TY - JOUR AB - Ageing significantly impacts lung function and increases susceptibility to chronic lung diseases. The lung is a complex organ with multiple cell types that undergo cellular age-related perturbations or hallmarks. As knowledge of ageing mechanisms has progressed, we have a better understanding how intracellular adaptations impact cellular crosstalk and integrate to increase the susceptibility to age-related diseases in the lung. Herein, we discuss the prospects of exhaustion of lung progenitor cells, disrupted lung cell plasticity, perturbation in fibroblasts, impaired adaptive immune responses and alterations in lung microenvironment in the promotion of ageing and age-related lung diseases. Additionally, the ageing process trajectory of the lung depends on a combination of biological, genetic, metabolic, biomechanical and sociobehavioural factors that range from protective phenotypes to accelerated ageing phenotypes. We propose the concept of AgEnOmics, which expands the temporal dimension of lung ageing by distinguishing between chronological ageing and accelerated lung ageing phenotypes. Based on this concept, we define biomarkers of biological ageing that will help to define accelerated ageing and early interventions in biological ageing-related lung diseases. AU - Miller, Z.* AU - Twardowski, L.M.* AU - Reader, B.F.* AU - Rojas, M.* AU - Lehmann, M. AU - Mora, A.L.* C1 - 75227 C2 - 57859 CY - 442 Glossop Rd, Sheffield S10 2px, England TI - Mechanisms and markers of lung ageing in health and disease. JO - Eur. Respir. Rev. VL - 34 IS - 177 PB - European Respiratory Soc Journals Ltd PY - 2025 SN - 0905-9180 ER - TY - JOUR AB - Previous studies have explored the relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and the associated mechanisms have not been reviewed from a life-course perspective. Here, we provide a narrative review summarising recent evidence on the associations of metabolic profiles with air pollution exposure and lung function in children and adults. Twenty-six studies identified through a systematic PubMed search were included with 10 studies analysing air pollution-related metabolic profiles and 16 studies analysing lung function-related metabolic profiles. A wide range of metabolites were associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general population and with respiratory diseases such as asthma and COPD. The existing studies show that metabolomics offers the potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, but many studies suffer from small sample sizes, cross-sectional designs, a preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. The ongoing EXposome Powered tools for healthy living in urbAN Settings (EXPANSE) project aims to address some of these shortcomings by combining biospecimens from large European cohorts and harmonised air pollution exposure and exposome data. AU - Gruzieva, O.* AU - Jeong, A.* AU - He, S.* AU - Yu, Z.* AU - de Bont, J.* AU - Pinho, M.G.M.* AU - Eze, I.C.* AU - Kress, S.* AU - Wheelock, C.E.* AU - Peters, A. AU - Vlaanderen, J.* AU - de Hoogh, K.* AU - Scalbert, A.* AU - Chadeau-Hyam, M.* AU - Vermeulen, R.C.H.* AU - Gehring, U.* AU - Probst-Hensch, N.* AU - Melén, E.* C1 - 65924 C2 - 52488 TI - Air pollution, metabolites and respiratory health across the life-course. JO - Eur. Respir. Rev. VL - 31 IS - 165 PY - 2022 SN - 0905-9180 ER - TY - JOUR AB - The cellular origin of lung adenocarcinoma remains a focus of intense research efforts. The marked cellular heterogeneity and plasticity of the lungs, as well as the vast variety of molecular subtypes of lung adenocarcinomas perplex the field and account for the extensive variability of experimental results. While most experts would agree on the cellular origins of other types of thoracic tumours, great controversy exists on the tumour-initiating cells of lung adenocarcinoma, since this histologic subtype of lung cancer arises in the distal pulmonary regions where airways and alveoli converge, occurs in smokers as well as nonsmokers, is likely caused by various environmental agents, and is marked by vast molecular and pathologic heterogeneity. Alveolar type II, club, and their variant cells have all been implicated in lung adenocarcinoma progeny and the lineage hierarchies in the distal lung remain disputed. Here we review the relevant literature in this rapidly expanding field, including results from mouse models and human studies. In addition, we present a case for club cells as cells of origin of lung adenocarcinomas that arise in smokers. AU - Behrend, S.J. AU - Giotopoulou, G.A. AU - Spella, M.