Study design and subjects
This study included two parts with the first part as a cross-sectional study to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes and the second part as a prospective cohort study to explore the association between those identified signatures in the first part and asthma exacerbation in the 12 month followed-up. This study included patients with asthma based on the Australasian Severe Asthma Network (ASAN)13. Asthma participants in the discovery set (n=119) of the cross-sectional study and in the validation set (n=114) of the prospective cohort study were recruited from the Asthma Clinic of West China Hospital, Sichuan University, and 20 healthy volunteers were recruited by advertisement between March 2014 and April 2019. All of patients were aged ≥ 18 years with stable asthma (no respiratory tract infection and no exacerbation or systemic corticosteroid use in the previous 4 weeks). Asthma was diagnosed according to American Thoracic Society (ATS) guidelines14 and Global Initiative for Asthma (GINA)1. The subjects were excluded if they were pregnant or breast feeding, had cognitive impairment, current solid organ malignancy. Asthma inflammatory phenotype was assigned based on a sputum eosinophil cutoff of greater than 3% and a sputum neutrophil cutoff of greater than 61% (Patients with a sputum proportion of < 61% neutrophils and < 3% eosinophils were classified as PGA, with ≥ 61% neutrophils and < 3% eosinophils classified as NA, with < 61% neutrophils and ≥ 3% eosinophils classified as EA, respectively)2. This study was reviewed and approved by the institutional review board of West China Hospital, Sichuan University (Chengdu, China) (No.2014-30), and all subjects provided written informed consent.