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World Allergy Organization
WAO's mission: To be a global resource and advocate in the field of allergy, advancing excellence in clinical care through education, research and training as a world-wide alliance of allergy and clinical immunology societies.

Medical Journal Review

Posted: October 2009

Reviewed by Juan Carlos Ivancevich, MD, in collaboration with Richard Lockey, MD, WAO Web Editor-in-Chief.

1. EAACI/GA²LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria
This guideline, together with its sister guideline on the classification of urticaria, is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, a joint initiative of the European Academy of Allergy Asthma and Immunology (EAACI), the EU-funded network of excellence, GA²LEN, the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). Urticaria has a profound impact on the quality of life; therefore, effective treatment is required. The recommended first line treatment is new generation, non-sedating H1-antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase, second-line therapies, such as corticosteroids, cyclosporin, omalizumab or phototherapy, should be added to the antihistamine regimen. For second-line therapy, costs and risk/benefit are important to consider. Corticosteroids are not recommended for long-term treatment due to their serious adverse effects.
Editor's comment: This guideline is a review of the available literature on the subject of urticaria.
Zuberbier T et al., EAACI/GA²LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy. 2009;64(10):1417-1426.

2. Recommendations for appropriate sublingual immunotherapy (SLIT) clinical trials
Sublingual Immunotherapy (SLIT) is gaining widespread attention as an alternative to subcutaneous immunotherapy the treatment of allergic rhinoconjunctivitis. In addition, SLIT has been studied in other allergic disorders including asthma. However, a review of published studies indicates that there are deficiencies and considerable heterogeneity in both design and data interpretation of SLIT studies. These have made it difficult to assess the appropriate place of SLIT in guidelines for the therapy of allergic diseases. Moreover, several unpublished SLIT studies in the United States failed to meet primary endpoints. This article reviews data from SLIT trials and makes recommendations about appropriate designs of future SLIT studies. It is hoped that these recommendations will result in more adequately designed SLIT trials to facilitate the appropriate placement of this therapy to treat patients with other allergic diseases.
Editor's comment: This article should help design optimal studies to assess efficacy and safety of SLIT.
Casale TB et al., Recommendations for appropriate sublingual immunotherapy clinical trials. J Allergy Clin Immunol. 2009;124(4):665-670

3. Budesonide/formoterol (B/F) maintenance and reliever (M-R) therapy versus conventional best practice
Budesonide/formoterol (B/F) maintenance and reliever (M-R) therapy reduces asthma exacerbations and symptoms versus fixed-dose regimens plus short-acting β2-agonists (SABA) in double-blind trials. Information is lacking regarding its effectiveness versus conventional best practice (CBP). The authors conducted a pooled analysis of six, 6-month, randomized, open-label studies examining asthma control and exacerbation risk in asthmatics (aged≥12 years). Patients (N = 7855) symptomatic on inhaled corticosteroids (ICS) or stable/symptomatic on ICS/long-acting β2-agonists (LABA) received B/F M-R therapy (160/4.5 µg bid and as needed) or CBP (ICS or ICS/LABA ± other agents at an approved dose plus as-needed SABA). Overall asthma control was assessed comparing the incidence of exacerbations and levels of asthma control using the asthma control questionnaire (ACQ). B/F M-R therapy did not significantly reduce time to first severe exacerbation (primary variable) versus CBP. However, patients experienced 15% fewer exacerbations and used 27% less ICS.
Editor's comment: B/F M-R therapy can improve key aspects of asthma control versus physicians' choice of CBP.
Demoly P et al., Budesonide/formoterol maintenance and reliever therapy versus conventional best practice, Respiratory Medicine. 2009;103(11):1623-1632.

4. Study finds early daycare is no protection against asthma or atopy at 8 years
The authors prospectively studied 3,963 newborn children for 8 years, assessing daycare use and respiratory health by questionnaires, the association with older siblings with asthma symptoms, airway responsiveness, and allergic sensitization. They were interested in studying if daycare exposure defined as early (age 0-2 yr), late (age 2-4 yr), or none (no daycare before age 4 yr) prevents the development of asthma and allergy. Children with early daycare had more wheezing for their first years of life, but they had less wheezing and glucocorticoid use between 4 and 8 years of age. At 8 years of age, early daycare was not protective for asthma symptoms, allergic sensitization or airway hyperresponsiveness.
Editor's comment: These findings add further doubts about the hygiene hypothesis and the development of asthma and allergy.
Caudri D et al., Early daycare is associated with an increase in airway symptoms in early childhood but is no protection against asthma or atopy at 8 years, Am J Respir Crit Care Med. 2009;180(6):491-498.

5. The LOCAL Study, predictive value of local reactions in allergen immunotherapy
A retrospective analysis of an electronic immunotherapy database was performed over a 12-month period at a site that did not adjust doses for local reactions (LRs) to determine whether a LR predicts a subsequent LR. The authors recorded total injections, small LRs, large local reactions (LLRs), systemic reactions, and whether a LR was followed by another LR. 360 patients received a total of 9678 injections. 78.3% had at least 1 LR, and 7.5% had an LLR. The total LR rate was 16.3% (1574/9678); the small local reaction was 15.9% (1536/9678); and the LLR was 0.4% (38/9678). Of all the LRs followed by another injection, 27.2% were followed by another LR. The sensitivity and positive predictive value for a LR predicting a LR at the next injection were 26.2% and 27.2%, respectively.
Editor's comment: LRs do not necessarily predict a LR at the next injection.
Calabria CW et al., The LOCAL Study: Local reactions do not predict local reactions in allergen immunotherapy, J Allergy Clin Immunol, 2009;124(4):739-744.

