TY  - JOUR
AB  - INTRODUCTION: Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised. METHODS: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4). After nanoparticle exposure of pHBECs at air-liquid interface, cell cultures were characterised by functional assays, transcriptome and protein analysis, complemented by single-cell analysis in serial samples of pHBEC cultures focusing on basal cell differentiation. RESULTS: COPD-IV was characterised by a prosecretory phenotype (twofold increase in MUC5AC+) at the expense of the multiciliated epithelium (threefold reduction in Ac-Tub+), resulting in an increased resilience towards particle-induced cell damage (fivefold reduction in transepithelial electrical resistance), as exemplified by environmentally abundant doses of zinc oxide nanoparticles. Exposure of COPD-II cultures to cigarette smoke extract provoked the COPD-IV characteristic, prosecretory phenotype. Time-resolved single-cell transcriptomics revealed an underlying COPD-IV unique basal cell state characterised by a twofold increase in KRT5+ (P=0.018) and LAMB3+ (P=0.050) expression, as well as a significant activation of Wnt-specific (P=0.014) and Notch-specific (P=0.021) genes, especially in precursors of suprabasal and secretory cells. CONCLUSION: We identified COPD stage-specific gene alterations in basal cells that affect the cellular composition of the bronchial elevator and may control disease-specific epithelial resilience mechanisms in response to environmental nanoparticles. The identified phenomena likely inform treatment and prevention strategies.
AU  - Stoleriu, M.-G.
AU  - Ansari, M.
AU  - Strunz, M.
AU  - Schamberger, A.C.
AU  - Heydarian, M.
AU  - Ding, Y.
AU  - Voss, C.
AU  - Schneider, J.J.
AU  - Gerckens, M.
AU  - Burgstaller, G.
AU  - Castelblanco, A.
AU  - Kauke, T.*
AU  - Fertmann, J.*
AU  - Schneider, C.*
AU  - Behr, J.
AU  - Lindner, M.*
AU  - Stacher-Priehse, E.*
AU  - Irmler, M.
AU  - Beckers, J.
AU  - Eickelberg, O.
AU  - Schubert, B.
AU  - Hauck, S.M.
AU  - Schmid, O.
AU  - Hatz, R.A.*
AU  - Stöger, T.
AU  - Schiller, H.
AU  - Hilgendorff, A.
C1  - 69904
C2  - 55317
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
SP  - 524-537
TI  - COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors.
JO  - Thorax
VL  - 79
IS  - 6
PB  - Bmj Publishing Group
PY  - 2024
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - RATIONALE: Eosinophils are associated with airway inflammation in respiratory disease. Eosinophil production and survival is controlled partly by interleukin-5: anti-interleukin-5 agents reduce asthma and response correlates with baseline eosinophil counts. However, whether raised eosinophils are causally related to chronic obstructive pulmonary disease (COPD) and other respiratory phenotypes is not well understood. OBJECTIVES: We investigated causality between eosinophils and: lung function, acute exacerbations of COPD, asthma-COPD overlap (ACO), moderate-to-severe asthma and respiratory infections. METHODS: We performed Mendelian randomisation (MR) using 151 variants from genome-wide association studies of blood eosinophils in UK Biobank/INTERVAL, and respiratory traits in UK Biobank/SpiroMeta, using methods relying on different assumptions for validity. We performed multivariable analyses using eight cell types where there was possible evidence of causation by eosinophils. MEASUREMENTS AND MAIN RESULTS: Causal estimates derived from individual variants were highly heterogeneous, which may arise from pleiotropy. The average effect of raising eosinophils was to increase risk of ACO (weighted median OR per SD eosinophils, 1.44 (95%CI 1.19 to 1.74)), and moderate-severe asthma (weighted median OR 1.50 (95%CI 1.23 to 1.83)), and to reduce forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and FEV1 (weighted median estimator, SD FEV1/FVC: -0.054 (95% CI -0.078 to -0.029), effect only prominent in individuals with asthma). CONCLUSIONS: Broad consistency across MR methods may suggest causation by eosinophils (although of uncertain magnitude), yet heterogeneity necessitates caution: other important mechanisms may be responsible for the impairment of respiratory health by these eosinophil-raising variants. These results could suggest that anti-IL5 agents (designed to lower eosinophils) may be valuable in treating other respiratory conditions, including people with overlapping features of asthma and COPD.
AU  - Guyatt, A.L.*
AU  - John, C.*
AU  - Williams, A.T.*
AU  - Shrine, N.*
AU  - Reeve, N.F.*
AU  - Sayers, I.*
AU  - Hall, I.P.*
AU  - Wain, L.V.*
AU  - Sheehan, N.*
AU  - Dudbridge, F.*
AU  - SpiroMeta Consortium (Gieger, C.
AU  - Karrasch, S.
AU  - Schulz, H.)
C1  - 70149
C2  - 55022
SP  - 496-503
TI  - Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease.
JO  - Thorax
VL  - 78
IS  - 5
PY  - 2023
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - INTRODUCTION: Obesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults. METHODS: We used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I (t) to ECRHS II (t+1), and from ECRHS II (t) to ECRHS III (t+1). We excluded obese (body mass index≥30 kg/m2) individuals at visit t. The relative risk (RR) of obesity at t+1 associated with asthma at t was estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity. RESULTS: We included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II-III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association. CONCLUSION: This is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.
AU  - Moitra, S.*
AU  - Carsin, A.E.*
AU  - Abramson, M.J.*
AU  - Accordini, S.*
AU  - Amaral, A.F.S.*
AU  - Anto, J.*
AU  - Bono, R.*
AU  - Casas Ruiz, L.*
AU  - Cerveri, I.*
AU  - Chatzi, L.*
AU  - Demoly, P.*
AU  - Dorado-Arenas, S.*
AU  - Forsberg, B.*
AU  - Gilliland, F.*
AU  - Gislason, T.*
AU  - Gullón, J.A.*
AU  - Heinrich, J.
AU  - Holm, M.*
AU  - Janson, C.*
AU  - Jõgi, R.*
AU  - Gómez Real, F.*
AU  - Jarvis, D.*
AU  - Leynaert, B.*
AU  - Nowak, D.*
AU  - Probst-Hensch, N.*
AU  - Sánchez-Ramos, J.L.*
AU  - Raherison-Semjen, C.*
AU  - Siroux, V.*
AU  - Guerra, S.*
AU  - Kogevinas, M.*
AU  - Garcia-Aymerich, J.*
C1  - 65038
C2  - 52135
SP  - 128-135
TI  - Long-term effect of asthma on the development of obesity among adults: An international cohort study, ECRHS.
JO  - Thorax
VL  - 78
IS  - 2
PY  - 2023
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - INTRODUCTION: Chronic lung disease, that is, bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants and develops as a consequence of the misguided formation of the gas-exchange area undergoing prenatal and postnatal injury. Subsequent vascular disease and its progression into pulmonary arterial hypertension critically determines long-term outcome in the BPD infant but lacks identification of early, disease-defining changes. METHODS: We link impaired bone morphogenetic protein (BMP) signalling to the earliest onset of vascular pathology in the human preterm lung and delineate the specific effects of the most prevalent prenatal and postnatal clinical risk factors for lung injury mimicking clinically relevant conditions in a multilayered animal model using wild-type and transgenic neonatal mice. RESULTS: We demonstrate (1) the significant reduction in BMP receptor 2 (BMPR2) expression at the onset of vascular pathology in the lung of preterm infants, later mirrored by reduced plasma BMP protein levels in infants with developing BPD, (2) the rapid impairment (and persistent change) of BMPR2 signalling on postnatal exposure to hyperoxia and mechanical ventilation, aggravated by prenatal cigarette smoke in a preclinical mouse model and (3) a link to defective alveolar septation and matrix remodelling through platelet derived growth factor-receptor alpha deficiency. In a treatment approach, we partially reversed vascular pathology by BMPR2-targeted treatment with FK506 in vitro and in vivo. CONCLUSION: We identified impaired BMP signalling as a hallmark of early vascular disease in the injured neonatal lung while outlining its promising potential as a future biomarker or therapeutic target in this growing, high-risk patient population.
AU  - Heydarian, M.
AU  - Oak, P.
AU  - Zhang, X.
AU  - Kamgari, N.
AU  - Kindt, A.S.D.*
AU  - Koschlig, M.
AU  - Pritzke, T.
AU  - Gonzalez-Rodriguez, E.
AU  - Förster, K.
AU  - Morty, R.E.*
AU  - Häfner, F.
