Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance.

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.

Bronchoalveolar lavage fluid findings following radiotherapy for non-small cell lung cancer.

PURPOSE: To evaluate the diagnostic potential of bronchoalveolar lavage fluid analysis in radiation-induced lung injury. METHODS AND MATERIALS: Thirty patients with inoperable non-small cell lung cancer received either high-dose hyperfractionated radiotherapy or radiotherapy and interferon, a potential radiosensitizer, or radiotherapy and N-acetylcysteine, a potential radioprotector. Bronchoalveolar lavages were performed before and immediately after radiotherapy, and thereafter 6-8 weeks and 3 months after radiotherapy. Total and differential cell counts were measured from the bronchoalveolar lavage fluid samples. Urea measured in serum and in bronchoalveolar lavage fluid was used to calculate epithelial lining fluid. The concentrations of protein and phosphatidylcholine, the major surfactant phospholipid, in epithelial lining fluid were measured. The extent of radiation-induced lung injury was assessed from computed tomographies performed before radiotherapy, and 6-8 weeks and 3 months after radiotherapy. RESULTS: More patients in the interferon-arm developed radiation pneumonitis than did patients in the other groups, but no significant differences in alveolar fluid indices were noted between the groups. When all the patients were studied together, radiation was shown to have induced a significant relative increase of lymphocytes in bronchoalveolar lavage fluid 6-8 weeks and 3 months after the end of radiotherapy. The concentration of phosphatidylcholine in epithelial lining fluid decreased significantly 6-8 weeks and 3 months after treatment. The increase in protein concentration in epithelial lining fluid reached a statistically significant level 6-8 weeks after radiotherapy. CONCLUSION: Analysis of bronchoalveolar lavage fluid predicts the degree of radiation pneumonitis; however, radiology remains to be "the gold standard."

Fire-eater's lung.

Acute pneumonitis following aspiration of petroleum products is usually related to accidental poisonings in children. We describe here two cases of hydrocarbon pneumonitis in fire-eaters, caused by accidental aspiration of petroleum during the performance of fire-eating. Both patients had cough, dyspnoea, chest pain and fever. Chest X-rays showed basal lung infiltrates and, 2 weeks later, pneumatocele formations. Reversible bronchial hyperresponsiveness and restrictive ventilatory limitation were demonstrated in one of the patients. The bronchoalveolar lavage specimen showed cytoplasmic vacuolation of the macrophages and neutrophilia. After treatment with antibiotics and corticosteroids the symptoms disappeared and the lung function values returned to normal within 2-3 weeks. Radiological resolution of the pneumatoceles occurred within 2-12 months.

Relationship of serum selenium and antioxidants to plasma lipoproteins, platelet aggregability and prevalent ischaemic heart disease in Eastern Finnish men.

In a cross-sectional population study of 1132 unselected Eastern Finnish men aged 54 years, serum selenium concentration had a weak positive association with plasma HDL cholesterol (standardised partial regression coefficient, beta = 0.061, P = 0.019) and a fairly strong inverse relationship (beta = -0.223, P less than 0.001) with the extent of ADP-induced platelet aggregation. Neither plasma ascorbate concentration nor alpha-tocopherol to total cholesterol ratio had any association with plasma lipoproteins, platelet aggregability or prevalent ischaemic heart disease (IHD). When a covariance-correction was applied, men with ischaemic ECG findings at exercise had a lower mean serum selenium than others (81.5 micrograms/l vs. 85.9 micrograms/l, P less than 0.01 for difference). This difference was equally large for men with neither symptoms nor previous diagnosis of IHD.

Postoperative radiation therapy and adjuvant chemoimmunotherapy in breast cancer. Aspects of timing and immune competence.

The effects of radiation therapy and adjuvant chemoimmunotherapy on the immune competence of patients with breast cancer were investigated. The tests performed included intradermal tuberculin tests, T- and B-lymphocyte counts, and lymphocyte blast transformation tests; phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PWM) were used as mitogens. Enhancement in lymphocyte proliferative response to mitogenic stimulation by PHA and PWM was seen in patients after 3 courses of chemotherapy + levamisole, whereas irradiation given after chemotherapy caused long-lasting depression in response to PHA (p = 0.039) and PWM (not significant). T-lymphocyte counts were also lower after irradiation than after chemoimmunotherapy (p = 0.007). Clinically, the 16 patients treated with radiation therapy after chemotherapy exhibited a higher recurrence rate than the 24 patients treated first by irradiation. Enhanced reactivity to tuberculin tests occurred generally in patients receiving a planned treatment including irradiation, chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) and levamisole. Enhancement of reactivity was seen more often in patients who had not relapsed.