Allergic Disorders (allergic + disorders)

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Distribution within Medical Sciences


Selected Abstracts


Genetic variation in CRTh2 influences development of allergic phenotypes

ALLERGY, Issue 10 2009
L. Cameron
Background:, Allergic disorders are characterized by an increase in the Th2 cytokines IL-4, IL-5 and IL-13, produced primarily by Th2 cells. These cells are marked by the expression of CRTh2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), a receptor for prostaglandin D2. As genetic variation plays a significant role in the predisposition for allergic disorders, we investigated the influence of single nucleotide polymorphisms (SNPs) in CRTh2. Methods:, In a large study population of German children (n = 4264) from the International Study of Asthma and Allergy in Children (ISAAC II), six polymorphisms in CRTh2 were genotyped. Statistical analyses were performed using single SNP and haplotype analyses. Results:, Uncorrected associations among ,6373G>A, +1431G>C and +1538A>G were observed with a number of allergic phenotypes (P < 0.05). After correction, association between +1431C and specific IgE to food allergens remained significant (P = 0.04). Associations of haplotype (H)3 (containing +1538G) with reduced risk for asthma and H2 (containing +1431C) with increased risk for specific IgE to food allergens also remained significant after correction for multiple testing (P = 0.004). Conclusions:, Genetic variation within CRTh2 modifies the development of allergic sensitization and asthma in a population of German children. [source]


Allergy related disorders among 2-yrs olds in a general population.

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2p1 2010
The PACT Study
Smidesang I, Saunes M, Storrø O, Øien T, Holmen TL, Johnsen R, Henriksen AH. Allergy related disorders among 2-yrs olds in a general population. The PACT Study. Pediatr Allergy Immunol 2010: 21: 315,320. © 2009 John Wiley & Sons A/S Allergic disorders represent a major health problem in most developed countries, but few population-based studies have focused on these disorders in early childhood. The aims of the present study were to investigate the prevalence, gender differences and distribution of allergy related disorders and their association to sensitization among unselected children, 2 yrs of age, in a general population. A population-based study with parental self reported questionnaire data involving allergy related symptoms and results from allergy tests from 4783 two-yr-old children was conducted, and skin prick tests (SPT) of a randomly selected sample comprising 390 children were performed. In the total population the prevalence of reported wheeze was 26%, doctor diagnosed asthma (DDAsthma) 7.0%, atopic dermatitis (AD) 17% and allergic rhinoconjunctivitis (ARC) 3%. Of the 1008 (21%) allergy tested children 59% reported a positive test, but of the randomly selected children only 8% had a positive SPT. Children with AD were most frequently sensitized and children with ARC were most likely to have other allergy related disorders (70%). More boys than girls had an allergy related disorder or a positive allergy test. In conclusion, two in five had an allergy related disorder, but less than 10% had a positive SPT. Having one allergic disorder, especially ARC, increased substantially the risk of having another, and having AD was most strongly associated to a positive allergy test. Moreover, boys were more likely than girls to have an allergy related disorder or a positive SPT indicating a gender difference in the natural history of allergy related disorders. [source]


Helminths, allergic disorders and IgE-mediated immune responses: Where do we stand?

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2007
Klaus
Abstract Th2 responses induced by allergens or helminths share many common features. However, allergen-specific IgE can almost always be detected in atopic patients, whereas helminth-specific IgE is often not detectable and anaphylaxis often occurs in atopy but not helminth infections. This may be due to T regulatory responses induced by the helminths or the lack of helminth-specific IgE. Alternatively non-specific IgE induced by the helminths may protect from mast cell or basophil degranulation by saturating IgE binding sites. Both of these mechanisms have been implicated to be involved in helminth-induced protection from allergic responses. An article in the current issue of the European Journal of Immunology describes the generation of an anti- Nippostrongylus brasiliensis -specific IgE antibody which was used to identify a novel N. brasiliensis antigen (Nb-Ag1). The authors demonstrated that Nb-Ag1 specific IgE could only be detected for a short period of time during infection, and that these levels were sufficient to prime mast cells thereby leading to active cutaneous anaphylaxis after the application of Nb-Ag1. This is the first report clearly showing that a low level of helminth-specific IgE, transiently produced, is able to induce mast cell degranulation in the presence of large amounts of polyclonal IgE. See accompanying article: http://dx.doi/10.1002/eji.200737135 [source]


The human basophil , a novel target of the neuropeptide alpha-melanocyte-stimulating hormone

