In chronic obstructive pulmonary disease both smaller and larger airways are affected. Forced expiratory volume in one second (FEV1) mainly reflects large airways obstruction, while the later fraction of forced exhalation reflects reduction in terminal expiratory flow.
To evaluate the relationship between spirometric ratios, including the ratio of forced expiratory volume in 3 and 6 seconds (FEV3/FEV6), and small airway measures and gas trapping in quantitative chest computed tomography (CT), and clinical outcomes in the COPDGene cohort.
7,853 current and ex-smokers were evaluated for airflow obstruction using recently-defined linear iteratively-derived equations of Hansen et al.1 to determine lower limits of normal equations for pre-bronchodilator FEV1/FVC, FEV1/FEV6, FEV3/FEV6 and FEV3/FVC. General linear and ordinal regression models were applied to the relation between pre-bronchodilator spirometry and radiologic and clinical data.
Of the 10,311 participants included in the COPDGene Phase 1 study, participants with incomplete quantitative CT or relevant spirometric data were excluded, resulting in 7,853 participants in the present study. Of 4,386 participants with ratio of FEV1 to forced vital capacity (FEV1/FVC) greater than lower limit of normal, 15.4% had abnormal FEV3/FEV6. Compared to participants with normal FEV3/FEV6 and FEV1/FVC, abnormal FEV3/FEV6 was associated with significantly greater gas trapping, St. George Respiratory Questionnaire score, mMRC dyspnea score, BODE index, and shorter six-minute walking distance (all P < 0.0001), but not CT-evidence of emphysema.
Current and ex-smokers with pre-bronchodilator FEV3/FEV6 < lower limit of normal as the sole abnormality identifies a distinct population with evidence of small airway disease in quantitative CT, impaired indices of physical function and quality of life otherwise deemed normal by current spirometric definition.