Blood inflammatory phenotypes were associated with distinct clinical expressions of asthma in adults from a large population-based cohort

BACKGROUND: Asthma is an inflammatory heterogeneous disease. Asthma inflammatory phenotypes based on blood eosinophil and neutrophil counts have never been identified and characterized in population-based studies. METHODS: Adults with current asthma and available blood eosinophil and neutrophil counts from the French population-based CONSTANCES cohort were included. Current asthma was defined by reports of asthma attacks, symptoms or treatments in the last 12 months. Inflammatory phenotypes were based on low (L) and high (H) blood (B) eosinophil (E) (LBE/HBE: </⩾0·25 × 10(9)/L, respectively) and neutrophil (N) (LBN/HBN: </⩾5 × 10(9)/L, respectively) cut-offs. Associations between inflammatory phenotypes and the clinical expressions of asthma were studied using logistic models adjusted for age, sex, smoking status, body mass index, education level, French deprivation index and treatment. Other cut-offs were applied. Stratified analyses according to age or sex were performed. FINDINGS: Among 15,019 adults with asthma (56% women, 59%≥40 years), the LBE/LBN (reference), LBE/HBN, HBE/LBN and HBE/HBN phenotypes accounted for 57%, 6%, 33% and 4% respectively. The LBE/HBN phenotype was associated with being awaken by an attack of coughing, chronic bronchitis, and dyspnoea (adjusted(a)OR ranging from 1·21 to 1·42). The HBE/LBN and HBE/HBN phenotypes were associated with asthma attacks (aOR=1·31[1·20-1·42], 1·25[1·02-1·53]) and asthma symptom score (p for trend<0·0001, p for trend=0·001, respectively). The HBE/LBN phenotype was also associated with being awaken with chest tightness (aOR=1·30[1·20-1·40]). Results were unchanged whatever the cut-offs used. No statistically significant heterogeneity was observed according to age or sex. INTERPRETATION: Differences in the clinical expressions of asthma were found between the phenotypes, reproducible whatever the cut-offs used, and similar to those observed in case-control and clinical studies. Such phenotypes are of interest to improve asthma management and study its environmental risk factors. FUNDING: The CONSTANCES cohort receives grants from ANR (ANR-11-INBS-0002), the Caisse nationale d'assurance maladie-CNAM and the Ministry of research. CONSTANCES also receives funding from MSD, AstraZeneca, Lundbeck and L'Oréal, managed by INSERM-Transfert. T.Tsiavia is supported by a PhD grant from the Fondation pour le Recherche Médicale (ECO202006011654).