Determinants of airway morphology in asthma: Inflammatory and noninflammatory factors

Background: Patients with asthma may exhibit impaired airway tree morphology. The impact of difficult-to-treat traits on airway tree morphology remains unclear. Objective: We sought to identify determinants of total airway branch count (TAC) detectable via computed tomography and explore associated blood and sputum biomarkers in nonsmokers and smokers with asthma. Methods: Baseline computed tomography scans and pulmonary function tests (spirometry, diffusion capacity of carbon monoxide, and lung volume) were analyzed from the Hokkaido Severe Asthma Cohort (N = 190). TAC, segmental airway, visually evident mucus plugging and bronchiectasis, and parenchymal and extrapulmonary indices, such as the Lund-Mackay score, were evaluated. Relationships between TAC, difficult-to-treat traits, and blood/sputum biomarkers were analyzed using crude or multivariable regression models, adjusted for demographic factors. Results: Blood or sputum eosinophilia, mucus plugs, high body mass index (BMI), asthma duration, and higher Lund-Mackay score correlated with low TAC. Low TAC was linked to airflow obstruction and heterogeneous ventilation (low alveolar volume/total lung capacity). BMI was inversely associated with TAC, independent of age, sex, smoking status, sputum eosinophil ratio, and asthma duration. The presence of bronchiectasis correlated with an increase in TAC. Sputum IL-5, IL-6, RANTES, and circulating YKL-40 (chitinase-3-like-1 protein) and leptin also inversely correlated with TAC. Conclusions: BMI, asthma duration, sinusitis, and the presence of bronchiectasis are significant determinants of airway tree morphology in asthma, alongside inflammation and mucus plugs. Both inflammatory and noninflammatory biomarkers were associated with low TAC.