Li Zhang1,2, Xin Zhang1,2,3, Jing Zheng4, Ying Liu1,2, Ji Wang1,2, Gang Wang1,2,3, Hong Ping Zhang1,2, De Ying Kang6, Zu Gui Peng7, Yu Lin Ji3, Lei Wang1,2, Peter Gerard Gibson8, Gang Wang1,2,3. 1. Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China. 2. Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China. 3. Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China. 4. Department of Integrated Traditional Chinese and Western Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China. 5. West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China. 6. Department of Evidence-based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, China. 7. Department of Psychiatry, The Mental Health Center, West China Hospital, Sichuan University, Chengdu, China. 8. Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Priority Research Centre for Healthy Lungs, University of Newcastle, Newcastle, New South Wales, Australia.
Abstract
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, CCL17 and CCL22 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.
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, CCL17 and CCL22 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: Asthmapatients 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.
Authors: Katherine M Littlefield; Renée O Watson; Jennifer M Schneider; Charles P Neff; Eiko Yamada; Min Zhang; Thomas B Campbell; Michael T Falta; Sarah E Jolley; Andrew P Fontenot; Brent E Palmer Journal: PLoS Pathog Date: 2022-05-26 Impact factor: 7.464
Authors: Martín Ignacio González-Rodríguez; Noora Nurminen; Laura Kummola; Olli H Laitinen; Sami Oikarinen; Anirudra Parajuli; Tanja Salomaa; Iida Mäkelä; Marja I Roslund; Aki Sinkkonen; Heikki Hyöty; Ilkka S Junttila Journal: Immun Inflamm Dis Date: 2021-12-06