July 10, 2014

Epidermal Permeability Barrier Defects and Barrier Repair Therapy in Atopic Dermatitis



Review
  Open Access



     


Allergy Asthma Immunol Res. 2014 Jul;6(4):276-287. English.
Published online 2014 March 21.  http://dx.doi.org/10.4168/aair.2014.6.4.276 
Copyright © 2014 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease
Hae-Jin Lee,1 and Seung-Hun Lee2
1Medical Corps of Sangmudae Army Service Support Group, Republic of Korea Army Training and Doctrine Command, Jangsung, Korea.
2Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.

 Correspondence to: Seung Hun Lee, MD, PhD, Department of Dermatology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 135-720, Korea. Tel: +82-2-2019-3360; Fax: +82-2-3463-6136; Email: ydshderm@yuhs.ac 
Received December 08, 2013; Accepted January 06, 2014.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease perpetuated by gene-environmental interactions and which is characterized by genetic barrier defects and allergic inflammation. Recent studies demonstrate an important role for the epidermal permeability barrier in AD that is closely related to chronic immune activation in the skin during systemic allergic reactions. Moreover, acquired stressors (e.g.,Staphylococcus aureus infection) to the skin barrier may also initiate inflammation in AD. Many studies involving patients with AD revealed that defective skin barriers combined with abnormal immune responses might contribute to the pathophysiology of AD, supporting the outside-inside hypothesis. In this review, we discuss the recent advances in human and animal models, focusing on the defects of the epidermal permeability barrier, its immunologic role and barrier repair therapy in AD.
Keywords: Atopic dermatitisbarrier repair therapyskin barrier.

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Satisfaction level and asthma control among Malaysian asthma patients on Symbicort Maintenance and Reliever Therapy (SMART) in the primary care setting (SMARTEST study)

Chong-Kin Liam, Yong-Kek Pang, Keong-Tiong Chua

Abstract

Objective: To evaluate Malaysian patients’ satisfaction levels and asthma control with Symbicort SMART® in the primary care setting.
Method: This is a cross-sectional, multicentre study involving adult patients with persistent asthma who were prescribed only Symbicort SMART in the preceding one month prior to recruitment. Patients’ satisfaction with Symbicort SMART and asthma control were evaluated using the self-administered Satisfaction with Asthma Treatment Questionnaire (SATQ) and the Asthma Control Test (ACT).
Results: Asthma was controlled (ACT score >20) in 189 (83%) of 228 patients. The mean overall SATQ score for patients with controlled asthma was 5.65 indicating a high satisfaction level, which was positively correlated with high ACT scores. There were differences in asthma control based on ethnicity, number of unscheduled visits and treatment compliance.
Conclusions: Symbicort SMART resulted in a high satisfaction level and asthma control among Malaysian patients treated in the primary care setting and it is an effective and appealing treatment for asthmatic patients.
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Parameters of lung inflammation in asthmatic as compared to healthy children in a contaminated city

Research article

Open Access

Benigno Linares SegoviaGabriela Cortés SandovalNorma Amador LiconaJuan Manuel Guízar MendozaEstela Núñez LemusDiana Olivia Rocha AmadorXóchitl Sofía Ramírez Gómez and Rebeca Monroy Torres
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BMC Pulmonary Medicine 2014, 14:111  doi:10.1186/1471-2466-14-111
Published: 8 July 2014

Abstract (provisional)

Background

The impact of air pollution on the respiratory system has been estimated on the basis of respiratory symptoms and lung function. However; few studies have compared lung inflammation in healthy and asthmatics children exposed to high levels of air pollution. The aim of the study was to elucidate the modulatory effect of air pollution on Cysteinyl-leukotrienes (Cys-LTs) levels in exhaled breath condensate (EBC) among healthy and asthmatic children.

Methods

We performed a cross-sectional comparative study. Children between 7-12 years of age, asthmatics and non-asthmatics, residents of a city with high levels of PM10 were included. In all cases, forced spirometry, Cys-LTs levels in EBC, and the International Study of Asthma and Allergies in Childhood questionnaire were evaluated. We also obtained average of PM10, CO, SO2 and O3 levels during the period of the study by the State Institute of Ecology.

