Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity

Abstract

Smokers are assessed for chronic obstructive pulmonary disease (COPD) using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation that is not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusing capacity of the lung for carbon monoxide (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these "normal spirometry/low DLCO" smokers is unknown.From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, complete blood count, urinalysis, HIV status, α1-antitrypsin level, chest radiography, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and total lung capacity. Throughout the study, all continued to be active smokers.In the normal spirometry/normal DLCO group assessed over 45±20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41±31 months, 22% developed GOLD-defined COPD.Despite appearing "normal" according to GOLD, smokers with normal spirometry but low DLCO are at significant risk of developing COPD with obstruction to airflow.

Figure 1

Lung function assessment over time of 59 active smokers with baseline normal history, physical exam and laboratory tests, and with normal spirometry, lung volumes, and normal diffusion capacity (normal spirometry/normal DLCO). The abscissa shows time in months. Each symbol represents an individual, with lines connecting the follow-up data over time for the same individual. The dashed lines represent the limit of normal. Orange data points indicate individuals that initially had normal values at baseline but became abnormal over time. Blue data points indicate individuals that had normal values at baseline and remained normal over time.A. FEV1 (% predicted); B. FVC (% predicted); C. DLCO (% predicted); and D. FEV1/FVC (% observed).

Figure 2

Lung function assessment over time in 46 active smokers with normal history, physical exam and laboratory tests, and with normal spirometry, lung volumes, but low diffusion capacity (normal spirometry/low DLCO). The abscissa shows time in months. Each symbol represents an individual, with lines connecting the follow-up data over time for the same individual. The dashed lines represent the limit of normal. Orange data points indicate individuals that initially had normal values but became abnormal over time. Blue data points indicate individuals that had normal values at baseline and remained normal over time. A. FEV1 (% predicted); B. FVC (% predicted); C. DLCO (% predicted); and D. FEV1/FVC (% observed).

Figure 3

Lung function changes from baseline to the last pulmonary function test in the normal spirometry/normal DLCO group (A-D) and normal spirometry/low DLCO group (E-H) comparing individuals who did not develop COPD (white bars) to those who did develop COPD (grey bars). A, E. FEV1 (% predicted); B, F. FVC (% predicted); C, G. DLCO (% predicted); and D, H. FEV1/FVC (% observed). Data is presented as mean ± standard deviation.