April 14, 2014

Diagnosis and management of eosinophilic asthma: a US perspective



Review

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Authors: Walford HH, Doherty TA

Published Date April 2014 Volume 2014:7 Pages 53 - 65
DOI: http://dx.doi.org/10.2147/JAA.S39119

Received:06 December 2013
Accepted:15 January 2014
Published:11 April 2014
Hannah H Walford,1,2 Taylor A Doherty1
1Department of Medicine, 2Department of Pediatrics, University of California, La Jolla, CA, USA

Abstract: Eosinophilic asthma is now recognized as an important subphenotype of asthma based on the pattern of inflammatory cellular infiltrate in the airway. Eosinophilic asthma can be associated with increased asthma severity, atopy, late-onset disease, and steroid refractoriness. Induced sputum cell count is the gold standard for identifying eosinophilic inflammation in asthma although several noninvasive biomarkers, including fractional exhaled nitric oxide and periostin, are emerging as potential surrogates. As novel therapies and biologic agents become increasingly available, there is an increased need for specific phenotype-directed treatment strategies. Greater recognition and understanding of the unique immunopathology of this asthma phenotype has important implications for management of the disease and the potential to improve patient outcomes. The present review provides a summary of the clinical features, pathogenesis, diagnosis, and management of eosinophilic asthma.

Keywords: asthma, eosinophil, allergy, Th2, IL-4, IL-13


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Adult mastocytosis: a review of the Santo António Hospital 's experience and an evaluation of World Health Organization criteria for the diagnosis of systemic disease


An Bras Dermatol. 2014 Jan-Feb; 89(1): 59–66.
PMCID: PMC3938355

Adult mastocytosis: a review of the Santo António Hospital 's experience and an evaluation of World Health Organization criteria for the diagnosis of systemic disease*

Iolanda Conde Fernandes,1 Maria dos Anjos Teixeira,2 Inês Freitas,2 Manuela Selores,3 Rosário Alves,2 and Margarida Lima4
Author information ► Article notes ► Copyright and License information ►

Abstract

BACKGROUND

Mastocytosis is a clonal disorder characterized by the accumulation of abnormal mast cells in the skin and/or in extracutaneous organs.

OBJECTIVES

To present all cases of mastocytosis seen in the Porto Hospital Center and evaluate the performance of World Health Organization diagnostic criteria for systemic disease.

METHODS

The cases of twenty-four adult patients with mastocytosis were reviewed. Their clinical and laboratorial characteristics were assessed, and the properties of the criteria used to diagnose systemic mastocytosis were evaluated.

RESULTS

The age of disease onset ranged from 2 to 75 years. Twenty-three patients had cutaneous involvement and 75% were referred by dermatologists. Urticaria pigmentosa was the most common manifestation of the disease. One patient with severe systemic mast cell mediator-related symptoms showed the activating V560G KIT mutation. The bone marrow was examined in 79% of patients, and mast cell immunophenotyping was performed in 67% of the participants. Systemic disease was detected in 84% of cases, and 81% of the sample had elevated serum tryptase levels. All the diagnostic criteria for systemic mastocytosis had high specificity and positive predictive value. Bone marrow biopsy had the lowest sensitivity, negative predictive value and efficiency, while the highest such values were observed for mast cell immunophenotyping. Patients were treated with regimens including antihistamines, sodium cromoglycate, alpha-interferon, hydroxyurea and phototherapy.

CONCLUSIONS

Cutaneous involvement is often seen in adult mastocytosis patients, with most individuals presenting with indolent systemic disease. Although serum tryptase levels are a good indicator of mast cell burden, bone marrow biopsy should also be performed in patients with normal serum tryptase, with flow cytometry being the most adequate method to diagnose systemic disease.
Keywords: Flow cytometry, Mast cells, Mastocytosis, cutaneous, Mastocytosis, systemic, Tryptases

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Diagnostic Approach to Primary Immunodeficiency Disorders