AU  - Hübener, C.*
AU  - Flemmer, A.W.*
AU  - Yildirim, A.Ö.
AU  - Sudheendra, D.*
AU  - Tian, X.*
AU  - Petrera, A.
AU  - Kirsten, H.*
AU  - Ahnert, P.*
AU  - Morrell, N.*
AU  - Desai, T.J.*
AU  - Sucre, J.*
AU  - Spiekerkoetter, E.*
AU  - Hilgendorff, A.
C1  - 64984
C2  - 52008
SP  - 1176-1186
TI  - Relationship between impaired BMP signalling and clinical risk factors at early-stage vascular injury in the preterm infant.
JO  - Thorax
VL  - 77
IS  - 12
PY  - 2022
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - BACKGROUND: No data on healthcare utilisation and associated costs for the many rare entities of children's interstitial lung diseases (chILD) exist. This paper portrays healthcare utilisation structures among individuals with chILD, provides a pan-European estimate of a 3-month interval per-capita costs and delineates crucial cost drivers. METHODS: Based on longitudinal healthcare resource utilisation pattern of 445 children included in the Kids Lung Register diagnosed with chILD across 10 European countries, we delineated direct medical and non-medical costs of care per 3-month interval. Country-specific utilisation patterns were assessed with a children-tailored modification of the validated FIMA questionnaire and valued by German unit costs. Costs of care and their drivers were subsequently identified via gamma-distributed generalised linear regression models. RESULTS: During the 3 months prior to inclusion into the registry (baseline), the rate of hospital admissions and inpatient days was high. Unadjusted direct medical per capita costs (€19 818) exceeded indirect (€1 907) and direct non-medical costs (€1 125) by far. Country-specific total costs ranged from €8 713 in Italy to €28 788 in Poland. Highest expenses were caused by the disease categories 'diffuse parenchymal lung disease (DPLD)-diffuse developmental disorders' (€45 536) and 'DPLD-unclear in the non-neonate' (€47 011). During a follow-up time of up to 5 years, direct medical costs dropped, whereas indirect costs and non-medical costs remained stable. CONCLUSIONS: This is the first prospective, longitudinal study analysing healthcare resource utilisation and costs for chILD across different European countries. Our results indicate that chILD is associated with high utilisation of healthcare services, placing a substantial economic burden on health systems.
AU  - Seidl, E.*
AU  - Schwerk, N.*
AU  - Carlens, J.*
AU  - Wetzke, M.*
AU  - Cunningham, S.*
AU  - Emiralioğlu, N.*
AU  - Kiper, N.*
AU  - Lange, J.*
AU  - Krenke, K.*
AU  - Ullmann, N.*
AU  - Krikovszky, D.*
AU  - Maqhuzu, P.N.
AU  - Griese, C.A.*
AU  - Schwarzkopf, L.
AU  - Griese, M.*
C1  - 64375
C2  - 51966
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
SP  - 781–789
TI  - Healthcare resource utilisation and medical costs for children with interstitial lung diseases (chILD) in Europe.
JO  - Thorax
VL  - 77
PB  - Bmj Publishing Group
PY  - 2022
SN  - 0040-6376
ER  - 

TY  - JOUR
AU  - Standl, M.
C1  - 64515
C2  - 51969
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
TI  - Limited side effects of asthma treatment on growth and bone health in children.
JO  - Thorax
VL  - 77
IS  - 8
PB  - Bmj Publishing Group
PY  - 2022
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - To examine the role of smoking on the bacterial community composition of the upper and the lower respiratory tract, a monocentric, controlled prospective study was performed, including healthy smokers, ex-smokers and never-smokers. Smokers were further grouped according to their smoking history. Bacterial diversity was analysed using a molecular barcoding approach based on directly extracted DNA. Our study shows for the first time distinct bacterial response patterns in the upper and lower respiratory tract to cigarette smoking leading to a higher abundance of opportunistic pathogens. The clinical significance of these dysbioses for health needs to be further explored.
AU  - Pfeiffer, S.
AU  - Herzmann, C.*
AU  - Gaede, K.I.*
AU  - Kovacevic, D.*
AU  - Krauss-Etschmann, S.*
AU  - Schloter, M.
C1  - 62844
C2  - 51101
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
TI  - Different responses of the oral, nasal and lung microbiomes to cigarette smoke.
JO  - Thorax
VL  - 8
PB  - Bmj Publishing Group
PY  - 2021
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - We developed a MRI protocol using transverse (T2) and longitudinal (T1) mapping sequences to characterise lung structural changes in preterm infants with bronchopulmonary dysplasia (BPD). We prospectively enrolled 61 infants to perform 3-Tesla MRI of the lung in quiet sleep. Statistical analysis was performed using logistic Group Lasso regression and logistic regression. Increased lung T2 relaxation time and decreased lung T1 relaxation time indicated BPD yielding an area under the curve (AUC) of 0.80. Results were confirmed in an independent study cohort (AUC 0.75) and mirrored by lung function testing, indicating the high potential for MRI in future BPD diagnostics.
AU  - Förster, K.
AU  - Ertl-Wagner, B.
AU  - Ehrhardt, H.*
AU  - Busen, H.
AU  - Sass, S.
AU  - Pomschar, A.*
AU  - Naehrlich, L.*
AU  - Schulze, A.*
AU  - Flemmer, A.W.*
AU  - Hübener, C.*
AU  - Eickelberg, O.
AU  - Theis, F.J.
AU  - Dietrich, O.*
AU  - Hilgendorff, A.
C1  - 55972
C2  - 46663
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
SP  - 184-187
TI  - Altered relaxation times in MRI indicate bronchopulmonary dysplasia.
JO  - Thorax
VL  - 75
IS  - 2
PB  - Bmj Publishing Group
PY  - 2020
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.
AU  - Kanellakis, N.I.*
AU  - Asciak, R.*
AU  - Hamid, M.A.*
AU  - Yao, X.*
AU  - McCole, M.*
AU  - McGowan, S.*
AU  - Seraia, E.*
AU  - Hatch, S.*
AU  - Hallifax, R.J.*
AU  - Mercer, R.M.*
AU  - Bedawi, E.O.*
AU  - Jones, S.*
AU  - Verrill, C.*
AU  - Dobson, M.*
AU  - George, V.*
AU  - Stathopoulos, G.T.
AU  - Peng, Y.*
AU  - Ebner, D.*
AU  - Dong, T.*
AU  - Rahman, N.M.*
AU  - Psallidas, I.*
C1  - 60380
C2  - 49318
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
SP  - 1004-1008
TI  - Patient-derived malignant pleural mesothelioma cell cultures: A tool to advance biomarker-driven treatments.
JO  - Thorax
VL  - 75
IS  - 11
PB  - Bmj Publishing Group
PY  - 2020
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Background Antibiotic resistance is a major global threat. We hypothesised that the chronic obstructive pulmonary disease (COPD) airway is a reservoir of antimicrobial resistance genes (ARGs) that associate with microbiome-specific COPD subgroups. Objective To determine the resistance gene profiles in respiratory samples from COPD patients and healthy volunteers. Methods Quantitative PCR targeting 279 specific ARGs was used to profile the resistomes in sputum from subjects with COPD at stable, exacerbation and recovery visits (n=55; COPD-BEAT study), healthy controls with (n=7) or without (n=22) exposure to antibiotics in the preceding 12 months (EXCEED study) and in bronchial brush samples from COPD (n=8) and healthy controls (n=7) (EvA study). Results ARG mean (SEM) prevalence was greater in stable COPD samples (35.2 (1.6)) than in healthy controls (27.6 (1.7); p=0.004) and correlated with total bacterial abundance (r(2)=0.23; p<0.001). Prevalence of ARG positive signals in individuals was not related to COPD symptoms, lung function or their changes at exacerbation. In the COPD subgroups designated High gamma Proteobacteria and High Firmicutes, ARG prevalence was not different at stable state but significantly declined from stable through exacerbation to recovery in the former (p=0.011) without changes in total bacterial abundance. The ARG patterns were similar in COPD versus health, COPD microbiome-subgroups and between sputum and bronchoscopic samples independent of antibiotic exposure in the last 12 months. Conclusions ARGs are highly prevalent in sputum, broadly in proportion to bacterial abundance in both healthy and COPD subjects. Thus, COPD appears to be an ARG reservoir due to high levels of bacterial colonisation.
