Leptin and resistin in overweight patients with and without asthma.

BACKGROUND: Excess body mass increases the risk of development of asthmatic symptoms and their severity and decreases the treatment effectiveness. One of the hypotheses explaining the link between the two diseases concerns the adipokines, hormones produced by adipose tissue with a proinflammatory character. The aim of this study was to compare the levels of the adipokines (leptin and resistin) between overweight asthmatic patients, asthmatic patients with normal weight and overweight patients without asthma. METHODS: 80 peripheral blood samples were collected from patients and blood serum extracted. Three groups were selected: overweight asthmatic patients (BMI≥25), overweight patients without asthma and asthmatic patients with normal weight (BMI<25). Waist circumference of the patients was measured (cut-off points were 80cm for women and over 94cm for men) and a skin prick test performed. Comparison of adipokine concentration between the 3 groups was made and association between these concentrations and the measurements was performed. RESULTS: Although the concentrations of both adipokines were slightly higher for overweight asthmatic patients compared to overweight healthy patients, these differences were not significant. A significant association was found between leptin concentration and both BMI (p<0.01) and waist circumference (p<0.01). A difference for this cytokine was also found between asthmatic and non-asthmatic female patients (p<0.05). CONCLUSIONS: As expected overweight patients with BMI≥25 and patients with increased waist circumference showed higher leptin levels. We suggest that the studied cytokines, with a stronger indication for leptin, can elicit asthmatic inflammation in obese phenotype of asthma that affects more frequently women.

The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin.

BACKGROUND: Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. OBJECTIVE: We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma. METHODS: The Global Asthma and Allergy Network of Excellence (GA(2) LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. RESULTS: One thousand nine hundred and fifty-five subjects aged 16-77 years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P = 0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons. CONCLUSIONS AND CLINICAL RELEVANCE: Asthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures.

Aging and asthma - changes in CD45RA, CD29 and CD95 T cells subsets.

BACKGROUND: Aging is associated with thymus involution leading to a reduction in naive T cells and to an accumulation of effector-memory cells. Apoptosis is a key mechanism to clear the immune system from activated and harmful cells. In asthma the stimulation of T cells by environmental antigens can decrease naive cells and sustain activated cells. The aim of this work was to evaluate the imbalance between CD45RA and CD29 cells during the aging process and their changes in elderly asthma and to evaluate how elderly and chronic diseases like asthma can affect susceptibility to apoptosis. METHODS: Elderly and young adult healthy volunteers and elderly asthmatic patients were submitted to skin prick tests, immunoglobulin determination and flow cytometry analyses of CD3, CD4, CD8, CD45RA, CD29, and CD95. RESULTS: Serum IgE was increased in allergic patients (p=0.0001). Asthmatics presented an increase in CD4 cells (p<0.05). CD45RA was significantly decreased in elderly individuals (p<0.05) and this decrease was higher in asthmatics (p<0.05). CD29 was increased in elderly healthy individuals compared to the control young group (p=0.0001). A negative correlation between CD29 and CD45RA (p<0.05) was observed. CD95 lymphocytes increased in elderly (p=0.0001) and a positive correlation between age and CD95 (p<0.05) was found. Asthmatic patients showed significant decreases in CD95 (p=0. 0001). CONCLUSIONS: Naive cells are key cells in the defence against infections and their decrease in the elderly and in asthma is a bad prognosis factor. The reduction of apoptosis markers can promote the persistence of activated cells involved in chronic conditions.

Apoptosis and asthma in the elderly.

