This study was designed to assess the effect of differential leukocyte depletion during chemotherapy by monitoring the levels of exhaled hydrogen peroxide H 2 O 2 and nitric oxide (FeNO) present.In 39 patients with lung cancer (chronic obstructive pulmonary disorder up to stage II, median forced expiratory volume in one second 78% predicted), measurements were performed before a cycle of therapy (day 1), at least once during the cycle (day 8: n534; day 15: n519), and afterwards (days 21-29).There were significant changes in the level of H 2 O 2 , FeNO and peripheral blood cell differentials over the visits. The level of H 2 O 2 was decreased only on day 15, with a median (difference between the upper and lower quartiles) fall of 31 (57)%, while FeNO was reduced only on day 8, by 22 (40)%. Neutrophil numbers were unchanged on day 8 and decreased by 59 (48)% on day 15, while monocyte numbers were decreased on day 8 by 87 (39)%. On days 21-29, values had returned to baseline.Taken together with previous findings, the parallel course of levels of exhaled hydrogen peroxide and neutrophil counts suggests that a major part of exhaled hydrogen peroxide is due to neutrophils via the conducting airways. In contrast, the production of exhaled nitric oxide seems to be primarily associated with monocytes.

Differentiation of diffuse malignant mesothelioma (DMM) from pleural carcinomatous metastases, e.g., of lung cancer (LC) may be difficult both for the clinician and the pathologist [1, 2] because of the limited diagnostic accuracy of radiologic criteria and conventional light microscopy including histochemistry [3,4]. Immunohistochemical detection of carcinoembryonic antigen (CEA) in tumor biopsy material has been shown to be a valuable diagnostic adjunct, as DMMs, unlike LCs and other carcinomas, express this antigen only rarely (9-11%) [5]. In some cases, however, the only method of obtaining suitable biopsy material is by open thoracotomy [2, 6]. Moreover, immunohistochemical examinations are expensive and not generally readily available. We therefore decided to find out what conclusions may be drawn from the much simpler determination of CEA levels in serum and in pleural effusion fluid (EF).We measured CEA in serum and EF using our own, and five commercially available radioimmunoassays or enzyme immunoassays (Abbott, Behringwerke, CIS, Roche, Pharmacia) with a serum level of 3 mg/L as the upper limit of reference values. In an initial partly retrospective study (learning phase), we examined patients with histologically proven DMM (n = 94) or LC (n = 79). Using ROC analysis, cutoff levels (serum CEA: 5.2 rag/L, EF CEA: 4.5 mg/L) were set so as to produce the most statistically significant differentiation (x2-test) between DMM and LC ( Table 1). The discrimination values specified and published [7] after the learning phase were then evaluated in a strictly prospective fashion in two additional sets of patients. From 1991 to 1992, we determined serum and EF CEA levels in 146 patients participating in the multicentric German DMM study, in all of whom the diagnosis of DMM had been reviewed by a panel of experienced pathologists. For comparison, we analyzed 124 patients who had presented with pleural effusions of unknown aetiology and had subsequently been shown to be suffering from metastatic carcinoma. There was a statistically significant difference between the DMM and the metastatic carcinoma group in terms of the frequency of elevated CEA levels (x2-test, p < 0.01) ( Table I). These results show that simple determination of CEA provides information that is useful for distinguishing between DMM

To investigate the role of leukocytes and neutrophils in the peripheral blood on airway responsiveness, we studied nine patients with chronic bronchitis and histologically proved bronchial carcinoma before and after chemotherapy. The concentration of methacholine (in mg/ml) necessary to increase specific airway resistance by 100%, PC100SRaw, and the number of leukocytes and neutrophils (in cells x 10(6)/ml) were measured before, and 8 and 16 days after chemotherapy. Mean (SEM) total number of leukocytes decreased significantly (p less than 0.001) from 9.0 (0.8) to 4.4 (0.6) and 3.4 (0.4), and mean (SEM) number of neutrophils decreased significantly (p less than 0.005) from 5.1 (0.7) to 2.8 (0.5) and 1.0 (0.4), respectively. Mean (SEM) PC100SRaw was 3.3 (0.9) at baseline and 3.5 (1.2) and 3.8 (1.0) mg/ml at Days 8 and 16, respectively, without significant differences. These data suggest that a significant chemotherapy-induced leukocyte depletion in the peripheral blood does not influence airway responsiveness in patients with chronic bronchitis and bronchial carcinoma.

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