* AU - Stathopoulos, G.T. C1 - 63458 C2 - 51354 TI - A role for club cells in smoking-associated lung adenocarcinoma. JO - Eur. Respir. Rev. VL - 30 IS - 162 PY - 2021 SN - 0905-9180 ER - TY - JOUR AB - Healthy ageing of the lung involves structural changes but also numerous cell-intrinsic and cell-extrinsic alterations. Among them are the age-related decline in central cellular quality control mechanisms such as redox and protein homeostasis. In this review, we would like to provide a conceptual framework of how impaired stress responses in the ageing lung, as exemplified by dysfunctional redox and protein homeostasis, may contribute to onset and progression of COPD and idiopathic pulmonary fibrosis (IPF). We propose that age-related imbalanced redox and protein homeostasis acts, amongst others (e.g. cellular senescence), as a "first hit" that challenges the adaptive stress-response pathways of the cell, increases the level of oxidative stress and renders the lung susceptible to subsequent injury and disease. In both COPD and IPF, additional environmental insults such as smoking, air pollution and/or infections then serve as "second hits" which contribute to persistently elevated oxidative stress that overwhelms the already weakened adaptive defence and repair pathways in the elderly towards non-adaptive, irremediable stress thereby promoting development and progression of respiratory diseases. COPD and IPF are thus distinct horns of the same devil, "lung ageing". AU - Korfei, M.* AU - MacKenzie, B.* AU - Meiners, S. C1 - 59651 C2 - 49008 CY - 442 Glossop Rd, Sheffield S10 2px, England TI - The ageing lung under stress. JO - Eur. Respir. Rev. VL - 29 IS - 156 PB - European Respiratory Soc Journals Ltd PY - 2020 SN - 0905-9180 ER - TY - JOUR AB - Most chronic and acute lung diseases have no cure, leaving lung transplantation as the only option. Recent work has improved our understanding of the endogenous regenerative capacity of the lung and has helped identification of different progenitor cell populations, as well as exploration into inducing endogenous regeneration through pharmaceutical or biological therapies. Additionally, alternative approaches that aim at replacing lung progenitor cells and their progeny through cell therapy, or whole lung tissue through bioengineering approaches, have gained increasing attention. Although impressive progress has been made, efforts at regenerating functional lung tissue are still ineffective. Chronic and acute lung diseases are most prevalent in the elderly and alterations in progenitor cells with ageing, along with an increased inflammatory milieu, present major roadblocks for regeneration. Multiple cellular mechanisms, such as cellular senescence and mitochondrial dysfunction, are aberrantly regulated in the aged and diseased lung, which impairs regeneration. Existing as well as new human in vitro models are being developed, improved and adapted in order to study potential mechanisms of lung regeneration in different contexts. This review summarises recent advances in understanding endogenous as well as exogenous regeneration and the development of in vitro models for studying regenerative mechanisms. AU - Melo-Narváez, C. AU - Stegmayr, J.* AU - Wagner, D.E.* AU - Lehmann, M. C1 - 60376 C2 - 49387 CY - 442 Glossop Rd, Sheffield S10 2px, England TI - Lung regeneration: Implications of the diseased niche and ageing. JO - Eur. Respir. Rev. VL - 29 IS - 157 PB - European Respiratory Soc Journals Ltd PY - 2020 SN - 0905-9180 ER - TY - JOUR AB - Aim: There is growing interest in the health effects following exposure to ambient particles with a diameter <100 nm defined as ultrafine particles (UFPs), although studies so far have reported inconsistent results. We have undertaken a systematic review and meta-analysis for respiratory hospital admissions and emergency room visits following short-term exposure to UFPs. Methods: We searched PubMed and the Web of Science for studies published up to March 2019 to update previous reviews. We applied fixed-and random-effects models, assessed heterogeneity between cities and explored possible effect modifiers. Results: We identified nine publications, reporting effects from 15 cities, 11 of which were European. There was great variability in exposure assessment, outcome measures and the exposure lags considered. Our meta-analyses did not support UFP effects on respiratory morbidity across all ages. We found consistent statistically significant associations following lag 2 exposure during the warm period and in cities with mean daily UFP concentrations <6000 particles·cm‒3, which was approximately the median of the city-specific mean levels. Among children aged 0–14 years, a 10000 particle·cm‒3 increase in UFPs 2 or 3 days before was associated with a relative risk of 1.01 (95% CI 1.00–1.02) in respiratory hospital admissions. Conclusions: Our study indicates UFP effects on respiratory health among children, and during the warm season across all ages at longer lags. The limited evidence and the large heterogeneity of previous reports call for future exposure assessment harmonisation and expanded research. AU - Samoli, E.