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.

Relative contributions of emphysema and airway remodelling to airflow limitation in COPD: Consistent results from two cohorts.

BACKGROUND AND OBJECTIVE: The relative contributions of emphysema and airway remodelling to airflow limitation remain unclear in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the relative contributions of emphysema and airway wall thickness measured by quantitative computed tomography (CT) to the prediction of airflow limitation in two separate COPD cohorts. METHODS: Pulmonary function tests and whole-lung CT were performed in 250 male smokers with COPD, including 167 from University Medical Center at Ho Chi Minh City, Vietnam, and 83 from Shiga University of Medical Science Hospital, Japan. The same CT analysis software was used to measure the percentage of low attenuation volume (%LAV) at the threshold of -950 Hounsfield units and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10). The standardized coefficients in multiple linear regressions were used to evaluate the relative contributions of %LAV and Pi10 to predictions of FEV1 /FVC and FEV1 % predicted. RESULTS: Both %LAV and Pi10 independently predicted either forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) or FEV1 % predicted (P ≤ 0.001 for all standardized coefficients). However, the absolute values of the standardized coefficients were 2-3 times higher for %LAV than for Pi10 in all prediction models. The results were consistent in the two COPD cohorts. CONCLUSIONS: %LAV predicts both FEV1 /FVC and FEV1 better than Pi10 in patients with COPD. Thus, emphysema may make a greater contribution to airflow limitation than airway remodelling in COPD.

Airway wall area derived from 3-dimensional computed tomography analysis differs among lung lobes in male smokers.

BACKGROUND: It is time-consuming to obtain the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), a comparable index of airway dimensions in chronic obstructive pulmonary disease (COPD), from all airways of the whole lungs using 3-dimensional computed tomography (CT) analysis. We hypothesized that √Aaw at Pi10 differs among the five lung lobes and √Aaw at Pi10 derived from one certain lung lobe has a high level of agreement with that derived from the whole lungs in smokers. METHODS: Pulmonary function tests and chest volumetric CTs were performed in 157 male smokers (102 COPD, 55 non-COPD). All visible bronchial segments from the 3rd to 5th generations were segmented and measured using commercially available 3-dimensional CT analysis software. √Aaw at Pi10 of each lung lobe was estimated from all measurable bronchial segments of that lobe. RESULTS: Using a mixed-effects model, √Aaw at Pi10 differed significantly among the five lung lobes (R(2) = 0.78, P<0.0001). The Bland-Altman plots show that √Aaw at Pi10 derived from the right or left upper lobe had a high level of agreement with that derived from the whole lungs, while √Aaw at Pi10 derived from the right or left lower lobe did not. CONCLUSION: In male smokers, CT-derived airway wall area differs among the five lung lobes, and airway wall area derived from the right or left upper lobe is representative of the whole lungs.