EXPERIMENTAL DERMATOLOGY, Issue 8 2006
M. Böhm
There is increasing evidence that the basophil does not only play an important role in acute allergic reactions but also in the pathogenesis of chronic allergic disorders. Here we show that human basophils express melanocortin receptors (MC-Rs) and respond to alpha-melanocyte-stimulating hormone (alpha-MSH) with regulation of proallergic cytokine expression and modulation of basophil activation markers. Using primers against all known MC-R subtypes we demonstrate that the human basophil cell line KU812 expresses MC-1R. Expression of MC-1R on the surface of KU812 cells was confirmed by FACS analysis using an anti-MC-1R antibody. The MC-1R expressed by KU812 cells was functionally active as alpha-MSH induced intracellular cAMP in a dose-dependent manner. Moreover, alpha-MSH abrogated the effect of calcium ionophore A23187 on IL-4 mRNA expression in these cells. The relevance of the above findings was corroborated by showing that MC-1R surface expression is also detectable in basophils of leukocyte suspensions derived from whole human blood. Most interestingly, alpha-MSH was capable of suppressing the inductive effect of fMLP on surface expression of the basophil activation marker CD63 in leukocyte suspensions of atopic individuals. Likewise, alpha-MSH significantly blocked grass pollen-induced up-regulation of CD63 in leukocyte suspensions of patients with grass pollen allergy. Our findings highlight a novel functional dimension of alpha-MSH. In addition, MSH peptides may become a novel future therapeutic avenue in treating human allergic diseases. [source]


Is Headache Related to Asthma, Hay Fever, and Chronic Bronchitis?

HEADACHE, Issue 2 2007
The Head-HUNT Study
Objectives.,To examine the relationship between migraine and nonmigrainous headache and asthma, hay fever, and chronic bronchitis in a large cross-sectional population-based study. Background.,Associations between prevalence of migraine and asthma or allergy have been demonstrated in clinic-based and epidemiologic studies whereas studies on chronic bronchitis are scarce. Methods.,A total of 51,383 subjects completed a headache questionnaire and constituted the "Head-HUNT" Study. Of these 50,401 (98.1%) answered the questions about asthma and chronic bronchitis, and 47,029 (91.5%) answered the question about hay fever. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CI). Results.,Both migraine and nonmigrainous headache were approximately 1.5 times more likely among those with current asthma, asthma related symptoms, hay fever, and chronic bronchitis than those without. The association increased with increasing headache frequency. Conclusions.,This large questionnaire-based study confirms that migraine and other headaches are associated with respiratory and allergic disorders. The magnitude of the association between headache and asthma, hay fever, and chronic bronchitis tended to be in the same order. Headache frequency seems to have a greater impact on the association with respiratory or allergic conditions than headache diagnoses. Whether it is a causal relationship is uncertain, but the results underline the importance of considering comorbid disorders among patients with frequent headache. [source]


Histamine and prostaglandin E2 up-regulate the production of Th2-attracting chemokines (CCL17 and CCL22) and down-regulate IFN-,-induced CXCL10 production by immature human dendritic cells

IMMUNOLOGY, Issue 4 2006
Anne McIlroy
Summary Effector memory T helper 2 (Th2) cells that accumulate in target organs (i.e. skin or bronchial mucosa) have a central role in the pathogenesis of allergic disorders. To date, the factors that selectively trigger local production of Th2-attracting chemokines remain poorly understood. In mucosa, at the sites of allergen entry, immature dendritic cells (DC) are in close contact with mast cells. Histamine and prostaglandin E2 (PGE2) are two mediators released by allergen-activated mast cells that favour the polarization of maturing DC into Th2-polarizing cells. We analysed here the effects of histamine and PGE2 on the prototypic, Th2-(CCL17, CCL22) versus Th1-(CXCL10) chemokine production by human DC. We report that histamine and PGE2 dose-dependently up-regulate CCL17 and CCL22 by monocyte-derived immature DC. These effects were potentiated by tumour necrosis factor-,, still observed in the presence of the Th1-cytokine interferon-, (IFN-,) and abolished by the immunomodulatory cytokine interleukin-10. In addition, histamine and PGE2 down-regulated IFN-,-induced CXCL10 production by monocyte-derived DC. These properties of histamine and PGE2 were observed at the transcriptional level and were mediated mainly through H2 receptors for histamine and through EP2 and EP4 receptors for PGE2. Finally, histamine and PGE2 also up-regulated CCL17 and CCL22 and decreased IFN-,-induced CXCL10 production by purified human myeloid DC. In conclusion, these data show that, in addition to polarizing DC into mature cells that promote naïve T-cell differentiation into Th2 cells, histamine and PGE2 may act on immature DC to trigger local Th2 cell recruitment through a selective control of Th1/Th2-attracting chemokine production, thereby contributing to maintain a microenvironment favourable to persistent immunoglobulin E synthesis. [source]