Indian Pediatr 2013;50: 579-586
M Madkaikar, A Mishra and K Ghosh
From Department of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), 13th Floor, NMS Bldg, KEM Hospital, Parel, Mumbai, India.
Correspondence to: Dr Manisha Madkaikar, National Institute of Immunohaematology, 13th Floor, NMS Bldg, KEM Hospital, Parel, Mumbai 400 012, India. 
Email: madkaikarmanisha@icmr.org.in



Primary immunodeficiency disorders (PIDs) are a heterogeneous group of inherited disorders that affect different components of the immune system. There are more than 150 different disorders which have been described till date. Despite major advances in the molecular characterization of PIDs over the last 20 years, many patients remain undiagnosed or are diagnosed too late with severe consequences. Recognizing different clinical manifestations of PID is the first most important step. It should be followed by use of appropriate diagnostic tools from a vast number of investigations available. This review will focus on important presenting features of PID and laboratory approach for diagnosis of suspected cases of PID.
Key words: Antibody deficiency, Phagocytic defects, Immune dysregulation, Primary immunodeficiency disorders, Severe combined immunodeficiency (SCID).

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Potential Involvement of IL-17F in Asthma 


Journal of Immunology Research



Volume 2014 (2014), Article ID 602846, 8 pages
Review Article
Kyoko Ota,1 Mio Kawaguchi,1 Satoshi Matsukura,2 Masatsugu Kurokawa,3Fumio Kokubu,2 Junichi Fujita,1 Yuko Morishima,1 Shau-Ku Huang,4,5 Yukio Ishii,1 Hiroaki Satoh,1 and Nobuyuki Hizawa1
1Division of Clinical Medicine, Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan
2Department of Respiratory Medicine, Showa University Fujigaoka Hospital, 1-30 Aoba-ku, Yokohama 227-8501, Japan
3Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
4Johns Hopkins University, Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224-6801, USA
5National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan
Received 4 March 2013; Revised 3 December 2013; Accepted 5 December 2013; Published 14 April 2014
Academic Editor: Enric Esplugues
Copyright © 2014 Kyoko Ota 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

The expression of IL-17F is seen in the airway of asthmatics and its level is correlated with disease severity. Several studies have demonstrated that IL-17F plays a pivotal role in allergic airway inflammation and induces several asthma-related molecules such as CCL20. IL-17F-induced CCL20 may attract Th17 cells into the airway resulting in the recruitment of additional Th17 cells to enhance allergic airway inflammation. We have recently identified, for the first time, that bronchial epithelial cells are its novel cell source in response to IL-33 via ST2-ERK1/2-MSK1 signaling pathway. The receptor for IL-17F is the heterodimeric complex of IL-17RA and IL-17RC, and IL-17F activates many signaling pathways. In a case-control study of 867 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL-17F gene was associated with asthma. In atopic patients with asthma, prebronchodilator baseline FEV1/FVC values showed a significant association with the H161R variant. Moreover, this variant is a natural antagonist for the wild-type IL-17F. Moreover, IL-17F is involved in airway remodeling and steroid resistance. Hence, IL-17F may play an orchestrating role in the pathogenesis of asthma and may provide a valuable therapeutic target for development of novel strategies.
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April 12, 2014

Preparation and Identification of Per a 5 as a Novel American Cockroach Allergen 

Mediators of Inflammation
Volume 2014 (2014), Article ID 591468, 10 pages
http://dx.doi.org/10.1155/2014/591468
Research Article
Ji-Fu Wei,1,2 Haiwei Yang,3 Dongning Li,1 Peisong Gao,4 and Shaoheng He1,2
1Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, China
2Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
3Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
4Johns Hopkins Asthma & Allergy Center, Baltimore, MD 21224, USA
Received 24 November 2013; Revised 15 January 2014; Accepted 15 January 2014; Published 23 February 2014
Academic Editor: Huiyun Zhang
Copyright © 2014 Ji-Fu Wei 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

