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 FEV₁ is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV₁/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 FEV₁/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 FEV₁ and FEV₁/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 FEV₁/FVC criteria thresholds. Results: The discordant group had more CT defined emphysema and non-emphysematous gas trapping, lower post-bronchodilator FEV₁ 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 FEV₁/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 FEV₁ and FEV₁/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.