The Lancet COPD Commission: broader questions remain

We would like to congratulate Daiana Stolz and colleagues1Stolz D Mkorombindo T Schumann DM et al.Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission.Lancet. 2022; 400: 921-972Summary Full Text Full Text PDF PubMed Google Scholar for a comprehensive and authoritative Commission that undoubtedly constitutes an important landmark in the field. The emphasis on recognising risk and causative factors for chronic obstructive pulmonary disease (COPD) beyond tobacco smoking, such as other environmental exposures and early-life events as drivers of disease and lung function decline, is pivotal for the success of the mission towards earlier diagnosis and improved global prevention and treatment strategies. With exception to the section on acute exacerbations, we noted that there was little attention given to endogenous biological traits that not only put people at risk, but are modifiable more directly and readily by clinicians. One example is type-2 eosinophilic airway inflammation—a treatable trait easily recognised by simple biomarkers such as the blood eosinophil count and exhaled nitric oxide2Pavord ID Beasley R Agusti A et al.After asthma: redefining airway diseases.Lancet. 2018; 391: 350-400Summary Full Text Full Text PDF PubMed Scopus (620) Google Scholar—not only for its association with exacerbations, but also as a potential driver of lung function decline. A recent longitudinal cohort study of young healthy individuals showed an association between baseline blood eosinophil counts and development of obstructive lung disease, seen both in smokers and non-smokers, with a hazard ratio of 1·3 and an almost two-fold risk in people with blood eosinophil numbers greater than 200 cells per μL and more than 500 cells per μL, respectively.3Park HY Chang Y Kang D et al.Blood eosinophil counts and the development of obstructive lung disease: the Kangbuk Samsung Health Study.Eur Respir J. 2021; 582003823Crossref Scopus (15) Google Scholar Additional studies have correlated blood eosinophil count with lung function decline even in healthy individuals without asthma: Lee and colleagues suggested that a blood eosinophil count threshold of 200 per μL in smokers, and an even lower count at 100 per μL in non-smokers, might predict an accelerated decline in the the forced expiratory volume in 1 s (FEV1).4Lee S-H Ahn K-M Lee S-Y Kim S-S Park H-W Blood eosinophil count as a predictor of lung function decline in healthy individuals.J Allergy Clin Immunol Pract. 2021; 9 (e1): 394-399Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar Hancox and colleagues found that a three-fold increase in baseline blood eosinophils associated with a rate of FEV1 decline equivalent to that seen with a 10 pack-year history.5Hancox RJ Pavord ID Sears MR Associations between blood eosinophils and decline in lung function among adults with and without asthma.Eur Respir J. 2018; 511702536Crossref Scopus (78) Google Scholar Approximately 60% of asthmatic patients, 40% of COPD patients, and 5–10% of healthy individuals have high type-2 biomarkers.2Pavord ID Beasley R Agusti A et al.After asthma: redefining airway diseases.Lancet. 2018; 391: 350-400Summary Full Text Full Text PDF PubMed Scopus (620) Google Scholar, 6George L Brightling CE Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease.Ther Adv Chronic Dis. 2016; 7: 34-51Crossref PubMed Scopus (200) Google Scholar, 7Malinovschi A Fonseca JA Jacinto T Alving K Janson C Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects.J Allergy Clin Immunol. 2013; 132 (e1–5): 821-827Summary Full Text Full Text PDF PubMed Scopus (194) Google Scholar Although further research is required to understand the role of type-2 airway inflammation in the pathogenesis of chronic obstructive airways disease, the aforementioned studies suggest that it merits consideration as a trait to measure, and possibly target with inhaled corticosteroids and perhaps biologics, early in a patient's journey in an attempt to dampen or prevent airway remodelling and lung function decline. Combining sensitive lung function measures that can detect mild or early changes in the small airways, as recommended by the Commission, with measurement of accessible type-2 biomarkers might help identify individuals who are most at risk and who might benefit from early intervention. More research and clinical data are required in this area. NP is supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC); received grants from the University of Oxford and NIHR research capability funding from Oxford University Hospitals outside the submitted work; and received fees from AstraZeneca. IDP has received honoraria from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini, Genentech, Merck, Circassia, Chiesi, Knopp, and GSK; payments from AstraZeneca, GSK, Sanofi/Regeneron, and Teva; sponsorship from Boehringer Ingelheim, GSK, AstraZeneca, Teva, and Chiesi; received a grant from Chiesi; is co-patent holder of the rights to the Leicester Cough Questionnaire and received payments for its use from Merck, Bayer, and Insmed; and was an expert witness for a patent dispute involving AstraZeneca and Teva. SC received grants from the NIHR Oxford BRC, AstraZeneca, bioMérieux, Sanofi-Genzyme-Regeneron, and the Quebec Respiratory Health Research Network; is the holder of the Association Pulmonaire du Québec's Research Chair in respiratory medicine; received speaker honoraria from AstraZeneca, GSK, Sanofi/Regeneron, and Valeo Pharma; received consultancy fees from FirstThought; received sponsorship from AstraZeneca; and is an advisory board member and stock option holder for Biometry. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health of England. The Lancet COPD Commission: broader questions remainDaiana Stolz and colleagues1 in their proposed diagnostic algorithm (figure 11 of the Commission) list several alternative tests to aid in the diagnosis of chronic obstructive pulmonary disease (COPD) in people who have a forced expiratory volume in 1 s to forced vital capacity ratio of greater than or equal to 0·7, including diffusion, resistance, nitrogen washout, pathology, and the forced oscillation technique. Unfortunately, the authors did not include cardiopulmonary exercise testing (CPET) in this important list despite the growing body of literature showing that CPET can reveal considerable abnormalities in people with mild COPD and even in smokers with normal spirometry relative to healthy age-matched controls. Full-Text PDF The Lancet COPD Commission: broader questions remainI have read with interest the comprehensive Commission on chronic obstructive pulmonary disease (COPD) by Daiana Stolz and colleagues.1 The authors report that “The most efficient way to reduce the burden of COPD is to ban cigarette smoking in all its forms.” However, only a few sentences later the authors downplay the importance of smoking: “risk factors unrelated to tobacco are increasingly responsible for the burden of COPD, and are likely to surpass the risk attributable to smoking within the next two decades”. Full-Text PDF The Lancet COPD Commission: broader questions remain – Authors' replyWe thank Paulo CRP Corrêa for his interest in the Commission1 and wholeheartedly agree that the absence of meaningful tobacco control is unacceptable and in no way aimed to diminish its importance. In addition, we take no issue with the assertion that continued smoking among people with established chronic obstructive pulmonary disease (COPD) accounts for much of the disease burden. However, we think it is important to recognise that factors other than tobacco are increasingly accountable for incident cases of COPD, including e-cigarette use as Corrêa highlights. Full-Text PDF Towards the elimination of chronic obstructive pulmonary disease: a Lancet CommissionDespite substantial progress in reducing the global impact of many non-communicable diseases, including heart disease and cancer, morbidity and mortality due to chronic respiratory disease continues to increase. This increase is driven primarily by the growing burden of chronic obstructive pulmonary disease (COPD), and has occurred despite the identification of cigarette smoking as the major risk factor for the disease more than 50 years ago. Many factors have contributed to what must now be considered a public health emergency: failure to limit the sale and consumption of tobacco products, unchecked exposure to environmental pollutants across the life course, and the ageing of the global population (partly as a result of improved outcomes for other conditions). Full-Text PDF