May 30, 2013

Clinical Characteristics and Outcomes of Patients Undergoing Drug Provocation Tests (DPTs)


Clinical Characteristics and Outcomes of Patients Undergoing Drug Provocation Tests (DPTs) 

Meera Thalayasingam, 1 MBBCh (IRE), MRCPCH (UK), FRACP (AUS), Lucy J Davies, 2 , Genevieve V Llanora, 1 MD, Irvin F Gerez, 1 MD,  Hugo P Van Bever, 1,2MD, PhD, Lynette P Shek, 1,2MBBS (Hons), MRCP (UK), MRCPCH (UK) 

Abstract
Introduction: Patients who have an adverse drug reaction are frequently labelled drug allergic without undergoing proper evaluation and confi rmatory testing. These drug allergy labels may be inaccurate, leading to unnecessary lifelong avoidance. The aim of this study was to review the patients that underwent drug provocation tests (DPTs) in our centre and examine the usefulness of DPTs in confirming or rejecting a diagnosis of drug hypersensitivity. 
Materials and Methods: The study design was a retrospective chart review of all adult patients who underwent drug provocation in the allergy unit at the National University Hospital, Singapore, for single or multiple suspected drug allergies from the period January 2009 to June 2011. 
Results: Eighty-seven patients underwent 123 DPTs (median age 41; interquartile range 28 to 50). Twenty-one patients underwent multiple DPTs. The most common culprit drugs reported were antibiotics (43.9%) of which beta-lactams were implicated in 75.9% of the cases. This was followed by non-steroidal anti-infl ammatory drugs (NSAIDS) in 15.4%, paracetamol in 7.3% and both NSAIDs 
and paracetamol in 3.3%. Rash was the most commonly reported symptom (41.5%), followed by angioedema (32.5%), anaphylaxis (9.8%), and other symptoms including respiratory (2.4%), gastrointestinal (0.8%) and others (13.0%). The majority of DPTs were performed to antibiotics (43.9%), NSAIDs (19.5%) and paracetamol (6.5%). DPTs were negative in 93.5% of subjects and positive in 6.5%. Of the 8 positive DPTs, none had a serious reaction, with 5 patients requiring rescue therapy, which comprised solely of oral antihistamines. 
Conclusion: Suspected drug hypersensitivity is common but true drug allergy is rare. DPTs remain the gold standard and should be included as part of an investigative protocol. DPTs are a safe and valuable diagnostic tool in the hands of the experienced clinician.




Global strategies for reducing the burden from asthma


Online first

Inaugural lecture

Global strategies for reducing the burden from asthma 
A report of a lecture given at The University of Edinburgh, Edinburgh, UK, October 1st 2012


*Onno CP van Schayck

Department of General Practice, CAPHRI, Maastricht University; Honorary Professor, Centre for Population Health Services, The University of Edinburgh, UK

Received 21 December 2012 • Accepted 12 April 2013 • Online 24 May 2013


Abstract
Asthma is one of the most important chronic diseases in childhood. For several decades, a steady increase in prevalence has been observed worldwide. In the structural collaboration between the Centre for Population Health Services in Edinburgh and the Research Institute CAPHRI of Maastricht we investigated the possibilities for primary prevention of asthma in childhood. We found that a multifaceted approach might be effective in delaying or preventing asthma, whereas a mono-intervention does not seem to have such a protective effect. The most likely explanation is that the development of a multifactorial disease, such as asthma, is extremely difficult, if not impossible, to prevent by eliminating only one risk factor. Underdiagnosis of asthma is still a big problem in primary care. Most patients do not present bronchial symptoms to the general practitioner, even though they have decreased lung function, so they remain unknown and undiagnosed. However, patients who do present with respiratory problems and who have reduced lung function are not always recognised as such. We found that the perception of dyspnoea seems to determine, at least in part, the presentation to the general practitioner with symptoms. These observations show that both the prevention of the development of asthma in early childhood, as well as case finding of asthma in adulthood, do not seem to be very effective in primary care. More research is needed to clarify what steps can be taken to reduce the global burden from asthma.

