Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies

CADSET Clinical Research Collaboration

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Abstract

Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20–94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4–51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6–7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7–12·0; p<0·0001). Birth year-related increases in the FEV1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09–0·14; p<0·0001). Interpretation: If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity. Funding: The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme.

Original languageEnglish
Pages (from-to)83-94
Number of pages12
JournalThe Lancet Respiratory Medicine
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 2022
Externally publishedYes

Bibliographical note

Funding Information:
JPA has received speaker fees from Pulmonx, travel costs from Boehringer Ingelheim to deliver a lecture, and travel costs from GlaxoSmithKline to attend an advisory board meeting. YÇ received personal fees from Boehringer Ingelheim, AstraZeneca, and Sanofi Genzyme. HB has received payment from AstraZeneca and Boehringer Ingelheim for presentations made at scientific meetings. MvdB has received institutional research grants from GlaxoSmithKline, Roche, Genentech, and Novartis. GB has received honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Novartis, Sanofi, and TEVA. OCB has received grants or contracts, consulting fees, and payment or honoraria from AstraZeneca, Abbvie, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, MSD, Novartis, Roche, Takeda, and TEVA for lectures, presentations, speakers bureaus, manuscript writing, or educational events. RF has received research grants from GlaxoSmithKline, Menarini, AstraZeneca, ISC-III, and the Spanish Health Service, consulting fees from GlaxoSmithKline, and honoraria from Chiesi Farmaceutici. SH has received grants or contracts, consulting fees, and payment or honoraria from AstraZeneca, Abbvie, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, MSD, Novartis, Roche, Takeda, and TEVA for lectures, presentations, speakers bureaus, manuscript writing, or educational events. AL has received payment for lectures from Boehringer Ingelheim and travel costs from Novartis and AstraZeneca to attend meetings, has participated in an AstraZeneca advisory board, has contributed to the Norwegian Primary Care Respiratory Group, and has been a member of the Norwegian Health Directorate. BL has received grants from AstraZeneca and ThermoFisher and has participated in a Sanofi advisory board. SAAV has received support from AstraZeneca to attend meetings. SRAW has received travel grants from GlaxoSmithKline. PL has received institutional grants, personal consulting fees, and personal lecture fees from AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim. GCD has received institutional grants from Genentech and AstraZeneca, book chapter royalties from Elsevier, and payment from AstraZeneca and Novartis for participation in advisory boards. JAW has received institutional grants from GlaxoSmithKline, AstraZeneca, Chiesi Farmaceutici, Boehringer Ingelheim, Novartis, and Genentech, and has participated in a Virtus data and safety monitoring board. JV is supported by the National Institute for Health Research Manchester Biomedical Research Centre, has received a research grant from Boehringer Ingelheim, honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, and Novartis for presentations at meetings, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Novartis, and TEVA for participation in advisory boards, is a member of the Panel for Clinical and Translational Research for the Novo Nordisk Foundation, has chaired the Asthma UK Research Review Panel, and is a member of the Medical and Chemicals Technical Options Committee for the Montreal Protocol, the UN Environment Programme. LEGWV has received institutional grants from AstraZeneca, personal payments from AstraZeneca, GlaxoSmithKline, Boehringer, Linde, Novartis, Menarini, and Zambon for lectures, presentations, speakers bureaus, manuscript writing, or educational events, personal payments from AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim for participation on data safety monitoring boards or advisory boards, and payment from Chiesi Farmaceutici for medical writing. All other authors declare no competing interests.

Funding Information:
The CADSET European Respiratory Society Clinical Research Collaboration has been supported by financial contributions from the following consortium partners: the European Respiratory Society, AstraZeneca UK, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi Genzyme. The authors have not been paid to write this Article by a pharmaceutical company or other agency.

Publisher Copyright:
© 2022 Elsevier Ltd

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