Glutathione S-transferase (GST) from various arthropods can elicit allergic reactions. In the present study, Per a 5, a GST, was cloned from American cockroach (CR) and expressed in both baculovirus-infected insect cell (iPer a 5) and E. coli expression (bPer a 5) systems. The secondary structures were predicted to be 45.93 and 8.69% of α-helix β-sheets in iPer a 5 and 42.54 and 8.49% of α-helix and β-sheets in bPer a 5, respectively. It is found that 4 out of 16 (25%) sera from American CR allergy patients reacted to both bPer a 9 and iPer a 9 as assessed by ELISA and Western blotting analysis, confirming that Per a 5 is not a major allergen of American CR. Induction of upregulated expression of CD63 and CCR3 on passively sensitized human basophils (sera from American CR allergy patients) by approximately up to 4.5- and 3.2-fold indicates that iPer a 5 and bPer a 5 are functionally active. Recombinant Per a 5 (rPer a 5) should be a useful tool for studying and understanding the role of Per a 5 in CR allergy.
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Differential Regulation of Cysteinyl Leukotriene Receptor Signaling by Protein Kinase C in Human Mast Cells

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PLoS One. 2013; 8(8): e71536.
Published online Aug 15, 2013. doi:  10.1371/journal.pone.0071536
PMCID: PMC3744564

Differential Regulation of Cysteinyl Leukotriene Receptor Signaling by Protein Kinase C in Human Mast Cells

Vinay Kondeti,1 Ernest Duah,1 Nosayba Al-Azzam,1 Charles K. Thodeti,2 Joshua A. Boyce,3,4,5 and Sailaja Paruchuri1,*
Patricia T. Bozza, Editor
Author information ► Article notes ► Copyright and License information ►

Abstract

Cysteinyl leukotrienes (cys-LTs) are a group of lipid mediators that are potent bronchoconstrictors, powerful inducers of vascular leakage and potentiators of airway hyperresponsiveness. Cys-LTs play an essential role in asthma and are synthesized as well as activated in mast cells (MCs). Cys-LTs relay their effects mainly through two known GPCRs, CysLT1R and CysLT2R. Although protein kinase C (PKC) isoforms are implicated in the regulation of CysLT1R function, neither the role of PKCs in cys-LT-dependent MC inflammatory signaling nor the involvement of specific isoforms in MC function are known. Here, we show that PKC inhibition augmented LTD4 and LTE4-induced calcium influx through CysLT1R in MCs. In contrast, inhibition of PKCs suppressed c-fos expression as well MIP1β generation by cys-LTs. Interestingly, cys-LTs activated both PKCα and PKCε isoforms in MC. However, knockdown of PKCα augmented cys-LT mediated calcium flux, while knockdown of PKCε attenuated cys-LT induced c-fos expression and MIP1β generation. Taken together, these results demonstrate for the first time that cys-LT signaling downstream of CysLT1R in MCs is differentially regulated by two distinct PKCs which modulate inflammatory signals that have significant pathobiologic implications in allergic reactions and asthma pathology.

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Switching patients from other inhaled corticosteroid devices to the Easyhaler®: historical, matched-cohort study of real-life asthma patients


Original Research

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Authors: Price D, Thomas V, von Ziegenweidt J, Gould S, Hutton C, King C

Published Date April 2014 Volume 2014:7 Pages 31 - 51
DOI: http://dx.doi.org/10.2147/JAA.S59386

Received:18 December 2013
Accepted:28 January 2014
Published:10 April 2014
David Price,1,2 Vicky Thomas,2 Julie von Ziegenweidt,2 Shuna Gould,2 Catherine Hutton,2Christine King2
1Academic Centre of Primary Care, University of Aberdeen, Aberdeen, UK; 2Research in Real Life, Oakington, Cambridge, UK