A viewpoint of mucosal immunity in relation to early feeding method

INTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 4 2001
Michael Oladipo Ogundele
Summary Atopic diseases are common health problems in society and their incidence is increasing unabated. A number of studies in animal models have shown that antigen-specific IgE suppression could be induced for the treatment of allergic disorders. Many of the present therapeutic strategies in children have not been entirely successful and early breastfeeding could provide a practicable means of helping the affected children. An overview of the mucosal immune system is hereby presented to explain the natural mechanisms involved in protecting organisms from allergic reactions to food and other non-harmful antigens presented at the mucosal surfaces. The protective role of early breastfeeding in modulating this natural phenomenon is emphasized. The undeniable limitations of breastfeeding in the management of some peculiar cases of childhood dietary protein intolerance are also highlighted. [source]


Anti-allergic properties of Mangifera indica L. extract (Vimang) and contribution of its glucosylxanthone mangiferin

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2006
Dagmar García Rivera
Vimang is the brand name of formulations containing an extract of Mangifera indica L., ethnopharmacologically used in Cuba for the treatment of some immunopathological disorders, including bronchial asthma, atopic dermatitis and other allergic diseases. However, the effects of Vimang on allergic response have not been reported until now. In this study, the effects of Vimang and mangiferin, a C-glucosylxanthone isolated from the extract, on different parameters of allergic response are reported. Vimang and mangiferin showed a significant dose-dependent inhibition of IgE production in mice and anaphylaxis reaction in rats, histamine-induced vascular permeability and the histamine release induced by compound 48/80 from rat mast cells, and of lymphocyte proliferative response as evidence of the reduction of the amount of B and T lymphocytes able to contribute to allergic response. In these experiments, ketotifen, promethazine and disodium cromoglicate were used as reference drugs. Furthermore, we demonstrated that Vimang had an effect on an in-vivo model of inflammatory allergy mediated by mast cells. These results constitute the first report of the anti-allergic properties of Vimang on allergic models, as well as suggesting that this natural extract could be successfully used in the treatment of allergic disorders. Mangiferin, the major compound of Vimang, contributes to the anti-allergic effects of the extract. [source]


Comparison of suppressive potency between prednisolone and prednisolone sodium succinate against mitogen-induced blastogenesis of human peripheral blood mononuclear cells in-vitro

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2001
Kentaro Sugiyama
Clinically, both prednisolone and prednisolone sodium succinate are widely used as immunosuppressive agents for the treatment of various allergic disorders. However, whether prednisolone sodium succinate itself has immunosuppressive or anti-inflammatory effects is unclear, and prednisolone sodium succinate may exhibit its efficacy only after hydrolytic conversion to prednisolone in-vivo. If this is the case, the impairment of prednisolone sodium succinate conversion to prednisolone in some clinical conditions may attenuate the efficacy of prednisolone sodium succinate. We therefore compared the pharmacological efficacy of prednisolone with that of prednisolone sodium succinate in-vitro using human peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from 5 healthy subjects and 1 patient with pneumonia. The cells were incubated in the presence of concanavalin A and the cell growth was estimated by 3-(4,5-dimethyl thiazo-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Both prednisolone and prednisolone sodium succinate dose-dependently suppressed PBMC blastogenesis. Mean (s.d.) prednisolone and prednisolone sodium succinate IC50 (concentration of drug that gave 50% inhibition of cell growth) values were 580.0 (1037.9) and 3237.1 (4627.3) nm, respectively. The ratio of prednisolone IC50/prednisolone sodium succinate IC50 ranged from 0.005 to 0.230. Thus, prednisolone sodium succinate potency was markedly lower than that of prednisolone. After incubation of PBMCs with 100 ,m prednisolone sodium succinate, 22.7,42.9 ,m prednisolone was liberated into the culture medium, as determined by HPLC. The ratio of prednisolone liberation from prednisolone sodium succinate was not affected by the presence of fetal bovine serum or PBMC, or both, in the culture medium. These results suggested that the PBMC-suppressive effects of prednisolone sodium succinate might be due, at least partially, to prednisolone liberated from prednisolone sodium succinate into the culture medium. Prednisolone sodium succinate can be converted to prednisolone in the absence of serum or PBMCs, but the ratio of this conversion was very slow (t£frac12; > 4 days). Therefore, impairment of the enzymatic conversion of prednisolone sodium succinate to prednisolone in some pathological conditions such as liver diseases may result in attenuation of the clinical efficacy of prednisolone sodium succinate. [source]


