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Archives: Medical Journal Reviews

WAO Reviews - Editors' Choice

Posted: October 2012

Articles are selected for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases by Juan Carlos Ivancevich, MD, WAO Web Editor-in-Chief, and Phillip Lieberman, MD, WAO Reviews Editor.

1. The Severe Asthma Research Program (SARP) simplified algorithm to define five phenotypically distinct asthma clusters in a separate and diverse urban asthma population

Patrawalla P, Kazeros A, Rogers L, Shao Y, Liuet M et al. Application of the Asthma Phenotype Algorithm from the Severe Asthma Research Program to an urban population. PLoS ONE 2012; 7(9): e44540. doi:10.1371/journal.pone.0044540

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Editor's comment: The authors applied a simplified SARP algorithm to a diverse population of adult asthmatics recruited from the urban area of New York City. In doing so, they identified five distinct phenotypic groups similar to those originally described using the more detailed SARP algorithm. They concluded that these results support the use of the simplified SARP algorithm for classification of asthma phenotypes in future prospective studies designed to investigate treatment and outcome differences between these distinct groups.

2. Evidence confirming the therapeutic efficacy of systemic and targeted therapies in eosinophilic, high TH2 asthma

Ingram JL, Kraft M. IL-13 in asthma and allergic disease: Asthma phenotypes and targeted therapies. The Journal of Allergy and Clinical Immunology 2012; 130(4): 829-842. doi:10.1016/j.jaci.2012.06.034

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Editor's comment: This is an excellent comprehensive review of our current knowledge of the clinical and genetic heterogeneity of asthma. It discusses emerging phenotypes and subtypes, biomarker diagnostics, and the potential response to targeted therapy in well-characterized asthma phenotypes.

3. Tryptase would not be an optimal marker for the diagnosis of anaphylaxis

Sala-Cunill A, Cardona V, Labrador-Horrillo M, Luengoa O, Esteso O et al. Usefulness and limitations of sequential serum tryptase for the diagnosis of anaphylaxis in 102 patients. International Archives of Allergy and Immunology 2012; 160:192-199. doi:10.1159/000339749

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Editor's comment: The authors conducted an observational prospective study of cases of anaphylaxis by measuring sequential serum tryptase concentrations during anaphylactic events in order to evaluate the potential of serial determinations as a diagnostic marker. They concluded that tryptase is not an optimal marker for the diagnosis of anaphylaxis, since although the concentration of tryptase correlates with severity; levels are not increased in a considerable number of patients during acute anaphylaxis.

4. Complement activation in patients with urticaria and angioedema and autoimmune thyroid disease

Kirkpatrick CH. A mechanism for urticaria/angioedema in patients with thyroid disease. The Journal of Allergy and Clinical Immunology 2012;130(4): 988-990. doi:10.1016/j.jaci.2012.05.017

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Editor's comment: The author proposes that activation of complement by the complement controller domain of thyroperoxidase is an important contributor to the development of urticaria and angioedema in patients with thyroid autoimmunity and might be an amplification process responsible for a prolonged duration of symptoms.

5. Genome-Wide Association (GWA) studies of population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma

Ramasamy A, Kuokkanen M, Vedantam S, Gajdos ZK, Alves AC et al. Genome-Wide Association Studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA. PLoS ONE 2012; 7(9): e44008. doi:10.1371/journal.pone.0044008

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Editor's comment: The authors test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. They also present the first comprehensive search for genetic interactions with smoking status and hay fever. Finally, they provide evidence for several new genome-wide significant associations with asthma: one novel signal where there was prior suggestive evidence of association (RORA), one independent novel signal at a previously associated locus (the HLA region), and one previously associated locus with multiple independent signals (IL1RL1/IL18R1).

6. Evidence related to irritative agents causing occupational asthma or occupational COPD

Baur X, Bakehe P and Vellguth H. Bronchial asthma and COPD due to irritants in the workplace - an evidence-based approach. Journal of Occupational Medicine and Toxicology 2012; 7(1):19. doi:10.1186/1745-6673-7-19

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Editor's comment: The strongest evidence of association was found for 17 agents or work-sites, including: benzene-1,2,4-tricarboxylicacid-1,2-anhydride, chlorine, platinum salt, isocyanates, cement dust, grain dust, animal farming, environmental tobacco smoke, welding fumes or construction work. Phthalic anhydride, glutaraldehyde, sulphur dioxide, cotton dust, cleaning agents, potrooms, farming, and foundries were found to be moderately associated with occupational asthma or occupational COPD. A search for of additional occupational irritants that may cause airway disorders will be very important for diagnostics and preventive measures.

