July 26, 2013

Asthma and atopic dermatitis are associated with increased risk of clinical Plasmodium falciparummalaria


BMJ Open 3:e002835 doi:10.1136/bmjopen-2013-002835
  • Epidemiology

Asthma and atopic dermatitis are associated with increased risk of clinical Plasmodium falciparummalaria

  1. Richard Paul1
+Author Affiliations
  1. 1Institut Pasteur, Unité de la Génétique Fonctionnelle des Maladies Infectieuses, CNRS URA3012,  Paris, France
  2. 2Institut Pasteur de Dakar, Unité d'Epidémiologie des Maladies Infectieuses, Dakar, Senegal
  3. 3INSERM, U946, Genetic Variation and Human Diseases Unit, Paris, France
  4. 4Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France
  5. 5Institut de Recherche pour le Développement (IRD), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, URMITE CNRS-IRD 198 UMR 6236, Dakar, Sénégal
  6. 6Institut Pasteur, Unité d'Epidémiologie des Maladies Emergentes, Paris, France
  7. 7Conservatoire National des Arts et Métiers, Paris, France
  8. 8Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, CNRS URA2581, Paris, France
  9. 9Institut Pasteur, Unité de Biologie des Interactions Hôte Parasite, Paris, France
  10. 10Complex Systems Group, Faculty of Science, Mahidol University, Bangkok, Thailand
  11. 11Centre National de la Recherche Scientifique, Unité de Recherche Associée 2581, Paris, France
  1. Correspondence toDr Richard Paul; richard.paul@pasteur.fr
  • Received 5 March 2013
  • Revised 13 June 2013
  • Accepted 18 June 2013
  • Published 24 July 2013

Abstract

Objectives To assess the impact of atopy and allergy on the risk of clinical malaria.
Design A clinical and immunological allergy cross-sectional survey in a birth cohort of 175 children from 1 month to 14 years of age followed for up to 15 years in a longitudinal open cohort study of malaria in Senegal. Malaria incidence data were available for 143 of these children (aged 4 months to 14 years of age) for up to 15 years. Mixed-model regression analysis was used to determine the impact of allergy status on malaria incidence, adjusting for age, gender, sickle-cell trait and force of infection.
Main outcome measures Asthma, allergic rhinoconjunctivitis and atopic dermatitis status, the number of clinical Plasmodium falciparum malaria episodes since birth and associated parasite density.
Results 12% of the children were classified as asthmatic and 10% as having atopic dermatitis. These groups had respectively a twofold (OR 2.12 95%; CI 1.46 to 3.08; p=8×10−5) and threefold (OR 3.15; 1.56 to 6.33; p=1.3×10−3) increase in the risk of clinical P falciparummalaria once older than the age of peak incidence of clinical malaria (3–4 years of age). They also presented with higher P falciparum parasite densities (asthma: mean 105.3 parasites/μL±SE 41.0 vs 51.3±9.7; p=6.2×10−3. Atopic dermatitis: 135.4±70.7 vs 52.3±11.0; p=0.014). There was no effect of allergy on the number of non-malaria clinical presentations. Individuals with allergic rhinoconjunctivitis did not have an increased risk of clinical malaria nor any difference in parasite densities.
Conclusions These results demonstrate that asthma and atopic dermatitis delay the development of clinical immunity to P falciparum. Despite the encouraging decrease in malaria incidence rates in Africa, a significant concern is the extent to which the increase in allergy will exacerbate the burden of malaria. Given the demonstrated antiparasitic effect of antihistamines, administration to atopic children will likely reduce the burden of clinical malaria in these children, increase the efficacy of first-line treatment antimalarials and alleviate the non-infectious consequences of atopy.
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HTR4 gene structure and altered expression in the developing lung

Open Access
Research

HTR4 gene structure and altered expression in the developing lung

Emily HodgeCarl P NelsonSuzanne MillerCharlotte K BillingtonCeri E StewartCaroline SwanAnders Malarstig,Amanda P HenryCatherine GowlandErik MelénIan P Hall and Ian Sayers


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Respiratory Research 2013, 14:77 doi:10.1186/1465-9921-14-77
Published: 26 July 2013

Abstract (provisional)

Background

Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT4R) gene (HTR4) associated with lung function. The aims of this study were to i) investigate the expression profile of HTR4 in adult and fetal lung tissue and cultured airway cells, ii) further define HTR4 gene structure and iii) explore the potential functional implications of key SNPs using a bioinformatic approach.