Results

We studied 103 children (51 asthmatics and 52 non-asthmatics). Cys-LTs levels were higher in asthmatics than in non-asthmatics (77.3 +/- 21.6 versus 60.3 +/- 26.8 pg/ml; p = 0.0005). Also, Cys-LTs levels in children with intermittent asthma were lower than in children with persistent asthma (60.4 +/- 20.4 versus 84.7 +/- 19.2 pg / ml; p = 0.0001). In the multiple regression model, factors associated with levels of Cys-LTs were passive smoking (beta = 13.1, p 0.04) and to be asthmatic (beta = 11.5, p 0.03).

Conclusions

Cys-LTs levels are higher in asthmatic children than in healthy children in a contaminated city and its levels are also associated with passive smoking.

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Significance of Persistent Inflammation in Respiratory Disorders Induced by Nanoparticles

Journal of Immunology Research
Volume 2014 (2014), Article ID 962871, 8 pages
http://dx.doi.org/10.1155/2014/962871
Review Article
1Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan
2Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Japan
Received 22 February 2014; Revised 17 June 2014; Accepted 20 June 2014; Published 7 July 2014
Academic Editor: Mario Di Gioacchino
Copyright © 2014 Yasuo Morimoto 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.

Abstract

Pulmonary inflammation, especially persistent inflammation, has been found to play a key role in respiratory disorders induced by nanoparticles in animal models. In inhalation studies and instillation studies of nanomaterials, persistent inflammation is composed of neutrophils and alveolar macrophages, and its pathogenesis is related to chemokines such as the cytokine-induced neutrophil chemoattractant (CINC) family and macrophage inflammatory protein-1 and oxidant stress-related genes such as heme oxygenase-1 (HO-1). DNA damages occur chemically or physically by nanomaterials. Chemical and physical damage are associated with point mutation by free radicals and double strand brake, respectively. The failure of DNA repair and accumulation of mutations might occur when inflammation is prolonged, and finally normal cells could become malignant. These free radicals can not only damage cells but also induce signaling molecules containing immunoreaction. Nanoparticles and asbestos also induce the production of free radicals. In allergic responses, nanoparticles act as Th2 adjuvants to activate Th2 immune responses such as activation of eosinophil and induction of IgE. Taken together, the presence of persistent inflammation may contribute to the pathogenesis of a variety of diseases induced by nanomaterials.

A Model for the Determination of Pollen Count Using Google Search Queries for Patients Suffering from Allergic Rhinitis

Journal of Allergy
Volume 2014 (2014), Article ID 381983, 9 pages
http://dx.doi.org/10.1155/2014/381983
Research Article
Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, 50924 Cologne, Germany
Received 27 February 2014; Revised 22 May 2014; Accepted 26 May 2014; Published 19 June 2014
Academic Editor: Carlos E. Baena-Cagnani
Copyright © 2014 Volker König and Ralph Mösges. 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

Background. The transregional increase in pollen-associated allergies and their diversity have been scientifically proven. However, patchy pollen count measurement in many regions is a worldwide problem with few exceptions. Methods. This paper used data gathered from pollen count stations in Germany, Google queries using relevant allergological/biological keywords, and patient data from three German study centres collected in a prospective, double-blind, randomised, placebo-controlled, multicentre immunotherapy study to analyse a possible correlation between these data pools. Results. Overall, correlations between the patient-based, combined symptom medication score and Google data were stronger than those with the regionally measured pollen count data. The correlation of the Google data was especially strong in the groups of severe allergy sufferers. The results of the three-centre analyses show moderate to strong correlations with the Google keywords (up to >0.8 cross-correlation coefficient, ) in 10 out of 11 groups (three averaged patient cohorts and eight subgroups of severe allergy sufferers: high IgE class, high combined symptom medication score, and asthma). Conclusion. For countries with a good Internet infrastructure but no dense network of pollen traps, this could represent an alternative for determining pollen levels and, forecasting the pollen count for the next day.

Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality


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Original Research

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Authors: Kravchenko J, Akushevich I, Abernethy AP, Holman S, Ross Jr WG, Lyerly HK

Published Date June 2014 Volume 2014:9 Pages 613 - 627
DOI: http://dx.doi.org/10.2147/COPD.S59995

Julia Kravchenko,1 Igor Akushevich,2 Amy P Abernethy,3 Sheila Holman,4 William G Ross Jr,5 H Kim Lyerly1,6

1Department of Surgery, 2Center for Population Health and Aging, 3Duke Clinical Research Institute, Duke University Medical Center, Duke University, Durham, 4Division of Air Quality, North Carolina Department of Environment and Natural Resources, Raleigh, 5Nicholas School of the Environment, 6Department of Pathology, Duke University Medical Center, Duke University, Durham, NC, USA

Background: The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations.
Materials and methods: We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993–2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths.
Results: Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths–with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths–with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted.
Conclusion: Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina.

