A Mixed Phenotype of Airway Wall Thickening and Emphysema Is Associated with Dyspnea and Hospitalization for Chronic Obstructive Pulmonary Disease

Rationale: Quantitative computed tomography (CT) has been used to phenotype patients with chronic obstructive pulmonary disease (COPD). A mixed phenotype is defined as the presence of both airway wall thickening and emphysema on quantitative CT. Little is known about patients with COPD with the mixed phenotype. Objectives: To propose a method of phenotyping COPD based on quantitative CT and to compare clinically relevant outcomes between patients with COPD with the mixed phenotype and those with other CT-based phenotypes. Methods: Each of 427 male smokers (187 without COPD, 240 with COPD) underwent a complete medical interview, pulmonary function testing, and whole-lung CT on the same day. The percentage of low-attenuation volume at the threshold of -950 Hounsfield units (%LAV) and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10) were measured. Patients with COPD were classified into four distinct phenotypes based on the upper limits of normal for %LAV and Pi10, which were derived from the data of smokers without COPD by using quantile regression. Measurements and Main Results: Of 240 patients with COPD, 52 (21.7%) were classified as CT-normal phenotype, 39 (16.3%) as airway-dominant phenotype, 103 (42.9%) as emphysema-dominant phenotype, and 46 (19.2%) as mixed phenotype. Patients with COPD with the mixed phenotype were associated with more severe dyspnea than those with each of the remaining CT-based phenotypes (P < 0.01 for all comparisons). The number of hospitalizations for COPD exacerbations during the preceding year was 2.0 to 3.6 times higher in patients with the mixed phenotype than in those with each of the remaining CT-based phenotypes (P < 0.05 for all comparisons). Findings persisted after adjustment for age, pack-years of smoking, smoking status, body mass index, and FEV1. Conclusions: Patients with COPD with the mixed phenotype are associated with more severe dyspnea and more frequent hospitalizations than those with each of the remaining CT-based phenotypes. Thus, patients with COPD with the mixed phenotype may need more attention and interventions.