Pharmacokinetics and pharmacodynamics of clemastine in healthy horses

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2003
K. Törneke
Clemastine is an H1 antagonist used in certain allergic disorders in humans and tentatively also in horses, although the pharmacology of the drug in this species has not yet been investigated. In the present study we determined basic pharmacokinetic parameters and compared the effect of the drug measured as inhibition of histamine-induced cutaneous wheal formation in six horses. The most prominent feature of drug disposition after intravenous dose of 50 ,g/kg bw was a very rapid initial decline in plasma concentration, followed by a terminal phase with a half-life of 5.4 h. The volume of distribution was large, Vss = 3.8 L/kg, and the total body clearance 0.79 L/h kg. Notably, oral bioavailability was only 3.4%. There was a strong relationship between plasma concentrations and effect. The effect maximum (measured as reduction in histamine-induced cutaneous wheal formation) was 65% (compared with controls where saline was injected) and the effect duration after i.v. dose was approximately 5 h. The effect after oral dose of 200 ,g/kg was minor. The results indicate that clemastine is not appropriate for oral administration to horses because of low bioavailability. When using repeated i.v. administration, the drug has to be administered at least three to four times daily to maintain therapeutic plasma concentrations because of the short half-life. However, if sufficient plasma concentrations are maintained the drug is efficacious in reducing histamine-induced wheal formations. [source]


Specific immunotherapy suppresses Th2 responses via modulating TIM1/TIM4 interaction on dendritic cells

ALLERGY, Issue 8 2010
C.-Q. Zhao
To cite this article: Zhao C-Q, Li T-L, He S-H, Chen X, An Y-F, Wu W-K, Zhou X-H, Li P, Yang P-C. Specific immunotherapy suppresses Th2 responses via modulating TIM1/TIM4 interaction on dendritic cells. Allergy 2010; 65: 986,995 Abstract Background:, Specific immunotherapy (SIT) is the only curable remedy for allergic disorders currently; however, the underlying mechanism is not fully understood yet. This study aimed to elucidate the mechanism of SIT on suppressing TIM4 (T cell immunoglobulin mucin domain molecule 4) expression in dendritic cells (DCs) and modulating the skewed T helper 2 (Th2) responses in patients with airway allergy. Methods:, Twenty patients with allergic rhinitis (AR) were treated with SIT for 3 months. Before and after SIT, the expression of TIM4 in peripheral DC and TIM1 in Th2 cells was examined. The role of Fc gamma receptor (Fc,R) I and II in modulating the expression of TIM4 in DCs was investigated. Results:, The interaction of TIM1/TIM4 played a critical role in sustaining the polarization status of Th2 cells in AR patients. Cross-linking Fc,RI by antigen/IgG complexes increased the production of TIM4 by dendritic cells via upregulating tumor necrosis factor-alpha in DCs. Exposure to microbial products promoted the expression of Fc,RI in DCs that further increased the expression of TIM4. Exposure to specific antigens alone upregulated the expression of Fc,RII in DCs, that suppressed the expression of TIM4. Conclusions:, We conclude that SIT suppresses the skewed Th2 responses via disrupting the interaction of TIM1/TIM4 in antigen-specific Th2 cells. [source]


Genetic variation in CRTh2 influences development of allergic phenotypes

ALLERGY, Issue 10 2009
L. Cameron
Background:, Allergic disorders are characterized by an increase in the Th2 cytokines IL-4, IL-5 and IL-13, produced primarily by Th2 cells. These cells are marked by the expression of CRTh2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), a receptor for prostaglandin D2. As genetic variation plays a significant role in the predisposition for allergic disorders, we investigated the influence of single nucleotide polymorphisms (SNPs) in CRTh2. Methods:, In a large study population of German children (n = 4264) from the International Study of Asthma and Allergy in Children (ISAAC II), six polymorphisms in CRTh2 were genotyped. Statistical analyses were performed using single SNP and haplotype analyses. Results:, Uncorrected associations among ,6373G>A, +1431G>C and +1538A>G were observed with a number of allergic phenotypes (P < 0.05). After correction, association between +1431C and specific IgE to food allergens remained significant (P = 0.04). Associations of haplotype (H)3 (containing +1538G) with reduced risk for asthma and H2 (containing +1431C) with increased risk for specific IgE to food allergens also remained significant after correction for multiple testing (P = 0.004). Conclusions:, Genetic variation within CRTh2 modifies the development of allergic sensitization and asthma in a population of German children. [source]


Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis

ALLERGY, Issue 6 2009
C. Anandan
Background:, There is conflicting evidence on the use of omega 3 and omega 6 supplementation for the prevention of allergic diseases. We conducted a systematic review evaluating the effectiveness of omega 3 and 6 oils for the primary prevention of sensitization and development of allergic disorders. Methods:, We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, PsycInfo, AMED, ISI Web of Science and Google Scholar for double-blind randomized controlled trials. Two authors independently assessed articles for inclusion. Meta-analyses were undertaken using fixed effects modelling, or random effects modelling in the event of detecting significant heterogeneity. Results:, Of the 3129 articles identified, 10 reports (representing six unique studies) satisfied the inclusion criteria. Four studies compared omega 3 supplements with placebo and two studies compared omega 6 supplements with placebo. There was no clear evidence of benefit in relation to reduced risk of allergic sensitization or a favourable immunological profile. Meta-analyses failed to identify any consistent or clear benefits associated with use of omega 3 [atopic eczema: RR = 1.10 (95% CI 0.78,1.54); asthma: RR = 0.81 (95% CI 0.53,1.25); allergic rhinitis: RR = 0.80 (95% CI 0.34,1.89) or food allergy RR = 0.51 (95% CI 0.10,2.55)] or omega 6 oils [atopic eczema: RR = 0.80 (95% CI 0.56,1.16)] for the prevention of clinical disease. Conclusions:, Contrary to the evidence from basic science and epidemiological studies, our systematic review and meta-analysis suggests that supplementation with omega 3 and omega 6 oils is probably unlikely to play an important role as a strategy for the primary prevention of sensitization or allergic disease. [source]


Cross-sectional study of allergic disorders associated with breastfeeding in Japan: The Ryukyus Child Health Study

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2007
Yoshihiro Miyake
Uncertainties remain as to whether breastfeeding is protective against childhood allergic disorders. Positive relationships of breastfeeding with asthma and atopic eczema were observed in two previous Japanese studies. This cross-sectional study investigated the association between the feeding pattern after birth and the prevalence of allergic disorders during the past 12 months in Japanese schoolchildren. Study subjects were 24,077 children aged 6,15 yr in Okinawa. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Allowance was made for age, sex, number of siblings, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level. Breastfeeding, regardless of exclusivity, for 13 months or longer and exclusive breastfeeding for 4,11 months were independently associated with a higher prevalence of atopic eczema, particularly among children without a parental allergic history. A clear positive dose,response relationship was observed between prolonged duration of breastfeeding, regardless of exclusivity, but not exclusive breastfeeding, and the prevalence of atopic eczema. We found a significant positive trend for atopic eczema across the three categories (formula milk, partial and exclusive breastfeeding) in the first 4 months of life although the odds ratio for exclusive breastfeeding was not statistically significant. No material association was found between the feeding pattern after birth and the prevalence of wheeze or allergic rhinoconjunctivitis. Prolonged breastfeeding may be associated with a higher prevalence of atopic eczema in Japanese children. [source]


Functional symptoms confused with allergic disorders in children and adolescents

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 5 2002
Bodo Niggemann
The diagnosis of a functional respiratory disorder is sometimes difficult and time-consuming, because the symptoms often resemble those of organic diseases. The most common entities are hyperventilation syndrome, psychogenic cough, sighing dyspnea, and vocal cord dysfunction. Typical signs are heavy breathing or dyspnea, cough or sneezing, various breathing sounds, tightness of the throat or chest, pain, and fear. Criteria for differentiation include the lack of nocturnal symptoms, the sudden occurrence, no typical trigger factors, the variable duration, a quick regression, and that symptoms do not respond to adequate pharmacotherapy and finally normal results of diagnostic work-up. Therapeutic options comprise psychological intervention (by reassurance, relaxation techniques, and behaviour therapy) and physiotherapy (e.g. breathing therapy, voice training). Intensive efforts should be made to diagnose functional symptoms at an early stage because this will prevent stigmatization and fixation of symptoms and disease, and also prevent children from undergoing unnecessary and potentially harmful therapies. [source]


Prevalence of Skin Disorders in School Children in Ibadan, Nigeria

PEDIATRIC DERMATOLOGY, Issue 1 2005
A. O. Ogunbiyi F.M.C.P.
Recently, there has been considerable emphasis on hygiene and socio-economic impact on the incidence of allergic disorders in children. We determined the prevalence of skin diseases in a public primary school in Ibadan (southwest Nigeria). A questionnaire for assessing factors associated with the prevalence of diseases was completed, and a complete physical examination was carried out on 1066 students. The study included 529 (49.6%) boys and 537 (50.4%) girls with a mean age of 8.8 ± 2.5 years. The mean family size of the subjects was 6.7 ± 2.3 while the mean number of rooms in their homes was 2.6 ± 1.45. Infectious dermatosis was commonly observed. Of 375 children with a skin lesion, 162 (15.2%) had dermatophytosis, most often tinea capitis, 50 (4.7%) had pityriasis versicolor, and 50 (4.7%) had scabies. Other dermatoses observed included papular urticaria in 35 (3.3%) and angular cheilitis in 27 (2.5%) children. One or more melanocytic nevi were found in 40 (3.8%) children while 138 (12.9%) and 77 (7.25%) had tribal and scarification marks, respectively. Atopic eczema and viral warts were virtually absent. We concluded that fungal infections and scabies were the most common skin diseases in our study population, whereas allergic illnesses were nearly absent. [source]


