Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: Asthma is a heterogeneous chronic inflammatory disease in which host defense against respiratory viruses such as human rhinovirus (HRV) may be abnormal. This is a matter of some controversy, with some investigators reporting reduced type I interferon (IFN) synthesis and others suggesting that type I IFN synthesis is relatively normal in asthma. OBJECTIVE: The objective of this study was to examine the responsiveness of circulating mononuclear cells to HRV in a large cohort of participants with poorly controlled asthma and determine whether IFN-α and IFN-β synthesis varies across different inflammatory phenotypes. METHODS: Eligible adults with asthma (n = 86) underwent clinical assessment, sputum induction, and blood sampling. Asthma inflammatory subtypes were defined by sputum cell count, and supernatant assessed for IL-1β. Peripheral blood mononuclear cells (PBMCs) were exposed to HRV serotype 1b, and IFN-α and IFN-β release was measured by enzyme-linked immunosorbent assay. RESULTS: Participants (mean age, 59 years; atopy, 76%) had suboptimal asthma control (mean asthma control questionnaire 6, 1.7). In those with neutrophilic asthma (n = 12), HRV1b-stimulated PBMCs produced significantly less IFN-α than PBMCs from participants with eosinophilic (n = 35) and paucigranulocytic asthma (n = 35). Sputum neutrophil proportion and the dose of inhaled corticosteroids were independent predictors of reduced IFN-α production after HRV1b exposure. CONCLUSIONS: Antiviral type I IFN production is impaired in those with neutrophilic airway inflammation and in those prescribed high doses of inhaled corticosteroids. Our study is an important step toward identifying those with poorly controlled asthma who might respond best to inhaled IFN therapy during exacerbations.

Original publication

DOI

10.1016/j.chest.2015.12.018

Type

Journal article

Journal

Chest

Publication Date

03/2016

Volume

149

Pages

704 - 713

Keywords

asthma, inhaled corticosteroids, interferon, neutrophil, rhinovirus, Administration, Inhalation, Adrenal Cortex Hormones, Adult, Aged, Aged, 80 and over, Asthma, Chemokine CXCL10, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Forced Expiratory Volume, Glucocorticoids, HeLa Cells, Humans, Interferon-alpha, Interferon-beta, Interleukin-1beta, Interleukin-6, Interleukin-8, Leukocytes, Mononuclear, Male, Middle Aged, Neutrophils, Rhinovirus, Severity of Illness Index, Sputum, Vital Capacity, Young Adult