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RESEARCH ARTICLE

Diesel Exhaust Particles Induce Cysteine Oxidation and S-Glutathionylation in House Dust Mite Induced Murine Asthma

• Gerald B. Lee,
 
• Eric B. Brandt,
 
• Chang Xiao,
 
• Aaron M. Gibson,
 
• Timothy D. Le Cras,
 
• Lou Ann S. Brown,
 
• Anne M. Fitzpatrick,
• Gurjit K. Khurana Hershey mail

Abstract

Background

Diesel exhaust particle (DEP) exposure enhances allergic inflammation and has been linked to the incidence of asthma. Oxidative stress on the thiol molecules cysteine (Cys) and glutathione (GSH) can promote inflammatory host responses. The effect of DEP on the thiol oxidation/reduction (redox) state in the asthmatic lung is unknown.

Objective

To determine if DEP exposure alters the Cys or GSH redox state in the asthmatic airway.

Methods

Bronchoalveolar lavage fluid was obtained from a house dust mite (HDM) induced murine asthma model exposed to DEP. GSH, glutathione disulfide (GSSG), Cys, cystine (CySS), and s-glutathionylated cysteine (CySSG) were determined by high pressure liquid chromatography.

Results

DEP co-administered with HDM, but not DEP or HDM alone, decreased total Cys, increased CySS, and increased CySSG without significantly altering GSH or GSSG.

Conclusions

DEP exposure promotes oxidation and S-glutathionylation of cysteine amino acids in the asthmatic airway, suggesting a novel mechanism by which DEP may enhance allergic inflammatory responses.

Citation: Lee GB, Brandt EB, Xiao C, Gibson AM, Le Cras TD, et al. (2013) Diesel Exhaust Particles Induce Cysteine Oxidation and S-Glutathionylation in House Dust Mite Induced Murine Asthma. PLoS ONE 8(3): e60632. doi:10.1371/journal.pone.0060632

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Correlation between skin prick test and MAST-immunoblot results in patients with chronic rhinitis

Correlation between skin prick test and MAST-immunoblot results in patients with chronic rhinitis

Young Ha Kim, Byung Jae Yu, Woo Jin Kim, Ju Eun Kim, Guen-Ho Lee, Kyeong-Ah Lee, Jin Hee Cho

Abstract

Background and Objectives: The most reliable method for confirming the causative allergens of allergic rhinitis is the skin prick test, followed by the multiple allergen simultaneous test (MAST), which reportedly has acceptable sensitivity and specificity. This study was designed to confirm whether a novel MAST-immunoblot assay can reliably diagnose allergic rhinitis.

Methods: A retrospective chart review was conducted of chronic rhinitis patients who visited Yeouido St. Mary’s Hospital between January 2010 and June 2011.

Results: In total, 193 subjects (111 male, 82 female) were included, with a mean age of 30.08 years (range 6–77). The skin prick test detected 132 subjects as having one or more positive responses to allergens, and MAST detected 105 subjects as having one or more positive response. The sensitivity, specificity, and efficiency of the MAST assay were 63.16%, 65.57%, and 63.92%, respectively. Sensitivity, specificity and efficacy for common allergens were not high enough for MAST to replace skin prick test in detecting causative allergens. When correlation was defined as a difference between the classes of MAST and SPT of less than 2, the correlation rates for Dermatophagoides farina and Dermatophagoides pteronyssinus were 65.80% and 59.07%, respectively.

Conclusion: The correlation between MAST and the skin prick test is not sufficiently strong to use MAST as a diagnostic test to confirm the causative allergen in allergic rhinitis. Further studies to confirm the reliability of MAST should be conducted. 

