June 18, 2013

Smooth Muscle Hypercontractility in Airway Hyperresponsiveness: Innate, Acquired, or Nonexistent?

Journal of Allergy
Volume 2013 (2013), Article ID 938046, 4 pages
http://dx.doi.org/10.1155/2013/938046
Editorial

Smooth Muscle Hypercontractility in Airway Hyperresponsiveness: Innate, Acquired, or Nonexistent?

1Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, 2725 Chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada
2Département de Physiologie et Biophysique, Factulté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, QC, J1H 5N4, Canada
3Department of Infection, Immunity, and Inflammation, Institute for Lung Health (Glenfield Hospital), University of Leicester School of Medicine, University Road, Leicester LE1 9HN, UK
4Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Abramson Research Bulding, Room 410, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA
Received 21 February 2013; Accepted 21 February 2013
Copyright © 2013 Ynuk Bossé et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

June 17, 2013

Comparative analysis of the alveolar macrophage proteome in ALI/ARDS patients between the exudative phase and recovery phase

Open Access
Research article

Comparative analysis of the alveolar macrophage proteome in ALI/ARDS patients between the exudative phase and recovery phase

Haiyun DongJinxiu LiYoudi LvYanyan ZhouGuyi WangShuang HuXiaoyu HePing YangZhiguang ZhouXudong Xiang and Cong-Yi Wang
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BMC Immunology 2013, 14:25 doi:10.1186/1471-2172-14-25
Published: 17 June 2013

Abstract (provisional)

Background

Despite decades of extensive studies, the morbidity and mortality for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remained high. Particularly, biomarkers essential for its early diagnosis and prognosis are lacking.

Methods

Recent studies suggest that alveolar macrophages (AMs) at the exudative phase of ALI/ARDS initiate, amplify and perpetuate inflammatory responses, while they resolve inflammation in the recovery phase to prevent further tissue injury and perpetuated inflammation in the lung. Therefore, proteins relevant to this functional switch could be valuable biomarkers for ALI/ARDS diagnosis and prognosis. We thus conducted comparative analysis of the AM proteome to assess its dynamic proteomic changes during ALI/ARDS progression and recovery.

Results

135 proteins were characterized to be differentially expressed between AMs at the exudative and recovery phase. MALDI-TOF-MS and peptide mass fingerprint (PMF) analysis characterized 27 informative proteins, in which 17 proteins were found with a marked increase at the recovery phase, while the rest of 10 proteins were manifested by the significantly higher levels of expression at the exudative phase.

Conclusions

Given the role of above identified proteins played in the regulation of inflammatory responses, cell skeleton organization, oxidative stress, apoptosis and metabolism, they have the potential to serve as biomarkers for early diagnosis and prognosis in the setting of patients with ALI/ARDS.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Factors affecting readmission for acute asthmatic attacks in children.


Factors affecting readmission for acute asthmatic attacks in children

Nualanong Visitsunthorn, Weerapong Lilitwat, Orathai Jirapongsananuruk, Pakit Vichyanond

Abstract


Background: Readmission following acute asthmatic attack has an impact on children’s quality of life and the cost of hospitalization. The objective of this study was to define the risk factors associated with readmission following acute asthmatic attacks in children
Methods: This is a retrospective case-control study in children who were admitted because of acute asthmatic attacks at the Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok, Thailand. The admissions were classified into 2 groups, admission and readmission within one-month to one-year after the first admission. The medical records were reviewed and the factors that might affect readmission were evaluated.
Conclusion: A history of ICU admission at the first admission and the level of asthma control (partly controlled and uncontrolled according to Global of Initiative for Asthma guideline) increased the chances of readmission while influenza vaccination reduced the chances of readmission.Results: Seventy six children, 49 males and 27 females, were included. There were 56 children who were admitted only once and 20 children who were readmitted. The 1-year readmission rate for children with asthma was 26.3 %. The risk factors which made readmission more likely were a parental history of allergic disease (Odd Ratio, OR, = 3.17; 95% CI 1.10-9.10), a history of Intensive Care Unit (ICU) admission (OR 29.62; 95% CI 3.35-262.18),  methylprednisolone usage during the 1st admission (OR 8.33; 95% CI 2.46-28.19) and the level of asthma control. Increased risk of readmission was found in partly controlled asthma (OR 4.83; 95%CI 1.24-18.88) and uncontrolled asthma (OR 29; 95%CI 2.25-373.77).  The factor that decreased the chances of
readmission was a history of influenza vaccination (OR 0.24; 95% CI 0.16-0.36).
Full Text: PDF 