AU  - Ramsheh, M.Y.*
AU  - Haldar, K.*
AU  - Bafadhel, M.*
AU  - George, L.*
AU  - Free, R.C.*
AU  - John, C.*
AU  - Reeve, N.F.*
AU  - Ziegler-Heitbrock, L.
AU  - Gut, I.*
AU  - Singh, D.*
AU  - Mistry, V.*
AU  - Tobin, M.D.*
AU  - Oggioni, M.R.*
AU  - Brightling, C.*
AU  - Barer, M.R.*
C1  - 57363
C2  - 47758
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
SP  - 8-16
TI  - Resistome analyses of sputum from COPD and healthy subjects reveals bacterial load-related prevalence of target genes.
JO  - Thorax
VL  - 75
IS  - 1
PB  - Bmj Publishing Group
PY  - 2019
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Objective We assessed associations between physical activity and lung function, and its decline, in the prospective population-based European Community Respiratory Health Survey cohort. Methods FEV 1 and FVC were measured in 3912 participants at 27-57 years and 39-67 years (mean time between examinations=11.1 years). Physical activity frequency and duration were assessed using questionnaires and used to identify active individuals (physical activity ≥2 times and ≥1 hour per week) at each examination. Adjusted mixed linear regression models assessed associations of regular physical activity with FEV 1 and FVC. Results Physical activity frequency and duration increased over the study period. In adjusted models, active individuals at the first examination had higher FEV 1 (43.6 mL (95% CI 12.0 to 75.1)) and FVC (53.9 mL (95% CI 17.8 to 89.9)) at both examinations than their non-active counterparts. These associations appeared restricted to current smokers. In the whole population, FEV 1 and FVC were higher among those who changed from inactive to active during the follow-up (38.0 mL (95% CI 15.8 to 60.3) and 54.2 mL (95% CI 25.1 to 83.3), respectively) and who were consistently active, compared with those consistently non-active. No associations were found for lung function decline. Conclusion Leisure-time vigorous physical activity was associated with higher FEV 1 and FVC over a 10-year period among current smokers, but not with FEV 1 and FVC decline.
AU  - Fuertes, E.*
AU  - Carsin, A.E.*
AU  - Antò, J.M.*
AU  - Bono, R.*
AU  - Corsico, A.G.*
AU  - Demoly, P.*
AU  - Gislason, T.*
AU  - Gullón, J.A.*
AU  - Janson, C.*
AU  - Jarvis, D.*
AU  - Heinrich, J.
AU  - Holm, M.*
AU  - Leynaert, B.*
AU  - Marcon, A.*
AU  - Martinez-Moratalla, J.*
AU  - Nowak, D.*
AU  - Pascual Erquicia, S.*
AU  - Probst-Hensch, N.M.*
AU  - Raherison, C.*
AU  - Raza, W.*
AU  - Gómez Real, F.*
AU  - Russell, M.*
AU  - Sánchez-Ramos, J.L.*
AU  - Weyler, J.*
AU  - Garcia Aymerich, J.*
C1  - 53375
C2  - 44550
CY  - London
SP  - 376-384
TI  - Leisure-time vigorous physical activity is associated with better lung function: The prospective ECRHS study.
JO  - Thorax
VL  - 73
IS  - 4
PB  - Bmj Publishing Group
PY  - 2018
SN  - 0040-6376
ER  - 

TY  - JOUR
AU  - Fuertes, E.*
AU  - Carsin, A.E.*
AU  - Garcia-Larsen, V.*
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  - 56406
C2  - 47056
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
SP  - A229-A230
TI  - Is the association of physical activity with fev1 and fvc partially mediated by c-reactive protein levels?: The ecrhs study.
JO  - Thorax
VL  - 73
PB  - Bmj Publishing Group
PY  - 2018
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - It is undeniably one of the greatest findings in biology that (with some very minor exceptions) every cell in the body possesses the whole genetic information needed to generate a complete individual. Today, this concept has been so thoroughly assimilated that we struggle to still see how surprising this finding actually was: all cellular phenotypes naturally occurring in one person are generated from genetic uniformity, and thus are per definition epigenetic. Transcriptional mechanisms are clearly critical for developing and protecting cell identities, because a mis-expression of few or even single genes can efficiently induce inappropriate cellular programmes. However, how transcriptional activities are molecularly controlled and which of the many known epigenomic features have causal roles remains unclear. Today, clarification of this issue is more pressing than ever because profiling efforts and epigenome-wide association studies (EWAS) continuously provide comprehensive datasets depicting epigenomic differences between tissues and disease states. In this commentary, we propagate the idea of a widespread follow-up use of epigenome editing technology in EWAS studies. This would enable them to address the questions of which features, where in the genome, and which circumstances are essential to shape development and trigger disease states.
AU  - Griese, M.*
AU  - Seidl, E.*
AU  - Hengst, M.*
AU  - Reu, S.*
AU  - Rock, H.*
AU  - Anthony, G.*
AU  - Kiper, N.*
AU  - Emiralioğlu, N.*
AU  - Snijders, D.*
AU  - Goldbeck, L.*
AU  - Leidl, R.
AU  - Ley-Zaporozhan, J.*
AU  - Krüger-Stollfuss, I.*
AU  - Kammer, B.*
AU  - Wesselak, T.*
AU  - Eismann, C.*
AU  - Schams, A.*
AU  - Neuner, D.*
AU  - MacLean, M.*
AU  - Nicholson, A.G.*
AU  - Lauren, M.*
AU  - Clement, A.B.*
AU  - Epaud, R.*
AU  - de Blic, J.*
AU  - Ashworth, M.*
AU  - Aurora, P.*
AU  - Calder, A.A.*
AU  - Wetzke, M.*
AU  - Kappler, M.*
AU  - Cunningham, S.*
AU  - Schwerk, N.*
AU  - Bush, A.*
C1  - 52182
C2  - 43799
CY  - 6-9 Carlton House Terrace, London Sw1y 5ag, England
SP  - 231-239
TI  - International management platform for children's interstitial lung disease (chILD-EU).
JO  - Thorax
VL  - 73
IS  - 3
PB  - Royal Soc
PY  - 2018
SN  - 0040-6376
ER  - 

TY  - JOUR
AU  - Portas, L.*
AU  - Calciano, L.*
AU  - Corsico, A.G.*
AU  - Cazzoletti, L.*
AU  - Cerveri, I.*
AU  - Gerbase, M.W.*
AU  - Gislason, D.*
AU  - Gronseth, R.*
AU  - Heinrich, J.*
AU  - Jõgi, R.*
AU  - Johannessen, A.*
AU  - Marcon, A.*
AU  - Pin, I.*
AU  - Wacker, M.
AU  - Jarvis, D.*
AU  - Janson, C.*
AU  - Accordini, S.*
C1  - 56405
C2  - 47057
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
SP  - A249-A250
TI  - Cost variations of asthma over 10 years in adults.
JO  - Thorax
VL  - 73
PB  - Bmj Publishing Group
PY  - 2018
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD. While many studies have focused on the canonical WNT/β-catenin signalling pathway, recent reports highlight that non-canonical WNT signalling may also significantly contribute to chronic lung pathologies; these studies will be particularly featured in this review. We further discuss recent advances uncovering the role of WNT signalling early in life, the potential of pharmaceutically modulating WNT signalling pathways and highlight (pre)clinical studies describing promising new therapies for chronic lung diseases.
AU  - Baarsma, H.A.
AU  - Königshoff, M.
C1  - 50950
C2  - 42810
CY  - London
SP  - 746-759
TI  - 'WNT-er is coming': WNT signalling in chronic lung diseases.
JO  - Thorax
VL  - 72
IS  - 8
PB  - Bmj Publishing Group
PY  - 2017
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - RATIONALE: Evidence has suggested that exposure to environmental or microbial biodiversity in early life may impact subsequent lung function and allergic disease risk. OBJECTIVES: To investigate the influence of childhood living environment and biodiversity indicators on atopy, asthma and lung function in adulthood. METHODS AND MEASUREMENTS: The European Community Respiratory Health Survey II investigated ∼10 201 participants aged 26-54 years from 14 countries, including participants' place of upbringing (farm, rural environment or inner city) before age 5 years. A 'biodiversity score' was created based on childhood exposure to cats, dogs, day care, bedroom sharing and older siblings. Associations with lung function, bronchial hyper-responsiveness (BHR), allergic sensitisation, asthma and rhinitis were analysed. MAIN RESULTS: As compared with a city upbringing, those with early-life farm exposure had less atopic sensitisation (adjusted OR 0.46, 95% CI 0.37 to 0.58), atopic BHR (0.54 (0.35 to 0.83)), atopic asthma (0.47 (0.28 to 0.81)) and atopic rhinitis (0.43 (0.32 to 0.57)), but not non-atopic outcomes. Less pronounced protective effects were observed for rural environment exposures. Women with a farm upbringing had higher FEV1 (adjusted difference 110 mL (64 to 157)), independent of sensitisation and asthma. In an inner city environment, a higher biodiversity score was related to less allergic sensitisation. CONCLUSIONS: This is the first study to report beneficial effects of growing up on a farm on adult FEV1. Our study confirmed the beneficial effects of early farm life on sensitisation, asthma and rhinitis, and found a similar association for BHR. In persons with an urban upbringing, a higher biodiversity score predicted less allergic sensitisation, but to a lesser magnitude than a childhood farm environment.
