title: Symptomatic Respiratory Virus Infection and Chronic Lung Allograft Dysfunction.
abstract: BACKGROUND
  Chronic lung allograft dysfunction (CLAD) is a major cause of allograft loss post-lung transplantation. Prior studies have examined the association between respiratory virus infection (RVI) and CLAD were limited by older diagnostic techniques, study design, and case numbers. We examined the association between symptomatic RVI and CLAD using modern diagnostic techniques in a large contemporary cohort of lung transplant recipients (LTRs).
  
  
  METHODS
  We retrospectively assessed clinical variables including acute rejection, cytomegalovirus pneumonia, upper and lower RVI, and the primary endpoint of CLAD (determined by 2 independent reviewers) in 250 LTRs in a single university transplantation program. Univariate and multivariate Cox models were used to analyze the relationship between RVI and CLAD in a time-dependent manner, incorporating different periods of risk following RVI diagnosis.
  
  
  RESULTS
  Fifty patients (20%) were diagnosed with CLAD at a median of 95 weeks post-transplantation, and 79 (32%) had 114 episodes of RVI. In multivariate analysis, rejection and RVI were independently associated with CLAD (adjusted hazard ratio [95% confidence interval]) 2.2 (1.2-3.9), P = .01 and 1.9 (1.1-3.5), P = .03, respectively. The association of RVI with CLAD was stronger the more proximate the RVI episode: 4.8 (1.9-11.6), P < .01; 3.4 (1.5-7.5), P < .01; and 2.4 (1.2-5.0), P = .02 in multivariate analysis for 3, 6, and 12 months following RVI, respectively.
  
  
  CONCLUSIONS
  Symptomatic RVI is independently associated with development of CLAD, with increased risk at shorter time periods following RVI. Prospective studies to characterize the virologic determinants of CLAD and define the underlying mechanisms are warranted.
authors.affiliation: Department of Medicine, University of Washington.|Vaccine and Infectious Disease Division.
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Fisher
authors.affiliation: Department of Medicine, University of Washington.
authors.forename: Carl M
authors.initials: CM
authors.lastname: Preiksaitis
authors.affiliation: Department of Medicine, University of Washington.
authors.forename: Erika D
authors.initials: ED
authors.lastname: Lease
authors.affiliation: Department of Medicine, University of Washington.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Edelman
authors.affiliation: Department of Medicine, University of Washington.
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Kirby
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Leisenring
authors.affiliation: Department of Medicine, University of Washington.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.affiliation: Department of Medicine, University of Washington.|Vaccine and Infectious Disease Division.|Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.affiliation: Department of Medicine, University of Washington.
authors.forename: Ajit P
authors.initials: AP
authors.lastname: Limaye
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000209:etiology*; D006785:Hospitals, University; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000150:complications* / Q000821:virology; D012189:Retrospective Studies; D066027:Transplant Recipients; D014777:Virus Diseases / Q000150:complications*; D055815:Young Adult
keywords: bronchiolitis obliterans; chronic lung allograft dysfunction; lung transplantation; respiratory virus infection; restrictive allograft dysfunction