Further evidence for association of YKL-40 with severe asthma airway remodeling

Background: The chitinase-like protein YKL-40 is associated with airflow limitation on spirometry and airway remodeling in patients with asthma. It remains unclear whether YKL-40 is associated with morphologic changes in the airways and parenchyma or with future progression of airflow limitation in severe asthma. Objective: To evaluate the association of circulating YKL-40 levels with morphologic changes in the airways and parenchyma and with longitudinal progression of airflow limitation. Methods: The patients were participants in the Hokkaido Severe Asthma Cohort Study (n = 127), including smokers. This study consisted of 2 parts. In analysis 1, we analyzed associations between circulating YKL-40 levels and several asthma-related indices, including computed tomography–derived indices of proximal wall area percentage, the complexity of the airways (airway fractal dimension), and the parenchyma (exponent D) cross-sectionally (n = 97). In analysis 2, we evaluated the impact of circulating YKL-40 levels on forced expiratory volume in 1 second (FEV₁) decline longitudinally for a 5-year follow-up (n = 103). Results: Circulating YKL-40 levels were significantly associated with proximal wall area percentage and airway fractal dimension (r = 0.25, P = .01; r = −0.22, P = .04, respectively), but not with exponent D. The mean annual change in FEV₁ was −33.7 (± 23.3) mL/y, and the circulating YKL-40 level was a significant independent factor associated with annual FEV₁ decline (β = −0.24, P = .02), even after controlling for exponent D (β = −0.26, P = .01). Conclusion: These results provide further evidence for the association of YKL-40 with the pathogenesis of airway remodeling in severe asthma.