AU  - Campbell, B.*
AU  - Raherison, C.*
AU  - Lodge, C.J.*
AU  - Lowe, A.J.*
AU  - Gislason, T.*
AU  - Heinrich, J.
AU  - Sunyer, J.*
AU  - Gómez Real, F.*
AU  - Norbäck, D.*
AU  - Matheson, M.C.*
AU  - Wjst, M.
AU  - Dratva, J.*
AU  - de Marco, R.*
AU  - Jarvis, D.*
AU  - Schlünssen, V.*
AU  - Janson, C.*
AU  - Leynaert, B.*
AU  - Svanes, C.*
AU  - Dharmage, S.C.*
C1  - 49568
C2  - 40809
CY  - London
SP  - 1-9
TI  - The effects of growing up on a farm on adult lung function and allergic phenotypes: An international population-based study.
JO  - Thorax
VL  - 72
IS  - 3
PB  - Bmj Publishing Group
PY  - 2017
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - BACKGROUND: Measurement of FENO might substitute bronchial provocation for diagnosing asthma. We aimed to investigate the diagnostic accuracy of FENO measurement compared with established reference standard. METHODS: Systematic review and diagnostic meta-analysis. Data sources were Medline, Embase and Scopus up to 29 November 2015. Sensitivity and specificity were estimated using a bivariate model. Additionally, summary receiver-operating characteristic curves were estimated. RESULTS: 26 studies with 4518 participants (median 113) were included. Risk of bias was considered low for six of seven items in five studies and for five items in seven studies. The overall sensitivity in the meta-analysis was 0.65 (95% CI 0.58 to 0.72), the overall specificity 0.82 (0.76 to 0.86), the diagnostic OR 9.23 (6.55 to 13.01) and the area under the curve 0.80 (0.77 to 0.85). In meta-regression analyses, higher cut-off values were associated with increasing specificity (OR 1.46 per 10 ppb increase in cut-off) while there was no association with sensitivity. Sensitivities varied significantly within the different FENO devices, but not specificities. Neither prevalence, age, use of bronchoprovocation in >90% of participants or as exclusive reference standard test, nor risk of bias were significantly associated with diagnostic accuracy. CONCLUSIONS: There appears to be a fair accuracy of FENO for making the diagnosis of asthma. The overall specificity was higher than sensitivity, which indicates a higher diagnostic potential for ruling in than for ruling out the diagnosis of asthma.
AU  - Karrasch, S.
AU  - Linde, K.*
AU  - Rücker, G.*
AU  - Sommer, H.*
AU  - Karsch-Völk, M.*
AU  - Kleijnen, J.*
AU  - Jörres, R.A.*
AU  - Schneider, A.*
C1  - 49045
C2  - 41608
CY  - London
SP  - 109-116
TI  - Accuracy of FENO for diagnosing asthma: A systematic review.
JO  - Thorax
VL  - 72
IS  - 2
PB  - Bmj Publishing Group
PY  - 2017
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - BACKGROUND: Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2(+)CD4(+) T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2(+) cell populations might either increase or decrease disease pathogenesis depending on their subtype. OBJECTIVE: To investigate the role of CCR2(+)CD4(+) T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis. METHODS: Pulmonary CCR2(+)CD4(+) T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments. RESULTS: Frequencies of CCR2(+)CD4(+) T cells were increased in experimental fibrosis-specifically the CD62L(-)CD44(+) effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2(+)CD4(+) T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2(+)CD4(+) T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3(+) CD25(+) cells within bronchoalveolar lavage fluid CCR2(+)CD4(+) T cells as compared with CCR2(-)CD4(+) T cells. CONCLUSION: Pulmonary CCR2(+)CD4(+) T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease.
AU  - Milger, K.
AU  - Yu, Y.
AU  - Brudy, E.
AU  - Irmler, M.
AU  - Skapenko, A.*
AU  - Mayinger, M.
AU  - Lehmann, M.
AU  - Beckers, J.
AU  - Reichenberger, F.*
AU  - Behr, J.*
AU  - Eickelberg, O.
AU  - Königshoff, M.
AU  - Krauss-Etschmann, S.
C1  - 51685
C2  - 43418
CY  - London
SP  - 1007-1020
TI  - Pulmonary CCR2+CD4+  T cells are immune regulatory and attenuate lung fibrosis development.
JO  - Thorax
VL  - 72
IS  - 11
PB  - Bmj Publishing Group
PY  - 2017
SN  - 0040-6376
ER  - 

TY  - JOUR
AU  - Kanellakis, N.I.*
AU  - Giannou, A.D.*
AU  - Pepe, M.
AU  - Agalioti, T.*
AU  - Zazara, D.E.*
AU  - Vreka, M.
AU  - Lilis, I.*
AU  - Giopanou, I.*
AU  - Spella, M.*
AU  - Marazioti, A.*
AU  - Rahman, N.*
AU  - Pavord, I.D.*
AU  - Psallidas, I.*
AU  - Stathopoulos, G.T.
C1  - 50665
C2  - 42442
CY  - London
SP  - A7-A7
TI  - Mouse lung adenocarcinoma cell lines reveal PRL2C2 as a novel lung tumour promoter.
JO  - Thorax
VL  - 71
PB  - Bmj Publishing Group
PY  - 2016
SN  - 0040-6376
ER  - 

TY  - JOUR
AU  - Psallidas, I.*
AU  - Kanellakis, N.I.*
AU  - Vreka, M.
AU  - Giannou, A.D.*
AU  - Maniatis, L.*
AU  - Moschos, C.*
AU  - Giopanou, I.*
AU  - Agalioti, T.*
AU  - Lilis, I.*
AU  - Magkouta, S.*
AU  - Kalomenidis, I.*
AU  - Rahman, N.M.*
AU  - Pavord, I.D.*
AU  - Stathopoulos, G.T.
C1  - 50666
C2  - 42441
CY  - London
SP  - A7-A7
TI  - Osteopontin as an airway epithelial tumour promoter.
JO  - Thorax
VL  - 71
PB  - Bmj Publishing Group
PY  - 2016
SN  - 0040-6376
ER  - 

TY  - JOUR
AU  - Staab-Weijnitz, C.A.
AU  - Eickelberg, O.
C1  - 48831
C2  - 41450
CY  - London
SP  - 675-676
TI  - Repositioning compounds from cancer drug discovery to IPF: PI3K inhibition.
JO  - Thorax
VL  - 71
IS  - 8
PB  - Bmj Publishing Group
PY  - 2016
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.
AU  - Bousquet, J.*
AU  - Antò, J.M.*
AU  - Berkouk, K.*
AU  - Gergen, P.J.*
AU  - Pinto Antunes, J.*
AU  - Augé, P.*
AU  - Camuzat, T.*
AU  - Bringer, J.*
AU  - Mercier, J.*
AU  - Best, N.*
AU  - Bourret, R.*
AU  - Akdis, M.*
AU  - Arshad, S.H.*
AU  - Bedbrook, A.*
AU  - Berr, C.*
AU  - Bush, A.*
AU  - Cavalli, G.*
AU  - Charles, M.A.*
AU  - Clavel-Chapelon, F.*
AU  - Gillman, M.*
AU  - Gold, D.R.*
AU  - Goldberg, M.*
AU  - Holloway, J.W.*
AU  - Iozzo, P.*
AU  - Jacquemin, S.*
AU  - Jeandel, C.*
AU  - Kauffmann, F.*
AU  - Keil, T.*
AU  - Koppelman, G.H.*
AU  - Krauss-Etschmann, S.
