Low smoking exposure and development and prognosis of COPD over four decades: A population-based cohort study

<bold>Background:</bold> 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. <bold>Methods:</bold> We followed non-obstructive adult smokers from the Copenhagen City Heart Study for COPD for 5 years according to baseline smoking and hereafter for up to four decades for severe exacerbations and death. <bold>Results:</bold> In 6098 non-obstructive smokers, 1781(29%) developed COPD after 5 years follow-up; 23% in individuals with <10 pack-years of smoking at baseline, 26% in those with 10-19.9 pack-years, 30% in those with 20-39.9 pack-years, and 39% in those with ≥40 pack-years. During four decades follow-up, we recorded 620 exacerbations and 5573 deaths. Compared to individuals without COPD with <10 pack-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 ≥10 pack-years, 2.83 (1.72-4.66) in those with COPD with <10 pack-years, 4.34 (2.93-6.43) in COPD with 10-19.9 pack-years, 4.39 (2.98-6.47) in COPD with 20-39.9 pack-years, and 4.98 (3.11-7.97) in COPD with ≥40 pack-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. <bold>Conclusions:</bold> Low smoking exposure below the critical threshold of 10 pack-years increases risk of COPD in middle-aged adults within 5 years, and that these individuals have increased risk of severe exacerbation and early death over four decades.