C-BIOPRED severe asthma clinical phenotypes: link to complement and coagulation pathways and galectin 10

Background Severe asthma is a heterogeneous airway inflammatory disease presenting with varying clinico-physiologic characteristics and response to treatments. Objectives To determine the clinical phenotypes of the Chinese C-BIOPRED cohort and their link to the sputum proteome. Methods Partition-around-medoids clustering was applied to a training set of 362 non-smoking, smoking or ex-smoking severe asthma, and non-smoking mild-moderate asthma using 8 clinico-physiologic variables, with validation performed in remaining 181. Results Three stable clusters were defined, with Cluster T1 composed of predominantly female patients with severe nonsmoking asthma experiencing frequent exacerbations with moderate airflow obstruction, and Cluster T3 of elderly male patients with smoking/ex-smoking late-onset severe asthma and severe airflow obstruction and a moderate number of exacerbations. Cluster T2 was composed of non-smokers with a mild to moderate airflow obstruction and no previous exacerbations. Validation clusters (V1, V2 and V3) were similar to the training set clusters. Differentially-expressed proteins in sputum supernatants measured by liquid chromatography with tandem mass spectrometry pointed to differences in the complement and coagulation cascade pathway between Cluster 1 (T1 and V1) and Cluster 3 (T3 and V3), as well as between Cluster 2 (T2 and V2) and Cluster 3. Galectin 10 was upregulated in Cluster 1 compared to Cluster 2, and correlated with exacerbations, fractional exhaled nitric oxide, blood and sputum eosinophil count, and oral corticosteroid dose in Cluster 1. Conclusion The clinical clusters were differentiated by smoking status, degree of airflow obstruction and exacerbation history, and by sputum complement and coagulation pathways, and galectin 10 levels.