期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 183, 期 8, 页码 1062-1070出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201005-0742OC
关键词
bronchiolitis obliterans syndrome; acute rejection; bronchoalveolar lavage
资金
- NIH [R01HL094622, R01HL85149, R01HL55397]
- American Thoracic Society
- Scleroderma Research Foundation
- ATS
- Nycomed
- Novartis
- AstraZeneca/MedImmune
- Elan
- Bayer
- Genzyme
- Quark
- Johnson/Centocor
- Gilead
- Boehringer Ingelheim
Rationale: 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. 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) 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.
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