Association Between Epithelial Cytokines and Clinical Phenotypes of Elderly Asthma

Abstract

PurposeAsthma in the elderly has different clinical features including more severe phenotypes with higher comorbidities. Epithelial cells are known to initiate innate/adaptive immune responses in asthmatic airways. We investigated clinical features and epithelial derived cytokine levels in elderly asthmatics compared to non-elderly asthmatics in a cross-sectional cohort of adult asthmatics in order to further understand its pathogenic mechanisms.MethodsA total of 1,452 adult asthmatics were enrolled from a single tertiary hospital and were classified into 2 groups: 234 elderly (≥ 60 years at initial diagnosis) and 1,218 non-elderly (< 60 years at initial diagnosis) asthmatics. Asthma-related clinical parameters were compared between the 2 groups. Serum levels of epithelial cell-derived cytokines including interleukin (IL)-31, IL-33, IL-8, eotaxin-2, transforming growth factor beta 1 (TGF-β1) and periostin were measured by enzyme-linked immunosorbent assay.ResultsSignificantly higher prevalence rates of late-onset asthma (onset age ≥ 40 years) and severe asthma, as well as the lower rate of atopy, blood/sputum eosinophil counts, total immunoglobulin E and eosinophil cationic protein levels were noted in elderly asthmatics compared to non-elderly asthmatics (P < 0.05, respectively). The forced expiratory volume in 1 second (FEV1, % predicted) level tended to be lower in elderly asthmatics (P = 0.07). In addition, serum IL-33 and IL-31 levels were significantly lower in elderly asthmatics, while no differences were found in the serum level of IL-8, eotaxin-2, TGF-β1 or periostin. Among elderly asthmatics, subjects with severe asthma had lower FEV1 (% predicted) value, but showed significantly higher serum levels of eotaxin-2 and TGF-β1, than those with non-severe asthma (P < 0.05 for each).ConclusionsThese findings suggest that age-related changes of epithelial cell-derived cytokines may affect clinical phenotypes and severity of elderly asthma: decreased levels of IL-33 and IL-31 may contribute to less Th2 phenotype, while increased levels of eotaxin-2 and TGF-β1 may contribute to severity.

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“…All patients and healthy donors provided written informed consent before the sample collection. Patients with asthma got the asthma diagnosis on the basis of recurrent episodes of wheezing, dyspnea, cough, and sputum production as well as evidence of either airway hyperresponsiveness to methacholine or reversible airway obstruction improved by a short‐acting β2 agonist ( 22 ). Among the enrolled patients with eosinophilic asthma, severe asthma was defined according to the definition by the International European Respiratory Society/American Thoracic Society guidelines ( 23 ).…”

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“…Asthma seems also to be related with particular phenotypes ( Kuruvilla et al., 2019 ). In elderly asthmatic patients serum IL-33 and IL-31 levels were found lower, and this may contribute to less Th2 phenotype and asthma severity ( Ulambayar et al., 2018 ). Bronchoalveolar lavage (BAL) fluids in asthmatic recipients showed elevated levels of IL-1RA, IL-1 α , IL-1 β , IL-2R α , IL-5, IL-6, IL-7, IL-8, G-CSF, GRO α (CXCL1), MIP-1 β (CCL4), MIG (CXCL9), RANTES (CCL5) and TRAIL, eosinophils and neutrophils ( Hosoki et al., 2015 ).…”