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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Early achievement and maintenance of stable asthma control using initially higher-dose inhaled corticosteroids as part of combination therapy

 

Drug Design, Development and Therapy

Early achievement and maintenance of stable asthma control using initially higher-dose inhaled corticosteroids as part of combination therapy: an open-label pilot study

Original Research

(658) Total Article Views

Authors: Cheng SL, Wang HC, Kuo SH

Published Date June 2013 Volume 2013:7 Pages 477 - 484

DOI: http://dx.doi.org/10.2147/DDDT.S44231

Received:	19 February 2013
Accepted:	01 May 2013
Published:	17 June 2013

Shih-Lung Cheng,^1–3 Hao-Chien Wang,³ Sow-Hsong Kuo^1
1Department of Internal Medicine, Far Eastern Memorial Hospital, ²Department of Chemical Engineering and Materials Science, Yuan-Ze University, ³Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan

Background: Uncontrolled asthma is characterized by considerable variability. Well controlled asthma is associated with less unplanned use of health care resources and fewer acute exacerbations. In this study, we attempted to increase inhaled corticosteroid (ICS) doses initially in suboptimally controlled asthmatics, hypothesizing that early achievement of asthma control using this strategy would be associated positively with a higher level of stability.
Methods: This was a randomized, open-label, prospective study including patients with uncontrolled asthma who were randomized to receive higher-dose (HD) ICS in combination with a long-acting beta-agonist (LABA) for one month and then shifted to doses suggested in the practice guidelines (GD) or to receive GD therapy alone. Lung function, ie, forced expiratory volume in one second (FEV₁), peak expiratory flow, Asthma Control Test scores, and frequency of acute exacerbations, was followed up for one year.
Results: Seventy-six patients were treated with the HD strategy and 80 with the GD strategy. The increase in FEV₁ from baseline was greater in the HD group than in the GD group, especially during the first month of treatment (304 ± 49 mL versus 148 ± 39 mL, respectively, P = 0.01). Numbers of patients with completely or well controlled asthma were higher in the HD group than in the GD group (92.1% versus 81.1%, respectively, P = 0.03). Further, there was a significant difference between the groups with regard to frequency of acute exacerbations (9.2% in the HD group versus 21.3% in the GD group, P = 0.02); this effect was more pronounced for patients in the HD group with partially controlled or uncontrolled asthma.
Conclusion: Patients receiving HD therapy achieved asthma control more rapidly and maintained greater stability than those receiving GD therapy. This represents a novel strategy for gaining disease control in patients with uncontrolled asthma.

Keywords: asthma, treatment, inhaled corticosteroids, higher doses



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The Clinical Impact of Vitamin D in Children With Atopic Dermatitis

Full Text

Editorial  Open Access

|    Allergy Asthma Immunol Res. 2013 Jul;5(4):179-180. English. Published online 2013 June 26.  http://dx.doi.org/10.4168/aair.2013.5.4.179  Copyright © 2013 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease The Clinical Impact of Vitamin D in Children With Atopic Dermatitis Jae-Won Oh Department of Pediatrics, Hanyang University College of Medicine, Guri, Korea.  Correspondence to: Jae-Won Oh, MD, PhD, Department of Pediatrics, Hanyang University College of Medicine, 153 Gyeongchun-ro, Guri 471-701, Korea. Tel: +82-31-560-2254; Fax: +82-31-552-9493; Email: jaewonoh@hanyang.ac.kr  Received May 27, 2013; Accepted May 27, 2013. 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.

