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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: July 2008

Reviewed by Dr. Mark Glaum, WAO Guest Editor

1. ASTHMA EXACERBATIONS DURING PREGNANCY INCREASE RISK OF CONGENITAL MALFORMATIONS
Asthma exacerbations are not unusual events during pregnancy. A Canadian cohort of 4344 pregnancies of asthmatic women was examined for evidence of asthma exacerbations during the first trimester. Incidence of congenital malformation at birth and at one year of life was compared in women who experienced asthma exacerbation vs. those who did not. The prevalence of malformations was 12.8% in women who had an exacerbation vs. 8.9% in women who did not. Editor's comment: Aggressive management of asthma and its comorbidities is important in pregnancy as maternal exacerbations appear to increase the risk of congenital malformations. Blais L, Forget A. J Allergy Clin Immunol 2008;121: 1379-84

2. DUST MITE ALLERGEN DIRECTLY STIMULATES DENDRITIC CELLS TO PRIME TOWARD TH2 AND TH17 RESPONSES
Interleukin 6 plays in important role in regulating T helper cell differentiation into Th1, Th2 and Th17 subsets. These investigators studied pathways in dendritic cells that promote IL-6 production. Incubation of murine dendritic cells with either dust mite allergen or cholera toxin directly resulted in increased surface expression c-Kit and its ligand, stem cell factor (SCF). As a result of this expression, IL-6 production was also enhanced. Interruption of dendritic cell c-Kit and IL-6 signaling abrogated Th2 and Th17 lymphocyte responses in airways of allergen-sensitized and challenged mice. Editor's comment: Multiple antigens, including dust mite allergen, directly target dendritic cells through c-Kit and IL-6 expression to promote allergic inflammation. Krishnamoorthy N, Oriss TB, Paglia M, et al. Nat Med 2008; 14: 565-73

3. GRASS POLLEN IMMUNOTHERAPY INDUCES EARLY IL-10 PRODUCTION PRIOR TO EXPRESSION OF IgG4
The aim of this study was to examine the relationship between clinical responsiveness to grass pollen immunotherapy (GIT), regulatory cytokine production and antibody responses to allergen. 18 subjects with severe seasonal allergic rhinitis were randomized to receive injections of grass allergen vaccine or placebo over one year. Subjects' sera were assayed for IL-10, IL-5, IFN-g, allergen-specific IgG4, IgE and IgA. Repeated testing of early and late phase skin responses to intradermal grass allergen was performed. Significant induction of IL-10 and a reduction in late phase skin reactions was observed after only four weeks in the GIT group as compared to placebo. Editor's comment: Grass pollen immunotherapy is associated with early expression of inhibitory cytokines and inhibition of late phase responses. Francis JN, James LK, Paraskevopoulos G, et al. J Allergy Clin Immunol 2008; 121: 1120-5

4. PRESENCE OF RHINOVIRUS IN LOWER AIRWAYS OF ASTHMATICS
Human rhinovirus (HRV) is a common cause of asthma exacerbations. The aim of this study is to determine if patients with stable asthma are more likely to harbor HRV in their bronchi than non-asthmatic controls. HRV was detected in endobronchial biopsies by in situ RT-PCR from 73% of stable asthmatics as compared to 22% of non-asthmatic controls (p<0.001). Asthmatics positive for HRV also demonstrated decreased FEV1, and increased numbers of eosinophils in peripheral blood and bronchial tissue. Editor's comment: Rhinovirus may become a chronic lower airway infection and contribute to the persistence and severity of asthma. Wos M, Sanak M, Soja J, et al. Am J Respir Crit Care Med 2008; 177:1082-9

5. POLYMORPHISMS IN FcεR1 ARE ASSOCIATED WITH ASPIRIN-SENSITIVE URTICARIA AND ATOPY
Chronic urticaria (CU) is a common, bothersome condition that affects a significant portion of the general population. In a Korean cohort, over 35% of CU patients were aspirin-sensitive following blinded oral provocation. Four polymorphisms of the beta and gamma subunits of the FcεR1 were analyzed by genotype and haplotype in 119 aspirin-sensitive CU subjects, 154 aspirin-tolerant CU subjects and 224 healthy controls. Two polymorphisms (one in the beta and one in the gamma subunit) were associated with a higher frequency of atopy (positive skin-prick testing to one or more common aeroallergens) in the aspirin-sensitive CU subjects (p = 0.02 and p = 0.04 respectively) but not in other CU subjects or controls. Editor's comment: Polymorphisms in the FcεR1 receptor may predispose toward certain phenotypes of urticaria and atopy. Palikhe N, Kim S, Yang E, et al. Allergy Asthma Proc 2008; 29: 250-7