Methods

Following reverse transcription (RT)-PCR in human brain, 5[prime] rapid amplification of cDNA ends (5[prime] RACE) was used to examine the exonic structure of HTR4 at the 5[prime] end. Quantitative (Q)-PCR was used to quantify HTR4 mRNA expression in total RNA from cultured airway cells and whole lung tissue. Publically available gene microarray data on fetal samples of estimated gestational age 7--22 weeks were mined for HTR4 expression. Immunohistochemistry (IHC; in adult and fetal lung tissue) and a radioligand binding assay (in cultured airway cells) were used to analyze 5-HT4R protein expression.

Results

IHC in adult lung, irrespective of the presence of chronic obstructive pulmonary disease (COPD), suggested low level expression of 5-HT4R protein, which was most prominent in alveolar pneumocytes. There was evidence of differential 5-HT4R protein levels during gestation in fetal lung, which was also evident in gene expression microarray data. HTR4 mRNA expression, assessed by Q-PCR, was -0.5% relative to brain in total adult lung tissue and in human airway smooth muscle (HASM) and bronchial epithelial cells (HBEC) derived from adult donors. Radioligand binding experiments also indicated that HBEC and HASM cells did not express a significant 5-HT4R population. 5[prime] RACE in brain identified a novel N-terminal variant, containing an extended N-terminal sequence. The functional significance of key HTR4 SNPs was investigated using the encyclopedia of DNA elements consortium (ENCODE) dataset. These analyses identified multiple alterations in regulatory motifs for transcription factors implicated in lung development, including Foxp1.

Conclusions

Taken together, these data suggest a role for HTR4 in lung development, which may at least in part explain the genetic association with lung function.

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Allergic conjunctivitis and the most common allergens in Northern Greece

Open Access
Original research

Allergic conjunctivitis and the most common allergens in Northern Greece

Diamantis AlmaliotisPavlos MichailopoulosDimitrios GioulekasPaschalina GioulekaDespina PapakostaThomas Siempis and Vasileios Karampatakis
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World Allergy Organization Journal 2013, 6:12 doi:10.1186/1939-4551-6-12
Published: 16 July 2013

Abstract (provisional)

Background

Ocular allergies affect a great part of the general population and often co exist with other allergic manifestations. In the present study, the prevalence of allergic conjunctivitis and the commonest allergens in allergic patients at an outpatient unit in Thessaloniki, Greece were evaluated.

Methods

This is a retrospective study regarding allergic patients who referred to an outpatient clinic between the 1st of January of 1996 and the 31st of December 2010. They completed relative questionnaires concerning their allergic condition. The patients who were included in our study had allergic conjunctivitis confirmed by ophthalmologists and were divided into 4 groups. The criteria used were the existence of allergic conjunctivitis alone or with other allergic co- morbidities. The patients then underwent skin prick tests after consent according to current guidelines.

Results

The archives of 1239 allergic patients were evaluated and 497 patients (40,11%) who manifested eye allergic symptoms were included in our study. 448 patients (90.14%) had allergic conjunctivitis in conjunction with asthma or rhinitis or both. 370 patients underwent skin prick tests and 284 of them (124 males-160 females) were positive for at least 1 of the 8 tested allergens (76.75%). 166 were positive to a grass mix (58.45%), 130 to olea European (45.77%), 124 to dust mites mix (43.66%), 58 to cypress (20.42%), 71 to parietaria officinalis (25.00%), 67 to cat dander (23.59%), 35 to dog dander (12.32%) and 32 to Altenaria (11.26%).

Conclusions

Symptoms of ocular allergy are very common in patients with allergic rhinitis and asthma. Men had slightly higher percentages of positive skin prick tests, except for dog dander and Altenaria. Conjunctivitis should not be overlooked as an allergic entity when evaluating allergic patients.

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Factors associated with cord blood IgE levels

 

Factors associated with cord blood IgE levels

Mohammad Nabavi, Raheb Ghorbani, Amir Massod Asadi, Mohammad Faranoush

Abstract


Background:  The cord blood IgE level is thought to be a predictor of allergic disorders in childhood. It is not well understood how this marker is influenced by the fetal environment, such as maternal, paternal, placenta, and fetal characteristics. 
Objective: We aimed to investigate the association between cord blood IgE levels and various genetic and environmental factors.
Methods: This was a cross-sectional study including a total of 181 neonates and their mothers. A questionnaire asking about demographic data, delivery characteristics, maternal past medical history and information on exposure to known environmental allergens was distributed to pregnant women. Blood samples from them and neonatal cord blood samples were taken at the same time for IgE assay.
Conclusion: Among the evaluated factors, the presence of any kind of allergic disorder in the mother or her family and elevated maternal blood IgE level are associated with the  cord blood IgE of the child. Maternal age and smoking, neonatal gender, type of delivery, season of birth and parity are probable predictors. 
Results:  By univariate analysis we found an association between cord blood IgE levels and higher number of previous pregnancies, delivery season, type of delivery, history of allergy during pregnancy, but not the type of allergic disease and history of allergic disease before pregnancy, were associated with elevated cord blood IgE
levels. The maternal blood level of IgE was correlated with its level in cord blood. By multivariate analysis, the number of previous pregnancies, the type and season of delivery and a history of allergy during pregnancy and maternal age and blood IgE levels were variables which had a significant association with cord blood IgE levels. 
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Beta-blockers: friend or foe in asthma?