Purpose: To investigate the clinical and cost effectiveness of switching real-life asthma patients from other types of inhalers to the Easyhaler® (EH) for the administration of inhaled corticosteroids (ICS).
Patients and methods: Historical, matched-cohort study of 1,958 asthma patients (children and adults) treated in UK primary-care practices, using data obtained from the Optimum Patient Care Research Database and Clinical Practice Research Datalink. Other inhalers (OH) included pressurized metered-dose inhalers, breath-actuated inhalers, and dry-powder inhalers, delivering beclomethasone, budesonide, fluticasone, or ciclesonide. Patients remaining on OH unchanged (same drug, dosage, and device; n=979) were matched 1:1 with those switched to the EH (beclomethasone or budesonide) at the same or lower ICS dosage (n=979), based on age, sex, year of index patient review/switch, most recent ICS drug, dosage, and device, and the number of severe exacerbations and average daily short-acting β2 agonist (SABA) dosage in the preceding year. Clinical outcomes and health care costs were compared between groups for 12 months before and after the switch. Co-primary clinical outcomes were: 1) risk domain asthma control (RDAC) – no asthma-related hospitalization, acute oral steroid use, or lower respiratory tract infection (LRTI); 2) exacerbation rate (American Thoracic Society [ATS] definition) – where exacerbation is asthma-related hospitalization or acute oral steroid use; 3) exacerbation rate (clinical definition) – where exacerbation is ATS exacerbation or LRTI; and 4) overall asthma control (OAC) – RDAC plus average salbutamol-equivalent SABA dosage -200 μg/day. Non-inferiority (at least equivalence) of EH was tested against OH for the four co-primary outcomes in order (hierarchical approach) by comparing the difference in proportions of patients [EH-OH] achieving asthma control or having no exacerbations in the outcome year, using a limit of 10% difference.
Results: Non-inferiority was shown for the EH for all four co-primary outcomes. There were no significant differences between groups for RDAC or exacerbation rates, but EH patients were significantly more likely to achieve OAC (adjusted odds ratio [95% confidence interval]: 1.26 [1.05, 1.52]), as significantly more EH than OH patients had an average SABA dosage of ≤200 µg/day (52% versus 47%, respectively; P-0.001). Mean asthma-related health care costs increased from baseline to outcome years in both groups, but SABA costs increased significantly more in OH than EH patients (mean difference £5.5/patient/year) and consultation costs decreased significantly more in EH than OH patients (mean difference £13.5/patient/year).
Conclusion: Typical asthma patients may be switched from other ICS devices to the Easyhaler®with no reduction in clinical effectiveness or increase in cost.

Keywords: asthma, ICS, inhaler, Easyhaler, cost



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Diagnosis of Asthma in Primary Health Care: A Pilot Study 

Journal of Allergy
Volume 2014 (2014), Article ID 898965, 8 pages
http://dx.doi.org/10.1155/2014/898965
Clinical Study
Karin C. Ringsberg,1,2 Paula Bjärneman,2 Ronny Larsson,3 Elisabeth Wallström,3 and Olle Löwhagen2
1Nordic School of Public Health, 402 42 Gothenburg, Sweden
2Sahlgrenska Academy, University of Gothenburg, 413 90 Gothenburg, Sweden
3Kungsten Health Care Centre, 414 74 Gothenburg, Sweden
Received 6 September 2013; Revised 5 March 2014; Accepted 16 March 2014; Published 10 April 2014
Academic Editor: Steven Nordin
Copyright © 2014 Karin C. Ringsberg 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

Some patients with an asthma diagnosis have a poor controlled asthma. One explanation may be an incorrect diagnosis. Aim. The aim of the study was to diagnose and classify patients with non-infectious lower respiratory tract problems in primary health care using internationally applied diagnostic criteria and diagnostic tests. 
Patients and Methods. New adult patients visiting a primary health care centre due to lower airway problems were included. The diagnostic tests included FEV1, FVC, PEF, two questionnaires, methacholine test, and skin prick test. 
Results. The patients () could be divided into four groups: asthma (28%), asthma-like disorder (44%), idiopathic cough (12%), and a nonreversible bronchial obstructive group (16%). The asthma and asthma-like groups showed similar patterns of airway symptoms and trigger factors, not significantly separated by a special questionnaire. Phlegm, heavy breathing, chest pressure/pain, cough, and wheezing were the most common symptoms. Physical exercise and scents were the dominating trigger factors. 
Conclusions. Nonobstructive asthma-like symptoms seem to be as common as bronchial asthma in primary health care. Due to the similarities in symptoms and trigger factors the study supports the hypothesis that asthma and nonobstructive asthma-like disorders are integrated in the same “asthma syndrome,” including different mechanisms, not only bronchial obstruction.
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