Clinical and Radiologic Disease in Smokers With Normal Spirometry
Authors: Elizabeth A. Regan, David A. Lynch, Douglas Curran-Everett, Jeffrey L. Curtis, John H. M. Austin, Philippe A. Grenier, Hans-Ulrich Kauczor, William C. Bailey, Dawn L. DeMeo, Richard H. Casaburi, Paul Friedman, Edwin J. R. Van Beek, John E. Hokanson, Russell P. Bowler, Terri H. Beaty, George R. Washko, MeiLan K. Han, Victor Kim, Song Soo Kim, Kunihiro Yagihashi, Lacey Washington, Charlene E. McEvoy, Clint Tanner, David M. Mannino, Barry J. Make, Edwin K. Silverman, James D. Crapo
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. <h3>Objective</h3> To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. <h3>Design, Setting, and Participants</h3> Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV<sub>1</sub>] to forced vital capacity &gt;0.7 and FEV<sub>1</sub>≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011. <h3>Main Outcomes and Measures</h3> Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life. <h3>Results</h3> One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George's Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers;<i>P</i> &lt; .001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV<sub>1</sub>percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease. <h3>Conclusions and Relevance</h3> Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.