To test the hypothesis that a greater proportion of women than men react to methacholine challenge and investigate the possible reasons for any differences observed, we recruited 495 subjects 20 to 44 yr of age (50.9% male) in Paris and 304 subjects (51.3% male) in Montpellier (France), as part of the European Community Respiratory Health Survey. The proportion of responders (PD20 < or = 4 mg methacholine) was 33.7% in women and 11.9% in men (odds ratio = 3.8; 95% confidence interval = 2.4-6.0) in Paris and 43.2% in women and 29.5% in men (odds ratio = 1.8; 95% confidence interval = 1.1-2.9) in Montpellier. These differences could not be explained by asthma, respiratory symptoms, atopy, or lung function parameters. In stepwise logistic regressions including sex, asthma, and asthma-like symptoms, nasal allergies, atopy, baseline FEV1, FEV1%pred, FVC, and FEV1%FVC, the odds-ratios for the effect of female sex on PD20 < or = 4 mg methacholine were 5.2 (3.0-9.0) in Paris and 2.2 (1.2-3.8) in Montpellier. Reacting to low doses of methacholine (PD20 < or = 0.5 mg) was associated with asthma and atopy in both men and women. In contrast, reacting to doses between 0.5 and 4 mg was associated with asthma and atopy only in men and with heavy tobacco consumption only in women. We conclude that the excess of hyperresponsiveness in women is not due to their having smaller lung size or airway caliber than men and may be related to a greater susceptibility to smoking.

Cancer is a serious global public health problem. Cancer incidence and mortality have been steadily rising throughout the past century in most places of the world. There are several epidemiological evidences that support a protective role of probiotics against cancer. Lactic acid bacteria and their probioactive cellular substances exert many beneficial effects in the gastrointestinal tract, and also release various enzymes into the intestinal lumen and exert potential synergistic (LAB) effects on digestion and alleviate symptoms of intestinal malabsorption. Consumption of fermented dairy products with LAB may elicit anti-tumor effects. These effects are attributed to the inhibition of mutagenic activity, the decrease in several enzymes implicated in the generation of carcinogens, mutagens, or tumor-promoting agents, suppression of tumors, and epidemiology correlating dietary regimes and cancer. Specific cellular components in lactic acid bacteria seem to induce strong adjuvant effects including modulation of cell-mediated immune responses, activation of the reticulo-endothelial system, augmentation of cytokine pathways, and regulation of interleukins and tumor necrosis factors. Studies on the effect of probiotic consumption on cancer appear promising, since recent in vitro and in vivo studies have indicated that probiotic bacteria might reduce the risk, incidence and number of tumors of the colon, liver and bladder. The protective effect against cancer development may be ascribed to binding of mutagens by intestinal bacteria, may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine, reduction of the enzymes beta-glucuronidase and beta-glucosidase and deconjugation of bile acids, or merely by enhancing the immune system of the host. There are isolated reports citing that administration of LAB results in increased activity of anti-oxidative enzymes or by modulating circulatory oxidative stress that protects cells against carcinogen-induced damage. These include glutathione-S-transferase, glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. However, there is no direct experimental evidence for cancer suppression in human subjects as a result of the consumption of probiotic cultures in fermented or unfermented dairy products, but there is a wealth of indirect evidence based largely on laboratory studies.

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