Association between asthma, rhinitis and atopic dermatitis with leprosy: A case-control study.

Background Considering the cross-regulation of Th1 and Th2 responses, we hypothesised that atopic diseases (Th2) inhibit the protective Th1 immune response to Mycobacterium leprae and exacerbates leprosy. Objective In this study, we aimed to evaluate the association between leprosy and atopic diseases. Methods To evaluate the association of atopic diseases with leprosy, we conducted a case-control study that included leprosy patients (n = 333) and their household contacts (n = 93). The questionnaire from the International Study of Asthma and Allergies in Childhood, which is validated in several countries for epidemiological diagnosis of atopic diseases, was applied to determine the occurrence of atopic diseases, allergic rhinitis, asthma, and atopic dermatitis among leprosy patients and the household contacts. Results Considering clinical and epidemiological data, among the leprosy group 51.6% (n = 172) were determined to have at least one atopic disease, while atopy was observed less frequently at 40.86% among household contacts (n = 38). When two or more atopic diseases were assessed, the frequency was significantly higher among the leprosy patients than in the household contacts (21.9% vs. 11.8%; P-value = 0.03). Likewise, the frequency of asthma was significantly higher among leprosy patients (21%) than in the household contacts (10.8%; P-value = 0.02). Thus, our analyses revealed an association of atopic diseases with leprosy, with a significant linear increase in the occurrence of leprosy with an increase in the number of atopic diseases (P-value = 0.01). Limitation Due to the difficulties in recruiting household contacts that have prolonged contact with patients, but are not genetically related to the patient, the household contacts group is smaller than the leprosy patient group. Conclusion The data reveal an association between atopic diseases and leprosy outcomes. This knowledge could improve the treatment of leprosy patients with co-incident atopic diseases.

Estimation of conditional and marginal odds ratios using the prognostic score.

Introduced by Hansen in 2008, the prognostic score (PGS) has been presented as 'the prognostic analogue of the propensity score' (PPS). PPS-based methods are intended to estimate marginal effects. Most previous studies evaluated the performance of existing PGS-based methods (adjustment, stratification and matching using the PGS) in situations in which the theoretical conditional and marginal effects are equal (i.e., collapsible situations). To support the use of PGS framework as an alternative to the PPS framework, applied researchers must have reliable information about the type of treatment effect estimated by each method. We propose four new PGS-based methods, each developed to estimate a specific type of treatment effect. We evaluated the ability of existing and new PGS-based methods to estimate the conditional treatment effect (CTE), the (marginal) average treatment effect on the whole population (ATE), and the (marginal) average treatment effect on the treated population (ATT), when the odds ratio (a non-collapsible estimator) is the measure of interest. The performance of PGS-based methods was assessed by Monte Carlo simulations and compared with PPS-based methods and multivariate regression analysis. Existing PGS-based methods did not allow for estimating the ATE and showed unacceptable performance when the proportion of exposed subjects was large. When estimating marginal effects, PPS-based methods were too conservative, whereas the new PGS-based methods performed better with low prevalence of exposure, and had coverages closer to the nominal value. When estimating CTE, the new PGS-based methods performed as well as traditional multivariate regression. Copyright © 2016 John Wiley & Sons, Ltd.

Attenuation of experimental asthma by mycobacterial protein combined with CpG requires a TLR9-dependent IFN-γ-CCR2 signalling circuit.

