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Biomedical subjects

E Laffond

Publications and source records attributed to E Laffond.

6 recordsLinked to original sources

Promoter genetic variants of prostanoid DP receptor (PTGDR) gene in patients with asthma.

BACKGROUND: PTGDR gene has been identified as an asthma-susceptibility gene. Recently, functional genetic variants have been associated with asthma. The objective of this work was to study -549T>C, -441C>T and -197T>C PTGDR promoter polymorphisms in a Spanish population. METHODS: In this study, 197 Caucasian individuals were included. Asthma was specialist-physician diagnosed according to the American Thoracic Society (ATS) criteria and classified following the Global Initiative for Asthma (GINA) guidelines. Skin prick tests were performed in all patients. The polymorphisms were analyzed by direct sequencing. RESULTS: -197T>C polymorphism was significantly associated with asthma [Fisher's P-value = 0.007, Monte Carlo P-value (10(4) simulations) = 0.004]. Multivariate analysis adjusted for age and sex confirmed this association with an increased risk of asthma (OR, 3.06; 95% CI, 1.28-7.32; P-value = 0.012). CCT CCC diplotype was associated with asthma (P-value < 0.0001; OR, 1.15; 95% CI, 1.07-1.23), specifically with allergic asthma (P-value < 0.0001). CCT CCC diplotype is unambiguous. All individuals carrying this diplotype had asthma. CONCLUSION: We identified a specific promoter variant of PTGDR that could be associated with asthma. This diplotype is a combination of the two highest transcriptional efficiency haplotypes, recently described. Our in vivo results would support for the first time what was demonstrated in vitro about high-transcriptional efficiency PTGDR haplotypes in asthma.

Adult↗

Analysis of 927T> C CYSLTRI and -444A > C LTC4S polymorphisms in patients with asthma.

BACKGROUND: The cysteinyl leukotrienes (cys-LTs) are proinflammatory mediators synthesized through the 5-lipoxygenase pathway of arachidonic acid metabolism. Cys-LTs exert their biological action by binding two types of G-protein-coupled seven transmembrane receptors, CYSLTR1 and CYSLTR2. The contribution of the cys-LT receptors to bronchial asthma has been established by the therapeutic efficacy of biosynthetic inhibitors and selective CYSLTR1 blockers. OBJECTIVE: The present study was designed to analyse two different polymorphisms 927T>C CYSLTR1 and -444A>C LTC4S, and to determine whether there is an association between these polymorphisms and the asthma phenotype in a Spanish population. METHODS: Both single nucleotide polymorphisms (SNPs) were analysed in 208 individuals (130 asthmatic subjects and 78 controls). A standardized history, physical examination, skin prick tests and lung function measurement were taken from all patients. Genotypes were determined by direct sequencing after polymerase chain reaction (PCR) amplification. RESULTS: In the group of male patients, the C allele of 927T> C CYSLTRI was more common among patients with asthma than controls. No association was detected between the -444A> C LTC4S polymorphism and the asthma phenotype. The combination of 927T CYSLTR1 and -444A LTC4S was less common in male patients with asthma than in controls (Fisher's P-value =.039; Monte Carlo P-value (after 104 simulations)= .045 and the combination of 927C CYSLTR1 and -444A LTC4S was slightly more frequent in patients with asthma. No differences were observed in the female group. CONCLUSIONS: The results suggest a certain trend of associations that could help to explain some controversial results in association studies of these genes from the leukotriene pathway, when considered individually. Further studies are needed to confirm such an association.

Adolescent↗

Tick-bite-induced anaphylaxis in Spain.

Although there are very few reports of human anaphylaxis induced by tick bites, two such cases have recently been seen in Salamanca, Spain. To identify the tick species responsible, salivary-gland extracts from six species of hard tick and two of soft tick were prepared and used as allergens/antigens in skin-prick tests and serological analyses. For each case, the results of the skin tests were positive for several species of hard tick but negative for the soft ticks. ELISA and western blots revealed high titres of IgG against hard ticks (but not soft ticks) in the sera from both cases. However, serum from only one of the cases was found to be ELISA- and western-blot-positive for tick-specific IgE. Accordingly, the anaphylaxis seen in one case was IgE-mediated whereas that in the other case appeared to be IgE-independent. In both cases, most of the tick-specific antibodies only recognized carbohydrate epitopes. High levels of cross-reactivity between the salivary-gland extracts from several species of hard tick made it impossible to identify which species was responsible for each anaphylactic reaction, although the immunological results seem to point to Ixodes ricinus.

Anaphylaxis↗

Hypersensitivity to latex, chestnut, and banana.