AU  - Kuh, D.*
AU  - Lehmann, S.*
AU  - Lodrup Carlsen, K.C.*
AU  - Maier, D.*
AU  - Méchali, M.*
AU  - Melén, E.*
AU  - Moatti, J.P.*
AU  - Momas, I.*
AU  - Nérin, P.*
AU  - Postma, D.S.*
AU  - Ritchie, K.*
AU  - Robine, J.M.*
AU  - Samolinski, B.*
AU  - Siroux, V.*
AU  - Slagboom, P.E.*
AU  - Smit, H.A.*
AU  - Sunyer, J.*
AU  - Valenta, R.*
AU  - van de Perre, P.*
AU  - Verdier, J.M.*
AU  - Vrijheid, M.*
AU  - Wickman, M.*
AU  - Yiallouros, P.K.*
AU  - Zins, M.*
C1  - 43427
C2  - 36368
CY  - London
SP  - 595-597
TI  - Developmental determinants in non-communicable chronic diseases and ageing.
JO  - Thorax
VL  - 70
IS  - 6
PB  - Bmj Publishing Group
PY  - 2015
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - BACKGROUND: Recently, several proteins of the extracellular matrix have been characterised as active contributors to allergic airway disease. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein abundant in the lung, whose biological functions remain poorly understood. In the current study we investigated the role of MFAP4 in experimental allergic asthma. METHODS: MFAP4-deficient mice were subjected to alum/ovalbumin and house dust mite induced models of allergic airway disease. In addition, human healthy and asthmatic primary bronchial smooth muscle cell cultures were used to evaluate MFAP4-dependent airway smooth muscle responses. RESULTS: MFAP4 deficiency attenuated classical hallmarks of asthma, such as eosinophilic inflammation, eotaxin production, airway remodelling and hyperresponsiveness. In wild-type mice, serum MFAP4 was increased after disease development and correlated with local eotaxin levels. MFAP4 was expressed in human bronchial smooth muscle cells and its expression was upregulated in asthmatic cells. Regarding the underlying mechanism, we showed that MFAP4 interacted with integrin αvβ5 and promoted asthmatic bronchial smooth muscle cell proliferation and CCL11 release dependent on phosphatidyloinositol-3-kinase but not extracellular signal-regulated kinase pathway. CONCLUSIONS: MFAP4 promoted the development of asthmatic airway disease in vivo and pro-asthmatic functions of bronchial smooth muscle cells in vitro. Collectively, our results identify MFAP4 as a novel contributor to experimental asthma, acting through modulation of airway smooth muscle cells.
AU  - Pilecki, B.*
AU  - Schlosser, A.*
AU  - Wulf-Johansson, H.*
AU  - Trian, T.*
AU  - Moeller, J.B.*
AU  - Marcussen, N.*
AU  - Aguilar-Pimentel, J.A.
AU  - Hrabě de Angelis, M.
AU  - Vestbo, J.*
AU  - Berger, P.*
AU  - Holmskov, U.*
AU  - Sorensen, G.L.*
C1  - 45107
C2  - 37223
CY  - London
SP  - 862-872
TI  - Microfibrillar-associated protein 4 modulates airway smooth muscle cell phenotype in experimental asthma.
JO  - Thorax
VL  - 70
IS  - 9
PB  - Bmj Publishing Group
PY  - 2015
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - BACKGROUND: Increased bronchial responsiveness is characteristic of asthma. Gas cooking, which is a major indoor source of the highly oxidant nitrogen dioxide, has been associated with respiratory symptoms and reduced lung function. However, little is known about the effect of gas cooking on bronchial responsiveness and on how this relationship may be modified by variants in the genes GSTM1, GSTT1 and GSTP1, which influence antioxidant defences. METHODS: The study was performed in subjects with forced expiratory volume in one second at least 70% of predicted who took part in the multicentre European Community Respiratory Health Survey, had bronchial responsiveness assessed by methacholine challenge and had been genotyped for GSTM1, GSTT1 and GSTP1-rs1695. Information on the use of gas for cooking was obtained from interviewer-led questionnaires. Effect modification by genotype on the association between the use of gas for cooking and bronchial responsiveness was assessed within each participating country, and estimates combined using meta-analysis. RESULTS: Overall, gas cooking, as compared with cooking with electricity, was not associated with bronchial responsiveness (β=-0.08, 95% CI -0.40 to 0.25, p=0.648). However, GSTM1 significantly modified this effect (β for interaction=-0.75, 95% CI -1.16 to -0.33, p=4×10(-4)), with GSTM1 null subjects showing more responsiveness if they cooked with gas. No effect modification by GSTT1 or GSTP1-rs1695 genotypes was observed. CONCLUSIONS: Increased bronchial responsiveness was associated with gas cooking among subjects with the GSTM1 null genotype. This may reflect the oxidant effects on the bronchi of exposure to nitrogen dioxide.
AU  - Amaral, A.F.*
AU  - Ramasamy, A.*
AU  - Castro-Giner, F.*
AU  - Minelli, C.*
AU  - Accordini, S.*
AU  - Sørheim, I.C.*
AU  - Pin, I.*
AU  - Kogevinas, M.*
AU  - Jõgi, R.*
AU  - Balding, D.J.*
AU  - Norbäck, D.*
AU  - Verlato, G.*
AU  - Olivieri, M.*
AU  - Probst-Hensch, N.*
AU  - Janson, C.*
AU  - Zock, J.P.*
AU  - Heinrich, J.
AU  - Jarvis, D.L.*
C1  - 30838
C2  - 33942
CY  - London
SP  - 558-564
TI  - Interaction between gas cooking and GSTM1 null genotype in bronchial responsiveness: Results from the European Community Respiratory Health Survey.
JO  - Thorax
VL  - 69
IS  - 6
PB  - Bmj Publishing Group
PY  - 2014
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Epithelial-mesenchymal transition (EMT) is a process when epithelial cells gradually transform into mesenchymal-like cells losing their epithelial functionality and characteristics. EMT is thought to be involved in the pathogenesis of numerous lung diseases ranging from developmental disorders, fibrotic tissue remodelling to lung cancer. The most important question-namely what is the importance and contribution of EMT in the pathogenesis of several chronic lung conditions (asthma, COPD, bronchiolitis obliterans syndrome and lung fibrosis)-is currently intensely debated. This review gives a brief insight into the mechanism and assessment methods of EMT in various pulmonary diseases and summarises the recent literature highlighting the controversial experimental data and conclusions.
AU  - Bartis, D.*
AU  - Mise, N.
AU  - Mahida, R.Y.*
AU  - Eickelberg, O.
AU  - Thickett, D.R.*
C1  - 29302
C2  - 33644
CY  - London
SP  - 760-765
TI  - Epithelial-mesenchymal transition in lung development and disease: Does it exist and is it important?
JO  - Thorax
VL  - 69
IS  - 8
PB  - Bmj Publishing Group
PY  - 2014
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average particulate matter (PM10, PM2.5, PMabsorbance, PMcoarse), NO2, nitrogen oxides (NOx) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. RESULTS: 15 279 and 10 537 participants respectively were included in the main NO2 and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO2 and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PMcoarse OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM10 with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM2.5abs (black carbon) exposures. CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations.
AU  - Cai, Y.*
AU  - Schikowski, T.*
AU  - Adam, M.*
AU  - Buschka, A.*
AU  - Carsin, A.E.*
AU  - Jacquemin, B.*
AU  - Marcon, A.*
AU  - Sanchez, M.*
AU  - Vierkötter, A.*
AU  - Al-Kanaani, Z.*
AU  - Beelen, R.*
AU  - Birk, M.
AU  - Brunekreef, B.*
AU  - Cirach, M.*
AU  - Clavel-Chapelon, F.*
AU  - Declercq, C.*
AU  - de Hoogh, K.*
AU  - de Nazelle, A.*
AU  - Ducret-Stich, R.E.*
AU  - Ferretti, V.*
AU  - Forsberg, B.*
AU  - Gerbase, M.W.*
AU  - Hardy, R.*
AU  - Heinrich, J.
AU  - Hoek, G.*
AU  - Jarvis, D.*
AU  - Keidel, D.*
AU  - Kuh, D.*
AU  - Nieuwenhuijsen, M.J.*
AU  - Ragettli, M.S.*
AU  - Ranzi, A.*
AU  - Rochat, T.*
AU  - Schindler, C.*
AU  - Sugiri, D.*
AU  - Temam, S.*
AU  - Tsai, M.Y.*
AU  - Varraso, R.*
AU  - Kauffmann, F.*
AU  - Krämer, U.*
AU  - Sunyer, J.*
AU  - Künzli, N.*
AU  - Probst-Hensch, N.*
AU  - Hansell, A.L.*
C1  - 32619
C2  - 35167
CY  - London
SP  - 1005-1014
TI  - Cross-sectional associations between air pollution and chronic bronchitis: An ESCAPE meta-analysis across five cohorts.