6. Impact of chlorinated swimming pool exposure on adolescent respiratory health
The authors examined 847 students, 13-18 years, who had utilized chlorinated pools in order to estimate the association of allergic diseases with chlorinated pool exposure. Of them, 114 had utilized a non-chlorinated pool and served as controls. They measured total and specific immunoglobulin E (IgE) and screened for exercise-induced bronchoconstriction. Outcomes were respiratory symptoms, allergic rhinitis, and asthma diagnosed at any time (during lifetime) or treated with medication and/or associated with exercise-induced bronchoconstriction (asthma presently). Among atopics, asthma symptoms and asthma during lifetime or current asthma increased with the number of hours spent in chlorinated pools, with a greater risk of allergic rhinitis. Such associations were not found among adolescents without atopy or with non-chlorinated pool use.
Editor's comment: Chlorinated pool exposure contributes to the burden of asthma and respiratory allergies among adolescents.
Bernard A et al., Impact of chlorinated swimming pool attendance on the respiratory health of adolescents, Pediatrics, 2009;124(4);1110-1118.

7. In vitro basophil activation and aspirin-exacerbated respiratory disease (AERD)
Cytokine secretion and increased expression of surface activation markers were studied to make a comprehensive analysis of basophil responses to aspirin in aspirin-exacerbated respiratory disease (AERD). The authors studied the in vitro effects of aspirin on the concurrent release of histamine, leukotriene C4 (LTC4) and IL-4 and evaluated changes in surface activation markers (CD63, CD69 and CD203c) using basophil-enriched cell suspensions from 10 patients with AERD and 10 healthy volunteers. Aspirin-induced expression of CD63, CD69 and CD203c yielded 30%, 80% and 70% sensitivity, respectively, with poor specificity. There was no significant difference in LTC4 synthesis. None of the patients released IL-4. A high dose of aspirin, 5 mg/mL, had non-specific effects on basophils.
Editor's comment: Evaluation of in vitro basophil activation has no clinical value in identifying AERD.
Çelik GE et al., Effect of in vitro aspirin stimulation on basophils in patients with aspirin-exacerbated respiratory disease, Clin Exp Allergy, 2009;39(10):1522-1531.

8. United airways study shows chronic rhinosinusitis impact on quality of life in patients with bronchiectasis
Patients with bronchiectasis (B) (n = 80) were evaluated for chronic rhinosinusitis (CRS) and nasal polyps (NP) using EP³OS (European Position Paper on Rhinosinusitis and Nasal Polyps) criteria, and severity of B using chest HRCT-scans (high resolution computed tomography) in a prospective study. Quality of Life (QoL) was assessed by using specific questionnaires [Sinonasal Outcome Test-20 (SNOT-20), St George Respiratory Questionnaire (SGRQ)], and generic (Short Form-36; SF-36). Patients with CRS with or without polyps had worse QoL than those without, and the authors found correlations between all questionnaires and with forced expiratory volume in 1 s. These results suggest that CRS, with or without nasal polyps, has a considerable impact on the QoL of patients with B.
Editor's comment: These findings reinforce the concept of united airways.
Guilemany JM et al., United airways: the impact of chronic rhinosinusitis and nasal polyps in bronchiectasic patient's quality of life, Allergy, 2009:64(10);1524-1529.

9. Administration of influenza vaccine in children allergic to egg
The authors identified articles about influenza vaccine in children allergic to eggs using PubMed and the search terms "influenza" and "egg allergy". Additional references were utilized. Most evidence about this subject was obtained from two randomized clinical trials and from small case series. The authors recommend that egg-free, mammalian culture-based flu vaccines should be given preferentially to individuals allergic to egg. If an egg-free vaccine is not available, only vaccines with a stated maximum egg content of < 1.2 µg/ml (0.6 µg per dose) should be utilized. If an egg-based vaccine is utilized for an individual with egg allergy, it should be administered in a center experienced and prepared to manage anaphylaxis. A single dose protocol is recommended for those with a history of allergy, whereas a two dose, split protocol is recommended for those with a history of anaphylaxis to egg or those with moderate or uncontrolled asthma.
Editor's comment: This paper contains important information in view of the influenza A pandemic.
Erlewyn-Lajeunesse M et al., Recommendations for the administration of influenza vaccine in children allergic to egg, BMJ, 2009;339:b3680.

10. Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis.
To determine the chemokine receptor (CCR) pattern of epidermal dendritic cells (DC) subtypes and chemokine ligands (CCL) expression in relation to the state of atopic dermatitis (AD), the authors obtained shave biopsy specimens from patients with AD before and after 24 and 72 hours of atopy patch testing and from patients with chronic AD, psoriasis and healthy skin to determine the CCR pattern of epidermal dendritic cells (DC) subtypes and CCL expression in relation to the severity of AD. CCR expression of epidermal DCs was studied and chemokine mRNA levels in the skin quantified. The total number of CD1a(+) epidermal DCs increased and the proportion of Langerin-positive CD1a(+) DCs decreased whereas the percentage of Langerin-negative CD1a(+) DCs increased after allergen application. Expression of CCL1, CCL3, CCL4, and CCL11 mRNA were greater in acute versus chronic AD.
Editor's comment: Expression of CCR5 and CCR6 of Langerin-negative CD1a(+) DCs was characteristic for acute AD.
Gros E et al., Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis, J Allergy Clin Immunol, 2009;124(4):753-760.