Genome-wide association analysis of 350 000 Caucasians from the UK Biobank identifies novel loci for asthma, hay fever and eczema.

Even though heritability estimates suggest that the risk of asthma, hay fever and eczema is largely due to genetic factors, previous studies have not explained a large part of the genetics behind these diseases. In this genome-wide association study, we include 346 545 Caucasians from the UK Biobank to identify novel loci for asthma, hay fever and eczema and replicate novel loci in three independent cohorts. We further investigate if associated lead single nucleotide polymorphisms (SNPs) have a significantly larger effect for one disease compared to the other diseases, to highlight possible disease-specific effects. We identified 141 loci, of which 41 are novel, to be associated (P ≤ 3 × 10-8) with asthma, hay fever or eczema, analyzed separately or as disease phenotypes that includes the presence of different combinations of these diseases. The largest number of loci was associated with the combined phenotype (asthma/hay fever/eczema). However, as many as 20 loci had a significantly larger effect on hay fever/eczema only compared to their effects on asthma, while 26 loci exhibited larger effects on asthma compared with their effects on hay fever/eczema. At four of the novel loci, TNFRSF8, MYRF, TSPAN8, and BHMG1, the lead SNPs were in Linkage Disequilibrium (LD) (>0.8) with potentially casual missense variants. Our study shows that a large amount of the genetic contribution is shared between the diseases. Nonetheless, a number of SNPs have a significantly larger effect on one of the phenotypes, suggesting that part of the genetic contribution is more phenotype specific.

Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial.

Importance: Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. Objective: To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. Design, Setting, and Participants: A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Interventions: Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). Main Outcomes and Measures: Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Results: Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was -0.18 (95% CI, -1.25 to 0.90; [P = .75]). Conclusions and Relevance: Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up. Trial Registration: clinicaltrials.gov Identifier: NCT01335139; EudraCT Number: 2010-023536-16.

Plant food allergy in patients with pollinosis from the Mediterranean area.

BACKGROUND: Patients with pollinosis develop symptoms after intake of plant food more often than the general population. In order to study the prevalence of the presentation of allergic symptoms to plant foods in pollinosis, we selected a representative sample of the population from our Mediterranean area. METHODS: All patients completed a questionnaire, provided a blood sample and underwent a battery of skin and other complementary tests (prick-prick, oral challenge test) when necessary. The pollen counts were obtained from the Elche pollen station. In addition, sera from a subgroup of patients were checked with an allergen molecule panel on an Advia Centaur XP platform. RESULTS: Of the final sample (n = 233), 39.9% of the patients with pollinosis were sensitized and 30.9% had clinical allergy to at least one of the plant foods studied. Regression analysis showed that age and sensitization to the extracts of Platanus acerifolia and Artemisia vulgaris were the most important variables for discriminating between groups. Patients with pollinosis at a risk of allergy to plant foods had significantly higher Pru p 3 values [odds ratio (OR) 3.3; 95% confidence interval (95% CI) 2.3-4.8], and the value increased according to the number of plant food sensitizations. CONCLUSION: Plant food allergy is more common in patients with pollinosis than in the general population. The use of the London plain tree (P. acerifolia) and mugwort (A. vulgaris) in the skin tests may help identify such patients in our Mediterranean area, but determination of rPru p 3 could also be very useful in patients suspected of having plant food allergy.

Genetic variant rs4982958 at 14q11.2 is associated with allergic rhinitis in a Chinese Han population running title: 14q11.2 is a susceptibility locus for allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is one of the most common diseases caused by the combined effects of intrinsic factors (susceptibility genes and immunological status) and the external environment. Analyses of ascendant family history of atopic disease suggest that AR and atopic dermatitis might share a similar genetic background. OBJECTIVE: To conduct a case-control study in a Chinese Han population to evaluate the potential influence of single nucleotide polymorphisms (SNPs) at FLG, 5q22.1, 11q13.5, 14q11.2 and 20q13.33 on AR. METHODS: Ten SNPs--rs11204971 and rs3126085 at FLG, rs10067777, rs7701890, rs13360927, and rs13361382 at 5q22.1, rs6010620 at 20q13.33, rs7936562 and rs7124842 at 11q13.5, and rs4982958 at 14q11.2 were genotyped in 363 cases and 668 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. RESULTS: The T allele of rs4982958 at 14q11.2 was observed to be significantly associated with AR (P = .002, OR = 0.73, P(Bonferront) = .02). Genotype-based association testing revealed that the recessive model might provide the best fit for rs4982958 (P(Bonferroni) = .01). In subphenotype analyses, the rs4982958 T allele was also significantly associated with persistent AR (P = .01) and more than 2 positive skin prick tests (P = .038). CONCLUSION: We identified a novel susceptibility locus 14q11.2 for AR that might bear candidate genes conferring susceptibility to AR and affecting disease phenotypes.

