Format

Send to

Choose Destination
Clin Exp Allergy. 2019 Jun;49(6):770-780. doi: 10.1111/cea.13346. Epub 2019 Feb 18.

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

Zhang L1,2, Zhang X1,2,3, Zheng J4, Liu Y1,2, Wang J1,2, Wang G1,5, Zhang HP1,2, Kang Y6, Peng ZG7, Ji YL3, Wang L1,2, Gibson PG8, Wang G1,2,3.

Author information

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.

KEYWORDS:

airway inflammation phenotype; asthma; bronchodilator response; depressive symptoms; systemic inflammation

PMID:
30675924
DOI:
10.1111/cea.13346

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center