Association of polymorphisms in CASP10 and CASP8 with FEV1/FVC and bronchial hyperresponsiveness in ethnically diverse asthmatics

CLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2008
Alicia K. Smith
Summary Background Several chromosomal regions have been identified using family-based linkage analysis to contain genes contributing to the development of asthma and allergic disorders. One of these regions, chromosome 2q32-q33, contains a gene cluster containing CFLAR, CASP10 and CASP8. These genes regulate the extrinsic apoptosis pathway utilized by several types of immune and structural cells that have been implicated in the pathogenesis of asthma. Objective To assess the role of genetic variation in CFLAR, CASP10 and CASP8 in asthma and related phenotypes in individuals of diverse ethnic backgrounds. Methods We tested 26 single nucleotide polymorphisms (SNPs) in the CFLAR, CASP10 and CASP8 gene cluster for association with asthma and related phenotypes in African-American, non-Hispanic whites, and Hispanic case,control populations (cases, N=517, controls, N=644). Results Five CASP10 SNPS were associated with forced expiratory volume in 1 s (FEV1)/forced expiration volume capacity (FVC) in the African-American subjects with asthma (P=0.0009,0.047). Nine SNPs, seven in CASP10 and two in CASP8, were also associated with the degree of bronchial hyperresponsiveness (BHR) (as determined by PC20) in race-specific analysis, predominately in the Non-Hispanic white cases. Two SNPs, rs6750157 in CASP10 and rs1045485 in CASP8 were modestly associated with asthma in the African-American (P=0.025) and Hispanic (P=0.033) populations, respectively. Conclusion These data suggest a role for CASP10 as a potential modifier of the asthma phenotype, specifically with measures of airway obstruction and BHR. [source]


MALDI-TOF MS analysis of labile Lolium perenne major allergens in mixes

CLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2008
S. G. Irañeta
Summary Background It is well known that allergen extracts used for specific therapy of allergic disorders are commonly stored as mixtures, causing an alteration of its stability. Objective The aim of this report is to identify pollen allergens susceptible to degradation during storage of mixtures containing different sources of proteases in the absence of glycerol as a preserving agent. Methods Mixes containing Lolium perenne (Lol p) pollen extract with either Aspergillus fumigatus or Periplaneta americana extracts were prepared and co-incubated for 90 days at 4 °C. Samples were taken off at fixed times and comparatively tested by in vitro and in vivo assays with atopic patients. Selected pollinic allergens were subjected to MALDI-TOF MS analysis. Results ELISA inhibition evidenced the loss of potency from ryegrass extract, and immunoblotting assays showed the degradation of specific pollinic allergens during storage of mixtures containing protease-rich sources. An in vivo intradermal skin assay confirmed the gradual loss of the biological activity of L. perenne pollen extract co-incubated with non-related protease-rich extracts in comparison with that of the control pollen extract. MALDI-TOF MS analysis allowed us to determine that Lol p 1 and Lol p 5 are susceptible to proteolysis whereas Lol p 4 was found to be resistant to degradation during storage. Conclusions Lol p 1 and Lol p 5 degradation is responsible for the loss of the biological activity of L. perenne pollen extract when co-incubated with protease-rich fungal and cockroach extracts in the same vial for months in the absence of glycerol as a preserving agent. The integrity of these major allergens must be preserved to increase the vaccine stability and to assure efficacy when mixes are used for immunotherapy. [source]


Will Systematized Nomenclature of Medicine-Clinical Terms improve our understanding of the disease burden posed by allergic disorders?

CLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2007
C. R. Simpson
Summary Analysis of data collected through the use of high-quality computerized systems is vital if we are to understand the health burden from allergic disease. Coding systems currently used, such as the World Health Organization's International Classification of Diseases and the Read system, have however been criticized as being unduly restrictive and hence inadequate for the detailed coding of allergic problems. Greater granularity of coding can be achieved by using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) system, which will be adopted by several countries including the United States and United Kingdom. Before the introduction of SNOMED-CT, it is important that several issues are resolved, including ensuring that adequate mapping occurs from existing systems, that the SNOMED-CT is trialled before general implementation, and that training is provided for users new to coding as part of their clinical practice. Of particular importance is that the allergy fraternity bring to light any gaps in allergy coding through the creation of a working group to advise the newly formed International Healthcare Terminology Standards Development Organisation. There is also a role for allergy experts, working in conjunction with government agencies and professional bodies, to determine a recommended set of codes, which will obviate some of the inevitable challenges raised by a very fluid coding structure for those wishing to undertake secondary analysis of health care datasets. [source]