The incidence of latex-allergic patients is probably higher than suspected. A spectrum of IgE-dependent allergic reactions to latex products including urticaria, rhinitis, asthma, angioedema, and life-threatening anaphylaxis has been increasingly reported in recent years. We describe three patients with rubber hypersensitivity and allergy to fruit (banana and chestnut). Immediate positive responses were obtained in prick tests with latex, banana, and chestnut extracts. Histamine release was positive and specific IgE antibodies to all three extracts were detected by fluorescence radioimmunoassay. In the RAST-inhibition studies, the extract of latex inhibited the binding of chestnut and banana, but chestnut and banana extracts did not inhibit the binding of latex. These results suggest a sensitivity to crossreacting antigens in latex allergy associated with allergy to certain fruits.

Adult↗

[Viral infection and asthma: immunologic mechanisms].

The role of viral respiratory infections in lactating infants and other children continues to generate controversy. The debate concerns the difference, or the apparent differences, in the natural history of wheezing. Viral infections frequently provoke wheezing episodes in non-asthmatic small children but in the majority of these the wheezing disappears without the child subsequently developing asthma. In some cases, however, the wheezing persists and in others the child has asthma. Both the role of viral infection and the mechanisms by which wheezing can be produced in a previously healthy child or exacerbated in asthmatic children are unknown. Several hypotheses have been put forward to explain the relationship between viral infections and persistent wheezing and asthma: 1. Altered immune response to various allergens, whether producing sensitization to these allergens or inhibiting tolerance response to airborne allergens. The number of such patients is increasing, among them those with bronchiolitis, asthma, positive skin tests and specific IgE antibodies. Although there is no unanimity on the matter, these patients also present elevated IL-4 levels and reduced IFN-gamma levels. 2. Induction of inflammation typical of allergic asthma. This occurs when the virus interacts with T lymphocytes; (the natural response to viral infection is Th0 and Th1 lymphocyte differentiation and release of IFN-gamma, which has antiviral properties. In children infected with respiratory syncytial virus Th2 lymphocyte differentiation is produced, which is characteristic of allergic reactions, to the detriment of Th1); epithelial cells (in these cells active viral infection activates nuclear transcription kappa-beta and nuclear IL-6 factor, producing the release of numerous pro-inflammatory cytokines and chemokines as well as expression of adhesion molecules); eosinophils (inducing variable eosinophilia which, to a certain degree, has predictive value for the persistence of wheezing) and other inflammatory cells such as neutrophils and macrophages. In the same context, during viral respiratory infection, the presence of mediators (leukotrienes, especially LTC4, histamine, prostaglandins and tryptase) are observed in respiratory secretions and a correlation between levels of specific IgE mediators can be observed. 3. Increased allergic inflammation--producing bronchial hyperreactivity, mediator release by the various inflammatory cells and neuropeptides from C-sensitive fibers, and even interfering with nitric oxide bronchodilators. In spite of all of the above, it seems that recurrent wheezing after childhood bronchiolitis is not exclusively the result of viral infection and that other factors also play a role in this disease.

Allergens↗

[Preventive measures for allergic diseases].

Allergic diseases, particularly asthma and asthma equivalents, are among the most frequent disorders seen in the pediatric clinic. Approximately 25% of children from developed countries have presented wheezing in recent years, and half of these children later experience major asthma attacks. Likewise, 25% of children between 8 and 11 years have at some time used beta agonists and at least 10% of them use preventive asthma medication. Prevention measures for allergic asthma include: 1) avoiding allergic sensitization; 2) avoiding the presentation of disease in sensitized patients; and 3) preventing symptoms after the disease has appeared. Allergic diseases have a multifactorial origin that includes genetic, perinatal, and specific and non-specific environmental factors. From a genetic point of view, asthma is a multifactorial and heterogeneous pathology with a variable degree of penetration and phenocopy. Allergy is more frequent among the offspring of atopic parents. Genetic variations in different chromosomes affect molecules and receptors involved in atopy: IgE elevation, Fce1 receptor and chromosome 11; IL-4 and chromosome 3; gamma interferon and chromosome 12; TcR a/d receptor and chromosome 14; TcR-beta and chromosome 7; and the main histocompatibility complex HLA I and II and chromosome 6. Likewise, it has been confirmed that genetic variants affect structures in the impact organs, such as the beta 2 receptors of IL-4 soluble receptors, which favor bronchial hyperreactivity. Recently, somatometric measures have been related (low weight and large head circumference at birth) with a later increase in IgE and the occurrence of asthma. The environmental factors most closely involved in the occurrence of asthma are: diet (early exposure to sensitizing foods); domestic, outside, and occupational seroallergens; pollution (particularly smoking and urban and industrial pollution); and infections, particularly viral infections. In the present study, the methods used for the early identification of children at risk are evaluated, as well as the role of the primary care pediatrician in the early detection of allergic children and the interventions that they carry out. Finally, an analysis is made of the preventive measures that should be taken in children at risk of allergic disease, particularly: 1) increasing awareness of health, 2) reduction of exposure to smoking. 3) reduction of urban and industrial pollution, 4) delayed introduction of certain foods, reduction in the level of domestic allergens, 6) control of infections, and 7) pharmacological measures designed to prevent the occurrence of asthma in children.

Adult↗