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.