No abstract

Background: The role of bronchoalveolar lavage fluid (BALF) cell profiles in predicting the clinical outcome of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is still under discussion. Objective: To determine whether BALF cell profiles affect the survival of patients with UIP diagnosed by surgical lung biopsy/autopsy at the early stage of IPF. Methods: This hospital-based retrospective cohort study used 81 Japanese patients with histologically proven IPF/UIP who underwent BAL examination. The BALF samples were obtained from non-current smokers: NCS (n = 41) and current smokers: CS (n = 40). The Kaplan-Meier and Cox’s proportional hazard methods were used to estimate the survival and evaluate the risk ratio for death in the two groups. To detect the multicollinearity, a stepwise regression was employed. Results: A slight increase in the absolute numbers of BALF neutrophils tended to relate to a decrease in the relative risk for death in NCS patients and CS patients in the univariate analysis. In stepwise regression, the increase in percent vital capacity and the increase in the BALF CD4/CD8 ratio in NCS was detected as a favorable predictor, while increased BALF cells affected the results due to chronic smoking in CS. Conclusions: Based on the study bias of the biopsy-proven IPF/UIP patients at stable stages, an independent variable indicating a favorable outcome was an increased BALF CD4/CD8 ratio in NCS patients, while it was difficult to identify definite prognosticators in CS patients.

The clinical features of sarcoidosis vary in different ethnic groups, suggesting that different genetic or environmental backgrounds influence the disease. In Scandinavian sarcoidosis patients, we have previously described a correlation between lung-accumulated CD4+ T cells expressing the T-cell receptor (TCR) V alpha 2.3 gene segment and a particular HLA type (DR3[17],DQ2). For purposes of comparison, we have in this study investigated TCR V gene usage and gamma delta TCR expression in CD4+ and CD8+ T cells in bronchoalveolar lavage (BAL) fluid and peripheral blood in an ethnically distinct and homogenous group of individuals consisting of Japanese sarcoidosis patients and healthy controls. We used a panel of 13 monoclonal antibodies (Mab) specific for different TCR V genes, which altogether stained approximately 50% of the T cells, and triple staining techniques with flow cytometry. The patients and controls were also HLA-typed. Our results show a high degree of expression of gamma delta TCR in peripheral blood T cells of close to half of the patients. Expansions of T-cell subsets were readily detected in the CD8+ T-cell population, while a more homogenous staining pattern was found in the CD4+ T-cell population. These findings show the importance of ethnic origin and environment in discussions of TCR V gene usage.

Background: Various factors such as serum angiotensin-converting enzyme (sACE) activity, bronchoalveolar lavage (BAL) fluid lymphocyte percent, CD4/CD8 ratio, and shadows on chest radiograph have been identified as indexes of disease activity in patients with sarcoidosis. However, it remains to be confirmed whether these factors can predict clinical outcomes. Objective: To examine whether the interleukin-1 receptor antagonist (IL-1ra)/IL-1β ratio can predict the clinical course, we prospectively followed the clinical courses of 30 patients with pulmonary sarcoidosis 4 years after measurement of immunoreactive amounts of IL-1ra or IL-1β in the culture supernatants obtained from BAL fluid macrophages. Methods: Immunoreactive amounts of IL-1ra or IL-1β were measured using ELISA. Changes in pulmonary function, sACE activity, and shadows on chest radiographs during observation periods were evaluated as markers of changes in disease activity. Results: We found that the patients whose shadows on chest radiographs showed improvement had a higher molar IL-1ra/IL-1β ratio than the patients whose shadows persistently remained 4 years after BAL examination (p < 0.05). The molar ratio was found to be positively correlated with improvement of percent vital capacity (p < 0.05) and negatively correlated with the ratio of sACE activity at the time of the last observation to sACE activity at the time of BAL (sACE_LAST/sACE_BAL, p < 0.01). The sACE_LAST/sACE_BAL ratio was significantly lower in patients whose shadows on chest radiographs decreased than in those whose shadows remained unchanged (p < 0.005). Conclusion: The IL-1ra/IL-1β ratio in the BAL fluid macrophage culture supernatants in patients with pulmonary sarcoidosis could be a useful marker in predicting the persistence of granulomatous lesions (chronicity).