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Medical Journal Review

August 2016

WAO Reviews - Editors' Choice

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 John J. Oppenheimer, MD - FACAAI - FAAAAI, WAO Reviews Editor. 

1. A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation.

Williams NC, Johnson MA, Shaw DE, Spendlove I, Vulevic J, Sharpe MA, Hunter KA. A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation. British Journal of Nutrition 2016; published online ahead of print, August 3. (doi:10.1017/S0007114516002762).

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As gut microbes have a substantial influence on systemic immune function and allergic sensitization, it is hoped that manipulating the gut microbiome with the use of prebiotics could be a potential strategy to influence the immunopathology of asthma. In this study, Williams and colleagues examined the effect of the prebiotic Bimuno-galactooligosaccharide (B-GOS) supplementation on the surrogate of exercise-induced bronchoconstriction, and airway inflammation hyperpnoea-induced bronchoconstriction (HIB), a. Ten adults with asthma and HIB and eight controls without asthma were randomized to receive 5·5 g/d of either B-GOS or placebo for three weeks separated by a 2-week washout period. The maximal fall in forced expiratory volume in 1 s (FEV1) following eucapnic voluntary hyperpnoea (EVH) defined HIB severity. Also, markers of airway inflammation were measured at baseline and after EVH.

They found that B-GOS supplementation reduced the severity of HIB, and this was accompanied by a reduction in systemic concentrations of TH2-driven inflammatory markers. This suggests that B-GOS, through its impact on the gut microbiota may modulate the underlying immunopathology of asthma, with resultant attenuation of AHR associated with HIB/EIB. The authors reinforce that the precise mechanism(s) by which B-GOS may modulate immune function and reduces airway inflammation remains unclear and warrants further exploration.

2. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life.

Davies ER, Kelly JFC, Howarth PH, Wilson DI, Holgate ST et al. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life. JCI Insight 2016; 1(11): e87632. (doi:10.1172/jci.insight.87632).

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As noted by the authors of this paper, while most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Through the use of a mouse model, Davies and colleagues report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma.

They demonstrated that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and appears to play a role in airway remodeling, independent of inflammation. Confirming this is the fact that remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. They also show that either induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, they demonstrated that sADAM33-induced airway remodeling is reversible, which suggests the therapeutic potential of targeting ADAM33 in asthma.

3. The effect of allergen-specific immunotherapy on offspring.

Bozek A, Jarzab J, Bednarski P. The effect of allergen-specific immunotherapy on offspring. Allergy and Asthma Proceedings 2016; 37(4): 59-63. (doi:10.2500/aap.2016.37.3960).


In light of the rise in the incidence of allergic diseases, there is a need for effective primary prevention of allergies. Bozek and colleagues examined whether those patients (allergic) who underwent allergen-specific immunotherapy (ASIT) had a reduction in the development of allergies in their progeny. A total of 194 children with at least one parent with an allergy who underwent ASIT were compared with control individuals whose allergic parents did not receive ASIT. Their risk of allergy, based on medical history, examination, allergy skin-prick tests, serum total immunoglobulin E and specific immunoglobulin E concentrations was assessed and they found that children of parents who received immunotherapy demonstrated a significant reduction in clinical symptoms of allergic disease. The odds ratios (OR) of any allergic disease and asthma were significantly lower in children with one or both parents with allergy after ASIT compared with the children with parents with allergy and without ASIT: OR 0.73 (95% confidence interval [CI], 0.59–0.86) versus OR 1.85 (95% CI, 1.73–2.2) for any allergic disease and OR 0.63 (95% CI, 0.53– 0.79) versus OR 1.36 (95% CI, 1.22–1.67) for asthma.

4. The path to personalized medicine in asthma.

Bagnasco D, Ferrando M, Bernardi S, Passalacqua G, Canonica GW. The path to personalized medicine in asthma. Expert Review of Respiratory Medicine 2016; published online ahead of print, July 11. (doi:10.1080/17476348.2016.1205490)


With newly available biologic agents, we have been striving to develop a better understanding of the pathophysiological mechanisms, distinguishing asthmatic patients based upon the cellular population that drives the inflammatory process.  As pointed out by the authors this has resulted in a change in asthma intervention from a ‘one size fits all’ therapy to a ‘precision medicine’ model, where physicians can endeavor to prescribe the most appropriate treatment for each patient. Moreover, in the near future, the possibility to intervene with a ‘sequential bio-combination therapy’ is likely, using multiple biologic agents acting through different pathophysiological mechanisms simultaneously in the same patient. 

5. Health-related quality of life in food allergy. Impact, correlates, and predictors.

Galvin AD, Hourihane JOB. Health-related quality of life in food allergy. Impact, correlates, and predictors. Bundesgesundheitsblatt 2016; 59(7): 841-848. (doi:10.1007/s00103-016-2368-x)


In this review, Galvin and Hourihane explore both quantitative and qualitative research findings to provide an in-depth picture of the impact of food allergy on the concerns and the everyday lives of children, teens, adults, as well as their parents. The authors close by examining methodological and design issues in relation to the measurement of health-related quality of life in food allergy and offer recommendations for both research and clinical practice.