BACKGROUND: Asthma is a chronic inflammatory disorder of the airways. The persistence of airway inflammation depends on a decrease in apoptosis of T lymphocytes and eosinophils and survival of these activated cells. T lymphocytes expressing gamma delta receptors can be identified in human lungs and play an important role in immune defence against pathogens and in the regulation of chronic inflammation. Aging is associated with evidence of some immune dysregulation. OBJECTIVE: The aim of this study was to analyze the apoptosis receptors of T lymphocytes in long-lasting asthma, to establish their correlation with activation markers such as CD25+ and human leukocyte antigen (HLA)-DR+, and to analyze the gama delta T cell expression in this disease. METHODS: A group of 64 individuals (group A) who had had asthma for more than 30 years (mean age [+/-SD] 72 +/- 5 years) and 61 healthy individuals acting as controls--group B with 41 individuals (mean age 79 +/- 7 years) and group C with 20 individuals (mean age 38 +/- 12 years) were included in the study. All subjects underwent clinical evaluation and spirometric testing. Peripheral blood cells were stained with monoclonal antibodies anti-CD3, anti-CD4, anti-CD8, anti-CD25, anti-TCR gamma delta, anti-HLA-DR and anti-CD95. Statistical comparisons were performed between the asthmatics and the elderly control group and between the elderly control group and the adult control group. RESULTS: The average percentage of predicted forced expiratory volume in the first second was 73.6 gamma delta 25.3. The mean values of T cell receptors for asthma group A vs elderly control group B vs adult control group C respectively, were the following: CD3, 74.9+/-7 vs. 74.8 +/- 8.8 (P=ns) vs. 76.7 +/- 4.2 (P=ns); CD4, 48.8 +/- 8.7 vs. 43.5 +/- 10.2 (P=ns) vs. 44.8 +/- 3.8 (P=ns); CD8, 23.3 +/- 7.9 vs. 25.7 +/- 10.2 (P=ns) vs. 25.6 +/- 4.5 (P=ns); CD25, 14.3 +/- 5.9 vs. 22.4 +/- 7.8 (P = .0001) vs. 5.5 +/- 2.4 (P = .0001); TCR gamma delta, 2.8 +/- 2.1 vs. 4.1 +/- 3.3 (P < .05) vs. 4.6 +/- 2.1 (P=ns); HLA-DR, 18.4 +/- 9.2 vs. 17.8 +/- 5.9 (P=ns) vs. 15.4 +/- 5.1 (P=ns) and CD95, 49.3 +/- 13.7 vs. 52.6 +/- 12.1 (P=ns) vs. 13.8 +/- 10.8 (P = .0001). CONCLUSIONS: The immunological and inflammatory changes related to ageing may cause an increase in CD95 and CD25 T cell expression. In asthma, blood cells may express increased activation and apoptosis markers but in elderly patients taking steroids, these receptors remain within normal ranges. The number of gamma delta T cells may be lower in long-lasting asthma, and have a limited modulatory effect on allergic inflammatory reactions. The evaluation of patients with long-lasting asthma should take into account the immunological and inflammatory changes present in the elderly in order to avoid results being misinterpreted.

Neopterin in tuberculous and neoplastic pleural fluids.

Neopterin is derived from guanosine-triphosphate, produced by stimulated macrophages under the influence of gamma interferon of lymphocyte origin. It has been suggested as an excellent marker for activation of the monocyte/macrophage axis in some clinical situations. We evaluated its concentration in the pleural effusions of 25 individuals (10 tuberculous and 15 neoplastic) as well as in the blood of 22 of them (8 tuberculous and 14 neoplastic), comparing these levels with those of a control group in 99 normal individuals. The concentration of neopterin was determined by radioimmunologic assay. This showed a significant increase (p less than 0.001) of neopterin levels in the tuberculous pleural fluid, compared to the neoplastic group (42 +/- 23/17 +/- 9 nmol/L). In the blood, values were nearly identical to the pleural fluid (41.3 +/- 25/15.8 +/- 6.9 nmol/L), although with significant differences between them and in relation to the control group (p less than 0.001), which had a normal serum value (5.11 +/- 1.92 nmol/L). We emphasize the influence of the neopterin levels in the pleural fluid on the diagnosis of causes of pleurisy and its importance as a marker of immunologic cellular activity.

[Humoral immunity and the argon-laser]. / L'immunité humorale et argon-laser.

We have done two argon-laser iridotomies 24 and 72 hours before cataract surgery, to study ocular inflammation. We have taken aqueous samples to study IgA, IgG, C3 and AAT by laser immunonephelometry. All the proteins raised in the first 24 hours (P less than or equal to 0.01) except IgA in aqueous humor, taken with control levels, but only AAT (P less than or equal to 0.05), albumine at 72 hours (P less than or equal to 0.01) in aqueous humor. We tried to understand the observed gap by immunomodulation of released mediators.