JO  - Thorax
VL  - 69
IS  - 11
PB  - Bmj Publishing Group
PY  - 2014
SN  - 0040-6376
ER  - 

TY  - JOUR
AU  - Gesierich, W.
AU  - Samitas, K.
AU  - Behr, J.
C1  - 31613
C2  - 34805
CY  - London
SP  - 289-290
TI  - Determining collateral ventilation during bronchoscopy: Unanswered questions.
JO  - Thorax
VL  - 69
IS  - 3
PB  - Bmj Publishing Group
PY  - 2014
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Rationale Rationale Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce. This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD. Methods Methods Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63 +/- 6 years, 68% male) were matched with 65 smoking controls (62 +/- 7 years, 75% male). PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry. Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics. Results Results PA was significantly lower in COPD versus smoking controls (7986 +/- 2648 vs 9765 +/- 3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49 +/- 0.21 vs 1.62 +/- 0.24 PAL respectively, all p < 0.05). Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (T-L,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA. Multiple regression analysis identified 6 MWD and T-L,co as independent predictors of PA in COPD. Conclusions Conclusions The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD. Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity.
AU  - Bousquet, J.*
AU  - Antò, J.M.*
AU  - Heinrich, J.
AU  - Keil, T.*
AU  - Postma, D.S.*
AU  - Sunyer, J.*
C1  - 26082
C2  - 32060
SP  - 964
TI  - Correspondence on the paper by Krauss-Etschmann S, Bush A, Bellusci S, et al.
JO  - Thorax
VL  - 68
IS  - 10
PB  - BMJ Publishing
PY  - 2013
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of prenatal and/or early postnatal lung development will have important implications for future lung function and risk of CLD throughout life. This view represents a fundamental change of current pathophysiological concepts and treatment paradigms, and holds the potential to develop novel preventative and/or therapeutic strategies. However, for the successful development of such approaches, key questions, such as a clear understanding of underlying mechanisms of impaired lung development, the identification and validation of relevant preclinical models to facilitate translational research, and the development of concepts for correction of aberrant development, all need to be solved. Accordingly, a European Science Foundation Exploratory Workshop was held where clinical, translational and basic research scientists from different disciplines met to discuss potential mechanisms of developmental origins of CLD, and to identify major knowledge gaps in order to delineate a roadmap for future integrative research.
AU  - Krauss-Etschmann, S.
AU  - Bush, A.*
AU  - Bellusci, S.*
AU  - Brusselle, G.G.*
AU  - Erik K Dahlén, S.*
AU  - Dehmel, S.
AU  - Eickelberg, O.
AU  - Gibson, G.*
AU  - Hylkema, M.N.*
AU  - Knaus, P.*
AU  - Königshoff, M.
AU  - Lloyd, C.M.*
AU  - Macciarini, P.*
AU  - Mailleux, A.*
AU  - Marsland, B.J.*
AU  - Postma, D.S.*
AU  - Roberts, G.*
AU  - Samakovlis, C.*
AU  - Stocks, J.*
AU  - Vandesompele, J.*
AU  - Wjst, M.
AU  - Holloway, J.*
C1  - 8213
C2  - 30043
SP  - 380-384
TI  - Of flies, mice and men: A systematic approach to understanding the early life origins of chronic lung disease.
JO  - Thorax
VL  - 68
IS  - 4
PB  - BMJ Publishing Group
PY  - 2013
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of unknown aetiology. It has a very poor prognosis and no effective treatment. There are two major barriers to the development of novel treatments in IPF: an incomplete understanding of its pathogenesis and the fact that current models of the disease are poorly predictive of therapeutic response. Recent studies suggest an important role for the alveolar epithelium in the pathogenesis of IPF. However, practical limitations associated with isolation and culture of primary alveolar epithelial cells have hampered progress towards further elucidating their role in the pathogenesis of the disease or developing disease models that accurately reflect the epithelial contribution. The practical limitations of primary alveolar epithelial cell culture can be divided into technical, logistical and regulatory hurdles that need to be overcome to ensure rapid progress towards improved treatment for patients with IPF. To develop a strategy to facilitate alveolar epithelial cell harvest, retrieval and sharing between IPF research groups and to determine how these cells contribute to IPF, a workshop was organised to discuss the central issues surrounding epithelial cells in IPF (ECIPF). The central themes discussed in the workshop have been compiled as the proceedings of the ECIPF.
AU  - Jenkins, G.*
AU  - Blanchard, A.*
AU  - Borok, Z.*
AU  - Bradding, P.*
AU  - Ehrhardt, C.*
AU  - Fisher, A.*
AU  - Hirani, N.*
AU  - Johnson, S.*
AU  - Königshoff, M.
AU  - Maher, T.M.*
AU  - Millar, A.*
AU  - Parfrey, H.*
AU  - Scotton, C.*
AU  - Tetley, T.*
AU  - Thickett, D.*
AU  - Wolters, P. *
C1  - 5789
C2  - 29029
SP  - 179-182
TI  - In search of the fibrotic epithelial cell: Opportunities for a collaborative network.
JO  - Thorax
VL  - 67
IS  - 2
PB  - BMJ Publishing Group
PY  - 2012
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Although women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population. METHODS: Gender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8-10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens. RESULTS: Asthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma. CONCLUSIONS: This study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.
AU  - Leynaert, B.*
AU  - Sunyer, J.*
AU  - García-Esteban, R.*
AU  - Svanes, C.*
AU  - Jarvis, D.*
AU  - Cerveri, I.*
AU  - Dratva, J.*
AU  - Gislason, T.*
AU  - Heinrich, J.
AU  - Janson, C.*
AU  - Kuenzli, N.*
AU  - de Marco, R.*
AU  - Omenaas, E.*
AU  - Raherison, C.*
AU  - Real, F.G.*
AU  - Wjst, M.
AU  - Zemp, E.*
AU  - Zureik, M.*
AU  - Burney, P.G.J.*
AU  - Antò, J.M.*
AU  - Neukirch, F.*
C1  - 7671
C2  - 29794
SP  - 625-631
TI  - Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma: A population-based cohort.
JO  - Thorax
VL  - 67
IS  - 7
PB  - BMJ Publishing Group
PY  - 2012
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Background Organic dust is a complex mixture of particulate matter from microbial, plant or animal origin. Occupations with exposure to animal products have been associated with an increased lung cancer risk, while exposure to microbial components (eg, endotoxin) has been associated with a decreased risk. To date there has not been a comprehensive evaluation of the possible association between occupational organic dust exposure (and its specific constituents) and lung cancer risk in the general population. Methods The SYNERGY project has pooled information on lifetime working and smoking from 13 300 lung cancer cases and 16 273 controls from 11 case-control studies conducted in Europe and Canada. A newly developed general population job-exposure matrix (assigning no, low or high exposure to organic dust, endotoxin, and contact with animals or fresh animal products) was applied to determine level of exposure. ORs for lung cancer were estimated by logistic regression, adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. Results Occupational organic dust exposure was associated with increased lung cancer risk. The second to the fourth quartile of cumulative exposure showed significant risk estimates ranging from 1.12 to 1.24 in a dose-dependent manner (p<0.001). This association remained in the highest quartile after restricting analyses to subjects without chronic obstructive pulmonary disease or asthma. No association was observed between lung cancer and exposure to endotoxin or contact with animals or animal products. Conclusion Occupational exposure to organic dust was associated with increased lung cancer risk in this large pooled case-control study.
AU  - Peters, S.*
AU  - Kromhout, H.*
AU  - Olsson, A.C.*
AU  - Wichmann, H.-E.
AU  - Brüske, I.
