Heterogeneous burden of lung disease in smokers with borderline airflow obstruction

Background The identification of smoking-related lung disease in current and former smokers with normal FEV 1 is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV 1 /FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of airflow obstruction. We hypothesized that the discordant group of ever-smokers with FEV 1 /FVC between the LLN and 0.70 is heterogeneous, and aimed to characterize the burden of smoking-related lung disease in this group. Methods We compared spirometry, chest CT characteristics, and symptoms between 161 ever-smokers in the discordant group and 940 ever-smokers and 190 never-smokers with normal FEV 1 and FEV 1 /FVC > 0.70 in the SPIROMICS cohort. We also estimated sensitivity and specificity for diagnosing objective radiographic evidence of chronic obstructive pulmonary disease (COPD) using different FEV 1 /FVC criteria thresholds. Results The discordant group had more CT defined emphysema and non-emphysematous gas trapping, lower post-bronchodilator FEV 1 and FEF 25–75 , and higher respiratory medication use compared with the other two groups. Within the discordant group, 44% had radiographic CT evidence of either emphysema or non-emphysematous gas trapping; an FEV 1 /FVC threshold of 0.70 has greater sensitivity but lower specificity compared with LLN for identifying individuals with CT abnormality. Conclusions Ever-smokers with normal FEV 1 and FEV 1 /FVC < 0.70 but > LLN are a heterogeneous group that includes significant numbers of individuals with and without radiographic evidence of smoking-related lung disease. These findings emphasize the limitations of diagnosing COPD based on spirometric criteria alone.