Dan Med J. 2013 Jul;60(7):B4687. Risk factors for developing atopic dermatitis. Carson CG. Source COPSAC (COpenhagen Prospective Studies on Asthma in Childhood), Gentofte University Hospital, Ledreborg Alle 34, 2820 Gentofte, Denmark. c_giwercman@hotmail.com. Abstract The aim of this thesis was to investigate possible risk factors affecting the development of AD. AD is a frequent disease among children and has a substantial impact on the lives of both the child and its family. A better understanding of the disease would enable better treatment, prevention and information to the families involved. Previous risk factor studies have been hampered by an unsuitable study design and/or difficulties in standardization when diagnosing AD, which limit their conclusions. In paper I, we conducted a traditional cross-sectional analysis testing 40 possible risk factors for developing AD at 3 years of age. Our data suggested a strong heredity of AD and confirmed the risk associated with the non-functional FLG allele mutations after adjustments for confounders. Besides this mother's dermatitis and father's allergic rhinitis were found to increase the risk of AD. Perinatal exposure to dog was the only environmental exposure that significantly reduced the disease manifestation, suggesting other, yet unknown environmental factors affecting the increasing prevalence of AD in children. Length at birth was shown to be inversely associated with the risk of later developing AD. This traditional risk factor analysis led to two borderline significant results: duration of exclusive breastfeeding and mother's alcohol intake during the 3rd trimester. Since these possible two risk factors could neither be rejected nor accepted, we decided to do two in-depth studies, further investigating these, using longitudinal data information and data analysis instead of the traditional cross-sectional approach (paper II & III). In paper II, we investigated the risk of developing AD and wheezy symptoms until age 2 years depending on duration of breastfeeding. We found an increased risk of AD, but a protective effect on wheezy disorders in infancy from exclusive breastfeeding. The effect of exclusive breastfeeding on the risk of development of AD was significant after adjustment for demographics, FLG variants R501X and 2282del4 status, parent's AD and pets at home (RR 2.09, 95% CI 1.15-3.80, p=0.016). In addition, there was a significant effect of duration of exclusive breastfeeding (p=0.043), as the relative risk of AD was increased in proportion to increased duration of breastfeeding. The risk associated with exclusive breastfeeding was not explained by the fatty acid composition of mother's milk, though a trend showed higher risk of AD if mother's milk had low concentrations of n-3 fatty acids. In paper III, we found that alcohol intake during pregnancy was associated with a significantly higher risk of developing AD in the offspring, with the effect persisting throughout the whole 7 years follow-up period (HR 1.44, 95% CI 1.05-1.99, p=0.024). The increased risk was still significant after confounder adjustment for mother's education, AD and smoking habits during the 3rd trimester. There was no association between alcohol intake during pregnancy and other atopic endpoints (wheeze episodes, asthma, allergic rhinitis, blood eosinophil count, total IgE, sensitization, cord blood IgE and nasal eosinophilia). However, the underlying explanation was not clear. The thesis is based on data collected as part of the ongoing COPSAC cohort. The cohort is a longitudinal, prospective birth cohort following 411 children born to mothers with asthma. This selection of high-risk children restricts the interpretation of the results and they cannot necessarily be expanded to apply to the general population. PMID:   23809981   [PubMed - in process]  Free full text DAN MED J 2013;60(7):B4687

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Seeking allergy when it hides: which are the best fitting tests?

Review

Seeking allergy when it hides: which are the best fitting tests?

Cristoforo Incorvaia, Nicola Fuiano and Giorgio W Canonica

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World Allergy Organization Journal 2013, 6:11 doi:10.1186/1939-4551-6-11

Published: 1 July 2013

Abstract (provisional)

In the common practice of respiratory allergy, the confirmation by IgE tests of the relationship between the occurrence and duration of symptoms and the exposure to specific inhalant allergens allows an aetiological diagnosis. However, to see patients with suggestive history but negative IgE tests is not rare, and this generally lead to a diagnosis of nonallergic rhinitis or asthma. In many cases, such diagnosis is wrong, because the patient may be revealed as allergic by using additional testing. This is true for local allergic rhinitis, characterized by an exclusive IgE production in the nasal mucosa, that may be correctly diagnosed by performing a nasal IgE measurement or a nasal provocation test with the suspected allergen (s). Another misleading issue is the role of T cell-mediated, delayed hypersensitivity in the pathophysiology of rhinitis and asthma. Recent studies showed that in patients with rhinitis or asthma and negative IgE tests, especially when there is a positive history for current or past atopic dermatitis, the clinical symptoms are actually driven by such mechanism, that may be detected by performing an atopy patch test (APT). The allergen source most frequently responsible for this kind of allergy is the house dust mite, but other allergens may also be involved. Thus, before delivering a diagnosis of nonallergic rhinitis or asthma in patients with negative result to common allergy testing, further tests are needed. To miss the diagnosis of allergy has obvious consequences in terms of management, including allergen avoidance, patient's education, and specific immunotherapy.

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