© 2008 American Thoracic Society
Prognostic Significance of Bronchoalveolar Lavage Cellular Analysis in Scleroderma Lung DiseaseFrom the Authors:We thank Drs. Kinder and King for their thoughtful remarks on our article, which considered bronchoalveolar lavage (BAL) neutrophilia as a prognostic indicator in interstitial lung disease (1). They comment on three recent BAL reports that address this issue, in addition to our study (1), including retrospective analyses performed in 156 patients with idiopathic pulmonary fibrosis (IPF) (2) and 141 patients with scleroderma-related interstitial lung disease (SSc-ILD) (3), as well as our prospective randomized control trial in 158 patients with SSc-ILD. In each case, patients with BAL neutrophils in excess of 3% exhibited significantly worse pulmonary function and/or chest high-resolution computed tomography (HRCT) findings at baseline, suggesting that BAL cellularity might define a unique subgroup or a subset with more advanced disease. However, in the two SSc-ILD studies, there were no differences in either progression of pulmonary function changes or in overall mortality when results were adjusted for these baseline differences. Furthermore, in the Scleroderma Lung Study (4), neutrophilia was not found to be an independent predictor of clinical responses to cyclophosphamide. As such, both of the SSc-ILD studies concluded that addition of a bronchoscopy with BAL is not likely to add important clinical information to the treatment of these patients. Exactly how these findings in SSc-ILD relate to IPF remains to be resolved. While all of the patients reported by Kinder and coworkers had biopsy-proven usual interstitial pneumonia (UIP), the majority of SSc-ILD patients exhibit findings consistent with nonspecific interstitial pneumonia (NSIP). This may account for the significant difference in mortality, which averaged 43% at 24 months in the IPF subjects followed by Kinder and coworkers, but only 4 to 17% over the same interval in the two SSc-ILD studies. It is possible that BAL neutrophilia adds to the prediction of mortality in IPF subjects in a manner that is not directly relevant to patients with SSc-ILD. Additional studies in IPF patients that allow correction for baseline HRCT findings (as performed in the two SSc-ILD studies), better control for other variables and treatment effects (i.e., a prospective design), or directly compare results in subjects with UIP with those with NSIP (to examine differences between these diseases) might be useful in addressing this question. Furthermore, there might be other features of the BAL, such as profiles of cytokines, chemokines, and/or growth factors, that provide important new insights. While BAL might not fulfill the criteria for a first-line clinical tool in the management of patients with SSc-ILD, we agree with the general conclusion by Drs. Kinder and King that continued research employing BAL to address these and other questions should be promoted.
Medical University of South Carolina
David Geffen School of Medicine at UCLA FOOTNOTES Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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