Clinical profile of a Mediterranean population sensitised to date palm pollen (Phoenix dactylifera). A retrospective study

Background: Date palm pollen allergy is frequently associated with polysensitisation. Observational studies have suggested that date-palm-sensitised individuals could be included in a distinct group of polysensitised patients. The objectives of the study were to analyse the clinical characteristics of a group of patients diagnosed of date-palm pollen allergy and to compare them with pollen allergic patients without date-palm sensitisation. Methods: Forty-eight palm-pollen sensitised individuals were classified as Group A. A control group of 48 patients sensitised to pollens but without palm-pollen allergy were included as Group B. All individuals were skin prick tested with a common battery of aeroallergens. Information about age, sex, family history of atopy, respiratory symptoms, food allergy and sensitisation to other pollens were considered variables of the study. Specific IgE and the allergogram todate-palm pollen were determined in a subgroup of Group A. Results: Significant differences in the family history of atopy and number of sensitisations were observed. Both parameters were significantly higher in Group A. Group A showed high prevalence of asthma and higher level of sensitisation to foods (p < 0.05). Significant differences were obtained for sensitisation to epithelia and pollens. Pho d 2 was the most commonly recognised allergen (83.3%) in the palm-pollen allergic group. Conclusions: Date-palm pollen allergic patients constitute a homogeneous group characterised for showing bronchial asthma, sensitisation to food allergens and polysensitisation. These results suggest that the reasons for sensitisation to date-palm pollen remain to be elucidated, but could relate to the existence of as yet non-identified pan-allergens (AU)

Inverse association between Helicobacter pylori infection and allergic rhinitis in young Japanese.

BACKGROUND AND AIM: The prevalence of allergic disorders, including asthma, atopic dermatitis, and allergic rhinitis has been increasing, and the prevalence of Helicobacter pylori (H. pylori) infection has been decreasing. Chronic bacterial infection during childhood is reported to protect the development of allergic diseases. The aim of the present study was to identify whether H. pylori infection influences the prevalence of allergic rhinitis, which has become a serious social problem, especially in the developed countries. METHODS: We initially investigated the association between the prevalence of H. pylori and pollinosis symptoms in 97 healthy volunteers. We had investigated the association between the serum H. pylori-immunoglobulin (Ig) G antibodies and specific IgE antibodies for pollen, mites, and house dust in 211 consecutive patients. RESULTS: There were 52.2% (36/69) of H. pylori-negative volunteers with allergic symptoms, which was significantly higher than H. pylori-positive volunteers (14.3%, 4/28, P < 0.05). The risk of pollinosis symptoms by H. pylori infection was 0.148 (95% confidence interval): 0.046-0.475, P < 0.05). The prevalence of H. pylori infection increased according to age, whereas that of specific IgE-positive patients gradually decreased. Among the IgE-positive patients, the prevalence of H. pylori-negative patients was significantly higher than H. pylori-positive patients who were younger in age (P < 0.05). CONCLUSION: H. pylori infection decreased the pollinosis effects, especially among the younger volunteers. However, the prevalence of pollinosis in patients who were 50 years or older were almost same between H. pylori-positive and H. pylori-negative patients; therefore, the recent increase of pollinosis might relate to not only H. pylori infection, but also change in social environment.

Evaluation of the psychological status in seasonal allergic rhinitis patients.

OBJECTIVE: To investigate the psychological status of Chinese adults with seasonal allergic rhinitis (SAR) in the allergic season, and evaluate the effects of nasal symptoms on their psychological status. METHODS: The Symptom Checklist 90 (SCL-90) or Self-Reporting Inventory was employed to analyze the psychological status of 337 SAR patients. RESULTS: The SCL-90 scores of the SAR patients were statistically higher than those of nonallergic adults in terms of somatization, depression, anxiety, hostility and psychosis. No statistical discrepancies existed in gender or age, the impact of disease course was limited to somatization, compulsion and phobic disorders and the impact of the educational level was that the lower the level of education, the more obvious the hostility. The behavior of somatization, compulsion, depression and anxiety in patients with a history of eczema or asthma was much more obvious than in patients without such a history. Nasal obstruction had a conspicuous impact on somatization, compulsion, interpersonal sensitivity, depression, anxiety and psychosis, while nasal itching contributed to somatization, depression and anxiety. CONCLUSION: The psychological status of SAR patients is evidently worse than that of nonallergic adults. Symptoms such as nasal obstruction and nasal itching had an obvious impact on the psychological status of the patients.

