Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children

Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.     

Withholding or starting antibiotic treatment in patients with dementia and pneumonia: prediction of mortality with physicians' judgment of illness severity and with specific prognostic models.

BACKGROUND: To help decision makers plan treatment, the authors assessed clinical predictors of mortality from nursing home-acquired pneumonia in patients with dementia. METHODS: Pneumonia patients treated without (n = 165) or with antibiotics (n = 541) were enrolled in a prospective cohort study in 61 nursing homes. RESULTS: In both groups, clinical judgment of illness severity was a strong predictor for 1-week mortality. Despite large differences in frailty and mortality (83% in untreated patients and 15% in treated patients), separate multivariable logistic models included similar specific predictors. DISCUSSION: Despite profound differences between the 2 independent groups, predictors for short-term mortality were largely similar. We found that, when combined with physicians' clinical judgment, 3 readily assessed predictors (respiratory rate, fluid intake, and eating dependency) helped predict mortality. Our results, if confirmed in an independent population, can help make decision making about antibiotic treatment of pneumonia in patients with dementia more evidence-based.     

Clustering of modifiable cardiovascular risk factors in adults living in Salvador (BA), Brazil]

OBJECTIVE: To estimate the frequency of modifiable cardiovascular risk factors, with and without inclusion of arterial hypertension, occurring simultaneously in a racially-mixed population. METHOD: A cross-sectional study was carried out with 1,298 adults aged > or = 20 years in the city of Salvador, Brazil, in 2000. Eight modifiable cardiovascular risk factors were assessed, in any combination: total cholesterol > or = 240 mg/dL; high density-lipoprotein cholesterol (HDL-c) < 40 mg/dL; triglycerides > or = 200 mg/dL; glycemia > or = 126 mg/dL + well-controlled diabetes; body mass index > or = 25 kg/m2, waist > or = 102 cm for males and > or = 88 cm for females, smoking and alcoholism. The results were stratified according to the number of simultaneous risk factors (zero to five or more and two or more risk factors). The data were analyzed in terms of estimated proportions and 95% confidence intervals (95%CI), with and without the inclusion of arterial hypertension (VI Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [JNC-VI], United States of America), ratio of proportions and chi-square for proportions as a measure of association. RESULTS: Among men (41.4% of participants), 7.5% (95%CI: 2.5 to 9.7) did not present risk factors; 68.8% (95%CI: 65.0 to 72.8) presented two or more risk factors, not including hypertension. After inclusion of hypertension, 73.4% (95%CI: 69.7 to 77.1) presented two or more risk factors. Among women, 11.6% did not present risk factors. The presence of two or more risk factors, not including hypertension, was observed in 67.7% (95%CI: 64.8 to 71.4). After inclusion of hypertension, 71.7% (95%CI: 68.5 to 74.9) of the women presented two or more risk factors. Significant differences were observed for the presence of two or more risk factors in men with not more than 4 years of schooling vs. 5 to less than 11 years of schooling (P < 0.05); in women with not more than 4 years of schooling vs. 5 to less than 11 years of schooling; in women with not more than 4 years of schooling vs. 11 or more years of schooling (P < 0.01); and in black vs. white women (P < 0.01). CONCLUSIONS: The high proportion of clustering cardiovascular risk factors in Salvador, with or without hypertension, especially in the population with little schooling and in black individuals, suggests the need for broad social strategies to reduce social inequality, promote health, and facilitate the treatment of cardiovascular risk factors.     

The relation between child death and child maltreatment.

The death of a child is a sentinel event in a community, and a defining marker of a society's policies of safety and health. Child death as a result of abuse and neglect is a tragic outcome that occurs in all nations of the world. The true incidence of fatal child abuse and neglect is unknown. The most accurate incidence data of such deaths have been obtained from countries where multi-agency death review teams analyse the causes of child fatalities, as is done in the United States and Australia.     

Sustained effect of inhaled diesel exhaust particles on T-lymphocyte-mediated immune responses against Listeria monocytogenes.

Studies have shown that exposure to diesel exhaust particles (DEP) suppresses pulmonary host defense against bacterial infection. The present study was carried out to characterize whether DEP exposure exerts a sustained effect in which inhaled DEP increase the susceptibility of the lung to bacterial infection occurring at a later time. Brown Norway rats were exposed to filtered air or DEP by inhalation at a dose of 21.2 +/- 2.3 mg/m3, 4 h/day for 5 days, and intratracheally instilled with saline or 100,000 Listeria monocytogenes (Listeria) 7 days after the final DEP exposure. Bacterial growth and cellular responses to DEP and Listeria exposures were examined at 3 and 7 days post-infection. The results showed that inhaled DEP prolonged the growth of bacteria, administered 7 days post DEP exposure, in the lung as compared to the air-exposed controls. Pulmonary responses to Listeria infection were characterized by increased production of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-12, and IL-10 by alveolar macrophages (AM) and increased presence of T lymphocytes and their CD4+ and CD8+ subsets in lung draining lymph nodes that secreted elevated levels of IL-2, IL-6, IL-10, and interferon (IFN)-gamma. Diesel exhaust particles were found to inhibit Listeria-induced production of IL-1beta and TNF-alpha, which are responsible for the innate immunity, and IL-12, which initiates the development of T helper (Th)1 responses, but enhance Listeria-induced AM production of IL-10, which prolongs Listeria survival in these phagocytes. The dual action of DEP on AM production of IL-12 and IL-10 correlated with an inhibition of the development of bacteria-specific T lymphocytes by DEP. Cytokine production by lymphocytes from DEP- and Listeria-exposed rats showed a marked decrease in the production of IL-2, IL-10, and IFN-gamma compared to Listeria infection alone, suggesting either that DEP inhibit the production of cytokines by lymphocytes or that these lymphocytes contained T-cell subsets that are different from those of Listeria infection alone and less effective in mediating Th1 immune responses. This study demonstrates that inhaled DEP, after a 7-day resting period, increase the susceptibility of the lung to bacterial infection occurring at a later time by inhibiting macrophage immune function and suppressing the development of T-cell-mediated immune responses. The results support the epidemiological observations that exposure to DEP may be responsible for the pulmonary health effects on humans.     

Exposure of brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation.

Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m3) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m3), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4+ and CD8+ subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway inflammatory responses.