Determining factors of patient compliance in allergic rhinitis


Determining factors of patient compliance in allergic rhinitis

Juliane Köberlein, Anna Christina Kothe, Jochen Sieber, Ralph Mösges

Abstract


Background: Compliance with prescribed treatment is essential for reducing costs of health care and improving efficacy of treatment in patients with allergic rhinitis.
Objective: To evaluate the extent of compliance and identify predictive factors and risk profiles for patient noncompliance with the therapeutic regiments of sublingual immunotherapy and H1-antihistamines.
Methods: In this retrospective study we analysed data from two non-interventional studies: one study with a total of 42,111 patients taking H1-antihistamines and one study with 354 patients receiving sublingual immunotherapy. Both studies were approved by the local ethics committees and competent authorities. By performing univariate and multivariate logistic regression analysis we calculated odds ratios with a 95% confidence interval for given characteristics.
Conclusion: Compliance with intake of sublingual immunotherapy and H1-antihistamines is high. However, our findings point out that patients with characteristics such as a comorbid bronchial asthma or mild symptoms have higher odds for noncompliance and require attentive monitoring to reduce healthcare costs and morbidity. 
Results: There was a compliance rate of 79.6% with the administration of sublingual immunotherapy. Factors associated with compliance were severe nasal, eye and airways symptoms, and strong impairment in social and work life. Compliance with the intake of H1-antihistamines was 98%. Patients with a concomitant disease, especially with a bronchial
asthma or a psychiatric disorder had higher odds for being non-compliant.
Full Text: PDF 

Mitochondrial Dysfunction in Metabolic Syndrome and Asthma

Journal of Allergy
Volume 2013 (2013), Article ID 340476, 12 pages
http://dx.doi.org/10.1155/2013/340476
Review Article

Mitochondrial Dysfunction in Metabolic Syndrome and Asthma

Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India
Received 20 March 2013; Accepted 21 May 2013
Academic Editor: Anurag Agrawal
Copyright © 2013 Ulaganathan Mabalirajan and Balaram Ghosh. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Though severe or refractory asthma merely affects less than 10% of asthma population, it consumes significant health resources and contributes significant morbidity and mortality. Severe asthma does not fell in the routine definition of asthma and requires alternative treatment strategies. It has been observed that asthma severity increases with higher body mass index. The obese-asthmatics, in general, have the features of metabolic syndrome and are progressively causing a significant burden for both developed and developing countries thanks to the westernization of the world. As most of the features of metabolic syndrome seem to be originated from central obesity, the underlying mechanisms for metabolic syndrome could help us to understand the pathobiology of obese-asthma condition. While mitochondrial dysfunction is the common factor for most of the risk factors of metabolic syndrome, such as central obesity, dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, the involvement of mitochondria in obese-asthma pathogenesis seems to be important as mitochondrial dysfunction has recently been shown to be involved in airway epithelial injury and asthma pathogenesis. This review discusses current understanding of the overlapping features between metabolic syndrome and asthma in relation to mitochondrial structural and functional alterations with an aim to uncover mechanisms for obese-asthma.

June 16, 2013

Using eQTL weights to improve power for genome-wide association studies: a genetic study of childhood asthma


Front. Genet., 31 May 2013 | doi: 10.3389/fgene.2013.00103

Using eQTL weights to improve power for genome-wide association studies: a genetic study of childhood asthma

Lin Li1†Michael Kabesch2, Emmanuelle Bouzigon3,4, Florence Demenais3,4, Martin Farrall5, Miriam F. Moffatt6, Xihong Lin1 and Liming Liang1,7*
  • 1Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
  • 2Department of Pediatric Pneumology and Allergy, KUNO University Children's Hospital Regensburg, Regensburg, Germany
  • 3INSERM, Genetic Variation and Human Diseases Unit, U946, Paris, France
  • 4Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France
  • 5Wellcome Trust Centre for Human Genetics, Oxford, UK
  • 6Molecular Genetics and Genomics Section, National Heart and Lung Institute, Imperial College London, London, UK
  • 7Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
Increasing evidence suggests that single nucleotide polymorphisms (SNPs) associated with complex traits are more likely to be expression quantitative trait loci (eQTLs). Incorporating eQTL information hence has potential to increase power of genome-wide association studies (GWAS). In this paper, we propose using eQTL weights as prior information in SNP based association tests to improve test power while maintaining control of the family-wise error rate (FWER) or the false discovery rate (FDR). We apply the proposed methods to the analysis of a GWAS for childhood asthma consisting of 1296 unrelated individuals with German ancestry. The results confirm that eQTLs are enriched for previously reported asthma SNPs. We also find that some SNPs are insignificant using procedures without eQTL weighting, but become significant using eQTL-weighted Bonferroni or Benjamini–Hochberg procedures, while controlling the same FWER or FDR level. Some of these SNPs have been reported by independent studies in recent literature. The results suggest that the eQTL-weighted procedures provide a promising approach for improving power of GWAS. We also report the results of our methods applied to the large-scale European GABRIEL consortium data.

Keywords: asthma, family-wise error rate, false discovery rate, eQTL, genome-wide association study, weighted hypothesis test
Citation: Li L, Kabesch M, Bouzigon E, Demenais F, Farrall M, Moffatt MF, Lin X and Liang L (2013) Using eQTL weights to improve power for genome-wide association studies: a genetic study of childhood asthma. Front. Genet4:103. doi: 10.3389/fgene.2013.00103
Received: 16 August 2012; Accepted: 21 May 2013;
Published online: 31 May 2013.
Edited by:
Barbara E. Stranger, University of Chicago, USA
Reviewed by:
Eli Stahl, Mt. Sinai School of Medicine, USA
Matti Pirinen, University of Helsinki, Finland
Copyright © 2013 Li, Kabesch, Bouzigon, Demenais, Farrall, Moffatt, Lin and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Liming Liang, Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Building 2, Room 211A, 655 Huntington Ave., Boston, MA 02115, USA. e-mail: lliang@hsph.harvard.edu
Present address: Lin Li, Bio Stat Solutions, Inc., Mt Airy, MD, USA.