7. Cow's milk allergy (CMA) as the most common cause of recurrent perianal inflammation in infants

El-Hodhod MAA, Hamdy AM, El-Deeb M, Elmaraghy MO. Cow's milk allergy is a major contributor in recurrent perianal dermatitis of infants. ISRN Pediatrics 2012; 2012(408769). doi:10.5402/2012/408769

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Editor's comment: In a follow up clinical study the authors found that causes of perianal dermatitis in infants included CMA, bacterial dermatitis, moniliasis, enterobiasis and lactose intolerance. The presence of bloody and/or mucoid stools, other atopic manifestations, anal fissures, or recurrent vomiting, are associated with CMA as an etiology.

8. Allergen-specific immunotherapy (ASIT) with aluminium-precipitated antigen extract was not shown to be a risk factor for contact allergy to aluminium

Netterlid E, Hindsén M, Siemund I, Björk J, Werner S et al. Does allergen-specific immunotherapy induce contact allergy to aluminium? Acta Dermato Venereologica 2012; 92: Accepted 26 March 2012; Published online before print. doi:10.2340/00015555-1409

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Editor's comment: The main aim of this study was to investigate whether ASIT with allergen preparations containing aluminium hydroxide would induce contact allergy to aluminium: the authors found a high proportion of contact allergy to aluminium in atopic patients with allergic rhinitis and asthma, but it did not demonstrate nor exclude that ASIT is a risk factor for induction of aluminium allergy.

9. Dysfunctional breathing (DB) is not infrequent in asthma patients

Agache IO, Ciobanu CM, Paul G, Rogozea L. Dysfunctional breathing phenotype in adults with asthma - incidence and risk factors. Clinical and Translational Allergy 2012; 2(18). doi:10.1186/2045-7022-2-18

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Editor's comment: The authors screened for the DB phenotype in adults with asthma using the Nijmegen questionnaire and confirmed the presence of DB by progressive exercise testing. They found that independent risk factors for DB were psychopathology, the frequent exacerbator asthma phenotype and uncontrolled asthma. Asthma medication (ICS, LABA or LTRA) had no significant relation with dysfunctional breathing. Finally, they suggest that DB should be evaluated in asthma patients presenting with psychopathology, frequent severe asthma exacerbations or uncontrolled asthma.

10. Factors determining the health-related quality of life in patients with asthma according to the EuroQol-5D questionnaire

Gonzalez-Barcala FJ, De la Fuente R, Tafalla M, Nuevo J. Caamano-Isorna F. Factors associated with health-related quality of life in adults with asthma. A cross-sectional study. Multidisciplinary Respiratory Medicine 2012; 7(32) doi:10.1186/2049-6958-7-32

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Editor's comment: The authors found that advanced age, lower educational level and poor control of asthma showed a considerable detrimental effect on the HRQoL of asthmatics and were significantly associated with a worse quality of life in all the dimensions assessed by the EQ-5D scale. The baseline severity of asthma and being admitted to the hospital were related to a worse quality of life in 5 of the 6 dimensions analyzed.

11. The relationship between asthma and obesity in epidemiological studies depends on the definition adopted

Cetlin AA, Gutierrez MR, Bettiol H, Barbieri MA, Vianna EO. Influence of asthma definition on the asthma-obesity relationship. BMC Public Health 2012; 12:844. doi:1186/1471-2458-12-844

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Editor's comment: This cross-sectional study investigated the influence of the definition of asthma employed on the asthma-obesity association. It added evidence to the asthma-obesity relationship because the authors tested this association with two definitions: bronchial hyperresponsiveness-confirmed asthma and physician-diagnosed asthma. They concluded that further studies are necessary to establish the diagnosis of asthma that is truly associated with obesity.

12. A bitter taste receptor polymorphism underlies susceptibility to upper respiratory infection

Lee RJ, Xiong G, Kofonow JM, Chen B, Lysenko A et al. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. The Journal of Clinical Investigation 2012; doi:10.1172/JCI64240

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Editor's comment: The authors concluded that the bitter taste receptor, T2R38, genotype regulates mucosal respiratory innate defense. Their data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection. These data provide motivation to conduct a clinical trial to prospectively define the clinical course of patients with various T2R38 genotypes.

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