title: A mechanistic role for type III IFN-λ1 in asthma exacerbations mediated by human rhinoviruses.
abstract: BACKGROUND
  Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear.
  
  
  OBJECTIVE
  To determine the role of HRV in pediatric asthma exacerbations and the mechanisms mediating wheezing.
  
  
  METHODS
  We prospectively studied 409 children with asthma presenting with upper respiratory infection in the presence or absence of wheezing. Candidate viral and immune mediators of illness were compared among children with asthma with different degrees of severity of acute asthma.
  
  
  RESULTS
  HRV infections specifically associated with asthma exacerbations, even after adjusting for relevant demographic and clinical variables defined a priori (odds ratio, 1.90; 95% confidence interval, 1.21-2.99; P = 0.005). No difference in virus titers, HRV species, and inflammatory or allergic molecules was observed between wheezing and nonwheezing children infected with HRV. Type III IFN-λ(1) levels were higher in wheezing children infected with HRV compared with nonwheezing (P < 0.001) and increased with worsening symptoms (P < 0.001). Moreover, after adjusting for IFN-λ(1), children with asthma infected with HRV were no longer more likely to wheeze than those who were HRV-negative (odds ratio, 1.18; 95% confidence interval, 0.57-2.46; P = 0.66).
  
  
  CONCLUSIONS
  Our findings suggest that HRV infections in children with asthma are specifically associated with acute wheezing, and that type III IFN-λ(1) responses mediate exacerbations caused by HRV. Modulation of IFN- λ(1) should be studied as a therapeutic target for exacerbations caused by HRV.
authors.affiliation: Department of Pediatrics, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: E Kathryn
authors.initials: EK
authors.lastname: Miller
authors.forename: Johanna Zea
authors.initials: JZ
authors.lastname: Hernandez
authors.forename: Vera
authors.initials: V
authors.lastname: Wimmenauer
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: Diego
authors.initials: D
authors.lastname: Hijano
authors.forename: Romina
authors.initials: R
authors.lastname: Libster
authors.forename: M Elina
authors.initials: ME
authors.lastname: Serra
authors.forename: Niranjan
authors.initials: N
authors.lastname: Bhat
authors.forename: Juan P
authors.initials: JP
authors.lastname: Batalle
authors.forename: Yassir
authors.initials: Y
authors.lastname: Mohamed
authors.forename: Andrea
authors.initials: A
authors.lastname: Reynaldi
authors.forename: Andrea
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Monica
authors.initials: M
authors.lastname: Otello
authors.forename: Nestor
authors.initials: N
authors.lastname: Pisapia
authors.forename: Jimena
authors.initials: J
authors.lastname: Bugna
authors.forename: Miguel
authors.initials: M
authors.lastname: Bellabarba
authors.forename: David
authors.initials: D
authors.lastname: Kraft
authors.forename: Silvina
authors.initials: S
authors.lastname: Coviello
authors.forename: F Martin
authors.initials: FM
authors.lastname: Ferolla
authors.forename: Aaron
authors.initials: A
authors.lastname: Chen
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.forename: John V
authors.initials: JV
authors.lastname: Williams
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Polack
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000150:complications* / Q000503:physiopathology / Q000821:virology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007372:Interferons; D015850:Interleukin-6 / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D008297:Male; D010850:Picornaviridae Infections / Q000150:complications* / Q000503:physiopathology; D011446:Prospective Studies; D012135:Respiratory Sounds / Q000503:physiopathology; D012229:Rhinovirus; D012720:Severity of Illness Index; D019562:Viral Load / Q000502:physiology; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D015850:Interleukin-6; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda