Depressive symptom‐associated IL ‐1β and TNF ‐α release correlates with impaired bronchodilator response and neutrophilic airway inflammation in asthma

Background: Depressive symptoms worsen asthma outcomes; however, the mechanism remains largely unexplored. Objective: This study aimed to determine whether depressive symptom‐associated immune inflammation correlates with impaired bronchodilator response (BDR ) and airway inflammatory phenotypes. Methods: Eligible adults with asthma (n = 198) underwent clinical assessment, sputum induction and blood sampling. Depressive symptoms were defined by scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS ‐D). Pre‐ and post‐bronchodilator spirometry was performed for BDR . Airway inflammatory phenotypes were defined by sputum cell counts. CRP , IL ‐1β, IL ‐5, IL ‐6, IL ‐8, TNF ‐α, IFN ‐γ, CCL 17 and CCL 22 in serum and sputum were detected. Results: Compared with the non‐depressive group (n = 174), the depressive group (n = 24) exhibited impaired BDR (P = 0.032) and increased sputum neutrophils (P = 0.023), which correlated with the HADS ‐D scores (P = 0.027 and P = 0.029). Levels of IL ‐1β, TNF ‐α and IFN ‐γ in the serum and those of IL ‐1β and IFN ‐γ in the sputum were elevated in the depressive group compared to those in the non‐depressive group (all P < 0.05). Multiple regression models indicated that TNF ‐α in the sputum and IL ‐1β, IL ‐6 and IFN ‐γ in both the serum and sputum were inversely associated with BDR ; TNF ‐α in the sputum and IL ‐1β in both the serum and sputum were positively correlated with sputum neutrophils. Mediation analyses revealed that IL ‐1β and TNF ‐α in the sputum and IL ‐1β in both the serum and sputum mediate the correlations of the HADS ‐D scores with BDR and sputum neutrophils, respectively. Conclusions and Clinical Relevance: Asthma patients with depressive symptoms present worse asthma control, which is most likely explained by impaired BDR and neutrophilic airway inflammation. IL ‐1β and TNF ‐α, which are two key pro‐inflammatory cytokines that mediate the correlation of depressive symptoms with impaired BDR and neutrophilic airway inflammation, may serve as targeted biomarkers in the neuropsychological phenotype of asthma; however, this result needs to be further validated.