O)/MET ratio correlated positively with the relative PMN number (r = 0.70; p < 0.0002) and inversely with the relative AM number (r = -0.67; p < 0.0002). In the group with CB, the MET(O)/MET ratio correlated inversely with forced expiratory volume in one second (FEV1) % pred. (r = -0.77) and FEV1/inspiratory vital capacity (IVC) % pred. (r = -0.89). We conclude that oxidative pulmonary processes in AB and CB are reflected in an increase of the MET(O) content in the BALF protein, which is predominantly mediated by PMN.
AU  - Maier, K.L.
AU  - Leuschel, L.
AU  - Costabel, U.
C1  - 40551
C2  - 38780
SP  - 651-658
TI  - Increased oxidized methionine residues in BAL fluid proteins in acute or chronic bronchitis.
JO  - Eur. Respir. J.
VL  - 5
IS  - 6
PY  - 1992
SN  - 0903-1936
ER  -