Category Archives: J Allergy Clin Immunol

Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.

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Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.

J Allergy Clin Immunol. 2015 Oct 15;

Authors: Hartmann K, Escribano L, Grattan C, Brockow K, Carter MC, Alvarez-Twose I, Matito A, Broesby-Olsen S, Siebenhaar F, Lange M, Niedoszytko M, Castells M, Oude Elberink JN, Bonadonna P, Zanotti R, Hornick JL, Torrelo A, Grabbe J, Rabenhorst A, Nedoszytko B, Butterfield JH, Gotlib J, Reiter A, Radia D, Hermine O, Sotlar K, George TI, Kristensen TK, Kluin-Nelemans HC, Yavuz S, Hägglund H, Sperr WR, Schwartz LB, Triggiani M, Maurer M, Nilsson G, Horny HP, Arock M, Orfao A, Metcalfe DD, Akin C, Valent P

Abstract
Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.

PMID: 26476479 [PubMed – as supplied by publisher]

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Immunoactive prebiotics transiently prevent occurrence of early atopic dermatitis among low-atopy-risk infants.

Immunoactive prebiotics transiently prevent occurrence of early atopic dermatitis among low-atopy-risk infants.

J Allergy Clin Immunol. 2015 Sep 25;

Authors: Grüber C,…

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Revisiting the Dutch hypothesis.

Revisiting the Dutch hypothesis.
J Allergy Clin Immunol. 2015 Sep;136(3):521-529
Authors: Postma DS, Weiss ST, van den Berge M, Kerstjens HA, Koppelman GH
Abstract
The Dutch hypothesis was first artic… Continue reading

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Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study.

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Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study.

J Allergy Clin Immunol. 2015 Jul 25;

Authors: Garne E, Hansen AV, Morris J, Zaupper L, Addor MC, Barisic I, Gatt M, Lelong N, Klungsøyr K, O’Mahony M, Nelen V, Neville AJ, Pierini A, Tucker D, de Walle H, Wiesel A, Loane M, Dolk H

Abstract
BACKGROUND: Pregnant women with asthma need to take medication during pregnancy.
OBJECTIVE: We sought to identify whether there is an increased risk of specific congenital anomalies after exposure to antiasthma medication in the first trimester of pregnancy.
METHODS: We performed a population-based case-malformed control study testing signals identified in a literature review. Odds ratios (ORs) of exposure to the main groups of asthma medication were calculated for each of the 10 signal anomalies compared with registrations with nonchromosomal, nonsignal anomalies as control registrations. In addition, exploratory analyses were done for each nonsignal anomaly. The data set included 76,249 registrations of congenital anomalies from 13 EUROmediCAT registries.
RESULTS: Cleft palate (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had significantly increased odds of exposure to first-trimester use of inhaled β2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled β2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heart defects in general, or tetralogy of Fallot. None of the 4 literature signals of exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal atresia, and hypospadias). Exploratory analyses found an association between renal dysplasia and exposure to the combination of long-acting β2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85).
CONCLUSIONS: The study confirmed increased odds of first-trimester exposure to inhaled β2-agonists for cleft palate and gastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting β2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids during the first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.

PMID: 26220526 [PubMed – as supplied by publisher]

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Ambient air pollution, lung function, and airway responsiveness in asthmatic children.

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Ambient air pollution, lung function, and airway responsiveness in asthmatic children.

J Allergy Clin Immunol. 2015 Jun 29;

Authors: Ierodiakonou D, Zanobetti A, Coull BA, Melly S, Postma DS, Boezen HM, Vonk JM, Williams PV, Shapiro GG, McKone EF, Hallstrand TS, Koenig JQ, Schildcrout JS, Lumley T, Fuhlbrigge AN, Koutrakis P, Schwartz J, Weiss ST, Gold DR, Childhood Asthma Management Program Research Group

Abstract
BACKGROUND: Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking.
OBJECTIVE: We sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications.
METHODS: We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders.
RESULTS: Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P < .05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, -6% [95% CI, -11% to -1.5%]). Treatment augmented the negative short-term CO effect on PC20.
CONCLUSIONS: Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.

