AbstractIntroductionCytomegalovirus (CMV) seropositivity has been recently linked to severity and progression of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). To date, no longitudinal study has addressed the relation of CMV serology to levels and decline of lung function in the general adult population.MethodsWe evaluated 403 participants from the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD) who at enrollment were aged 28–55 years and completed lung function tests. During follow‐up, the 403 participants completed on average 7.2 lung function tests per subject for a total of 2908 observations over a mean period of 14.7 years. We tested CMV serology in serum samples from enrollment and categorized participants into low, medium, and high CMV serology based on tertiles. The relation of CMV serology at enrollment to lung function levels and decline during follow‐up was tested in multivariate random coefficients models.ResultsAfter full adjustment, participants in the highest CMV serology tertile had faster declines of forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) compared with subjects in the lowest tertile (by −7.9 ml/year 95% confidence interval [−13.9 ml/year, −1.93 ml/year], and by −0.13%/year [−0.23%/year, −0.026%/year], respectively). These CMV effects were additive with those of cigarette smoking. No associations were found between CMV serology and FVC, indicating specific effects of CMV seropositivity on airflow limitation.ConclusionHigh CMV serology in young to mid‐adult life may be linked to increased COPD risk through an accelerated decline of lung function.