Cite as: van Schayck OCP. Global strategies for reducing the burden from asthma. Prim Care Respir J 2013; Available from: URL: http://dx.doi.org/10.4104/pcrj.2013.00052

Keywords
Asthma, global burden, prevalence, diagnosis, prevention, case finding, primary care, research

Corresponding author. Onno CP van Schayck Tel: 0031-433882152 Fax: 0031-433882152 Email: Onno.vanschayck@maastrichtuniversity.nl

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A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water-Damaged Buildings, Mold, and Mycotoxins

The Scientific World Journal
Volume 2013 (2013), Article ID 767482, 20 pages
http://dx.doi.org/10.1155/2013/767482
Review Article

A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water-Damaged Buildings, Mold, and Mycotoxins

Environmental Medicine, 304 W. Los Olivos Street, Santa Barbara, CA 93105, USA
Received 15 January 2013; Accepted 10 February 2013
Academic Editors: O. Aruoma, P. Maček, and J. B.T. Rocha
Copyright © 2013 Janette Hope. 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

Physicians are increasingly being asked to diagnose and treat people made ill by exposure to water-damaged environments, mold, and mycotoxins. In addition to avoidance of further exposure to these environments and to items contaminated by these environments, a number of approaches have been used to help persons affected by exposure to restore their health. Illness results from a combination of factors present in water-damaged indoor environments including, mold spores and hyphal fragments, mycotoxins, bacteria, bacterial endotoxins, and cell wall components as well as other factors. Mechanisms of illness include inflammation, oxidative stress, toxicity, infection, allergy, and irritant effects of exposure. This paper reviews the scientific literature as it relates to commonly used treatments such as glutathione, antioxidants, antifungals, and sequestering agents such as Cholestyramine, charcoal, clay and chlorella, antioxidants, probiotics, and induced sweating.

Ara h 1 CD4+ T cell epitope-based peptides: candidates for a peanut allergy therapeutic

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Ara h 1 CD4+ T cell epitope-based peptides: candidates for a peanut allergy therapeutic

  1. S. R. Prickett1,2
  2. A. L. Voskamp1,2
  3. T. Phan1,2
  4. A. Dacumos-Hill1,2
  5. S. I. Mannering3
  6. J. M. Rolland1,2
  7. R. E. O'Hehir1,2,*
Article first published online: 28 MAY 2013
DOI: 10.1111/cea.12113
Clinical & Experimental Allergy

Clinical & Experimental Allergy

Volume 43Issue 6pages 684–697June 2013

Summary

Background

Peanut allergy is a life-threatening condition; there is currently no cure. While whole allergen extracts are used for specific immunotherapy for many allergies, they can cause severe reactions and even fatalities in peanut allergy.

Objective

To identify short, HLA-degenerate CD4+ T cell epitope-based peptides of the major peanut allergen Ara h 1 that target allergen-specific T cells without causing IgE-mediated inflammatory cell activation, as candidates for safe peanut-specific immunotherapy.

Methods

Ara h 1-specific CD4+ T cell lines (TCL) were generated from peripheral blood mononuclear cells (PBMC) of peanut-allergic subjects using CFSE-based methodology. T cell epitopes were identified using CFSE and thymidine-based proliferation assays. Epitope HLA-restriction was investigated using blocking antibodies, HLA-genotyping and epitope prediction algorithms. Functional peanut-specific IgE reactivity to peptides was assessed by basophil activation assay.

Results

A total of 145 Ara h 1-specific TCL were generated from 18 HLA-diverse peanut-allergic subjects. The TCL recognized 20-mer peptides throughout Ara h 1. Nine 20-mers containing the most frequently recognized epitopes were selected and their recognition confirmed in 18 additional peanut-allergic subjects. Ten core epitopes were mapped within these 20-mers. These were HLA-DQ and/or HLA–DR restricted, with each presented on at least two different HLA-molecules. Seven short (≤ 20 aa) non-basophil-reactive peptides encompassing all core epitopes were designed and validated in peanut-allergic donor PBMC T cell assays.

Conclusions and Clinical Relevance

Short CD4+ T cell epitope-based Ara h 1 peptides were identified as novel candidates for a safe, T cell targeted peanut-specific immunotherapy for HLA-diverse populations.