Allergic rhinitis in Korean immigrants to the United States.

The prevalence of allergic rhinitis among Korean immigrants to the United States is unknown. However, after arrival in the United States, many develop allergic rhinitis for the first time. This study is undertaken to investigate and establish some contributing environmental factors and the time until onset of allergic rhinitis in Korean immigrants to the United States living in Chicago. Information regarding 246 patients of Korean origin who presented to a Chicago allergy/immunology clinic from 1993 to 1998 were analyzed by retrospective chart review. The diagnosis of allergic rhinitis was established by history, physical examination, and skin testing for immediate hypersensitivity to airborne allergens. The mean residential time in the United States of our patients was 13.5 years (range, 2-38 years). The mean interval from arrival in the United States to onset of symptoms was 8 years (range, 0-24 years) The most commonly identified allergens were ragweed pollen (59%), cat pelt (44%), cocklebur pollen (41%), house-dust mite (35%), and Penicillium (29%). We conclude that the spectrum of responsible allergens in Korean immigrants closely resembles that seen in native citizens of the United States and that environmental factors play an important role in the pathogenesis of allergic rhinitis in this population.

Different slopes for different folks: socioeconomic and racial/ethnic disparities in asthma and hay fever among 173,859 U.S. men and women.

Although allergic diseases such as asthma and hay fever are a major cause of morbidity in industrialized countries, most studies have focused on patterns of prevalence among children and adolescents, with relatively few studies on variations in prevalence by race/ethnicity and socioeconomic position among adults. Our study examined racial/ethnic and socioeconomic patterns in the prevalence of asthma overall, asthma with hay fever, asthma without hay fever, and hay fever overall, in a population of 173,859 women and men in a large prepaid health plan in northern California. Using education as a measure of socioeconomic position, we found evidence of a positive gradient for asthma with hay fever with increasing level of education but an inverse gradient for asthma without hay fever. Hay fever was also strongly associated with education. Compared with their White counterparts, Black women and men were more likely to report asthma without hay fever, and Black women were less likely to have asthma with hay fever. Asian men were also more likely to report asthma with hay fever, and Asian women and men were much more likely to have hay fever. Racial/ethnic disparities in prevalence of allergic diseases were largely independent of education. We discuss implications for understanding these social inequalities in allergic disease risk in relation to possible differences in exposure to allergens and determinants of immunologic susceptibility and suggest directions for future research.

Migration and atopic disorder in Swedish conscripts.

We have studied asthma and allergic rhinitis prevalence in Swedish conscripts born 1973-1977 according to the military service conscription register in relation to the socio-economic status and country of birth of the conscripts and their parents, and age when granted residency in Sweden. There was an increase in prevalence of asthma and allergic rhinitis over time in all groups irrespective of country of birth or ethnic origin. Conscripts who themselves were born in Africa, Asia, Latin America and the Mediterranean had a significantly lower risk for asthma and allergic rhinitis than Swedish-born conscripts. The risk of atopic disorder among the foreign-born conscripts increased with time of residency in Sweden. Conscripts with mothers from Latin America, Asia and Africa were identified as having the highest risk for atopic disorder among Swedish-born conscripts with high socio-economic status; the adjusted risk ratio (RR) for asthma was 2.6 (95% CI 1.7-4.0) and that for allergic rhinitis was 2.0 (1.5-2.6). The conscripts with mothers from the Mediterranean had the lowest risk for atopic disorders of the Swedish-born conscripts with low socio-economic status; the RR for asthma was 0.43 (0.34-0.56) and that for allergic rhinitis was 0.84 (0.76-0.93). This study demonstrates that factors related to migration and ethnicity are important determinants of atopic disorder among Swedish conscripts.

Age at adoption, ethnicity and atopic disorder: a study of internationally adopted young men in Sweden.

Epidemiological and laboratory studies have implied that the environment during early childhood is important for the risk of developing atopic disorders. In this study we analyzed the prevalence of asthma, hayfever and eczema among 1901 internationally adopted young men at the military-induction medical examination in relation to indicators of their early childhood environment. The adopted young men who came to Sweden before 2 years of age suffered from asthma, hayfever and eczema significantly more often than those who came to Sweden between 2 and 6 years of age; the risk ratios (RR) were 1.6, 2.5 and 2.1, respectively. The young men who were born in the Far East were identified as being particularly susceptible to the development of hayfever and eczema, with RRs of 1.3 and 1.7. This study demonstrates that the environment during the first 6 years of life has a profound influence on the risk of suffering from atopic disorders as young adults.