BACKGROUND: Allergic asthma is a chronic pulmonary disease characterized by a Th2 inflammatory response. The modulation of a Th2 immune response based on immune deviation to a Th1 pattern or induction and migration of regulatory T cells to the lungs constitutes one of the major therapeutic approaches that is being investigated for the treatment of allergic asthma. The potentials of Mycobacterium leprae 65-kD heat-shock protein or Toll-like receptor 9 ligand (CpG oligodeoxynucleotides) as immune modulators for the treatment of airway allergic disease have been studied individually. OBJECTIVE: Mycobacterial protein combined with CpG was used as immunotherapy for airway allergy. METHODS: Using an ovalbumin-induced asthma model, mice were sensitized and challenged, and then treated with mycobacterial heat-shock protein (Hsp65) combined with CpG. RESULTS: The treatment of mice with established allergy led to the attenuation of eosinophilia, Th2 cytokines and airway hyperresponsiveness. Hsp65 plus CpG treatment also induced an increase in OVA-specific IFN-γ levels and in the frequency of lung inflammatory monocytes. Moreover, we show that the reduction of eosinophilia and the recruitment of inflammatory monocytes to the lungs required early triggering of TLR9, IFN-γ and CCR2 by immunotherapy components. CONCLUSION: In addition to immune deviation to a Th1 response in the modulation of Th2 allergic inflammation, our findings also attribute an important role to the innate response mediated by TLR9, associated with the recruitment of CCR2-dependent monocytes. CLINICAL RELEVANCE: Our findings show that the Hsp65/CpG treatment is a promising strategy for consideration in translational studies.

No relationship between lung function and high-sensitive C-reactive protein in adolescence.

INTRODUCTION: Several studies on adults have indicated that lower spirometric lung function may be associated with increased systemic inflammation, but no studies have investigated if this association is already present in adolescence. OBJECTIVE: We explored the temporal relationship between changes in lung function and concentrations of plasma C-reactive protein (CRP) in a population-based cohort study at ages 14 and 20 years using a high-sensitivity CRP assay. METHODS: CRP measurements were performed in a total of 420 subjects at mean age of 13.9 years. Of these, 262 subjects (62%) participated in the follow-up investigation at mean age of 20.1 years. RESULTS: Levels of log-CRP at age 14 were not significantly associated with forced expiratory volume (FEV(1) ) or FEV(1) / forced vital capacity (FVC) ratio at age 20, nor with the change in FEV(1) , FVC or FEV(1) /FVC ratio between 14 and 20 years after controlling for body mass index (BMI), airway hyperresponsiveness (AHR), eosinophil cationic protein (ECP), asthma, smoking, sex, and height at 14 years, and change in height between 14 and 20 years. Sex, BMI, AHR, ECP and change in height between 14 and 20 years were identified as independent factors associated with the change in FEV(1) , FVC and FEV(1) /FVC ratio in adolescence. CONCLUSION: We did not find an association between CRP levels at age 14 and change in lung function by age 20; whereas, sex, change in height, BMI, AHR and ECP were associated with lung function change in adolescence. Our findings indicate that systemic inflammation is of less importance for change in lung function in adolescence. Please cite this paper as: Nybo M, Hansen HS, Siersted HC and Rasmussen F. No relationship between lung function and high-sensitive C-reactive protein in adolescence.

Lower prevalence of reported asthma in adolescents with symptoms of rhinitis that received neonatal BCG.

BACKGROUND: BCG is a vaccine used against tuberculosis and leprosy and is an immunostimulant that primes T(H)1 lymphocytes to produce cytokines that antagonize atopy both in animal models and in man. Considering that atopy is the main risk factor for asthma, one can hypothesize that vaccination inducing T(H)1 responses, such as BCG, can be protective against asthma. OBJECTIVE: To estimate the association between neonatal BCG vaccination and prevalence of asthma among adolescents. STUDY DESIGN: Cross-sectional study with schoolchildren aged 12-16 years. The presence of a scar compatible with BCG was used as a surrogate of neonatal vaccination. A self administered structured questionnaire was prepared based on that used by the International Study of Asthma and Allergies in Childhood. The prevalence of asthma was categorized according to the report of lifetime wheeze, lifetime asthma, lifetime asthma among those referring allergy and among those referring allergy and sneezing. RESULTS: Neonatal BCG vaccination was not associated with the overall prevalence of reported wheezing or asthma. However, in the subgroup reporting current allergy and sneezing, neonatal BCG was associated with a 37% reduction of prevalence of lifetime asthma. CONCLUSIONS: In the population we surveyed, neonatal BCG scar was associated with a reduction in the risk of asthma only in individuals with a past history suggestive of allergic rhinitis.

Innate immune responses to mycobacteria and the downregulation of atopic responses.

