title: High rhinovirus burden in lower airways of children with cystic fibrosis.
abstract: BACKGROUND
  Rhinovirus (RV)-induced pulmonary exacerbations are common in cystic fibrosis (CF) and have been associated with impaired virus clearance by the CF airway epithelium in vitro. Here, we assess in vivo the association of RV prevalence and load with antiviral defense mechanisms, airway inflammation, and lung function parameters in children with CF compared with a control group and children with other chronic respiratory diseases.
  
  
  METHODS
  RV presence and load were measured by real-time reverse transcription-polymerase chain reaction in BAL samples and were related to antiviral and inflammatory mediators measured in BAL and to clinical parameters.
  
  
  RESULTS
  BAL samples were obtained from children with CF (n = 195), non-CF bronchiectasis (n = 40), or asthma (n = 29) and from a control group (n = 35) at a median (interquartile range [IQR]) age of 8.2 (4.0-11.7) years. RV was detected in 73 samples (24.4%). RV prevalence was similar among groups. RV load (median [IQR] x 10(3) copies/mL) was higher in children with CF (143.0 [13.1-1530.0]), especially during pulmonary exacerbations, compared with children with asthma (3.0 [1.3-25.8], P = .006) and the control group (0.5 [0.3-0.5], P < .001), but similar to patients with non-CF bronchiectasis (122.1 [2.7-4423.5], P = not significant). In children with CF, RV load was negatively associated with interferon (IFN)- b and IFN- l , IL-1ra levels, and FEV 1 , and positively with levels of the cytokines CXCL8 and CXCL10.
  
  
  CONCLUSIONS
  RV load in CF BAL is high, especially during exacerbated lung disease. Impaired production of antiviral mediators may lead to the high RV burden in the lower airways of children with CF. Whether high RV load is a cause or a consequence of inflammation needs further investigation in longitudinal studies.
authors.affiliation: Division of Pediatric Respiratory Medicine, Department of Pediatrics, University Hospital, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kieninger
authors.affiliation: Division of Pediatric Respiratory Medicine, Department of Pediatrics, University Hospital, Bern, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Singer
authors.affiliation: Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Tapparel
authors.affiliation: Division of Pediatric Respiratory Medicine, Department of Pediatrics, University Hospital, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Marco P
authors.initials: MP
authors.lastname: Alves
authors.affiliation: Division of Pediatric Respiratory Medicine, Department of Pediatrics, University Hospital, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Latzin
authors.affiliation: Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, England.
authors.forename: Hui-Leng
authors.initials: HL
authors.lastname: Tan
authors.affiliation: Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, England.
authors.forename: Cara
authors.initials: C
authors.lastname: Bossley
authors.affiliation: Division of Pediatric Respiratory Medicine, Department of Pediatrics, University Hospital, Bern, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Casaulta
authors.affiliation: Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, England.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
authors.affiliation: Department of Pediatric Respiratory Medicine, Royal Brompton Hospital, London, England.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Davies
authors.affiliation: Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Kaiser
authors.affiliation: Division of Pediatric Respiratory Medicine, Department of Pediatrics, University Hospital, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland. Electronic address: nicolas.regamey@insel.ch.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Regamey
mesh_terms: D001980:Bronchi / Q000821:virology*; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D001999:Bronchoscopy; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000821:virology*; D016207:Cytokines / Q000032:analysis; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D015851:Interleukin-7 / Q000032:analysis; D008297:Male; D012229:Rhinovirus / Q000502:physiology*; D019562:Viral Load; D014779:Virus Replication; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D015851:Interleukin-7; D000094632:Thymic Stromal Lymphopoietin