Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis.

BACKGROUND: Serum surfactant protein (SP) A and SP-D had prognostic value for mortality in patients with idiopathic pulmonary fibrosis (IPF) in prior studies before the reclassification of the idiopathic interstitial pneumonias. We hypothesized that baseline serum SP-A and SP-D concentrations would be independently associated with mortality among patients with biopsy-proven IPF and would improve a prediction model for mortality. METHODS: We evaluated the association between serum SP-A and SP-D concentrations and mortality in 82 patients with surgical lung biopsy-proven IPF. Regression models with clinical predictors alone and clinical and biomarker predictors were used to predict mortality at 1 year. RESULTS: After controlling for known clinical predictors of mortality, we found that each increase of 49 ng/mL (1 SD) in baseline SP-A level was associated with a 3.3-fold increased risk of mortality (adjusted hazard ratio, 3.27; 95% confidence interval, 1.49 to 7.17; adjusted p = 0.003) in the first year after presentation. We did not observe a statistically significant association between serum SP-D and mortality (adjusted hazard ratio, 2.04; p = 0.053). Regression models demonstrated a significant improvement in the 1-year mortality prediction model when serum SP-A and SP-D (area under the receiving operator curve [AROC], 0.89) were added to the clinical predictors alone (AROC, 0.79; p = 0.03). CONCLUSIONS: Increased serum SP-A level is a strong and independent predictor of early mortality among patients with IPF. A prediction model containing SP-A and SP-D was substantially superior to a model with clinical predictors alone.

Rheumatoid arthritis (RA)-specific autoantibodies in patients with interstitial lung disease and absence of clinically apparent articular RA.

The purpose of this study was to identify rheumatoid arthritis (RA)-related autoantibodies in subjects with interstitial lung disease (ILD) and no articular findings of RA, supporting the hypothesis that RA-related autoimmunity may be generated in non-articular sites, such as the lung. This was a retrospective chart review utilizing clinic databases of patients with ILD to identify cases with lung disease, RA-related autoantibody positivity, and no clinical evidence of articular RA. Four patients with ILD, RF, and anti-CCP positivity and no articular findings of RA were identified. All four patients were male with a mean age at time of diagnosis of ILD of 70 years old. All had a history of smoking. Three patients died within 2 years of diagnosis of ILD and never developed articular symptoms consistent with RA; the final case met full criteria for articular RA several months after stopping immunosuppressive treatment for ILD. RF and anti-CCP can be present in smokers with ILD without clinical evidence of articular RA and in one case symptomatic ILD and autoantibody positivity preceded the development of articular RA. These findings suggest that RA-specific autoimmunity may be generated due to immunologic interactions in the lung and may be related to environmental factors such as smoking.

Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis.

BACKGROUND: The prognostic value of BAL fluid cell count differential in patients with idiopathic pulmonary fibrosis (IPF) is unknown. We hypothesized that baseline BAL fluid cell count differential (ie, elevated levels of neutrophils and eosinophils, or reduced levels of lymphocytes) would predict higher mortality among persons with IPF. METHODS: We evaluated the association of BAL fluid cell count differential and mortality among 156 persons with surgical lung biopsy-proven IPF who underwent bronchoscopy with BAL and cell count differential measurements at presentation. Vital status was obtained among all participants. Cox regression analysis evaluated the association of BAL fluid cell count differential and mortality. RESULTS: After controlling for known clinical predictors of mortality, we found that each doubling of baseline BAL fluid neutrophil percentage was associated with a 30% increased risk of mortality (adjusted hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.01 to 1.62; adjusted p = 0.04) in the first year after presentation. We observed no association with BAL fluid lymphocyte percentage and mortality (adjusted HR per doubling, 0.99; 95% CI, 0.76 to 1.29; p = 0.93) or eosinophil percentage and mortality (adjusted HR per doubling, 0.99; 95% CI, 0.69 to 1.40; p = 0.95). CONCLUSIONS: Increased BAL fluid neutrophil percentage is an independent predictor of early mortality among persons with IPF. Alternatively, BAL fluid lymphocyte and eosinophil percentages were not associated with mortality. The clinical utility of BAL at the time of diagnosis of IPF should be reconsidered.