An international collaborative pathologic study of surgical lung biopsies from mustard gas-exposed patients.

BACKGROUND: Recent studies have shown strong evidence that bronchiolitis obliterans is the major long-term sequelae of exposure to sulfur mustard (SM). This study is the first to examine the histopathologic spectrum of changes in a large number of surgical lung biopsies from patients exposed to SM. METHOD: Fifteen patients with chronic respiratory disease from mustard gas exposure were divided into severe (6 cases) and mild exposure (9 cases). All had surgical (open or thoracoscopic) lung biopsy, pulmonary function tests (PFTs) and chest high-resolution computed tomography scan (HRCT). RESULT: The mean age of the cases was 43.8+/-9.6 (range 33-65). All patients had dyspnea and cough as the two main complaints. Only one patient was a smoker. Thirteen patients had normal PFTs, while one had obstruction and one had mild restriction. Six (66.6%) patients in the mild exposure and 3 (50%) in the severe exposure group showed evidence of more than 25% air trapping on chest HRCT. Among the mild group, 3 had features of constrictive bronchiolitis and another had features suggestive of this (bronchiolectasis and mucus stasis). The next most common finding was a mild-to-moderate chronic cellular bronchiolitis (3 patients). Two among the 6 in the severe group showed constrictive bronchiolitis and one showed features suggestive of constrictive bronchiolitis. CONCLUSION: We conclude that about half of patients had diagnostic constrictive bronchiolitis, or bronchiolectasis and mucus stasis consistent with more proximal luminal compromise. The fact that there were no differences between the low- and high-dose groups suggests that effects of SM are not solely dependent on the severity of exposure. The results also indicate that the diagnosis of chronic lung disease due to SM may be difficult. Surgical lung biopsy may be helpful in difficult cases, as constrictive (obliterative) bronchiolitis can be present in symptomatic patients with normal PFTs and chest HRCT.

Use of immunohistochemistry techniques in patients exposed to sulphur mustard gas.

We performed a pathologic study with further using an immunohistochemical technique (using anti-p63 and anti-CK5) on tissues obtained by open lung biopsy from 18 patients with previous exposure to sulphur mustard (SM) as case group and 8 unexposed patients (control group). The most frequent pathologic diagnosis was constrictive bronchiolitis (44.4%), followed by respiratory (22.2%) and chronic cellular bronchiolitis (16.7%) in the case group, and hypersensitivity bronchiolitis (50%) in the control group. The pathologic diagnoses were significantly different in the case and control groups (P = 0.042). In slides stained by anti-p63 and anti-CK5, the percent of stained cells and the mean number of epithelial cells were lower in the case group in comparison to the control group. This difference was significant for the mean number of cells stained by anti-CK5 (P = 0.042). Furthermore, there was a significant correlation between pathologic diagnosis and total number of cells and mean number of cells stained with anti-p63 and anti-CK5 (P value = 0.002, <0.001, 0.044). These results suggest that constrictive bronchiolitis may be the major pathologic consequence of exposure to SM. Moreover, decrease of p63 in respiratory tissues affected by SM may suggest the lack of regenerative capacity in these patients.