AU  - Consonni, D.*
AU  - Landi, M.T.*
AU  - Caporaso, N.*
AU  - Siemiatycki, J.*
AU  - Richiardi, L.*
AU  - Mirabelli, D.*
AU  - Simonato, L.*
AU  - Gustavsson, P.*
AU  - Plato, N.*
AU  - Jöckel, K.-H.*
AU  - Ahrens, W.*
AU  - Pohlabeln, H.*
AU  - Boffetta, P.*
AU  - Brennan, P.*
AU  - Zaridze, D.*
AU  - Cassidy, A.*
AU  - Lissowska, J.*
AU  - Szeszenia-Dabrowska, N.*
AU  - Rudnai, P.*
AU  - Fabianova, E.*
AU  - Forastiere, F.*
AU  - Bencko, V.*
AU  - Foretova, L.*
AU  - Janout, V.*
AU  - Stücker, I.*
AU  - Dumitru, R.S.*
AU  - Benhamou, S.*
AU  - Bueno-de-Mesquita, H.B.*
AU  - Kendzia, B.*
AU  - Pesch, B.*
AU  - Straif, K.*
AU  - Brüning, T*
AU  - Vermeulen, R.*
C1  - 7173
C2  - 29517
SP  - 111-116
TI  - Occupational exposure to organic dust increases lung cancer risk in the general population.
JO  - Thorax
VL  - 67
IS  - 2
PB  - BMJ Publishing Group
PY  - 2012
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - There are few longitudinal studies that have examined the association of lung function decline with indoor mould and dampness. Lung function decline in relation to dampness and mould in the home has studied in adults over a 9 year period. Spirometry was performed twice in participants in the European Respiratory Health Survey (ECRHS I and II) who were initially examined aged 20-45 years, in 1990-1995 and 9 years later (n=6443). Information on their current home was collected twice by interview. Dampness (water damage or damp spots) and indoor mould, ever and in the last 12 months, were assessed. A dampness score and a mould score were calculated. In addition, 3118 homes at 22 centres were inspected directly at follow-up for the presence of dampness and mould. Dampness and mould were common. Overall, 50.1% reported any dampness and 41.3% any indoor mould in either ECRHS I or ECRHS II. Women with dampness at home had an additional decline in forced expiratory volume in 1 s (FEV(1)) of -2.25 ml/year (95% CI -4.25 to -0.25), with a significant trend in increased lung function decline in relation to the dampness score (p=0.03). The association in women was significant when excluding those with asthma at baseline. Observed damp spots in the bedroom was associated with a significant additional decline in FEV(1) of -7.43 ml/year (95% CI -13.11 to 1.74) in women Dampness and indoor mould growth is common in dwellings, and the presence of damp is a risk factor for lung function decline, especially in women.
AU  - Norbäck, D.*
AU  - Zock, J.P.*
AU  - Plana, E.*
AU  - Heinrich, J.
AU  - Svanes, C.*
AU  - Sunyer, J.*
AU  - Künzli, N.*
AU  - Villani, S.*
AU  - Olivieri, M.*
AU  - Soon, A.*
AU  - Jarvis, D.*
C1  - 6322
C2  - 28504
CY  - London, England
SP  - 396-401
TI  - Lung function decline in relation to mould and dampness in the home: The longitudinal European Community Respiratory Health Survey ECRHS II.
JO  - Thorax
VL  - 66
IS  - 5
PB  - B M J Publishing Group
PY  - 2011
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - BACKGROUND: Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). METHODS: 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990-2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. RESULTS: Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p<0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. CONCLUSION: This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.
AU  - Castro-Giner, F.*
AU  - de Cid, R.*
AU  - Gonzalez, J.R.*
AU  - Jarvis, D.*
AU  - Heinrich, J.
AU  - Janson, C.*
AU  - Omenaas, E.R.*
AU  - Matheson, M.C.*
AU  - Pin, I.*
AU  - Antò, J.M.*
AU  - Wjst, M.
AU  - Estivill, X.*
AU  - Kogevinas, M.*
C1  - 2284
C2  - 27271
SP  - 124-131
TI  - Positionally cloned genes and age-specific effects in asthma and atopy: An international population-based cohort study (ECRHS).
JO  - Thorax
VL  - 65
IS  - 2
PB  - BMJ Publishing Group Ltd.
PY  - 2010
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Background Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited responsiveness to available treatments. It is characterised by epithelial cell injury, fibroblast activation and proliferation and extracellular matrix deposition. Serotonin (5-hydroxytryptamine; 5-HT) induces fibroblast proliferation via the 5-HTR2A and 5-HTR2B receptors, but its pathophysiological role in IPF remains unclear. A study was undertaken to determine the expression of 5-HT receptors in IPF and experimental lung fibrosis and to investigate the effects of therapeutic inhibition of 5-HTR2A/B signalling on lung fibrosis in vivo and in vitro. Methods and results Quantitative RT-PCR showed that the expression of 5-HTR1A/B and 5-HTR2B was significantly increased in the lungs of patients with IPF (n = 12) and in those with non-specific interstitial pneumonia (NSIP, n = 6) compared with transplant donors (n = 12). The expression of 5-HTR2A was increased specifically in IPF lungs but not in NSIP lungs. While 5-HTR2A protein largely localised to fibroblasts, 5-HTR2B localised to the epithelium. To assess the effects of 5HTR(2A/B) inhibition on fibrogenesis in vivo, mice were subjected to bleomycin-induced lung fibrosis and treated with the 5-HTR2A/B antagonist terguride (or vehicle) in a therapeutic approach (days 14-28 after bleomycin). Terguride-treated mice had significantly improved lung function and histology and decreased collagen content compared with vehicle-treated mice. Functional in vitro studies showed that terguride is a potent inhibitor of transforming growth factor beta(1)- or WNT3a-induced collagen production. Conclusion The studies revealed an increased expression of 5-HTR2A specifically in IPF. Blockade of 5-HTR2A/B signalling by terguride reversed lung fibrosis and is thus a promising therapeutic approach for IPF.
AU  - Königshoff, M.
AU  - Dumitrascu, R.
AU  - Udalov, S
AU  - Amarie, O.V.
AU  - Reiter, R.
AU  - Grimminger, F.
AU  - Seeger, W.
AU  - Schermuly, R.T.
AU  - Eickelberg, O.
C1  - 643
C2  - 27938
CY  - London
SP  - 949-955
TI  - Increased expression of 5-hydroxytryptamine(2A/B) receptors in idiopathic pulmonary fibrosis: A rationale for therapeutic intervention.
JO  - Thorax
VL  - 65
IS  - 11
PB  - BMJ Publishing Group
PY  - 2010
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - BACKGROUND: Early life development may influence subsequent respiratory morbidity. The impact of factors determined in childhood on adult lung function, decline in lung function and chronic obstructive pulmonary disease (COPD) was investigated. METHODS: European Community Respiratory Health Survey participants aged 20-45 years randomly selected from general populations in 29 centres underwent spirometry in 1991-3 (n = 13 359) and 9 years later (n = 7738). Associations of early life factors with adult forced expiratory volume in 1 s (FEV(1)), FEV(1) decline and COPD (FEV(1)/FVC ratio <70% and FEV(1) <80% predicted) were analysed with generalised estimating equation models and random effects linear models. RESULTS: Maternal asthma, paternal asthma, childhood asthma, maternal smoking and childhood respiratory infections were significantly associated with lower FEV(1) and defined as "childhood disadvantage factors"; 40% had one or more childhood disadvantage factors which were associated with lower FEV(1) (men: adjusted difference 95 ml (95% CI 67 to 124); women: adjusted difference 60 ml (95% CI 40 to 80)). FEV(1) decreased with increasing number of childhood disadvantage factors (> or =3 factors, men: 274 ml (95% CI 154 to 395), women: 208 ml (95% CI 124 to 292)). Childhood disadvantage was associated with a larger FEV(1) decline (1 factor: 2.0 ml (95% CI 0.4 to 3.6) per year; 2 factors: 3.8 ml (95% CI 1.0 to 6.6); > or =3 factors: 2.2 ml (95% CI -4.8 to 9.2)). COPD increased with increasing childhood disadvantage (1 factor, men: OR 1.7 (95% CI 1.1 to 2.6), women: OR 1.6 (95% CI 1.01 to 2.6); > or =3 factors, men: OR 6.3 (95% CI 2.4 to 17), women: OR 7.2 (95% CI 2.8 to 19)). These findings were consistent between centres and when subjects with asthma were excluded. CONCLUSIONS: People with early life disadvantage have permanently lower lung function, no catch-up with age but a slightly larger decline in lung function and a substantially increased COPD risk. The impact of childhood disadvantage was as large as that of heavy smoking. Increased focus on the early life environment may contribute to the prevention of COPD.
AU  - Svanes, C.*
AU  - Sunyer, J.*
AU  - Plana, E.*
AU  - Dharmage, S.*
AU  - Heinrich, J.
AU  - Jarvis, D.*
AU  - de Marco, R.*
AU  - Norbäck, D.*
AU  - Raherison, C.*
AU  - Villani, S.*
AU  - Wjst, M.
