Mesenchymal stromal cells in bronchoalveolar lavage as predictors of bronchiolitis obliterans syndrome

Abstract

Rationale: Bronchoalveolar lavage fluid (BAL) from human lung allografts demonstrates the presence of a multipotentmesenchymal 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. Objectives: 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. Measurements and Main 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) andmultivariate (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.