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Origins of increased airway smooth muscle mass in asthma

Rachid Berair, Ruth Saunders and Christopher E Brightling^*

• *Corresponding author: Christopher E Brightling ceb17@le.ac.uk

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BMC Medicine 2013, 11:145 doi:10.1186/1741-7015-11-145

Published: 6 June 2013

Abstract

Asthma is characterized by both chronic inflammation and airway remodeling. Remodeling - the structural changes seen in asthmatic airways - is pivotal in the pathogenesis of the disease. Although significant advances have been made recently in understanding the different aspects of airway remodeling, the exact biology governing these changes remains poorly understood. There is broad agreement that, in asthma, increased airway smooth muscle mass, in part due to smooth muscle hyperplasia, is a very significant component of airway remodeling. However, significant debate persists on the origins of these airway smooth muscle cells. In this review article we will explore the natural history of airway remodeling in asthma and we will discuss the possible contribution of progenitors, stem cells and epithelial cells in mesenchymal cell changes, namely airway smooth muscle hyperplasia seen in the asthmatic airways.

Keywords: 

Airway remodeling; Airway smooth muscle; Asthma; Fibrocytes; Mesenchymal stem cells

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Peripheral Blood Eosinophil Counts Predict the Prognosis of Drug Eruptions

Original Article

Peripheral Blood Eosinophil Counts Predict the Prognosis of Drug Eruptions

J Yang,1 X Yang,2,3 M Li1

1Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China 2Divison of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China 3Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China

J Investig Allergol Clin Immunol 2013; Vol. 23(4): 248-255

Abstract Background: Previous studies indicated that eosinophils infiltrate the skin during drug eruptions and that counts may become elevated in circulation. However, little is known about the role of eosinophils in the prognosis of patients with drug eruption. Objective: This study aims to investigate the correlation between circulating eosinophil counts and the prognosis of patients with drug eruption. Methods: A total of 113 patients were enrolled in this study. Clinical features, peripheral blood eosinophil counts, and liver function were analyzed in patients and controls. Results: Our study indicated that eosinophils changed dynamically in different types of drug eruption and that mean eosinophil counts in patients with erythema multiforme–type drug eruption were significantly higher than in patients with other types of eruption. Most patients with eosinophilia had poor liver function, prolonged corticosteroid use, and extended hospitalization, all of which indicate severe disease. Conclusions: Our data suggest that circulating eosinophil counts were positively correlated with the severity of the drug eruption. Therefore, corticosteroids may be needed to treat patients with eosinophilia in clinical practice. Key words: Drug eruptions. Prognosis. Eosinophils.   Free Full-Text (PDF)   How to use PDF documents

Immunopathogenesis of Allergic Asthma: More Than the Th2 Hypothesis

Review  Open Access

|    Allergy Asthma Immunol Res. 2013 Jul;5(4):189-196. English. Published online 2013 April 12.  http://dx.doi.org/10.4168/aair.2013.5.4.189  Copyright © 2013 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease Immunopathogenesis of Allergic Asthma: More Than the Th2 Hypothesis You-Me Kim, You-Sun Kim, Seong Gyu Jeon and Yoon-Keun Kim Department of Life Science, Pohang University of Science and Technology (POSTECH), Pohang, Korea.  Correspondence to: Yoon-Keun Kim, MD, PhD, POSTECH Biotech Center, 55 Jigok-ro, Nam-gu, Pohang 790-834, Korea. Tel: +82-54-279-2125; Fax: +82-54-279-8449; Email: juinea@postech.ac.kr  Received September 15, 2012; Accepted October 10, 2012. 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 Asthma is a chronic obstructive airway disease that involves inflammation of the respiratory tract. Biological contaminants in indoor air can induce innate and adaptive immune responses and inflammation, resulting in asthma pathology. Epidemiologic surveys indicate that the prevalence of asthma is higher in developed countries than in developing countries. The prevalence of asthma in Korea has increased during the last several decades. This increase may be related to changes in housing styles, which result in increased levels of indoor biological contaminants, such as house dust mite-derived allergens and bacterial products such as endotoxin. Different types of inflammation are observed in those suffering from mild-to-moderate asthma compared to those experiencing severe asthma, involving markedly different patterns of inflammatory cells and mediators. As described in this review, these inflammatory profiles are largely determined by the involvement of different T helper cell subsets, which orchestrate the recruitment and activation of inflammatory cells. It is becoming clear that T helper cells other than Th2 cells are involved in the pathogenesis of asthma; specifically, both Th1 and Th17 cells are crucial for the development of neutrophilic inflammation in the airways, which is related to corticosteroid resistance. Development of therapeutics that suppress these immune and inflammatory cells may provide useful asthma treatments in the future. Keywords: Allergic asthma, endotoxin, immunopathogenesis, T helper cell.