PMID: 26187234 [PubMed – as supplied by publisher]

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Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels.

Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels.

J Allergy Clin Immunol. 2015 May 12;

Authors: de Jong K, Vonk JM, Timens W, Bossé Y, Sin DD, Hao K, Kromhout H, Vermeulen R, Postma DS, Boezen HM

Abstract
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by impaired lung function and airway obstruction resulting from interactions between multiple genes and multiple environmental exposures. Thus far, genome-wide association studies have largely disregarded environmental factors that might trigger the development of lung function impairment and COPD, such as occupational exposures, which are thought to contribute to 15% to 20% of the COPD prevalence.
OBJECTIVES: We performed a genome-wide interaction study to identify novel susceptibility loci for occupational exposure to biological dust, mineral dust, and gases and fumes in relation to FEV1 levels.
METHODS: We performed an identification analysis in 12,400 subjects from the LifeLines cohort study and verified our findings in 1436 subjects from a second independent cohort, the Vlagtwedde-Vlaardingen cohort. Additionally, we assessed whether replicated single nucleotide polymorphisms (SNPs) were cis-acting expression (mRNA) quantitative trait loci in lung tissue.
RESULTS: Of the 7 replicated SNPs that interacted with one of the occupational exposures, several identified loci were plausible candidates that might be involved in biological pathways leading to lung function impairment, such as PCDH9 and GALNT13. Two of the 7 replicated SNPs were cis-acting expression quantitative trait loci associated with gene expression of PDE4D and TMEM176A in lung tissue.
CONCLUSION: This genome-wide interaction study on occupational exposures in relation to the level of lung function identified several novel genes. Further research should determine whether the identified genes are true susceptibility loci for occupational exposures and whether these SNP-by-exposure interactions consequently contribute to the development of COPD.

PMID: 25979521 [PubMed – as supplied by publisher]

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A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis.

A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis.

J Allergy Clin Immunol. 2015 Jan 30;

Authors: Jin P, Andiappan AK, Quek JM, Lee B, Au B, Sio YY, Irwanto A, Schurmann C, Grabe HJ, Suri BK, Matta SA, Westra HJ, Franke L, Esko T, Sun L, Zhang X, Liu H, Zhang F, Larbi A, Xu X, Poidinger M, Liu J, Chew FT, Rotzschke O, Shi L, Wang Y

Abstract
BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a secretory protein that has been implicated in the pathogenesis of allergic rhinitis (AR), atopic asthma, and eczema, but it is currently unknown whether BDNF polymorphisms influence susceptibility to moderate-to-severe AR.
OBJECTIVE: We sought to identify disease associations and the functional effect of BDNF genetic variants in patients with moderate-to-severe AR.
METHODS: Tagging single nucleotide polymorphisms (SNPs) spanning the BDNF gene were selected from the human HapMap Han Chinese from Beijing (CHB) data set, and associations with moderate-to-severe AR were assessed in 2 independent cohorts of Chinese patients (2216 from Shandong province and 1239 living in Singapore). The functional effects of the BDNF genetic variants were determined by using both in vitro and ex vivo assays.
RESULTS: The tagging SNP rs10767664 was significantly associated with the risk of moderate-to-severe AR in both Singapore Chinese (P = .0017; odds ratio, 1.324) and Shandong Chinese populations (P = .039; odds ratio, 1.180). The coding nonsynonymous SNP rs6265 was in perfect linkage with rs10767664 and conferred increased BDNF protein secretion by a human cell line in vitro. Subjects bearing the AA genotype of rs10767664 exhibited increased risk of moderate-to-severe AR and displayed increased BDNF protein and total IgE levels in plasma. Using a large-scale expression quantitative trait locus study, we demonstrated that BDNF SNPs are significantly associated with altered BDNF concentrations in peripheral blood.
CONCLUSION: A common genetic variant of the BDNF gene is associated with increased risk of moderate-to-severe AR, and the AA genotype is associated with increased BDNF mRNA levels in peripheral blood. Together, these data indicate that functional BDNF gene variants increase the risk of moderate-to-severe AR.

