A Novel Spirometric Measure Identifies Mild COPD Unidentified by Standard Criteria

Background: In chronic obstructive pulmonary disease, both smaller and larger airways are affected. FEV₁ mainly reflects large airways obstruction, while the later fraction of forced exhalation reflects reduction in terminal expiratory flow. In this study, the objective was to evaluate the relationship between spirometric ratios, including the ratio of forced expiratory volume in 3 and 6 seconds (FEV₃/FEV₆), and small airways measures and gas trapping at quantitative chest CT scanning, and clinical outcomes in the Genetic Epidemiology of COPD (COPDGene) cohort.

Methods: Seven thousand eight hundred fifty-three current and ex-smokers were evaluated for airflow obstruction by using recently defined linear iteratively derived equations of Hansen et al to determine lower limit of normal (LLN) equations for prebronchodilator FEV₁/FVC, FEV₁/FEV₆, FEV₃/FEV₆, and FEV₃/FVC. General linear and ordinal regression models were applied to the relationship between prebronchodilator spirometric and radiologic and clinical data.

Results: Of the 10,311 participants included in the COPDGene phase I study, participants with incomplete quantitative CT scanning or relevant spirometric data were excluded, resulting in 7,853 participants in the present study. Of 4,386 participants with FEV₁/FVC greater than or equal to the LLN, 15.4% had abnormal FEV₃/FEV₆. Compared with normal FEV₃/FEV₆ and FEV₁/FVC, abnormal FEV₃/FEV₆ was associated with significantly greater gas trapping; St. George's Respiratory Questionnaire score; modified Medical Research Council dyspnea score; and BMI, airflow obstruction, dyspnea, and exercise index and with shorter 6-min walking distance (all P < .0001) but not with CT scanning evidence of emphysema.

Conclusions: Current and ex-smokers with prebronchodilator FEV₃/FEV₆ less than the LLN as the sole abnormality identifies a distinct population with evidence of small airways disease in quantitative CT scanning, impaired indexes of physical function and quality of life otherwise deemed normal by using the current spirometric definition.