Sensitivity to olea Europaea pollen in different populations in Israel.

Sensitivity to olive pollen was studied (by skin tests) in different Israeli populations suffering from respiratory allergies. The results were compared with aerobiological data, in order to correlate amount of exposure to prevalence of sensitization. It was found that in the Jewish population, sensitivity to olive pollen developed in direct proportion with the number of olive trees in the settlement: 66% where trees density is high, 29% where it is low. In the Arab population however, possibly genetically determined, the sensitization to olive pollen was low (only 14%) even though the density of trees is high.

Asthma, allergy and atopy in Asian immigrants in Melbourne.

OBJECTIVES: To compare the prevalence of asthma, hay fever and atopy in Asian immigrants in Melbourne with that in Australian-born non-Asians and Australian-born Asians, and to investigate the association of these conditions with atopic status, length of stay in Australia and IgE levels in Asian immigrants. DESIGN: We performed a cross-sectional study by telephone interviews, using standard questionnaire items on respiratory and allergic symptoms. A random sample of 636 recent Asian immigrants of ethnic Chinese origin, 109 Australian-born Asians and 424 Australian-born non-Asians were selected from the 1991 Melbourne Telephone Directory, using a presumptive surname list. Skin tests to determine atopic status were performed on 269 Asian immigrants and 167 of these also had serum levels of total and specific IgE estimated. RESULTS: In the under 20 years age group the prevalence of wheeze or asthma ever was higher in Australian-born non-Asians and Australian-born Asians than in Asian immigrants (P < 0.001), and the prevalence of hay fever was higher in Asian immigrants and Australian-born Asians than in Australian-born non-Asians. In those older than 20 years, hay fever was almost twice as common in Asian immigrants as in Australian-born non-Asians (P < 0.001 for 20-40 years age group; P < 0.01 for > 40 years). The prevalence of hay fever and, to a lesser degree, asthma in Asian immigrants increased significantly with length of stay in Australia, independent of age at arrival, sex and atopic status (trend test: P < 0.001 for hay fever; P = 0.05 for asthma). Atopy was more common in Asian immigrants and Australian-born Asians than in Australian-born non-Asians (P < 0.001) and was very strongly associated with both hay fever and asthma, irrespective of length of stay. Pollen and mite sensitivities were more common in Asian subjects (twice as common for Asian-born and 1.5 times for Australian-born) than non-Asian subjects (P < 0.01). Among Asian immigrants, elevated total IgE level (> 100 IU/mL) was strongly associated with a history of hay fever (P < 0.01) and wheeze or asthma ever (P < 0.05), atopy (P < 0.001) and the presence of specific IgE antibodies to grass pollen, dust mite, cockroach and Ascaris antigens (P < 0.05 for all). CONCLUSION: We found substantial differences in the prevalence of asthma, hay fever and atopy between Asian immigrants, Australian-born Asians and non-Asians. The prevalence of hay fever and asthma in Asian immigrants was strongly associated with length of stay in Australia, suggesting that environmental factors are important in the pathogenesis of these diseases.

[The role of the major histocompatibility complex antigens in the development of allergic diseases in the Korean population]. / Rol' antigenov glavnogo kompleksa gistosovmestimosti v razvitii allergicheskikh zabolevanii u Koreitsev.

Association has been detected between incidence of HLA-antigens and allergy prevalence in Koreans. Antigen B8 occurs significantly more frequently whereas A3 more rarely in Koreans with allergy. Determination of HLA-antigens distribution may be helpful in prognosis of allergic diseases possibility. Allergies are a rare finding in Koreans due to less common occurrence of antigens AI and B8 in them against Europeans.

The effect of plantation on increased allergic rhinitis in the eastern province of Saudi Arabia.

In a study done between 1982-1986, 129 patients with allergic rhinitis were followed-up in the Outpatient Department of King Fahd University Hospital, Al-Khobar (Saudi Arabia). Eighty patients were males (62%), 49 patients were females (38%); 71% Saudis, and 29% non-Saudis. Routine laboratory investigations, IgE and skin test were performed. The commonest allergens were pollens, house dust and cat danders. We found that males were significantly more affected than females, particularly in the cases of ages between 20-30 years. Beside the known causes, other factors such as the increase of plantation and local customs are discussed.