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Medical Journal Review

April 2016

WAO Reviews - Editors' Choice

1. Effect of avoidance on peanut allergy after early peanut consumption

Du Toit G, Sayre PH, Roberts G, Sever ML, Lawson K et al. Effect of avoidance on peanut allergy after early peanut consumption. New England Journal of Medicine 2016; published online ahead of print, March 4. (doi:10.1056/NEJMoa1514209)

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This is the follow-up study to the initial “LEAP study” which was a randomized trial that investigated the early introduction of peanuts in infants at high risk for allergy and demonstrated a reduced likelihood for the development of peanut allergy. In this follow-up, “LEAP ON” study, the investigators examined whether the rate of peanut allergy remained low after 12 months of peanut avoidance among the participants who had consumed peanuts during the preliminary trial (peanut consumption group), compared with those who had avoided peanuts (peanut avoidance group). The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age. They found that peanut allergy at 72 months was still significantly more prevalent among participants in the peanut-avoidance group compared to those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001).  They further discovered that fewer participants in the peanut-consumption group (vs. the peanut-avoidance group) had higher levels of Ara h2–specific IgE and peanut-specific IgE. In addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio.

2. Component-resolved diagnosis in anaphylaxis

Cardona V, Ansotegui IJ. Component-resolved diagnosis in anaphylaxis. Current Opinion in Allergy & Clinical Immunology 2016; published online ahead of print, March 2. (doi:10.1097/ACI.0000000000000261)


This review examines the utility of component-resolved diagnosis (CRD) in the diagnosis of anaphylaxis.

The authors stress the components associated with genuine sensitization and/or potential severity risk for hymenoptera venom (Api m1, Ves v 1, Ves v 5, and Pol d 5), food allergy (seed storage proteins and nonspecific lipid transfer proteins), cofactor-enhanced food allergy (v-5-gliadine, nonspecific lipid transfer proteins), red meat delayed anaphylaxis (a-gal), latex allergy (Hev b 1, Hev b 3, Hev b 5, and Hev b 6), and Anisakis allergy (Ani s 1, Ani s 4, Ani s 7, and Ani s 13) and compare them to other components which are primary associated with non-clinically relevant sensitizations, cross-reactivity, or mild reactions such as carbohydrate determinants and profilins.

3. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis

Boyle RJ, Ierodiakonou D, Khan T, Chivinge J. Robinson Z et al. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis. BMJ 2016; 352: 972. (doi:10.1136/bmj.i974)

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In this systematic review of the literature, the authors explore whether feeding infants at risk for allergic disease a hydrolysed formula reduces their risk of developing allergy. Using standard criteria, they found 37 eligible intervention trials of hydrolysed formula, which included over 19,000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall, however, there was no consistent evidence that partially or extensively hydrolysed formulas reduce the risk of allergic outcomes in infants at high pre-existing risk. Odds ratios for eczema at age 0-4, compared with standard cows’ milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I2=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I2=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I2=0%) for extensively hydrolysed whey based formula. The authors conclude that current recommendations to use hydrolysed formula in place of standard cows’ milk formula to prevent allergy in infants at high risk should be revised.

4. Novel approaches to the management of noneosinophilic asthma

Thomson NC. Novel approaches to the management of noneosinophilic asthma. Therapeutic Advances in Respiratory Disease 2016; published online ahead of print, February 28. (doi:10.1177/1753465816632638)


This is a wonderful review of non-eosinophilic asthma. This is an important asthmatic phenotype, it occurs in approximately 50% of adult asthmatic patients and is often the inflammatory cell type seen in the most severe asthmatics. In this article, the author’s main goal is to examine the targets for therapy in asthma for this subgroup by assessing clinical trials of licensed drugs, novel small molecules and biologic agents in non-eosinophilic inflammation. Looking for new compounds in this group of asthmatics is of great importance, as our present armamentarium is of reduced efficacy in the non-eosinophilic subgroup. The authors highlight that neutrophilia in asthma may be a consequence of use of corticosteroids, associated chronic pulmonary infection, smoking, altered airway microbiome or delayed neutrophil apoptosis. Further, the cause of poorly controlled non-eosinophilic asthma may differ between patients and involves several mechanisms including neutrophilic inflammation, T helper 2 (Th2)-low or other subtypes of airway inflammation or corticosteroid insensitivity as well as non-inflammatory pathways such as airway hyperreactivity and remodelling. The authors comprehensively review therapeutic options, including: macrolide antibiotics, low-dose theophylline, interleukin-17 and tumor necrosis factor TNF-α inhibitors. They also examine promising mechanistic approaches such as peroxisome proliferator-activated receptor gamma agonists and novel small molecules such as: chemokine receptor 2 antagonists, inhaled phosphodiesterase 4 inhibitors, dual PDE3 and PDE4 inhibitors, mitogen-activated protein kinase inhibitors, tyrosine kinase inhibitors and phosphoinositide 3 kinase inhibitors. In light of the importance of this subgroup of asthmatics, this review is a must read. 

5. Paving the way of systems biology and precision medicine in allergic diseases: The MeDALL success story

Bousquet J, Anto JM, Akdis M, Auffray C, Keil T et al. Paving the way of systems biology and precision medicine in allergic diseases: The MeDALL success story. Allergy 2016; published online ahead of print, March 10. (doi:10.1111/all.12880)


As noted in the introduction of this paper, allergic diseases such as asthma, rhinitis, and eczema are complex and associated with both allergen specific IgE and non-allergic mechanisms that often coexist in the same patient and are the consequence of multifactorial factors, including both genetic, life-style, and environmental components. These interactions start early in life, develop during infancy and childhood and may persist throughout life. In essence, allergic diseases are not separate diseases but are likely linked by complex and insufficiently defined interrelationships across the life cycle. To better understand this process the authors applied a systems approach proposed in systems biology to aid in understanding complex chronic diseases. The Mechanisms of the Development of ALLergy (MeDALL) proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: precisely phenotyped children followed in 14 birth cohorts throughout Europe were combined with systems biology (omics, IgE measurement using micro-arrays) and environmental data. Through this analysis, they found that multi-morbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitisation. IgE sensitisation should be considered differently in mono and polysensitized individuals. Further findings included that allergic multi-morbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The authors conclude that integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve our understanding of the genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Certainly much more is to come from this approach.