title: High fractional exhaled nitric oxide and sputum eosinophils are associated with an increased risk of future virus-induced exacerbations: A prospective cohort study.
abstract: BACKGROUND
  The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus-induced exacerbations is unknown.
  
  
  OBJECTIVE
  To assess whether type 2 inflammation is associated with an increased risk of virus-induced exacerbations of asthma.
  
  
  METHODS
  Stable asthmatics had spirometry, skin prick test, measurement of FeNO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR.
  
  
  RESULTS
  A total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow-up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus-induced exacerbation (HR 7.6 95% CI: 1.6-35.2, P=.010) as did having FeNO >25 ppb (HR 3.4 95% CI: 1.1-10.4, P=.033).
  
  
  CONCLUSIONS
  Established type 2 inflammation during stable disease is a risk factor for virus-induced exacerbations in a real-life setting. Measures of type 2 inflammation, such as sputum eosinophils and FeNO, could be included in the risk assessment of patients with asthma in future studies.
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.|Telethon Kids Institute, Perth, WA, Australia.|School of Paediatrics & Child Health, University of Western Australia, Perth, WA, Australia.
authors.forename: A
authors.identifier: http://orcid.org/0000-0001-8043-0171
authors.initials: A
authors.lastname: Bjerregaard
authors.affiliation: Telethon Kids Institute, Perth, WA, Australia.|School of Paediatrics & Child Health, University of Western Australia, Perth, WA, Australia.
authors.forename: I A
authors.initials: IA
authors.lastname: Laing
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: V
authors.initials: V
authors.lastname: Backer
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Sverrild
authors.affiliation: Telethon Kids Institute, Perth, WA, Australia.|School of Paediatrics & Child Health, University of Western Australia, Perth, WA, Australia.
authors.forename: S-K
authors.initials: SK
authors.lastname: Khoo
authors.affiliation: Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, WA, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Chidlow
authors.affiliation: Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, WA, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Sikazwe
authors.affiliation: Telethon Kids Institute, Perth, WA, Australia.|Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, WA, Australia.|School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia.
authors.forename: D W
authors.initials: DW
authors.lastname: Smith
authors.affiliation: School of Paediatrics & Child Health, University of Western Australia, Perth, WA, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Le Souëf
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Porsbjerg
mesh_terms: D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D001944:Breath Tests; D004804:Eosinophils / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011446:Prospective Studies; D013183:Sputum / Q000378:metabolism*; D014777:Virus Diseases / Q000378:metabolism* / Q000473:pathology
chemical_list: D009569:Nitric Oxide
keywords: Asthma; FeNO; eosinophils; exacerbation