title: Mesenchymal stromal cells in bronchoalveolar lavage as predictors of bronchiolitis obliterans syndrome.
abstract: BACKGROUND
  Bronchoalveolar lavage fluid (BAL) from human lung allografts demonstrates the presence of a multipotent mesenchymal stromal cell population. However, the clinical relevance of this novel cellular component of BAL and its association with bronchiolitis obliterans syndrome (BOS), a disease marked by progressive airflow limitation secondary to fibrotic obliteration of the small airways, remains to be determined.
  
  
  OBJECTIVE
  In this study we investigate the association of number of mesenchymal stromal cells in BAL with development of BOS in human lung transplant recipients.
  
  
  METHODS
  Mesenchymal colony-forming units (CFUs) were quantitated in a cohort of 405 BAL samples obtained from 162 lung transplant recipients. Poisson generalized estimating equations were used to determine the predictors of BAL mesenchymal CFU count.
  
  
  RESULTS
  Higher CFU counts were noted early post-transplantation; time from transplant to BAL of greater than 3 months predicted 0.4-fold lower CFU counts (P = 0.0001). BOS diagnosis less than or equal to 365 days before BAL was associated with a 2.11-fold higher CFU count (P = 0.02). There were 2.62- and 2.70-fold higher CFU counts noted in the presence of histologic diagnosis of bronchiolitis obliterans (P = 0.05) and organizing pneumonia (0.0003), respectively. In BAL samples obtained from BOS-free patients greater than 6 months post-transplantation (n = 173), higher mesenchymal CFU counts (≥10) significantly predicted BOS onset in both univariate (hazard ratio, 5.61; 95% CI, 3.03-10.38; P < 0.0001) and multivariate (hazard ratio, 5.02; 95% CI, 2.40-10.51; P < 0.0001) Cox regression analysis.
  
  
  CONCLUSIONS
  Measurement of mesenchymal CFUs in the BAL provides predictive information regarding future BOS onset.
authors.affiliation: 1500 East Medical Center Drive, 3916 Taubman Center, Ann Arbor, MI 48109-0360, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Badri
authors.forename: Susan
authors.initials: S
authors.lastname: Murray
authors.forename: Lyrica X
authors.initials: LX
authors.lastname: Liu
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Walker
authors.forename: Andrew
authors.initials: A
authors.lastname: Flint
authors.forename: Anish
authors.initials: A
authors.lastname: Wadhwa
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Chan
authors.forename: Galen B
authors.initials: GB
authors.lastname: Toews
authors.forename: David J
authors.initials: DJ
authors.lastname: Pinsky
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Vibha N
authors.initials: VN
authors.lastname: Lama
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001989:Bronchiolitis Obliterans / Q000209:etiology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D016012:Poisson Distribution; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000166:cytology; D055815:Young Adult
chemical_list: D015415:Biomarkers