PURPOSE OF REVIEW: Exposure to certain environmental microorganisms can promote the induction of T regulatory cells via the innate immune system. This review explores the possibility that reduced exposure to such organisms is leading to increased immunoregulatory disorders in a subset of individuals in whom this regulatory T-cell-inducing pathway is less efficient. We concentrate on mycobacteria and on asthma, because these are well documented. RECENT FINDINGS: The blood cells of the children of farmers, who are partly protected from allergies, express increased levels of messenger RNA encoding CD14 and TLR2, and polymorphisms of CD14 are linked to allergic manifestations in some studies. Polymorphisms of TLR2 (which recognizes mycobacterial components in concert with CD14) are involved in the pattern of response to mycobacteria, and in the type of leprosy that develops. Similarly, polymorphisms of Nramp1, which affect the response to mycobacteria, are linked with the diseases of immunodysregulation that are increasing in parallel with allergic disorders. Moreover, congenic mice bearing different variants of Nramp1 differ in their allergic responses. These parallels are suggestive, in view of the observation that a saprophytic environmental mycobacterium is a potent inducer of regulatory T cells, and has shown significant effects in several phase I/II studies in man. SUMMARY: The components of the innate immune system that are involved in responses to mycobacteria overlap with those implicated in allergic disorders. Polymorphisms might define the subset of individuals who develop immunoregulatory disorders. Understanding the role of the innate immune system will facilitate the design of clinical trials using microbial products.

Genetics and genomics of asthma and allergic diseases.

Asthma and eczema (atopic dermatitis) are characterized by a number of unexplained phenomena: the familial aggregation of disease, the initiation of disease by apparently trivial exposure to allergens, the preferential transmission of disease from affected mothers and the large increase in prevalence of disease in Westernized societies in the last century. A number of genes and chromosomal regions have been identified that consistently show linkage to asthma and its related phenotypes. Known loci modify the strength of the atopic response, nonspecific inflammation, the ability to respond to particular allergens and nonspecific airway reactivity. Eczema has been shown to be due to a different set of genetic loci that are shared with other skin diseases such as psoriasis and leprosy. Genetic and genomic studies both provide evidence that epithelial surfaces are active in the induction of allergic disease.

Genetics and genomics of asthma and allergic diseases

Asthma and eczema (atopic dermatitis) are characterized by a number of unexplained phenomena: the familial aggregation of disease, the initiation of disease by apparently trivial exposure to allergens, the preferential transmission of disease from affected mothers and the large increase in prevalence of disease in Westernized societies in the last century. A number of genes and chromosomal regions have been identified that consistently show linkage to asthma and its related phenotypes. Known loci modify the strength of the atopic response, nonspecific inflammation, the ability to respond to particular allergens and nonspecific airway reactivity. Eczema has been shown to be due to a different set of genetic loci that are shared with other skin diseases such as psoriasis and leprosy. Genetic and genomic studies both provide evidence that epithelial surfaces are active in the induction of allergic disease.

Serodiagnostic efficiency of phospholipid associated protein of Mycobacterium tuberculosis H37Rv.

The phospholipid-associated protein (55-67 kDa) fraction of Mycobacterium tuberculosis H37Rv was purified as the DE-V protein fraction. This DE-V fraction was used for diagnosis of tuberculosis by enzyme-linked immunosorbent assay (ELISA), detecting IgG antibody in sera collected from different categories of tuberculosis patients, i.e. with acid fast bacilli (AFB) culture-positive pulmonary tuberculosis, with AFB culture-negative, but radiologically suspected, pulmonary tuberculosis, extrapulmonary tuberculosis, and control groups of patients suffering from diseases other than tuberculosis (asthma and/or rhinitis, lepromatous leprosy) as well as from healthy volunteers. Encouraging operational ELISA validity could be achieved with 93% sensitivity, 100% specificity, 97% efficiency, 100% positive predictivity and 95% negative predictability even among the extrapulmonary and suspected pulmonary tuberculosis patients. The above assay was insensitive but with 100% specificity among control group of patients suffering from diseases other than tuberculosis. The DE-V protein fraction was associated with phosphatidyl inositol and phosphatidyl inositol mannosides. The dissociation of phospholipid-protein complex decreased ELISA specificity. ELISA reactivity of the DE-V fraction appeared to be thermostable; thus, it may have serodiagnostic utility in developing countries.