In Vitro Methods for Diagnosing Nonimmediate Hypersensitivity Reactions to Drugs

Reviews

In Vitro Methods for Diagnosing Nonimmediate Hypersensitivity Reactions to Drugs

C Mayorga,1 ML Sanz,2 P Gamboa,3 MC Garcia-Aviles,4 J Fernandez,5 MJ Torres,1 on behalf of the Spanish Society of Allergy and Clinical Immunology (SEAIC) Immunology and Drug Allergy Committee

1Allergy Service, Carlos Haya Hospital, Malaga, Spain 2Department of Allergology and Clinical Immunology, Navarra University Clinic, Pamplona, Spain 3Allergy Service, Basurto Hospital, Bilbao, Spain 4Allergy Service, Moncloa Hospital, Madrid, Spain 5Allergy Service, Alicante General Hospital, Alicante, Spain

J Investig Allergol Clin Immunol 2013; Vol. 23(4): 213-225

Abstract Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessary to establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs. Key words: Nonimmediate. Drug hypersensitivity. Diagnosis. Lymphocyte. In vitro.   Free Full-Text (PDF) Continual Medical Education   How to use PDF documents

Brief communication

The significance of diagnosing associated clonal mast cell diseases in patients with venom-induced anaphylaxis and the role of bone marrow investigation

Theo Gulen, Barbro Dahlén, Birgitta Sander, Hans Hägglund and Gunnar P Nilsson

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Clinical and Translational Allergy 2013, 3:22 doi:10.1186/2045-7022-3-22

Published: 4 July 2013

Abstract (provisional)

Hymenoptera venom allergy (HVA) represents a particular risk for exceptionally severe anaphylactic sting reactions in patients with clonal mast cell disorders (CMD). Nevertheless, conventional investigations are not sufficient to do accurate risk assessments. Increased levels of baseline serum tryptase (sBT) (>11.4 ug/L) is highly associated with severe anaphylactic reactions and with a possible underlying CMD. The measurement of baseline serum tryptase, thus, has opened the possibility to screen for CMD. In the present study, we sought to investigate whether bone marrow evaluation provides more accurate diagnosis in patients with HVA. Three patients of the same sex and similar age with HVA were enrolled in this clinical study. The patients underwent comprehensive allergy work-up including skin prick testing, measurements of serum total IgE concentrations and baseline serum tryptase. Bone-marrow biopsies were also performed in all three patients to assess underlying CMD. We evaluated characteristics of the bone marrow mast cells by pathology, flow cytometry and detection of D816V mutation by using current WHO-criteria, which led to changes in the final diagnosis compared to the assessments done by classical allergy work-up and measurements of sBT. Three distinct diagnostic outcomes including systemic mastocytosis, monoclonal mast cell activation syndrome and non-clonal HVA were revealed. We conclude that a bone marrow investigation is required for the correct diagnosis of hymenoptera venom-induced anaphylactic reactions in patients with elevated baseline tryptase levels (>11.4 ug/L), and this has important implications for management strategies.

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Research article

The health economic impact of disease management programs for COPD: a systematic literature review and meta-analysis

Melinde RS Boland, Apostolos Tsiachristas, Annemarije L Kruis, Niels H Chavannes and Maureen PMH Rutten-van Mölken

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BMC Pulmonary Medicine 2013, 13:40 doi:10.1186/1471-2466-13-40

Published: 3 July 2013

Abstract (provisional)

Background

There is insufficient evidence of the cost-effectiveness of Chronic Obstructive Pulmonary Disease (COPD) Disease Management (COPD-DM) programs. The aim of this review is to evaluate the economic impact of COPD-DM programs and investigate the relation between the impact on healthcare costs and health outcomes. We also investigated the impact of patient-, intervention, and study-characteristics.

Methods

We conducted a systematic literature review to identify cost-effectiveness studies of COPD-DM. Where feasible, results were pooled using random-effects meta-analysis and explorative subgroup analyses were performed.