* AU - Rodopoulou, S.* AU - Schneider, A.E. AU - Morawska, L.* AU - Stafoggia, M.* AU - Renzi, M.* AU - Breitner-Busch, S. AU - Lanki, T.* AU - Pickford, R. AU - Schikowski, T.* AU - Enembe, O.* AU - Zhang, S. AU - Zhao, Q.* AU - Peters, A. C1 - 60423 C2 - 49344 TI - Meta-analysis on short-term exposure to ambient ultrafine particles and respiratory morbidity. JO - Eur. Respir. Rev. VL - 29 IS - 158 PY - 2020 SN - 0905-9180 ER - TY - CONF AU - Meiners, S. AU - Lloyd, C.* AU - Chambers, R.C.* C1 - 53731 C2 - 44987 TI - Cell–matrix interactions in lung disease and regeneration: ERS lung science conference 2018 report. JO - Eur. Respir. Rev. VL - 27 IS - 148 PY - 2018 SN - 0905-9180 ER - TY - JOUR AB - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, with increasing prevalence, in particular in the elderly. COPD is characterised by abnormal tissue repair resulting in (small) airways disease and emphysema. There is accumulating evidence that ageing hallmarks are prominent features of COPD. These ageing hallmarks have been described in different subsets of COPD patients, in different lung compartments and also in a variety of cell types, and thus might contribute to different COPD phenotypes. A better understanding of the main differences and similarities between normal lung ageing and the pathology of COPD may improve our understanding of the mechanisms driving COPD pathology, in particular in those patients that develop the most severe form of COPD at a relatively young age, i.e. severe early-onset COPD patients.In this review, after introducing the main concepts of lung ageing and COPD pathology, we focus on the role of (abnormal) ageing in lung remodelling and repair in COPD. We discuss the current evidence for the involvement of ageing hallmarks in these pathological features of COPD. We also highlight potential novel treatment strategies and opportunities for future research based on our current knowledge of abnormal lung ageing in COPD. AU - Brandsma, C.A.* AU - de Vries, M.* AU - Costa, R. AU - Woldhuis, R.R.* AU - Königshoff, M. AU - Timens, W.* C1 - 52506 C2 - 44026 TI - Lung ageing and COPD: Is there a role for ageing in abnormal tissue repair? JO - Eur. Respir. Rev. VL - 26 IS - 146 PY - 2017 SN - 0905-9180 ER - TY - JOUR AB - Fibrotic lung diseases involve subject-environment interactions, together with dysregulated homeostatic processes, impaired DNA repair and distorted immune functions. Systems medicine-based approaches are used to analyse diseases in a holistic manner, by integrating systems biology platforms along with clinical parameters, for the purpose of understanding disease origin, progression, exacerbation and remission.Interstitial lung diseases (ILDs) refer to a heterogeneous group of complex fibrotic diseases. The increase of systems medicine-based approaches in the understanding of ILDs provides exceptional advantages by improving diagnostics, unravelling phenotypical differences, and stratifying patient populations by predictable outcomes and personalised treatments. This review discusses the state-of-the-art contributions of systems medicine-based approaches in ILDs over the past 5 years. AU - Greiffo, F.R. AU - Eickelberg, O. AU - Fernandez, I.E. C1 - 52012 C2 - 43648 TI - Systems medicine advances in interstitial lung disease. JO - Eur. Respir. Rev. VL - 26 IS - 145 PY - 2017 SN - 0905-9180 ER - TY - JOUR AB - Chronic lung diseases present tremendous health burdens and share a common pathobiology of dysfunctional epithelial repair. Lung adenocarcinoma, the leading cancer killer worldwide, is caused mainly by chemical carcinogens of tobacco smoke that induce mutations in pulmonary epithelial cells leading to uncontrolled epithelial proliferation. Lung epithelial cells that possess the capacity for self-renewal and regeneration of other lung cell types are believed to underlie the pathobiology of chronic obstructive, fibrotic and neoplastic lung disorders. However, the understanding of lung epithelial progenitor cell hierarchy and turnover is incomplete and a comprehensive model of the cellular and transcriptional events that underlie lung regeneration and carcinogenesis is missing. The mapping of these processes is extremely important, since their modulation would potentially allow effective cure and/or prevention of chronic lung diseases. In this review we describe current knowledge on cellular and molecular pathways at play during lung repair and carcinogenesis and summarise the critical lung cell populations with regenerative and cancerous potential. AU - Spella, M.* AU - Lilis, I.