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Epigenetics of human asthma and allergy: promises to keep.

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Epigenetics of human asthma and allergy: promises to keep.

Asian Pac J Allergy Immunol. 2013 Sep;31(3):183-9

Authors: Devries A, Vercelli D

Abstract
OBJECTIVE: The interest in asthma epigenetics is high because epigenetic mechanisms likely contribute to the environmental origins of the disease and its phenotypic variability. This review presents the main findings of asthma epigenetics and the challenges that still delay progress.
DATA SOURCES: We examined the current literature on asthma epigenetics (31 reviews and 25 original data publications).
STUDY SELECTIONS: We focused on DNA methylation studies in populations.
RESULTS: Both genome-wide and candidate gene studies have explored DNA methylation in allergic disease. Genome-wide studies ask whether and which regions of the genome are differentially methylated in relation to the phenotype of interest. Identification of such regions provides clues about the identity of the genes, pathways and networks underpinning a phenotype and connects these networks to the phenotype through epigenetic mechanisms. Candidate gene studies examine DNA methylation in genes chosen because of their known or hypothesized role in immunity, responses to environmental stimuli or disease pathogenesis. Most existing studies in asthma and allergy focused on candidate genes involved in the response to environmental pollutants.
CONCLUSION: Asthma epigenetics is still in its infancy. The paucity of primary literature originates from methodological and analytical challenges of genome-wide studies, the difficulties in interpreting small differences in DNA methylation, and the need to develop robust bioinformatic tools for pathway, network and system analyses of epigenetic data. Once these challenges have been overcome, epigenetic studies will likely provide important insights about the inception and pathogenesis of allergic disease and will help define disease endotypes.

PMID: 24053700 [PubMed - in process]

Hereditary angioedema with C1 inhibitor deficiency: clinical presentation and quality of life of 193 French patients.

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Hereditary angioedema with C1 inhibitor deficiency: clinical presentation and quality of life of 193 French patients.

Ann Allergy Asthma Immunol. 2013 Oct;111(4):290-4

Authors: Bouillet L, Launay D, Fain O, Boccon-Gibod I, Laurent J, Martin L, Montauban V, Finck K, Bouée S, Gompel A, Kanny G, French National Reference Center for Hereditary Angioedema (CREAK)

Abstract
BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially life-threatening disease. New specific treatments are available.
OBJECTIVE: To identify patients' features and patients' best therapeutic option.
METHODS: A 1-year, multicenter, retrospective study was performed. The primary objective was to examine the clinical presentation of HAE. Secondary objectives included patient characteristics, management of HAE over 12 months, and health-related quality of life using the SF-36v2 questionnaire.
RESULTS: One hundred ninety-three patients were included, and 69.4% were women. In the 12-month period, the mean number of HAE attacks was 7.6. Among the 568 reported attacks, localizations were the abdomen (57.1%), peripheral limbs (42.5%), upper airway (7.9%), and face (6.9%); 31.6% of attacks were severe and occurred statistically more often in women (P < .02). Compared with a population of allergic patients, all age- and sex-adjusted scores were significantly lower in patients with HAE (P < .05) except for the physical component summary. Health-related quality of life negatively correlated with the annual number of attacks and was markedly altered for patients having more than 5 attacks per year (P < .05 for all dimensions).
CONCLUSION: HAE is a severe disease that places a heavy burden on quality of life.

PMID: 24054366 [PubMed - in process]

Measurement of IgE to pollen allergen components is helpful in selecting patients for immunotherapy.

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Measurement of IgE to pollen allergen components is helpful in selecting patients for immunotherapy.