FSH and TSH in the Regulation of Bone Mass: The Pituitary/Immune/Bone Axis

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 382698, 6 pages
http://dx.doi.org/10.1155/2013/382698
Review Article

FSH and TSH in the Regulation of Bone Mass: The Pituitary/Immune/Bone Axis

Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
Received 1 March 2013; Revised 17 May 2013; Accepted 17 May 2013
Academic Editor: Giacomina Brunetti
Copyright © 2013 Graziana Colaianni 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

Recent evidences have highlighted that the pituitary hormones have profound effects on bone, so that the pituitary-bone axis is now becoming an important issue in the skeletal biology. Here, we discuss the topical evidence about the dysfunction of the pituitary-bone axis that leads to osteoporotic bone loss. We will explore the context of FSH and TSH hormones arguing their direct or indirect role in bone loss. In addition, we will focus on the knowledge that both FSH and TSH have influence on proinflammatory and proosteoclastogenic cytokine expression, such as TNFα and IL-1, underlining the correlation of pituitary-bone axis to the immune system.


Successful treatment of mastocytic anaphylactic episodes with reduction of skin mast cells after anti-IgE therapy

Successful treatment of mastocytic anaphylactic episodes with reduction of skin mast cells after anti-IgE therapy

G. Paraskevopoulos, E. Sifnaios, K. Christodoulopoulos, et al.

Abstract


Mastocytosis is a clonal disease derived from hematopoietic bone marrow progenitor cells. Clinical manifestations of the disease vary greatly depending on tissue involvement. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody licensed in the treatment of asthma with increasing reports of clinical efficiency in other allergic diseases. We describe a case of a patient with mastocytosis responsive clinically and patho-physiologically after anti-IgE treatment.

Keywords


Mastocytosis, omalizumab, mast cell, skin biopsy, treatment, anti-IgE
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A probabilistic model of biological ageing of the lungs for analyzing the effects of smoking, asthma and COPD

Open Access
Research

A probabilistic model of biological ageing of the lungs for analyzing the effects of smoking, asthma and COPD

Silvia ChiappaJohn WinnAna VinuelaHannah Tipney and Timothy David Spector
For all author emails, please log on.
Respiratory Research 2013, 14:60 doi:10.1186/1465-9921-14-60
Published: 30 May 2013

Abstract (provisional)

Background

Although a large body of literature is available that describes the effects of factors such as smoking, asthma and COPD on lung function, characterizations over the entire adulthood and analysis of co-occurrence of factors are still rare due to the high number of measurements required for reliable estimation in current approaches. Such a fragmentation, together with the way the effects are expressed, makes it also often difficult to compare results from multiple studies. Furthermore, current approaches consider one type of measurement only or several types separately.

Methods

We propose a probabilistic model that expresses effects on lung function as number of years added to chronological age or, in other words, that estimates the biological age of the lungs. Using biological age as a measure of the effects has the advantage of facilitating the understanding of their severity and comparison of results. In our model, chronological age and other factors affecting the health status of the lungs generate biological age, which in turn generates lung function measurements. This structure enables the use of multiple types of measurement to obtain a more precise estimate of the effects and parameter sharing for characterization over large age ranges and of co-occurrence of factors with little data. We treat the parameters that model smoking habits and lung diseases as random variables to obtain uncertainty in the estimated effects.

Results

We use the model to investigate the effects of smoking, asthma and COPD on the TwinsUK Registry. We find that combination of smoking with lung disease(s) has higher effect than smoking or lung disease(s) alone. Furthermore, in smokers, co-occurence of asthma and COPD is more detrimental than asthma or COPD alone.

Conclusions

The proposed model or other models based on a similar approach could be of help in improving the understanding of factors affecting lung function by enabling characterizations over large age ranges and of co-occurrence of factors with little data and the use of multiple types of measurement. The software implementing the model can be downloaded at the first author's webpage.

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


May 29, 2013

New Insights into Atopic Dermatitis: Role of Skin Barrier and Immune Dysregulation

 REVIEW ARTICLE
New Insights into Atopic Dermatitis: Role of Skin Barrier and Immune Dysregulation

doi:10.2332/allergolint.13-RAI-0564

Donald YM Leung [About this authors]
ABSTRACT
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is often associated with the development of food allergy and asthma. New insights into AD reveals an important role for structural abnormalities in the epidermis resulting in a leaky epithelial barrier as well as chronic immune activation that contribute to the pathophysiology of this common skin disease. Patients with AD have a predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus (HSV). Measures directed at healing and protecting the skin barrier and controlling the immune activation are needed for effective management of AD. Early intervention may improve outcomes for AD as well as reduce the systemic allergen sensitization that may lead to associated allergic diseases in other organs.
KEY WORDS:
atopic dermatitis, eczema, immune, infection, skin barrier
Received: 27 March 2013.
Allergology International 2013; 2: 151-161

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