PMID: 25649076 [PubMed – as supplied by publisher]

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Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma.

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Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma.

J Allergy Clin Immunol. 2015 Jan 21;

Authors: de Groot JC, van Roon EN, Storm H, Veeger NJ, Zwinderman AH, Hiemstra PS, Bel EH, Ten Brinke A

Abstract
BACKGROUND: Low levels of vitamin D are associated with asthma severity, airway remodeling, and exacerbation rate increase, especially in nonatopic asthma. Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms.
OBJECTIVE: We sought to evaluate the effect of vitamin D supplementation on eosinophilic and neutrophilic airway inflammation in patients with nonatopic asthma.
METHODS: In a double-blind, randomized, placebo-controlled trial, we investigated the effect of long-acting vitamin D3 (400,000 IU) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic (≥53%) and/or eosinophilic (≥3%) airway inflammation. Sputum induction was performed at baseline and after 9 weeks. Other measurements included questionnaires, blood samples, and pulmonary function.
RESULTS: Treatment with vitamin D did not significantly affect sputum neutrophils or eosinophils compared with treatment with placebo in the total group. Regarding sputum eosinophils, the effect of vitamin D appeared to be dependent on baseline sputum eosinophil levels (interaction P = .015). In patients with eosinophil levels of 26.2% or more (median in patients with sputum eosinophilia, >3%), eosinophils decreased from a median of 41.0% to 11.8% after vitamin D treatment as compared with an increase from 51.8% to 63.3% in patients receiving placebo (P = .034). Vitamin D treatment also resulted in slightly better Asthma Control Questionnaire scores (P = .08).
CONCLUSIONS: Vitamin D supplementation reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation, but did not affect sputum neutrophils. Also, a small effect on asthma control was observed. These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma.

PMID: 25617224 [PubMed – as supplied by publisher]

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Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.

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Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.

J Allergy Clin Immunol. 2014 Jul;134(1):46-55

Authors: van der Valk RJ, Duijts L, Timpson NJ, Salam MT, Standl M, Curtin JA, Genuneit J, Kerhof M, Kreiner-Møller E, Cáceres A, Gref A, Liang LL, Taal HR, Bouzigon E, Demenais F, Nadif R, Ober C, Thompson EE, Estrada K, Hofman A, Uitterlinden AG, van Duijn C, Rivadeneira F, Li X, Eckel SP, Berhane K, Gauderman WJ, Granell R, Evans DM, St Pourcain B, McArdle W, Kemp JP, Smith GD, Tiesler CM, Flexeder C, Simpson A, Murray CS, Fuchs O, Postma DS, Bønnelykke K, Torrent M, Andersson M, Sleiman P, Hakonarson H, Cookson WO, Moffatt MF, Paternoster L, Melén E, Sunyer J, Bisgaard H, Koppelman GH, Ege M, Custovic A, Heinrich J, Gilliland FD, Henderson AJ, Jaddoe VW, de Jongste JC, EArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium

