PT - JOURNAL ARTICLE AU - Çolak, Yunus AU - Løkke, Anders AU - Marott, Jacob L. AU - Lange, Peter AU - Vestbo, Jørgen AU - Nordestgaard, Børge G. AU - Afzal, Shoaib TI - Low smoking exposure and development and prognosis of COPD over four decades: A population-based cohort study AID - 10.1183/13993003.00314-2024 DP - 2024 Jan 01 TA - European Respiratory Journal PG - 2400314 4099 - https://publications.ersnet.org//content/early/2024/07/11/13993003.00314-2024.short 4100 - https://publications.ersnet.org//content/early/2024/07/11/13993003.00314-2024.full AB - A diagnosis of chronic obstructive pulmonary disease (COPD) is mainly considered in individuals with more than 10 pack-years of smoking. We tested the hypothesis that low smoking exposure, below the critical threshold of 10 pack-years, increases risk of COPD and leads to poor prognosis.We followed non-obstructive adult smokers from the Copenhagen City Heart Study for COPD, defined as forced expiratory volume in one second [FEV1]/forced vital capacity [FVC]<0.70 and FEV1<80% predicted, and for related clinical outcomes. First, we followed individuals for 5years according to baseline smoking for risk of developing COPD, and hereafter for up to four decades for severe exacerbations and death.In 6098 non-obstructive smokers, 1781(29%) developed COPD after 5 years follow-up; 23% in individuals with <10pack-years of smoking at baseline, 26% in those with 10–19.9pack-years, 30% in those with 20–39.9pack-years, and 39% in those with ≥40pack-years. During four decades follow-up, we recorded 620 exacerbations and 5573 deaths. Compared to individuals without COPD with <10pack-years of smoking, multivariable adjusted hazard ratios (HRs) for exacerbations were 1.94(95% confidence interval:1.36–2.77) in those without COPD with ≥10pack-years, 2.83(1.72–4.66) in those with COPD with <10pack-years, 4.34(2.93–6.43) in COPD with 10–19.9pack-years, 4.39(2.98–6.47) in COPD with 20–39.9pack-years, and 4.98(3.11–7.97) in COPD with ≥40pack-years. Corresponding HRs for all-cause mortality were 1.20(1.10–1.32), 1.33(1.14–1.56), 1.59(1.40–1.80),1.81(1.62–2.03), and 1.81(1.55–2.10), respectively.Low smoking exposure below the critical threshold of 10 pack-years increases risk of COPD in middle-aged adults within 5 years, and these individuals have increased risk of severe exacerbation and early death over four decades.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Y. Çolak reports grants from Sanofi, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Sanofi, and support for attending meetings from Sanofi.Conflict of interest: A. Løkke reports grants from AstraZeneca, Boehringer Ingelheim, Chiesi and Sanofi, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Sanofi.Conflict of interest: P. Lange reports grants from AstraZeneca and Sanofi, consultancy fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi.Conflict of interest: J. Vestbo reports consultancy fees from ALK, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Teva, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi and GlaxoSmithKline, and participation on a data safety monitoring board or advisory board with AstraZeneca.Conflict of interest: JLM, BGN, and SA have nothing to disclose.