title: The Burden and Long-term Respiratory Morbidity Associated with Respiratory Syncytial Virus Infection in Early Childhood.
abstract: BACKGROUND
  The REGAL (RSV Evidence-a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. The objective of this fifth publication was to determine the long-term respiratory morbidity associated with RSV lower respiratory tract infection (RSV LRTI) in early life.
  
  
  METHODS
  A systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015. This was supplemented by inclusion of papers published whilst drafting the manuscript. Studies reporting data on the incidence and long-term wheezing and asthma following RSV LRTI in early life were included. Study quality and strength of evidence (SOE) were graded using recognized criteria.
  
  
  RESULTS
  A total of 2337 studies were identified of which 74 were included. Prospective, epidemiologic studies consistently demonstrated that RSV LRTI is a significant risk factor for on-going respiratory morbidity characterized by transient early wheezing and recurrent wheezing and asthma within the first decade of life and possibly into adolescence and adulthood (high SOE). RSV LRTI was also associated with impaired lung function in these children (high SOE). Respiratory morbidity has been shown to result in reduced quality of life and increased healthcare resource use (moderate SOE). The mechanisms through which RSV contributes to wheezing/asthma development are not fully understood, but appear to relate to the viral injury, preexisting abnormal lung function and/or other factors that predispose to wheezing/asthma, including genetic susceptibility, altered immunology, eosinophilia, and associated risk factors such as exposure to environmental tobacco smoke (high SOE).
  
  
  CONCLUSIONS
  There is growing evidence that RSV LRTI in early childhood is associated with long-term wheezing and asthma and impaired lung function. Future research should aim to fully elucidate the pathophysiological mechanisms through which RSV causes recurrent wheezing/asthma.
authors.affiliation: Necker University Hospital and Paris 5 University, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Fauroux
authors.affiliation: University of Colorado School of Medicine, and Center for Global Health, Colorado School of Public Health, Aurora, CO, USA.
authors.forename: Eric A F
authors.initials: EAF
authors.lastname: Simões
authors.affiliation: Baylor College of Medicine, Texas Children's Hospital Houston, Houston, TX, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Checchia
authors.affiliation: Department of Paediatrics (Neonatal Division), McMaster University, Hamilton, Canada.
authors.forename: Bosco
authors.initials: B
authors.lastname: Paes
authors.affiliation: Hospital Clínic, Catedràtic de Pediatria, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Figueras-Aloy
authors.affiliation: Sant'Anna Hospital, Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Manzoni
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Bont
authors.affiliation: Hospital Clinic, Institut d'Investigacions Biomediques August Pi Suñer (IDIBAPS), Barcelona, Spain. carbonell@comb.cat.
authors.forename: Xavier
authors.initials: X
authors.lastname: Carbonell-Estrany
keywords: Asthma; Bronchial hyperreactivity; Bronchiolitis; Lower respiratory tract infection; Lung function; Recurrent wheezing; Respiratory morbidity; Sensitization; Wheezing