Abstract
BACKGROUND: The fraction of exhaled nitric oxide (Feno) value is a biomarker of eosinophilic airway inflammation and is associated with childhood asthma. Identification of common genetic variants associated with childhood Feno values might help to define biological mechanisms related to specific asthma phenotypes.
OBJECTIVE: We sought to identify the genetic variants associated with childhood Feno values and their relation with asthma.
METHODS: Feno values were measured in children age 5 to 15 years. In 14 genome-wide association studies (N = 8,858), we examined the associations of approximately 2.5 million single nucleotide polymorphisms (SNPs) with Feno values. Subsequently, we assessed whether significant SNPs were expression quantitative trait loci in genome-wide expression data sets of lymphoblastoid cell lines (n = 1,830) and were related to asthma in a previously published genome-wide association data set (cases, n = 10,365; control subjects: n = 16,110).
RESULTS: We identified 3 SNPs associated with Feno values: rs3751972 in LYR motif containing 9 (LYRM9; P = 1.97 × 10(-10)) and rs944722 in inducible nitric oxide synthase 2 (NOS2; P = 1.28 × 10(-9)), both of which are located at 17q11.2-q12, and rs8069176 near gasdermin B (GSDMB; P = 1.88 × 10(-8)) at 17q12-q21. We found a cis expression quantitative trait locus for the transcript soluble galactoside-binding lectin 9 (LGALS9) that is in linkage disequilibrium with rs944722. rs8069176 was associated with GSDMB and ORM1-like 3 (ORMDL3) expression. rs8069176 at 17q12-q21, but not rs3751972 and rs944722 at 17q11.2-q12, were associated with physician-diagnosed asthma.
CONCLUSION: This study identified 3 variants associated with Feno values, explaining 0.95% of the variance. Identification of functional SNPs and haplotypes in these regions might provide novel insight into the regulation of Feno values. This study highlights that both shared and distinct genetic factors affect Feno values and childhood asthma.

PMID: 24315451 [PubMed – indexed for MEDLINE]

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Understanding food allergen thresholds requires careful analysis of the available clinical data.

Understanding food allergen thresholds requires careful analysis of the available clinical data.
J Allergy Clin Immunol. 2014 Nov 22;
Authors: Taylor SL, Houben GF, Baumert JL, Crevel RR, Allen KJ, Dubois AE, Knulst … Continue reading

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Associations between the 17q21 region and allergic rhinitis in 5 birth cohorts.

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Associations between the 17q21 region and allergic rhinitis in 5 birth cohorts.

J Allergy Clin Immunol. 2014 Sep 24;

Authors: Fuertes E, Söderhäll C, Acevedo N, Becker A, Brauer M, Chan-Yeung M, Nicole Dijk F, Heinrich J, de Jongste J, Koppelman GH, Postma DS, Kere J, Kozyrskyj AL, Pershagen G, Sandford A, Standl M, Tiesler CM, Waldenberger M, Westman M, Carlsten C, Melén E

PMID: 25262464 [PubMed – as supplied by publisher]

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Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children.

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Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children.

J Allergy Clin Immunol. 2014…

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Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects.

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Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects.

J Allergy Clin Immunol. 2014 Aug 13;

Authors: …

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Genetic variants of inducible costimulator are associated with allergic asthma susceptibility.

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Genetic variants of inducible costimulator are associated with allergic asthma susceptibility.

J Allergy Clin Immunol. 2014 Aug 7;

Authors: …

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Predictors of new fragility fractures after diagnosis of indolent systemic mastocytosis.

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Predictors of new fragility fractures after diagnosis of indolent systemic mastocytosis.

J Allergy Clin Immunol. 2014 Jun 27;

Authors: van der…

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Meta-analysis of air pollution exposure association with allergic sensitization in European birth cohorts.

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Meta-analysis of air pollution exposure association with allergic sensitization in European birth cohorts.