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The Effectiveness of Modern Antihistamines for Treatment of Allergic Rhinitis

ORIGINAL ARTICLE The Effectiveness of Modern Antihistamines for Treatment of Allergic Rhinitis - An IPD Meta-Analysis of 140,853 Patients doi:10.2332/allergolint.12-OA-0486 Ralph Mösges, Volker König and Juliane Köberlein [About this authors] ABSTRACT Background: Allergic rhinitis represents a worldwide health problem. The prevalence is increasing. The aim of this study was to analyse the correlation between the severity of allergic rhinitis and an adequate treatment dose of modern oral antihistamines. Methods: From a comprehensive databank containing data from ten different open-label prospective observational studies including raw data of 140,853 patients with allergic rhinitis, symptomatology variables were analysed and scored to study the effects of treatment with four antihistamines (Desloratadine, Ebastine, Fexofenadine, Levocetirizine) alone or in combination with intranasal corticosteroids. The patient data were collected in 23,606 study centres from Germany, mostly medical specialist and some primary care physicians in private practice. The analyses were performed via individual patient data meta-analysis techniques. Results: Finally 92,900 patient data from nine of ten studies could be analysed. One study with data of 47,953 patients was excluded due to incomplete treatment documentation. Both monotherapy analysis subgroups (Total Symptom Score and Total Nasal Symptom Score) were significantly better than those of their combinations with intranasal steroids. Monotherapy with levocetirizine was determined to be significantly more effective in lowering the Total Symptom Score (p < 0.001) and the Total Nasal Symptom Score (p < 0.05) than the other antihistamines. In the next stage, a greater positive effect of levocetirizine was demonstrated in relation to the severity of the clinical symptoms of allergic rhinitis (Total Nasal Symptom Score in cases with severe symptomatology [effect size = -0.09]). Conclusions: Levocetirizine asserted itself as the only antihistamine compared with the others as significant in this analysis. The study authors recommend monotherapy with the new-generation antihistamine levocetirizine, especially in severe cases of allergic rhinitis. KEY WORDS: allergic rhinitis, Desloratadine, Ebastine, Fexofenadine, Levocetirizine, treatment ABBREVIATIONS: TNSS, Total Nasal Symptom Score; TOSS,Total Ocular Symptom Score; TSS, Total Symptom Score; IPD, Individual Patient Data. Received: 30 July 2012. Accepted: 28 November 2012. Allergology International : In Press [Full Text PDF (202k)]

CME

Specific Immunotherapy—Indications and Mode of Action

Dtsch Arztebl Int 2013; 110(9): 148-58; DOI: 10.3238/arztebl.2013.0148

Brehler, R; Klimek, L; Kopp, M V; Virchow, J C

Department of Dermatology, University Hospital of Münster: Prof. Dr. med. Brehler
Center for Rhinology and Allergology, Wiesbaden: Prof. Dr. med. Klimek
Pediatric Pneumology & Allergology, Department of Pediatric Medicine, University Medical Center Schleswig-Holstein, Campus Centrum Lübeck: Prof. Dr. med. Kopp
University of Rostock, Medical Clinics, Division of Pulmonology: Prof. Dr. med. Virchow

Background: It is estimated that up to 24% of the population in Germany suffers from allergic rhinoconjunctivitis and 5% from allergic asthma. Allergic rhinoconjunctivitis is closely related to other atopic diseases.

Methods: This review is based on pertinent publications retrieved by a selective search of the Medline database, guidelines from Germany and abroad, and Cochrane meta-analyses.

Results: Specific immunotherapy (SIT) is the only diseases-modifying treatment option for allergies. Meta-analysis reveals standardized mean differences in allergic rhinitis symptom scores of −0.73 for subcutaneous immunotherapy (SCIT) and −0.49 for sublingual immunotherapy (SLIT); the corresponding mean differences in medication scores are −0.57 and −0.32, respectively. The treatment should be carried out for at least three years. It is indicated when the symptoms are severe and allergen avoidance is not a realistic option. The efficacy of treatment depends on the allergen dose; thus, every allergen preparation should be evaluated individually, independent of route of administration. SCIT can cause systemic adverse effects, including anaphylaxis. SLIT is safer but often causes allergic symptoms of the oral mucosa at the beginning of treatment.