* AU - Stathopoulos, G.T. C1 - 51545 C2 - 43302 TI - Shared epithelial pathways to lung repair and disease. JO - Eur. Respir. Rev. VL - 26 IS - 144 PY - 2017 SN - 0905-9180 ER - TY - JOUR AB - Malignant pleural effusion (MPE) is a common but serious condition that is related with poor quality of life, morbidity and mortality. Its incidence and associated healthcare costs are rising and its management remains palliative, with median survival ranging from 3 to 12 months. During the last decade there has been significant progress in unravelling the pathophysiology of MPE, as well as its diagnostics, imaging, and management. Nowadays, formerly bed-ridden patients are genotyped, phenotyped, and treated on an ambulatory basis. This article attempts to provide a comprehensive overview of current advances in MPE from bench to bedside. In addition, it highlights unanswered questions in current clinical practice and suggests future directions for basic and clinical research in the field. AU - Psallidas, I.* AU - Kalomenidis, I.* AU - Porcel, J.M.* AU - Robinson, B.W.* AU - Stathopoulos, G.T. C1 - 48718 C2 - 41296 SP - 189-198 TI - Malignant pleural effusion: From bench to bedside. JO - Eur. Respir. Rev. VL - 25 IS - 140 PY - 2016 SN - 0905-9180 ER - TY - JOUR AB - Airway remodelling is a critical feature of chronic bronchial diseases, characterised by aberrant repair of the epithelium and accumulation of fibroblasts, which contribute to extracellular matrix (ECM) deposition resulting in fixed bronchial obstruction. Recently, epithelial-mesenchymal transition (EMT) has been identified as a new source of fibroblasts that could contribute to the remodelling of the airways. This phenomenon consists of the loss of the epithelial phenotype by bronchial epithelial cells and the acquisition of a mesenchymal phenotype. These cells are then able to migrate and secrete ECM molecules. Herein, we review the different types of EMT. We will then focus on the signalling pathways that are involved, such as transforming growth factor-β and Wnt, as well as the more recently described Sonic Hedgehog pathway. Finally, we will highlight the implication of EMT in airway remodelling in specific chronic bronchial pathologies, such as asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans following lung transplantation. Despite the limitations of in vitro models, future studies of EMT in vivo are warranted to shed new light on the pathomechanisms of bronchial obstruction. AU - Pain, M.* AU - Bermudez, O. AU - Lacoste, P.* AU - Royer, P.J.* AU - Botturi, K.* AU - Tissot, A.* AU - Brouard, S.* AU - Eickelberg, O. AU - Magnan, A.* C1 - 30882 C2 - 33977 SP - 118-130 TI - Tissue remodelling in chronic bronchial diseases: From the epithelial to mesenchymal phenotype. JO - Eur. Respir. Rev. VL - 23 IS - 131 PY - 2014 SN - 0905-9180 ER - TY - JOUR AU - Roemer, W.* AU - Hoek, G.* AU - Schouten, J.P.* AU - Baldini, G.* AU - Clench-Aas, J.* AU - Fischer, P.* C1 - 20935 C2 - 18981 SP - 125-130 TI - The PEACE project: general discussion. JO - Eur. Respir. Rev. VL - 8 PY - 1998 SN - 0905-9180 ER - TY - JOUR AB - Important properties of nebulizers for aerosol particle therapy are the water and solute output, and the initial particle size distribution. These properties have to be determined experimentally. The evaporation of the particles during transport is estimated to be less than 10% in most cases. The changes in particle size during inhalation, and particle deposition, are estimated with a hygroscopic particle lung deposition model. The regional deposition of aerosol particles of an arbitrary material and an arbitrary size distribution can now be estimated. This method is applied to two jet nebulizers (Pari Inhalierboy and Wiesbadener Doppelinhalator), and to an ultrasonic nebulizer (DeVilbiss 65). AU - Ferron, G.A. C1 - 40045 C2 - 37732 SP - 95-98 TI - Scientific basis for aerosol therapy using nebulizers. JO - Eur. Respir. Rev. VL - 4 IS - 18 PY - 1994 SN - 0905-9180 ER - TY - JOUR AB - New physical concepts in aerosol therapy are required for the successful application of new medical concepts in medical practice. In particular, drug dosimetry and targeting of lung regions with aerosol particles have to be improved. Targeting can be improved using monodisperse aerosols inspired as boluses into the target region, and dosimetry by additional application of aerosol photometry. Monodisperse aerosols need to be inspired with an apparatus combining bolus inhalation and aerosol photometry, thereby optimizing targeting of lung regions and rendering individual drug dosimetry possible. AU - Heyder, J. C1 - 39987 C2 - 40545 SP - 104-105 TI - New trends in aerosol therapy: The physicist's view. JO - Eur. Respir. Rev. VL - 4 IS - 18 PY - 1994 SN - 0905-9180 ER -