Keywords: chronic obstructive pulmonary disease, sulfur dioxide, carbon monoxide, nitrogen dioxide, particulate matter


Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

July 7, 2014

Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study


PLoS Med. Jul 2014; 11(7): e1001669.
Published online Jul 1, 2014. doi:  10.1371/journal.pmed.1001669
PMCID: PMC4077660
Cosetta Minelli, Academic Editor

Abstract

Background

Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.

Methods and Findings

We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values-0.001) and with childhood asthma (RR 2.56, 95% CI 1.38–4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16–2.07) per kg/m2,p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19–3.03) than for atopic asthma (1.37, 95% CI 0.89–2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11–1.79) per 0.5 kg and 2.25 (95% CI 1.23–4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.

Conclusions

Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century.
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July 6, 2014

Effects of ex vivo Gamma-Tocopherol on Airway Macrophage Function in Healthy and Mild Allergic Asthmatics



J Innate Immun. Author manuscript; available in PMC May 8, 2014.
Published in final edited form as:
Published online May 8, 2013. doi:  10.1159/000350234
PMCID: PMC3939603
NIHMSID: NIHMS539930
Marianne Geiser, PhD,a,c,*,1 John C. Lay, DVM, PhD,a,b William D. Bennett, PhD,a,c Haibo Zhou, PhD,a,d Xiaoyan Wang, PhD,a,d David B. Peden, MD, MPH,a,b,c and Neil E. Alexis, PhDa,b

Abstract

Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate gamma-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cell surface molecules associated with innate and adaptive immunity on sputum-derived macrophages. Cells from non-smoking healthy (n = 6) and mild house dust mite-sensitive (HDM) allergic asthmatics (n = 6) were treated ex vivo with GT (300 μM) or saline (control). Phagocytosis of opsonized Zymosan A bioparticles (S. cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (P - 0.05) internalization of attached Zymosan bioparticles and decreased (P - 0.05) macrophage expression of CD206, CD36 and CD86 in allergic asthmatics but not in controls. Overall, GT caused down-regulation of both innate and adaptive immune response elements and atopic status appears to be an important factor.
Keywords: allergy, asthma, macrophages, phagocytosis, flow cytometry, gamma-tocopherol, host defense

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Interferon-gamma regulates growth and controls Fcgamma receptor expression and activation in human intestinal mast cells

Research article

Open Access

Gernot SellgeMiriam BarkowskySigrid KramerThomas GebhardtLeif E SanderAxel Lorentz and Stephan C Bischoff
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BMC Immunology 2014, 15:27  doi:10.1186/1471-2172-15-27
Published: 5 July 2014

Abstract (provisional)

Background

Development and function of tissue resident mast cells (MCs) is tightly controlled by various cytokines, most of which belong to the typical T helper (Th) 2-type cytokines such as IL-3 and IL-4. The effects of the Th1-type cytokine IFN-gamma on human MCs is less clear.

Results

Here, we analyzed the effects of IFN-gamma on tissue-derived, mature human MCs. We found that INF-gamma decreases proliferation, without affecting apoptosis in human intestinal MCs cultured in the presence of optimal concentrations of stem cell factor (SCF) or SCF and IL-4. However, in the absence of growth factors or at suboptimal concentrations of SCF, INF-gamma promotes survival through inhibition of MC apoptosis. Interestingly, we found that INF-gamma has no effect on FcepsilonRI expression and FcepsilonRI-mediated release of histamine and leukotriene (LT)C4, while it has profound effects on FcgammaR expression and activation. We show that intestinal MCs express FcgammaRI, FcgammaRIIa, and FcgammaRIIc, whereas FcgammaRIIb expression was found in only 40% of the isolates and FcgammaRIII was never detectable. INF-gamma strongly increases FcgammaRI and decreases FcgammaRIIa expression. INF-gamma-naive MCs produce LTC4 but fail to degranulate upon crosslinking of surface-bound monomeric IgG. In contrast, INF-gamma-treated MCs rapidly release granule-stored histamine in addition to de novo-synthesized LTC4.

Conclusion

In summary, we identify INF-gamma as an important regulator of tissue-resident human MCs. IFN-gamma displays a dual function by blocking extensive MC proliferation, while decreasing apoptosis in starving MCs and enhancing FcgammaRI expression and activation. These results emphasize the involvement of mucosal MCs in Th1-mediated disorders.

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