Conclusion: Even though the efficacy of SIT is well documented, it is still underused. SIT should be offered as standard treatment to patients suffering from allergic rhinitis.

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Clinical Drug Investigation

March 2013,

Open Access

Economic Evaluation of 5-Grass Pollen Tablets Versus Placebo in the Treatment of Allergic Rhinitis in Adults

• Matteo Ruggeri, 
• Marco Oradei, 
• Franco Frati, 
• Paola Puccinelli, 
• Cristina Romao, 
• Ilaria Dell’Albani,
• Cristoforo Incorvaia, 
• Americo Cicchetti

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Abstract

Background

Allergen immunotherapy (AIT) is aimed at modifying the immune response to a causative allergen, thereby reducing clinical symptoms and symptomatic medication intake and improving quality of life. Long-term AIT research has led to the development of 5-grass pollen tablets, currently indicated for the treatment of grass pollen-induced allergic rhinitis (AR).

Methods

A post-hoc analysis was conducted using the Average Adjusted Symptom Score (AAdSS) to compare the effect of treatment of AR with 5-grass pollen tablets versus placebo treatment. Using the results of the VO34.04 and VO53.06 trials and economic data, cost-effectiveness analysis of 5-grass pollen tablet treatment was performed from the Italian third-party payer perspective with cost data derived from a study of 2008 updated to 2011. Also a societal perspective was considered by using the costs related to the losses of productivity by following the human capital approach. Using the results of the analysis, the estimated receiver-operating characteristic curve was plotted to evaluate medication effectiveness in terms of quality-adjusted life years (QALYs) and a decision tree constructed to model the possible outcomes and costs for adults and paediatric patients with a low, medium, and high AAdSS. Finally, probabilistic sensitivity analysis was conducted to test the robustness of the results as well as their consistency at an assumed cost-effectiveness threshold of € 30,000/QALY.

Results

The results indicate that compared to the placebo, the 5-grass pollen tablet treatment provides a benefit of 0.127 QALYs in medium AAdSS patients and of 0.143 QALYs in high AAdSS patients. The 5-grass pollen tablet treatment was found to cost € 1,024/QALY for patients with a medium AAdSS and € 1,035/QALY for patients with a high AAdSS. Of all the simulations performed in the probabilistic sensitivity analysis, 99 % indicated that the incremental cost-effectiveness ratio of the 5-grass pollen tablet treatment was below the threshold of € 30,000/QALY in patients with medium and high AAdSS, whereas it was found to be dominated in 67 % of simulations related to patients with low AAdSS.

Conclusion

The 5-grass pollen tablet is a cost-effective treatment for adult AR patients with a medium or high AAdSS. This finding should be carefully considered when deciding the management strategy for these patients.

Serum eosinophil cationic protein levels in Behçet’s disease and its relation to clinical activity

Serum eosinophil cationic protein levels in Behçet’s disease and its relation to clinical activity

Didem Arslan Tas, Huseyin T. E. Ozer, Eren Erken

Abstract

Background: Eosinophil cationic protein (ECP) is a matrix protein of eosinophils and has been reported to reflect eosinophil activity. Few studies have examined the role of eosinophils in the pathogenesis of Behçet’s disease.

Objective: The purpose of the present study was to investigate the serum ECP levels in BD and its relation to clinical activity.

Methods: Forty-seven consecutive patients with BD (22 active, 25 inactive), 21 age and sex matched patients with allergic rhinitis and 21 healthy controls were evaluated cross-sectionally. The serum ECP levels were measured by the flourescein enzyme immunoassay method.