Beta-blockers: friend or foe in asthma?


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Authors: Arboe B, Ulrik CS

Published Date July 2013 Volume 2013:6 Pages 549 - 555
DOI: http://dx.doi.org/10.2147/IJGM.S46592

Bente Arboe, Charlotte Suppli Ulrik

Department of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Hvidovre, Denmark

Background and aim: Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma.
Method: Systematic literature review.
Results: No significant increase in the number of patients requiring rescue oral corticosteroid for an exacerbation of asthma has been observed after initiation of β-blocker treatment. Patients with mild to moderate reactive airway disease, probably both asthma and chronic obstructive pulmonary disease, may have a limited fall in forced expiratory volume in 1 second (FEV1) following single-dose administration of β-blocker, whereas no change in FEV1 has been reported following long-term administration. In a murine model of asthma, long-term administration of β-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect. In keeping with this, long-term administration of a nonselective β-blocker to steroid-naïve asthma patients has shown a dose-dependent improvement in airway hyperresponsiveness, and either an asymptomatic fall in FEV1 or no significant change in FEV1. Furthermore, available studies show that bronchoconstriction induced by inhaled methacholine is reversed by salbutamol in patients on regular therapy with a β-blocker. On the other hand, a recent placebo-controlled trial of propranolol and tiotropium bromide added to inhaled corticosteroids revealed no effect on airway hyperresponsiveness and a small, not statistically significant, fall in FEV1 in patients classified as having mild to moderate asthma.
Conclusion: The available, although limited, evidence suggests that a dose-escalating model of β-blocker therapy to patients with asthma is well tolerated, does not induce acute bronchoconstriction, and, not least, may have beneficial effects on airway inflammation and airway hyperresponsiveness in some patients with asthma. Further studies addressing the potential role of β-blocker therapy for asthma are clearly needed, but careful selection of the target population is warranted.

Keywords: asthma, beta-blockers, lung function, airway responsiveness



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Age-Specific Characteristics of Inpatients with Severe Asthma Exacerbation

Abstract
 ORIGINAL ARTICLE
Age-Specific Characteristics of Inpatients with Severe Asthma Exacerbation


Kiyoshi Sekiya, Masami Taniguchi, Yuma Fukutomi, Kentaro Watai, Takafumi Minami, Hiroaki Hayashi, Jun Ito, Hidenori Tanimoto, Chiyako Oshikata, Naomi Tsurikisawa, Takahiro Tsuburai, Maki Hasegawa and Kazuo Akiyama [About this authors]
ABSTRACT
Background: The characteristics of inpatients with severe asthma exacerbation remain unclear. It is considered that the characteristics of inpatients with severe asthma vary depending on age. However, these are rarely investigated. The objective of this study is to investigate the differences in characteristics among different age groups. We considered that it is necessary to understand the characteristics of each age group so that we can establish strategies in preventing severe asthma exacerbation.
Methods: All asthma inpatients who were hospitalized between 2004 and 2011 with SpO2 -90% (in room air), were breathless at rest, and showed increased respiratory rate and pulse rate were examined. We compared the characteristics among the young age group, middle age group, and advanced age group.
Results: The total number of patients was 204. In the young age group, the percentages of patients with irregular visits and non visits to a medical institution were high. This group showed high percentages of smokers and pet owners. The percentage of continuous ICS users in this group was 25.9%. The middle age group had high rates of aspirin-intolerant asthma. The percentage of continuous ICS users in this group was 60.2%. In the advanced age group, the percentages of patients with hypertension/heart disease, diabetes mellitus, and COPD were high. This group showed good treatment adherence. The percentage of continuous ICS users in this group was 77.4%.
Conclusions: The characteristics of inpatients with severe asthma vary depending on age. We need to establish countermeasures for asthma exacerbation according to the characteristics of patients depending on age.
KEY WORDS:
acute exacerbation, asthma, asthma attack, asthma death, inhaled corticosteroid
Received: 4 December 2012.
Accepted: 21 February 2013.
Allergology International : In Press

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