title: Reduced Antiviral Interferon Production in Poorly Controlled Asthma Is Associated With Neutrophilic Inflammation and High-Dose Inhaled Corticosteroids.
abstract: 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.
authors.affiliation: Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, New Lambton, NSW, Australia; Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Callaghan, NSW, Australia. Electronic address: jodie.simpson@newcastle.edu.au.
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Simpson
authors.affiliation: School of Medicine, The University of Queensland, St Lucia, QLD, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Carroll
authors.affiliation: School of Medicine, The University of Queensland, St Lucia, QLD, Australia; Department of Thoracic Medicine, The Prince Charles Hospital, Chermside, QLD, Australia.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yang
authors.affiliation: Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia; Lung Research Laboratory, Hanson Institute, Adelaide, SA, Australia.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Reynolds
authors.affiliation: Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia; Lung Research Laboratory, Hanson Institute, Adelaide, SA, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hodge
authors.affiliation: Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; School of Medicine and Pharmacology, The University of Western Australia, Nedlands, WA, Australia.
authors.forename: Alan L
authors.initials: AL
authors.lastname: James
authors.affiliation: Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, New Lambton, NSW, Australia; Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Callaghan, NSW, Australia; Woolcock Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
authors.affiliation: School of Medicine, The University of Queensland, St Lucia, QLD, Australia; Department of Respiratory Medicine, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: Upham
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000276:immunology; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology; D016209:Interleukin-8 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D012229:Rhinovirus / Q000276:immunology*; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D054357:Chemokine CXCL10; D005938:Glucocorticoids; C508585:IL1B protein, human; D016898:Interferon-alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D016899:Interferon-beta
keywords: asthma; inhaled corticosteroids; interferon; neutrophil; rhinovirus