Results: Mean serum ECP levels of active patients with BD (34.28 ± 23.43 mg/L) were found to be significantly lower than those of the inactive patients (65.69 ± 46.32 mg/L, p <0.05) and the controls (62.92 ± 30.49 mg/L, p <0.01) . Behçet patients with oral aphthous lesions had significantly lower mean serum ECP levels (n=21, 38.82 ± 33.38 mg/L) than those without aphthous lesions (n=26, 60.81 ± 43.21mg/L) (p = 0.041). Similarly patients with arthritis had lower serum ECP values (n=6, 22.12 ± 9.47 mg/L) than those without arthritis  (n = 41, 55.21 ± 41.35 mg/L)
(p =0.029).

Conclusions: Lower ECP levels in the active phase of the disease may be a result of decreased production due to the activation of Th1 cytokines. 

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Kawasaki disease and subsequent risk of allergic diseases

Research article

Kawasaki disease and subsequent risk of allergic diseases: a population-based matched cohort study

Ho-Chang Kuo¹, Wei-Chiao Chang², Kuender D Yang^3,4, Hong-Ren Yu¹, Chih-Lu Wang⁵,Shu-Chen Ho⁶ and Chun-Yuh Yang^6*

• *Corresponding author: Chun-Yuh Yang chunyuh@kmu.edu.tw

Author Affiliations

¹Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

²Department of Clinical Pharmacy; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan

³The Department of Medical Research and Development of Pediatrics, Show Chwan Memorial Hospital in Chang Bing, Changhua, Taiwan

⁴Institute of Clinical Medical Sciences, National Yang Ming University, Taipei, Taiwan

⁵Department of Pediatrics, Po-Jen Hospital, Kaohsiung, Taiwan

⁶Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan

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BMC Pediatrics 2013, 13:38 doi:10.1186/1471-2431-13-38

The electronic version of this article is the complete one and can be found online at:http://www.biomedcentral.com/1471-2431/13/38

Received:	18 October 2012
Accepted:	19 March 2013
Published:	23 March 2013

© 2013 Kuo et al.; licensee BioMed Central Ltd. 

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The risk of allergic diseases among Kawasaki disease (KD) patients relative to the general population is not known. The aim of this study was to perform a population-based cohort study to investigate the risk of allergic diseases among children after KD in Taiwan- a country with the third highest incidence of KD in the world.

Methods

Data were obtained from the Taiwan National Health Insurance Research Database. In total, 253 patients who were 5 years of age or younger and had a first-time hospitalization with a diagnosis of KD between 1997 and 2005 were included as the study cohort and 1,012 non-KD patients matched for age and sex were included as comparison cohort. Multivariate Cox proportional hazard regression model was used to adjust for confounding and to compare the 6-year allergic-free survival rate between these two cohorts.

Results

The incidence rate of allergic diseases (184.66 per 1000 person-year) was significantly higher in the KD cohort than in the control cohort (124.99 per 1000 person-years). After adjusting for potential confounders, the adjusted hazard ratios of asthma and allergic rhinitis were 1.51 (95% confidence interval = 1.17-1.95) and 1.30 (95% confidence interval = 1.04-1.62), respectively.

Conclusion

We conclude that KD patients were at an increased risk for allergic diseases compared with the comparison cohort.

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Review

Drug provocation tests: up-date and novel approaches

Anca Mirela Chiriac and Pascal Demoly

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Allergy, Asthma & Clinical Immunology 2013, 9:12 doi:10.1186/1710-1492-9-12

Published: 3 April 2013

Abstract (provisional)

Drug provocation tests (DPTs) are often needed when evaluating patients with suspected drug hypersensitivity reactions. General considerations on DPTs, with regard to indications, contraindications, methods, limitations and interpretations have been thoroughly addressed and various protocols are published. However, the field of drug allergy is changing and DPTs make no exception. Novel (or sometimes, simply renewed) approaches arise, awaiting to be either validated or refuted in larger studies in the future. Instead of covering the whole topic of DPTs, this paper will address these recent and challenging aspects.

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