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Heterogeneous burden of lung disease in smokers with borderline airflow obstruction.

  • Author(s): Pirozzi, Cheryl S
  • Gu, Tian
  • Quibrera, Pedro M
  • Carretta, Elizabeth E
  • Han, MeiLan K
  • Murray, Susan
  • Cooper, Christopher B
  • Tashkin, Donald P
  • Kleerup, Eric C
  • Barjaktarevic, Igor
  • Hoffman, Eric A
  • Martinez, Carlos H
  • Christenson, Stephanie A
  • Hansel, Nadia N
  • Graham Barr, R
  • Bleecker, Eugene R
  • Ortega, Victor E
  • Martinez, Fernando J
  • Kanner, Richard E
  • Paine, Robert
  • NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS)
  • et al.


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.


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.


The discordant group had more CT defined emphysema and non-emphysematous gas trapping, lower post-bronchodilator FEV1 and FEF25-75, 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.


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.

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