J Allergy Clin Immunol. 2014 Mar;133(3):767-76.e7

Authors: Gruzieva O, Gehring U, Aalberse R, Agius R, Beelen R, Behrendt H, Bellander T, Birk M, de Jongste JC, Fuertes E, Heinrich J, Hoek G, Klümper C, Koppelman G, Korek M, Krämer U, Lindley S, Mölter A, Simpson A, Standl M, van Hage M, von Berg A, Wijga A, Brunekreef B, Pershagen G

Abstract
BACKGROUND: Evidence on the long-term effects of air pollution exposure on childhood allergy is limited.
OBJECTIVE: We investigated the association between air pollution exposure and allergic sensitization to common allergens in children followed prospectively during the first 10 years of life.
METHODS: Five European birth cohorts participating in the European Study of Cohorts for Air Pollution Effects project were included: BAMSE (Sweden), LISAplus and GINIplus (Germany), MAAS (Great Britain), and PIAMA (The Netherlands). Land-use regression models were applied to assess the individual residential outdoor levels of particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5), the mass concentration of particles between 2.5 and 10 μm in size, and levels of particulate matter with an aerodynamic diameter of less than 10 μm (PM10), as well as measurement of the blackness of PM2.5 filters and nitrogen dioxide and nitrogen oxide levels. Blood samples drawn at 4 to 6 years of age, 8 to 10 years of age, or both from more than 6500 children were analyzed for allergen-specific serum IgE against common allergens. Associations were assessed by using multiple logistic regression and subsequent meta-analysis.
RESULTS: The prevalence of sensitization to any common allergen within the 5 cohorts ranged between 24.1% and 40.4% at the age of 4 to 6 years and between 34.8% and 47.9% at the age of 8 to 10 years. Overall, air pollution exposure was not associated with sensitization to any common allergen, with odds ratios ranging from 0.94 (95% CI, 0.63-1.40) for a 1 × 10(-5) ∙ m(-1) increase in measurement of the blackness of PM2.5 filters to 1.26 (95% CI, 0.90-1.77) for a 5 μg/m(3) increase in PM2.5 exposure at birth address. Further analyses did not provide consistent evidence for a modification of the air pollution effects by sex, family history of atopy, or moving status.
CONCLUSION: No clear associations between air pollution exposure and development of allergic sensitization in children up to 10 years of age were revealed.

PMID: 24094547 [PubMed – indexed for MEDLINE]

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Novel childhood asthma genes interact with in utero and early-life tobacco smoke exposure.

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Novel childhood asthma genes interact with in utero and early-life tobacco smoke exposure.

J Allergy Clin Immunol. 2014 Mar;133(3):885-8

Authors: Scholtens S, Postma DS, Moffatt MF, Panasevich S, Granell R, Henderson AJ, Melén E, Nyberg F, Pershagen G, Jarvis D, Ramasamy A, Wjst M, Svanes C, Bouzigon E, Demenais F, Kauffmann F, Siroux V, von Mutius E, Ege MJ, Braun-Fahrländer C, Genuneit J, GABRIELA study group, Brunekreef B, Smit HA, Wijga AH, Kerkhof M, Curjuric I, Imboden M, Thun GA, Probst-Hensch N, Freidin MB, Bragina EIu, Deev IA, Puzyrev VP, Daley D, Park J, Becker A, Chan-Yeung M, Kozyrskyj AL, Pare P, Marenholz I, Lau S, Keil T, Lee YA, Kabesch M, Wijmenga C, Franke L, Nolte IM, Vonk J, Kumar A, Farrall M, Cookson WO, Strachan DP, Koppelman GH, Boezen HM

PMID: 24315450 [PubMed – indexed for MEDLINE]

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Lung expression quantitative trait loci data set identifies important functional polymorphisms in the asthma-associated IL1RL1 region.

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Lung expression quantitative trait loci data set identifies important functional polymorphisms in the asthma-associated IL1RL1 region.

J Allergy Clin…

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Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes.

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Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes.

J Allergy Clin Immunol. 2014…

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Association of IL33-IL-1 receptor-like 1 (IL1RL1) pathway polymorphisms with wheezing phenotypes and asthma in childhood.

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Association of IL33-IL-1 receptor-like 1 (IL1RL1) pathway polymorphisms with wheezing phenotypes and asthma in childhood.

J Allergy Clin Immunol. 2014 Feb 22;

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