6. IDENTIFICATION OF FIVE MAJOR QUANTITATIVE ASTHMA PHENOTYPE FACTORS
Asthma is a heterogeneous disease caused by a complex interaction between genetic and environmental factors. These investigators sought to determine the minimum number of features needed to characterize subjects with asthma focusing on important environmental and genetic contributors. Subjects aged 7-35 years with physician-diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families in the Genetics of Asthma International Network. Five distinct factors identified were baseline pulmonary function, specific allergen sensitization by skin testing, self-reported allergies, symptoms characteristic of rhinitis and symptoms characteristic of asthma. These factors correlated with serum IgE, methacholine PC20 and nocturnal asthma symptoms. Editor's comment: Efforts continue to better define asthma phenotypes. Pillai SD, Tang Y, van den Oord E, et al. Clin Exper Allergy 2008; 38: 421-9

7. MUCOSAL IMMUNE RESPONSE TO LARYNGOPHARYNGEAL REFLUX
Laryngopharyngeal reflux (LPR) is a common problem affecting up to 20% of the general population and is a common cause of chronic cough. This study examines the mucosal immune response to LPR. 12 subjects with previously diagnosed LPR and 11 control subjects underwent laryngeal biopsy. Specimens were examined by quantitative multi-color immunofluorescence microscopy for expression of cell-specific markers for lymphocytes, granulocytes, monocytes, classical and non-classical MHC molecules. An increase in percentage of mucosal area CD8+ lymphocytes but not other cell types was observed in LPR subjects (p<0.005). There was also colocalization of natural killer T cells (NKT) with CD1d in LPR subjects (p<0.01). Editor's comment: The nonclassical MHC molecule CD1d may be involved in the immune response associated with LPR suggesting new potential targets for diagnosis and treatment of this condition. Rees LEN, Laszlo P, Gutowska-Owsiak D, et al. Am J Respir Crit Care Med 2008; 177: 1187-93

8. TREATMENT OF OBSTRUCTIVE SLEEP APNEA REDUCES ELEVATIONS IN SERUM SOLUBLE TUMOR NECROSIS FACTOR-a RECEPTOR-1 (sTNFR-1)
Inflammation may play an important role in the development of cardiovascular complications from obstructive sleep apnea (OSA). The purpose of this study is to examine levels of serum and urinary inflammatory markers, and associate any effect of nasal continuous positive airway pressure (CPAP) on these markers in patients with OSA. 30 subjects with newly diagnosed OSA (AHI 43.8±27.0 h-1) and 15 healthy obese subjects were randomized to receive continuous positive airway pressure (CPAP) or sham CPAP for three months. Urinary levels of norepinephrine and epinephrine as well as plasma soluble tumor necrosis factor-a receptor-1 (sTNFR-1), TNF, IL-6 and leukotriene-B4 (LTB4) levels were obtained at baseline and at three months. Nocturnal urinary levels of norepinephrine, epinephrine, and sTNFR-1 (1053±269 vs. 820±166, pg/ml-1, p=0.032) were higher in OSA patients at baseline, however after three months of effective CPAP usage, only sTNFR-1 levels were significantly reduced (1053±269 vs. 899±254, pg/ml-1, p<0.05). Editor's comment: CPAP reduces one marker of inflammation in OSA. Arias MA, Garcia-Rio A, Alonso-Fernandez A, et al. Eur Respir J 2008; doi:10.1183/09031936.00007008

9. REVIEW OF ASTHMA PATHOGENESIS
This concise review of asthma pathogenesis provides an overview of the inflammatory airway immune response in asthma and discusses individual immunoreactive cell types involved in this process. Concepts of airway remodeling are covered and new approaches for categorizing asthma phenotypes are introduced. Editor's comment: Asthma is a complex "Syndrome of Syndromes." Holgate S. Clin Exp Allergy 2008: 38:872-97

10. EOSINOPHILS IN ALLERGY AND RELATED DISEASES
This entire issue of International Archives of Allergy and Immunology summarizes the work presented at the 19th annual workshop on Eosinophils in Allergy and Related Diseases held in Tokyo on June 30, 2007. Included in the Proceedings are 15 original papers and one review. Editor's comment: An excellent update on eosinophil biology. Makino S, Ishikawa T, Takeshi F, et al. Int Arch Allergy Immunol 2008: 146 (suppl 1):1-92