AU  - Svanes, K.*
AU  - Antò, J.M.*
C1  - 347
C2  - 27138
SP  - 14-20
TI  - Early life origins of chronic obstructive pulmonary disease.
JO  - Thorax
VL  - 65
IS  - 1
PB  - BMJ Publishing Group
PY  - 2010
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterised by accumulation of activated (myo)fibroblasts and excessive extracellular matrix deposition. The enhanced accumulation of (myo)fibroblasts may be attributed, in part, to the process of transforming growth factor beta1 (TGFbeta1)-induced epithelial-mesenchymal transition (EMT), the phenotypic switching of epithelial to fibroblast-like cells. Although alveolar epithelial type II (ATII) cells have been shown to undergo EMT, the precise mediators and mechanisms remain to be resolved. The objective of this study is to investigate the role of SNAI transcription factors in the process of EMT and in IPF. METHODS: Using quantitative reverse transcription-PCR (RT-PCR), immunofluorescence, immunohistochemistry, western blotting, as well as gain- and loss-of-function studies and functional assays, the role of SNAI1 and SNAI2 in TGFbeta1-induced EMT in ATII cells in vitro was assessed; and the expression of SNAI transcription factors was analysed in experimental and human IPF in vivo. RESULTS: TGFbeta1 treatment increased the expression and nuclear accumulation of SNAI1 and SNAI2, in concert with induction of EMT in ATII cells. SNAI overexpression was sufficient to induce EMT, and small interfering RNA (siRNA)-mediated SNAI depletion attenuated TGFbeta1-induced ATII cell migration and EMT. SNAI expression was elevated in experimental and human IPF and localised to hyperplastic ATII cells in vivo. CONCLUSIONS: The results demonstrate that TGFbeta1-induced EMT in ATII cells is essentially controlled by the expression and nuclear translocation of SNAI transcription factors. Increased SNAI1 and SNAI2 expression in experimental and human IPF in vivo suggests that SNAI-mediated EMT may contribute to the fibroblast pool in idiopathic pulmonary fibrosis.
AU  - Jayachandran, A.*
AU  - Königshoff, M.
AU  - Yu, H.*
AU  - Rupniewska, E.*
AU  - Hecker, M.*
AU  - Klepetko, W.*
AU  - Seeger, W.*
AU  - Eickelberg, O.
C1  - 204
C2  - 26730
CY  - London
SP  - 1053-1061
TI  - SNAI transcription factors mediate epithelial-mesenchymal transition in lung fibrosis.
JO  - Thorax
VL  - 64
IS  - 12
PB  - British Thoracic Society
PY  - 2009
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Early detection of airflow obstruction is particularly important among young adults because they are more likely to benefit from intervention. Using the forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) (FEV(1)/FVC) <70% fixed ratio, airflow obstruction may be underdiagnosed. The lower limit of normal (LLN), which is statistically defined by the lower fifth percentile of a reference population, is physiologically appropriate but it still needs a clinical validation. METHODS: To evaluate the characteristics and longitudinal outcomes of subjects misidentified as normal by the fixed ratio with respect to the LLN, 6249 participants (aged 20-44 years) in the European Community Respiratory Health Survey were examined and divided into three groups (absence of airflow obstruction by the LLN and the fixed ratio; presence of airflow obstruction only by the LLN; presence of airflow obstruction by the two criteria) for 1991-1993. LLN equations were obtained from normal non-smoking participants. A set of clinical and functional outcomes was evaluated in 1999-2002. RESULTS: The misidentified subjects were 318 (5.1%); only 45.6% of the subjects with airflow obstruction by the LLN were also identified by the fixed cut-off. At baseline, FEV(1) (107%, 97%, 85%) progressively decreased and bronchial hyperresponsiveness (slope 7.84, 6.32, 5.57) progressively increased across the three groups. During follow-up, misidentified subjects had a significantly higher risk of developing chronic obstructive pulmonary disease and a significantly higher use of health resources (medicines, emergency department visits/hospital admissions) because of breathing problems than subjects without airflow obstruction (p<0.001). CONCLUSIONS: Our findings show the importance of using statistically derived spirometric criteria to identify airflow obstruction.
AU  - Cerveri, I.*
AU  - Corsico, A.G.*
AU  - Accordini, S.*
AU  - Niniano, R.*
AU  - Ansaldo, E.*
AU  - Antò, J.M.*
AU  - Künzli, N.*
AU  - Janson, C.*
AU  - Sunyer, J.*
AU  - Jarvis, D.*
AU  - Svanes, C.*
AU  - Gislason, T.*
AU  - Heinrich, J.
AU  - Schouten, J.P.*
AU  - Wjst, M.
AU  - Burney, P.*
AU  - de Marco, R.*
C1  - 3334
C2  - 25803
SP  - 1040-1045
TI  - Underestimation of airflow obstruction among young adults using FEV1/FVC <70% as a fixed cut-off: A longitudinal evaluation of clinical and functional outcomes.
JO  - Thorax
VL  - 63
IS  - 12
PB  - BMJ Publishing Group
PY  - 2008
SN  - 0040-6376
ER  - 

TY  - JOUR
AU  - Wjst, M.
C1  - 2073
C2  - 25802
SP  - S. 474
TI  - Margarine: A supplement may be decisive.
JO  - Thorax
VL  - 63
IS  - 5
PB  - BMJ Publishing Group
PY  - 2008
SN  - 0040-6376
ER  - 

TY  - JOUR
AB  - Identification of the risk factors for bronchial hyperresponsiveness (BHR) would increase the understanding of the causes of asthma. The relationship between physical activity and BHR in men and women aged 28.0-56.5 years randomly selected from 24 centres in 11 countries participating in the European Community Respiratory Health Survey II was investigated. METHODS: 5158 subjects answered questionnaires about physical activity and performed BHR tests. Participants were asked about the frequency and duration of usual weekly exercise resulting in breathlessness or sweating. BHR was defined as a decrease in forced expiratory volume in 1 s of at least 20% of its post-saline value for a maximum methacholine dose of 2 mg. RESULTS: Both frequency and duration of physical activity were inversely related to BHR. The prevalence of BHR in subjects exercising or=4 times a week was 14.5%, 11.6% and 10.9%, respectively (p<0.001). The corresponding odds ratios were 1.00, 0.78 (95% CI 0.62 to 0.99) and 0.69 (95% CI 0.50 to 0.94) after controlling for potential confounding factors. The frequency of BHR in subjects exercising <1 h, 1-3 h and >or=4 h a week was 15.9%, 10.9% and 10.7%, respectively (p<0.001). The corresponding adjusted odds ratios were 1.00, 0.70 (95% CI 0.57 to 0.87) and 0.67 (95% CI 0.50 to 0.90). Physical activity was associated with BHR in all studied subgroups. CONCLUSIONS: These results suggest that BHR is strongly and independently associated with decreased physical activity. Further studies are needed to determine the mechanisms underlying this association.
AU  - Shaaban, R.*
AU  - Leynaert, B.*
AU  - Soussan, D.*
AU  - Antò, J.M.*
AU  - Chinn, S.*
AU  - de Marco, R.*
AU  - Garcia-Aymerich, J.*
AU  - Heinrich, J.
AU  - Janson, C.*
AU  - Jarvis, D.*
AU  - Sunyer, J.*
AU  - Svanes, C.*
AU  - Wjst, M.
AU  - Burney, P.G.*
AU  - Neukirch, F.*
AU  - Zureik, M.*
C1  - 4507
C2  - 24601
SP  - 403-410
TI  - Physical activity and bronchial hyperresponsiveness: European Community Respiratory Health Survey II.
JO  - Thorax
VL  - 62
IS  - 5
PB  - BMJ Publ. Group
PY  - 2007
SN  - 0040-6376
ER  - 

TY  - JOUR
AU  - Chinn, S.*
AU  - Jarvis, D.*
AU  - Burney, P.*
AU  - Luczynska, C.*
AU  - Ackermann-Liebrich, U.*
AU  - Antò, J.M.*
AU  - de Marco, R.*
AU  - Gislason, T.*
AU  - Heinrich, J.
AU  - Janson, C.*
AU  - Künzli, N.*
C1  - 869
C2  - 22196
SP  - 646-651
TI  - Increase in diagnosed asthma but not in symptoms in the European community respiratory health survey.
JO  - Thorax
VL  - 59
PY  - 2004
SN  - 0040-6376
ER  -