title: Effect of etiology and timing of respiratory tract infections on development of bronchiolitis obliterans syndrome.
abstract: BACKGROUND
  Among the many potential risk factors influencing the development of bronchiolitis obliterans syndrome (BOS), acute cellular rejection is the most frequently identified. Despite the unique susceptibility of the lung allograft to pathogens, the association with respiratory tract infections remains unclear. In this study we analyze the role respiratory tract infections have on the development of BOS after lung transplantation.
  
  
  METHODS
  Data from a single center were analyzed from 161 lung recipients transplanted from November 1990 to November 2005, and who survived >180 days. Univariate and multivariate Cox regression analyses were performed using BOS development and the time-scale was reported with hazard ratios (HRs) and confidence intervals (CIs).
  
  
  RESULTS
  Significant findings by univariate analysis per 100 patient-days prior to BOS onset included acute rejection, cytomegalovirus (CMV) pneumonitis, Gram-negative respiratory tract infections, Gram-positive respiratory tract infections and fungal pneumonias. Multivariate analysis indicated acute rejection, Gram-negative, Gram-positive and fungal pneumonias with HRs (CI) of 84 (23 to 309), 6.6 (1.2 to 37), 6,371 (84 to 485,000) and 314 (53 to 1,856) to be associated with BOS, respectively. Acute rejection, CMV pneumonitis, Gram-positive pneumonia and fungal pneumonitis in the first 100 days had HRs (CI) of 1.8 (1.1 to 3.2), 3.1 (1.3 to 6.9), 3.8 (1.5 to 9.4) and 2.1 (1.1 to 4.0), respectively, and acute rejection and fungal pneumonitis in the late post-operative period with HRs (CI) of 2.3 (1.2 to 4.4) and 1.5 (1.1 to 1.9), respectively.
  
  
  CONCLUSIONS
  In addition to acute rejection, pneumonias with GP, GN and fungal pathogens occurring prior to BOS are independent determinants of chronic allograft dysfunction. Early recognition and treatment of these pathogens in lung transplant recipients may improve long-term outcomes after transplantation.
authors.affiliation: Texas Transplant Center, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0772, USA. vgvalent@utmb.edu
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Valentine
authors.forename: Meera R
authors.initials: MR
authors.lastname: Gupta
authors.forename: James E
authors.initials: JE
authors.lastname: Walker
authors.forename: Leonardo
authors.initials: L
authors.lastname: Seoane
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Bonvillain
authors.forename: Gisele A
authors.initials: GA
authors.lastname: Lombard
authors.forename: David
authors.initials: D
authors.lastname: Weill
authors.forename: Gundeep S
authors.initials: GS
authors.lastname: Dhillon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001989:Bronchiolitis Obliterans / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology*; D016905:Gram-Negative Bacterial Infections / Q000453:epidemiology / Q000209:etiology; D016908:Gram-Positive Bacterial Infections / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D015994:Incidence; D016040:Lung Transplantation / Q000009:adverse effects / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000453:epidemiology / Q000209:etiology; D011014:Pneumonia / Q000453:epidemiology / Q000209:etiology; D011183:Postoperative Complications / Q000453:epidemiology*; D012141:Respiratory Tract Infections / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult