title: Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults.
abstract: In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response to damage, has been suggested as a link between viral infection and type 2 inflammation, but the role of TSLP in asthma exacerbations is unknown.
  
  
  
  To assess whether type 2 inflammation, as measured by sputum eosinophils and fractional exhaled nitric oxide (FeNO), is a feature of naturally occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation.
  
  
  
  Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum for differential counts and TSLP mRNA levels. Nasal swabs were collected for viral detection.
  
  
  
  Sputum eosinophils and FeNO were similar between virus-positive (n = 44) and negative patients (n = 44). In virus-positive patients, TSLP expression was lower at exacerbation than follow-up (p = 0.03). High TSLP at exacerbation was associated with lower sputum eosinophils (p = 0.01) and higher FEV1 (p = 0.03). In virus-positive patients, %-predicted FEV1 negatively correlated with both FeNO and sputum eosinophils (p = 0.02 and p = 0.05, respectively).
  
  
  
  Our findings support that type 2 inflammation is present in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo, in the setting of an asthma exacerbation, might be different than the type 2 inducing effects observed in experimental studies.
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; Telethon Kids Institute, Perth, Australia; School of Paediatrics & Child Health, University of Western Australia, Perth, Australia. Electronic address: asger.bjerregaard@dadlnet.dk.
authors.forename: Asger
authors.initials: A
authors.lastname: Bjerregaard
authors.affiliation: Telethon Kids Institute, Perth, Australia; School of Paediatrics & Child Health, University of Western Australia, Perth, Australia.
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Laing
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; Telethon Kids Institute, Perth, Australia; School of Paediatrics & Child Health, University of Western Australia, Perth, Australia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Poulsen
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Backer
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Asger
authors.initials: A
authors.lastname: Sverrild
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Markus
authors.initials: M
authors.lastname: Fally
authors.affiliation: Telethon Kids Institute, Perth, Australia; School of Paediatrics & Child Health, University of Western Australia, Perth, Australia.
authors.forename: Siew-Kim
authors.initials: SK
authors.lastname: Khoo
authors.affiliation: Institute for Respiratory Health, University of Western Australia, Perth, Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Barrett
authors.affiliation: Institute for Respiratory Health, University of Western Australia, Perth, Australia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Baltic
authors.affiliation: Institute for Respiratory Health, University of Western Australia, Perth, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Thompson
authors.affiliation: Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, Australia.
authors.forename: Glenys
authors.initials: G
authors.lastname: Chidlow
authors.affiliation: Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Chisha
authors.initials: C
authors.lastname: Sikazwe
authors.affiliation: Telethon Kids Institute, Perth, Australia; Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Smith
authors.affiliation: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, USA.
authors.forename: Yury A
authors.initials: YA
authors.lastname: Bochkov
authors.affiliation: School of Paediatrics & Child Health, University of Western Australia, Perth, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Le Souëf
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Celeste
authors.initials: C
authors.lastname: Porsbjerg
mesh_terms: D000208:Acute Disease; D000328:Adult; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004802:Eosinophilia / Q000821:virology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D012141:Respiratory Tract Infections / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D012720:Severity of Illness Index; D013147:Spirometry; D013183:Sputum / Q000166:cytology / Q000378:metabolism; D014777:Virus Diseases / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D009569:Nitric Oxide; D000094632:Thymic Stromal Lymphopoietin
keywords: Asthma; Eosinophils; Exacerbation; TSLP; Viral infection