Ann Allergy Asthma Immunol. 2013 Oct;111(4):295-7

Authors: Letrán A, Espinazo M, Moreno F

Abstract
BACKGROUND: Pollen allergy still represents an important cause of allergic morbidity worldwide. Accurate diagnostic methods are important to determine the disease-causing allergen.
OBJECTIVE: To describe the sensitization patterns of patients with spring pollinosis and to make a real-life evaluation of the usefulness of a predetermined IgE molecular profile compared with other sensitization methods for choosing the composition of immunotherapy.
METHODS: One hundred seventy-five patients with a diagnosis of spring pollinosis completed a skin prick test study with Olea europaea, Phleum pratense, palm profilin, and peach peel and an in vitro study of the application of a specific recombinant IgE protocol (nOle e1, rPhl p1-5b, rPhl p12, rPhl p7, and rPru p3). Immunotherapy using the 2 methods was compared.
RESULTS: A high sensitization to nOle e1 and rPhl p1-5b was found. Profilin, polcalcin, and lipid transfer proteins seemed irrelevant for the differential diagnosis of olea and grass pollen sensitization in the most southern area of the Iberian Peninsula. Application of the component resolved the diagnosis, and the choice of immunotherapy was changed in more than 50% of patients.
CONCLUSION: These results support the necessity of the habitual use of this kind of protocol in routine allergologic practice.

PMID: 24054367 [PubMed - in process]

Asthma related to cleaning agents: a clinical insight.

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OBJECTIVE: To determine the agents causing asthmatic reactions during specific inhalation challenges (SICs) in workers with cleaning-related asthma symptoms and to assess the pattern of bronchial responses in order to identify the mechanisms involved in cleaning-related asthma.

DESIGN: A retrospective case series analysis.

SETTING: The study included all participants who completed an SIC procedure with the cleaning/disinfection products suspected of causing work-related asthma over the period 1992-2011 in a tertiary centre, which is the single specialised centre of the French-speaking part of Belgium where all participants with work-related asthma are referred to for SIC.

RESULTS: The review identified 44 participants who completed an SIC with cleaning/disinfection agents. Challenge exposure to the suspected cleaning agents elicited a ≥20% fall in forced expiratory volume in 1 s (FEV1) in 17 (39%) participants. The cleaning products that induced a positive SIC contained quaternary ammonium compounds (n=10), glutaraldehyde (n=3), both of these agents (n=1) and ethanolamines (n=2). Positive SICs were associated with a significant decrease in the median (IQR) value of the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) from 1.4 (0.2-4.2) mg/mL at baseline to 0.5 (0.4-3.0) mg/mL after the challenge and a significant increase in sputum eosinophils from 1.8 (0.8-7.2)% at baseline to 10.0 (4.1-15.9)% 7 h after the challenge exposure while these parameters did not significantly change in participants with a negative SIC. Overall, 11 of 17 participants with positive SICs showed greater than threefold decrease in postchallenge histamine PC20 value, a >2% increase in sputum eosinophils, or both of these outcomes.

CONCLUSIONS: These data indicate that a substantial proportion of workers who experience asthma symptoms related to cleaning materials show a pattern of bronchial reaction consistent with sensitiser-induced occupational asthma. The results also suggest that quaternary ammonium compounds are the principal cause of sensitiser-induced occupational asthma among cleaners.

Immunotherapy for Mold Allergy.

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The objective of this article is to review the available studies regarding mold immunotherapy. A literature search was conducted in MEDLINE to identify peer-reviewed articles related to mold immunotherapy using the following keywords: mold, allergy, asthma, and immunotherapy. In addition, references cited within these articles were also reviewed. Articles were selected based on their relevance to the topic.

Allergic responses to inhaled mold antigens are a recognized factor in allergic rhinitis and asthma. There are significant problems with respect to the production of relevant allergen material for the diagnosis and treatment of mold allergy with immunotherapy. Mold allergens contain proteases and should not be mixed with other allergens for immunotherapy. Most of the immunotherapy studies focus on two molds, Alternaria and Cladosporium. There is a lack of randomized placebo-controlled trials when evaluating the efficacy of mold immunotherapy with trials only focusing on immunotherapy to Alternaria and Cladosporium.

Additional studies are needed regarding mold allergy and immunotherapy focusing on which molds are important for causing allergic disease.

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