Results

Sixteen papers describing 11 studies were included (7 randomized control trials (RCT), 2 pre-post, 2 case--control). Meta-analysis showed that COPD-DM led to hospitalization savings of [euro sign]1060 (95% CI: [euro sign]2040 to [euro sign]80) per patient per year and savings in total healthcare utilization of [euro sign]898 (95% CI: [euro sign]1566 to [euro sign]231) (excl. operating costs). In these health economic studies small but positive results on health outcomes were found, such as the St Georges Respiratory Questionnaire (SGRQ) score, which decreased with 1.7 points (95% CI: 0.5-2.9). There was great variability in DM interventions-, study- and patient-characteristics. There were indications that DM showed greater savings in studies with: severe COPD patients, patients with a history of exacerbations, RCT study design, high methodological quality, few different professions involved in the program, and study setting outside Europe.

Conclusions

COPD-DM programs were found to have favourable effects on both health outcomes and costs, but there is considerable heterogeneity depending on patient-, intervention-, and study-characteristics.

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 Journal of Asthma and Allergy

Infant anaphylaxis: the importance of early recognition

Review

(141) Total Article Views

Authors: Dosanjh A

Published Date July 2013 Volume 2013:6 Pages 103 - 107

DOI: http://dx.doi.org/10.2147/JAA.S42694

Received:	12 January 2013
Accepted:	23 April 2013
Published:	04 July 2013

A Dosanjh

Department of Pediatrics, Rady Children's Hospital, San Diego, CA, USA

Abstract: Anaphylaxis is an acute severe reaction involving multiple systems that results from a rapid release of inflammatory mediators. Patients with asthma and prior allergic reactions are at risk for anaphylaxis. Infants can present a special challenge, as the hallmark symptoms and signs of anaphylaxis may be mistaken as normal findings. These include drooling, vomiting or diarrhea, scratching, and drowsiness. The clinical manifestations of anaphylaxis are broad, as a result of it being a systemic response to an external agent. Among infants and children, there are often respiratory and cutaneous findings. There also can be subtle signs and symptoms, which can often be missed or the findings misinterpreted as normal for developmental age. The incidence of anaphylaxis has increased globally among children presenting with allergic reactions. Early recognition of the signs and symptoms is crucial to effective diagnosis and treatment. This is particularly true among infants 13 months of age or younger who are nonverbal and may have subtle signs and symptoms of a life-threatening reaction to allergens. The purpose of this article is to highlight the differential clinical presentations of young children with anaphylaxis.

Keywords: anaphylaxis, infant, food allergy



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Research

IL-17-producing peripheral blood CD117+ neutrophils increase in allergic asthmatic subjects

Carlos Ramirez-Velazquez, Elena Cristina Castillo, Leopoldo Guido-Bayardo and Vianney Ortiz-Navarrete

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Allergy, Asthma & Clinical Immunology 2013, 9:23 doi:10.1186/1710-1492-9-23

Published: 3 July 2013

Abstract (provisional)

Background

A T helper cell (TH) 17-biased response has been observed in patients with allergic asthma, particularly in those with neutrophil accumulation in the lung. Therefore, we sought to test the hypothesis that neutrophils might be an important source of interleukin (IL)-17 in allergic asthma.

Methods

Whole peripheral blood cells from non-asthmatic control subjects (n = 17) and patients with mild asthma (n = 7), moderate but persistent asthma (n = 4), or acute asthma (n = 6) were analyzed for IL-17A expression in CD177+ neutrophils. IL-17A expression was also analyzed in CD3+CD4+ and CD3+CD8+ lymphocyte populations. Asthmatic patients were classified as allergic to fungi, indoor allergens, or other allergens (e.g., pollen) based on a positive intradermal allergy test reaction.

Results

The percentage of CD177+ neutrophils in whole blood of asthmatic patients was higher than in healthy controls and highest in the moderate asthma group. Furthermore, the percentage of CD177+IL-17+ neutrophils was elevated in patients with mild asthma, whereas the CD4+ IL-17+ lymphocyte population was higher in asthmatic patients and highest in those with moderate but persistent asthma. We also found that the four patients that were allergic to fungi had the highest percentage of CD177+IL17+ neutrophils and CD8+IL17+ lymphocytes.

Conclusion

IL17+CD177+ Neutrophils increase in allergic asthma patients especially when allergic to fungi. This cell population, through release of IL-17, might be contributing during the initial phase asthmatic disease and/or during disease progression but its role has not yet been established

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