Too clean, or not too clean: the Hygiene Hypothesis and home hygiene

CLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2006
S. F. Bloomfield
Summary The ,hygiene hypothesis' as originally formulated by Strachan, proposes that a cause of the recent rapid rise in atopic disorders could be a lower incidence of infection in early childhood, transmitted by unhygienic contact with older siblings. Use of the term ,hygiene hypothesis' has led to several interpretations, some of which are not supported by a broader survey of the evidence. The increase in allergic disorders does not correlate with the decrease in infection with pathogenic organisms, nor can it be explained by changes in domestic hygiene. A consensus is beginning to develop round the view that more fundamental changes in lifestyle have led to decreased exposure to certain microbial or other species, such as helminths, that are important for the development of immunoregulatory mechanisms. Although this review concludes that the relationship of the hypothesis to hygiene practice is not proven, it lends strong support to initiatives seeking to improve hygiene practice. It would however be helpful if the hypothesis were renamed, e.g. as the ,microbial exposure' hypothesis, or ,microbial deprivation' hypothesis, as proposed for instance by Bjorksten. Avoiding the term ,hygiene' would help focus attention on determining the true impact of microbes on atopic diseases, while minimizing risks of discouraging good hygiene practice. [source]


Meeting the information needs of patients with allergic disorders: partnership is the key

CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2004
H. Pinnock
No abstract is available for this article. [source]


Effect of various stabilizing agents on Imperata cylindrica grass pollen allergen extract

CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2003
K. M. Bijli
Summary Background Allergen extracts are unstable, heat labile or susceptible to proteases. Stability of allergen extracts is important for proper diagnosis and therapy of allergic disorders. Objective The present study was undertaken to determine the preservation and stabilization conditions of Imperata cylindrica (Ic) grass pollen extract. Methods The Ic extract was kept with 0.1 m,-aminocaproic acid (EACA), 0.75 m sucrose, 5% glycerol, 0.03% human serum albumin (HSA) or 0.4% phenol for different time periods. The extracts were stored for 3, 6 and 12 months each at 4 °C, 4 °C with daily exposure to room temperature (RT) for 1 h, and RT. The quality of extracts was analysed by SDS-PAGE, Western blot, ELISA, ELISA inhibition and skin test. Results Extracts kept with EACA and sucrose retained most of the protein bands followed by glycerol as determined by SDS-PAGE and Western blot during all storage periods and conditions in comparison with standard extracts. The extracts kept with HSA, phenol and without preservative (WP) showed protein degradation below 33 kDa after 3 months storage at all conditions. However, a 67-kDa allergen was stable in these extracts. EACA extract required 75 to 120 ng of protein for 50% inhibition in IgE binding under different conditions, whereas standard extract required 70 ng for the same. ELISA also demonstrated high allergenic reactivity of EACA extract. ID test on allergy patients with EACA extract demonstrated same allergenic potency as that of standard extract. Conclusion EACA is the best preservative/stabilizing agent of Ic pollen extract, followed by sucrose and glycerol. Ic extract kept with phenol, HSA and without preservative showed degradation within 3 months. EACA preserved extract is equally potent as that of standard extract up to 1 year's storage. [source]


Blockade of superoxide generation prevents high-affinity immunoglobulin E receptor-mediated release of allergic mediators by rat mast cell line and human basophils

CLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2002
T. Yoshimaru
Summary Background Previous studies have shown that rat peritoneal mast cells and mast cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular reactive oxygen species (ROS) in response to antigen challenge. However, the physiological significance of the burst of ROS is poorly understood. Objective The present study was undertaken to investigate the role of superoxide anion in mediator release in rat and human cell systems. Methods RBL-2H3 cells were directly stimulated with anti-rat Fc,RI ,-subunit monoclonal antibody (mAb). For the analysis of human cell system, leucocytes were isolated by dextran sedimentation from healthy volunteers or from patients, and challenged either with anti-human Fc,RI mAb or with the relevant antigens. Superoxide generation was determined by chemiluminescence-based methods. The releases of histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben assay (ELISA). Results Cross-linking of Fc,RI on RBL-2H3 cells or on human leucocytes from healthy donors by the anti-Fc,RI mAb resulted in a rapid generation of superoxide anion, as determined by chemiluminescence using superoxide-specific probes. Similarly, leucocytes from patients generated superoxide anion in response to the challenge with the relevant allergen but not with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well-known inhibitor of flavoenzymes suppressed the superoxide generation and the release of histamine and LTC4 induced by the anti-Fc,RI mAb or by allergen in parallel. Conclusion These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon Fc,RI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders. [source]


Macrophage inflammatory protein-1, and C,C chemokine receptor-1 in allergen-induced skin late-phase reactions: relationship to macrophages, neutrophils, basophils, eosinophils and T lymphocytes

CLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2001
S. Ying
Background Macrophage inflammatory protein (MIP)-1, binds to C,C chemokine receptor (CCR)-1 with high affinity. CCR-1 is expressed on neutrophils, eosinophils, monocytes, T lymphocytes and basophils; cells characteristic of atopic allergic inflammation. In vitro, MIP-1, is chemotactic for monocytes, T cells and basophils and is also a potent histamine-releasing factor for basophils and mast cells. Although increased levels of MIP-1, were shown in atopic allergic disorders, the kinetics of expression of these CC chemokines in vivo is largely unknown. Objective To investigate the kinetics of expression of MIP-1, and receptor CCR-1 and the relationships between the expression and infiltration of inflammatory cells in allergen-induced cutaneous late-phase reactions in atopic subjects. Methods Cryostat sections, obtained from skin biopsies from 10 human atopic subjects at 6, 24, 48, 72 h and 7 days after allergen challenge, were processed for immunohistochemistry and in situ hybridization using 35S-labelled riboprobes. Results The peak expression of allergen-induced mRNA for MIP-1, and CCR-1 was 6 h. This was maintained at 24 h, and gradually returned to base line at 7 days. At 6 h, the number of cells expressing MIP-1, mRNA significantly correlated with elastase+ neutrophils and BB-1+ basophils. At 24 h, the MIP-1, mRNA+ cells significantly correlated with CD68+ macrophages. There were significant inverse correlations between the numbers of MIP-1, mRNA cells and the numbers of Tryptase+ mast cells at 6 and 24 h after allergen challenge. Conclusion Allergen-induced cutaneous late-phase reactions in humans were associated with increased expression of MIP-1, and CCR-1. This may be relevant to the infiltration of neutrophils, eosinophils, basophils and macrophages. [source]


Histamine H1 -receptor-mediated release of preformed mediators and cytokines and airway remodelling

CLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 3 2002
M. Triggiani
Summary Histamine is a chemical mediator synthesized and stored within secretory granules of human basophils and mast cells [1,2]. The central role of histamine as a mediator of allergic reactions is unchallenged and is also supported by the efficacy of antihistamines in relieving symptoms of the early-phase allergic response [3]. However, a recent hypothesis suggests that the role of histamine is not limited to the early-phase reaction, but may also have a role in the regulation of the late-phase response. This paper describes certain effects of histamine on human inflammatory cell activation, and in particular, its ability to directly activate human lung macrophages and the molecular mechanism for this interaction. These studies have important implications for the therapeutic potential of antihistamines in the treatment of patients with allergic disorders. [source]


The increasing prevalence of allergy: a challenge for the physician

CLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2002
R. Mösges
Summary The prevalence of allergic disorders has increased markedly throughout the world during the past three decades. There has been considerable controversy about the extent to which the increase is real, or attributable to increased awareness or better diagnosis. It seems probable that the increased prevalence is real because longitudinal studies have shown a rapid exponential increase in allergic disorders such as asthma. Since there is a marked difference in the occurrence of allergic disorders between Western and less developed countries, as well as between rural and urban areas, it is likely that environmental (,lifestyle') factors are aetiologically involved. It also seems probable that contact with microbial antigens, in the form of childhood infections, vaccinations and contact with farm animals, can exert some protection against the later development of allergies. Studies are in progress to determine whether reduction in risk factors or intervention with anti-allergic therapies can modify the long-term outcome in populations at high risk. [source]


A prospective 10-year study on children who had severe infantile colic

ACTA PAEDIATRICA, Issue 2005
Francesco Savino
Abstract Aim: To evaluate the association between infantile colic and gastrointestinal, allergic and psychological disorders in childhood. Methods: A prospective study was conducted on 103 infants aged 31,87 d. After 10 y, between 2001 and 2003, the children were recalled and a paediatrician evaluated the selected disorders by anamnesis, medical examination, laboratory tests and parent interviews. Results: Of the 103 infants enrolled, 96 completed the study. There was an association between infantile colic and recurrent abdominal pain (p=0.001) and allergic disorders: allergic rhinitis, conjunctivitis, asthmatic bronchitis, pollenosis, atopic eczema and food allergy (p<0.05). Sleep disorders, fussiness, aggressiveness and feelings of supremacy are more frequent in children who suffered from colic during early infancy (p<0.05). A family history of gastrointestinal diseases and atopic diseases was significantly higher in infants with colic than in controls (p<0.05). Conclusion: Susceptibility to recurrent abdominal pain, allergic and psychological disorders in childhood may be increased by infantile colic. Our findings confirm that severe infantile colic might be the early expression of some of the most common disorders in childhood. [source]