Flavonoids and asthma.

Nutrients 20135(6), 2128-2143; doi:10.3390/nu5062128
Review

Flavonoids and Asthma

Toshio Tanaka 1,2,email and Ryo Takahashi 1 email
1 Department of Clinical Application of Biologics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan2 Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
* Author to whom correspondence should be addressed.
Received: 1 April 2013; in revised form: 3 May 2013 / Accepted: 15 May 2013 / Published: 10 June 2013
(This article belongs to the Special Issue Nutrition and Respiratory Disease)
PDF Full-text Download PDF Full-Text [248 KB, uploaded 10 June 2013 13:56 CEST]
Abstract: Asthma is a chronic disease, characterized by airway inflammation, airflow limitation, hyper-reactivity and airway remodeling. It is believed that asthma is caused by the interaction between genetic and environmental factors. The prevalence of allergic diseases, including asthma, has increased worldwide during the past two decades. Although the precise reasons that have caused this increase remain unknown, dietary change is thought to be one of the environmental factors. Flavonoids, which are polyphenolic plant secondary metabolites ubiquitously present in vegetables, fruits and beverages, possess antioxidant and anti-allergic traits, as well as immune-modulating activities. Flavonoids are powerful antioxidants and anti-allergic nutrients that inhibit the release of chemical mediators, synthesis of Th2 type cytokines, such as interleukin (IL)-4 and IL-13, and CD40 ligand expression by high-affinity immunoglobulin E (IgE) receptor-expressing cells, such as mast cells and basophils. They also inhibit IL-4-induced signal transduction and affect the differentiation of naïve CD4+ T cells into effector T-cells through their inhibitory effect on the activation of the aryl hydrocarbon receptor. Various studies of flavonoids in asthmatic animal models have demonstrated their beneficial effects. The results of several epidemiological studies suggest that an increase in flavonoid intake is beneficial for asthma. Moreover, clinical trials of flavonoids have shown their ameliorative effects on symptoms related to asthma. However, these human studies are currently limited; further validation is required to clarify whether an appropriate intake of flavonoids may constitute dietary treatment and for part of a preventive strategy for asthma.
Keywords: asthma; diet; flavonoids; prevention; treatment and management

Is there any association between secretory IgA and lactoferrin concentration in mature human milk and foodallergy in breastfed children.


 2013 Jan-Mar;17(1):47-52.

Is there any association between secretory IgA and lactoferrin concentration in mature human milk and foodallergy in breastfed children.

Source

Department of Pediatrics, Oncology, Hematology and Diabetology Medical University of Lodz, Sporna Str. 36/50, Łódź, Poland, tel. (48 42) 617-77-50, fax (48 42) 617-79-89, e-mail: anna.hogendorf@gmail.com.

Abstract

Background: Breastfeeding is recommended as a protective method against the development of allergy. However, some studies have reported an increased risk of allergies development in breastfed infants of atopic mothers, which implies that atopic mothers may have an altered composition of breast milk. Aim: The aim of the study was to determine the concentration of secretory immunoglobulin A (S-IgA) and lactoferrin in human mature milk and to evaluate the association between the levels of these proteins in breast milk with food allergy in children, depending on the allergy status of the breastfeeding mother. Material and methods: Medical data was collected from birth to 24 months of age from 84 mother-child pairs participating in an EU-funded project "EuroPrevall - The prevalence, cost and basis of food allergy across Europe". The diagnosis of food allergy in children was based on the positive result of a double-blind placebo-controlled food challenge (DBPCFC). S-IgA and lactoferrin levels were measured in the whey of mature breast milk with commercial enzyme-linked immunosorbent assay (ELISA) kits. Statistical analysis (the U Mann-Whitney and Kruskal-Wallis tests as well as the Spearman's rank correlation coefficient) was performed using STATISTICA 8.0 PL (Statsoft, Tulsa, USA). Results: Ten out of eighty four participating children had positive skin prick tests (SPT) and/or sIgE to food antigens and in 7 (8.4%) DBPCFC confirmed food allergy. the median concentration of S-IgA was 476,83 μg/ml (range 6.51-1359.61 μg/ml). the median concentration of Lf was 15.68 μg/ml (range 11.68-36.43 μg/ml). The concentrations of S-IgA and Lf showed a moderate, negative, correlation R=-0.28; p=0.05. Conclusions: Mature breast milk of mothers of children with food allergy and of healthy children showed similar concentrations of both proteins. The level of S-IgA in the mature milk of mothers with atopic allergy was significantly lower, compared to non-atopic mothers. More studies are needed to reveal the mystery of the lack of protective effect of breastfeeding on allergy development in children.