INDUCED SPUTUM: A NON-INVASIVE TOOL FOR EVALUATION OF LUNG INVOLVEMENT AND ALVEOLAR INFLAMMATION IN SYSTEMIC SCLEROSIS

Background: Induced sputum (IS) is a noninvasive technique used to collect and analyze cellular and soluble materials from lung airways. In asthma and chronic obstructive pulmonary disease IS has been successfully applied as a complementary tool to invasive techniques, such as biopsy and bronchoalveolar lavage (BAL). So far, we have no information about the usefulness of IS in assessing alveolitis in patients (pts) with systemic sclerosis (SSc). BAL is well established tool for assessment of alveolitis in SSc. High percentage of neutrophils in BAL liquid is associated with extensive lung fibrosis. If differential cell counts of cell samples obtained by IS and BAL are comparable, invasive BAL technique could be replaced by noninvasive IS method in assessing lung disease in SSc. Objectives: To evaluate if IS may be a useful and safe tool to detect fibrosing alveolitis in pts with SSc. Methods: Forty five pts with SSc (mean age 55 years, mean disease duration 5 years and 10 months) and 20 healthy adults were selected for IS examination after a written informed consent. On 32 pts BAL was also performed. Safety of IS was assessed by comparison of FEV1, FEV1/FVC and PEF before and after the procedure. In SSc pts, cell compositions of BAL and IS were correlated, the IS total and differential cell counts were compared in SSc pts and controls, as well as in patients with limited (lSSc) and diffuse SSc (dSSc). Student's T-test, Mann-Whitney test, and Spearman's test were used for statistical analysis. Results: Compared to baseline, a significant improvement of mean FEV1 (84.9% vs. 89.1%, p=0.001) and FEV1/FVC (98.4% vs. 105.1%, p<0.001) was observed after the sputum induction. The mean value of PEF did not change significantly (87.9% vs. 84.2%, p=0.21). The total number of inflammatory cells was significantly higher in IS of SSc pts than in controls (2.4 million/ml vs. 1.5 million/ml, p=0.03). The mean percentage of neutrophils was higher in SSc pts than in healthy adults (56.0% vs. 26.5%, p=0.001), as well as mean percentage of lymphocytes (7.9% vs. 3.0%, p<0.001) and mean percentage of eosinophils (1.9% vs. 0.4%, p=0.002). The mean percentage of macrophages was higher in controls, compared to SSc pts (70.2% vs. 33.9%, p<0.001). The total number of inflammatory cells was significantly higher in BAL than in IS(p<0.001). In fluid recovered by BAL, most of cells were macrophages (67.9%), neutrophils (15.3%) and lymphocytes (14.9%) were less frequent, and eosinophils (1.8%) were rare. A similar pattern of cell composition was found in IS samples (43.7% macrophages, 42.1% neutrophils, 11.7% lymphocytes and 2.2% eosinophils). Strength of correlation between BAL and IS was significant for all cell types, except for lymphocytes. The total and differential cell counts did not differ significantly between patients with lSSc and dSSc. Conclusion: Our results showed strong correlation between IS and BAL in number of neutrophils, presumed indicators of extensive fibrotic disease in SSc, suggesting that IS may be a safe and useful tool to detect fibrosing alveolitis in SSc. IS method supplied information comparable to BAL findings in patients with SSc, indicating that invasive BAL technique could be replaced by noninvasive IS method in assessing lung disease in SSc.