Serum angiotensin converting enzyme in respiratory diseases.

More than 1700 estimations of serum angiotensin converting enzyme (SACE) were undertaken, mostly in respiratory disorders, to assess its value as a specific and/or a sensitive indicator of different diseases. Though highest levels were found in lepromatous leprosy consistently, it was also found almost always elevated in active stages of sarcoidosis. Since it is raised in a variety of respiratory disorders, it is not a specific diagnostic test. It is, however, a fairly sensitive index of disease activity in sarcoidosis whether on treatment or not. Sudden elevation, after a prolonged period of low or normal values may indicate relapse in sarcoidosis.

Temas de farmacología

Recopilación de temas de la cátedra de Farmacología de la Facultad de Medicina de la UNNE

Temas de farmacología

Recopilación de temas de la cátedra de Farmacología de la Facultad de Medicina de la UNNE

Hepatitis B virus infection among immunocompromised patients in Egypt.

Several workers reported an increased susceptibility to hepatitis B virus (HBV) in immunosuppressed patients. A study was carried out on 4 groups of supposedly immunocompromised patients for hepatitis B surface antigen (HBsAg), and anti-HBs. The 4 groups of patients were suffering from: Leprosy, Bronchial asthma, Diabetes and hepatosplenic Schistosomiasis. Serum specimens were obtained from 137 patients representing the 4 groups and from a control group of 25 healthy individuals. All sera were tested by ELISA technique for HBsAg and anti-HBs. Results indicated that HBsAg carrier rate was 4% for the control healthy group, 7% for Bronchial asthma, 10% for Diabetes, 24% for Leprosy and 28% for hepatosplenic Schistosomiasis. On the other hand, the anti-HBs was 21% for the control group, 29% for Schistosomiasis, 55% and 58% for Diabetes and Bronchial asthma respectively and 74% for Leprosy. This study shows that immunosuppressed patients particularly those suffering from leprosy and hepatosplenic Schistosomiasis experience higher HBsAg carrier rate than the control group for the endemic hepatitis B (6-7 times higher for leprosy and Schistosomiasis). An important observation was the diminished anti-HBs rate in hepatosplenic Schistosomiasis patients, despite the highest HBsAg carrier rate they exhibited. This may be due to an immunological defect, resulting in an unsatisfactory antibody response and chronic hepatitis B antigenemia. In Egypt, where Schistosomiasis is prevalent (40-50%), the problems caused by hepatitis B infection are increased.

Effects of ascorbate on normal and abnormal leucocyte functions.

The stimulatory effects of ascorbate on neutrophil motility in vitro and in vivo and lymphocyte transformation to mitogens following ingestion or intravenous injection of ascorbate have been found to be related entirely to inhibition of the autooxidative effect of the myeloperoxidase/hydrogen peroxide/halide system (MPO/H2O2/halide system). Stimulation of neutrophil migration and lymphocyte transformation following a single intravenous injection of 1 g of ascorbate was associated with inhibition of the MPO/H2O2/halide system. The immunostimulatory activity and peroxidase inhibitory activity was related entirely to the serum ascorbate level. The relationship between inhibition of the peroxidase/h2O2/halide system and stimulation of neutrophil motility and lymphocyte mitogen-induced transformation was further established by using the horseradish peroxidase (HRP)/H2O2/halide system in vitro. Neutrophils and lymphocytes, exposed to this system, manifested markedly impaired chemotactic responsiveness and mitogen-induced transformation, respectively. However inclusion of ascorbate with the peroxidative system protected the neutrophils and lymphocytes from these inhibitory effects. Further studies in 3 patients with chronic granulomatous disease (CGD) and 10 patients with bronchial asthma suggested that ascorbate may be of value to improve the primary immunological abnormalities (neutrophil motility and antimicrobial activity) in CGD and the secondary abnormalities (neutrophil motility and lymphocyte transformation) found in some individuals with bronchial asthma.