GETting to know the many causes and faces of COPD

Chronic obstructive pulmonary disease (COPD) is estimated to affect more than 350 million people globally and is responsible for 3·2 million deaths per year, making it the third leading cause of mortality worldwide. 1 WHOThe top 10 causes of death: 2019. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-deathDate: Dec 9, 2020 Date accessed: January 22, 2022 Google Scholar Beyond its direct impact in terms of human suffering, COPD contributes as a comorbidity to other leading causes of mortality, including COVID-19, pneumonia, cardiovascular diseases, stroke, and lung cancer, increasing the risk of these conditions and associated mortality by two to four times. 2 Gerayeli FV Milne S Cheung C et al. COPD and the risk of poor outcomes in COVID-19: a systematic review and meta-analysis. 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Lancet. 2009; 374: 712-719 Summary Full Text Full Text PDF PubMed Scopus (165) Google Scholar Despite the societal burden posed by COPD, research is poorly funded and the disease is often misunderstood. 6 Ballreich JM Gross CP Powe NR Anderson GF Allocation of National Institutes of Health funding by disease category in 2008 and 2019. JAMA Netw Open. 2021; 4e2034890 Crossref PubMed Scopus (7) Google Scholar One reason for this is the fallacy that COPD is self-inflicted (by tobacco smoking), irreversible, progressive, and untreatable. A Series of three papers in The Lancet Respiratory Medicine7 Yang IA Jenkins CR Salvi SS Chronic obstructive pulmonary disease in never-smokers: risk factors, pathogenesis, and implications for prevention and treatment. Lancet Respir Med. 2022; (published online April 12.)https://doi.org/10.1016/S2213-2600(21)00506-3 Summary Full Text Full Text PDF Google Scholar , 8 Cho MH Hobbs BD Silverman EK Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder. Lancet Respir Med. 2022; (published online April 12.)https://doi.org/10.1016/S2213-2600(21)00510-5 Summary Full Text Full Text PDF Google Scholar , 9 Agustí A Melén E DeMeo DL Breyer-Kohansal R Faner R Pathogenesis of chronic obstructive pulmonary disease: understanding the contributions of gene–environment interactions across the lifespan. Lancet Respir Med. 2022; (published online April 12.)https://doi.org/10.1016/S2213-2600(21)00555-5 Summary Full Text Full Text PDF Google Scholar dispels a number of myths about the nature and origins of COPD, providing a state-of-the-art overview of current evidence for a wide range of genetic and environmental risk factors for COPD, and highlighting a new framework to advance our understanding of COPD pathogenesis and the development of new strategies for treatment and prevention. Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorderChronic obstructive pulmonary disease (COPD) is a deadly and highly morbid disease. Susceptibility to and heterogeneity of COPD are incompletely explained by environmental factors such as cigarette smoking. Family-based and population-based studies have shown that a substantial proportion of COPD risk is related to genetic variation. Genetic association studies have identified hundreds of genetic variants that affect risk for COPD, decreased lung function, and other COPD-related traits. These genetic variants are associated with other pulmonary and non-pulmonary traits, demonstrate a genetic basis for at least part of COPD heterogeneity, have a substantial effect on COPD risk in aggregate, implicate early-life events in COPD pathogenesis, and often involve genes not previously suspected to have a role in COPD. Full-Text PDF Chronic obstructive pulmonary disease in never-smokers: risk factors, pathogenesis, and implications for prevention and treatmentChronic obstructive pulmonary disease (COPD) was traditionally thought to be caused by tobacco smoking. However, recognition of the importance of non-smoking-related risk factors for COPD has increased over the past decade, with evidence on the burden, risk factors, and clinical presentations of COPD in never-smokers. About half of all COPD cases worldwide are due to non-tobacco-related risk factors, which vary by geographical region. These factors include air pollution, occupational exposures, poorly controlled asthma, environmental tobacco smoke, infectious diseases, and low socioeconomic status. Full-Text PDF Pathogenesis of chronic obstructive pulmonary disease: understanding the contributions of gene–environment interactions across the lifespanThe traditional view of chronic obstructive pulmonary disease (COPD) as a self-inflicted disease caused by tobacco smoking in genetically susceptible individuals has been challenged by recent research findings. COPD can instead be understood as the potential end result of the accumulation of gene–environment interactions encountered by an individual over the life course. Integration of a time axis in pathogenic models of COPD is necessary because the biological responses to and clinical consequences of different exposures might vary according to both the age of an individual at which a given gene–environment interaction occurs and the cumulative history of previous gene–environment interactions. Full-Text PDF