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Medical Journal Review

September 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.) Early-Life Origins of Chronic Obstructive Pulmonary Disease.

Martinez FD. Early-life Origins of Chronic Obstructive Pulmonary Disease. The New England Journal of Medicine 2016; 375(9): 871-878. (doi:10.1056/NEJMra1603287).


Dr. Martinez provides us with a “must read” review regarding early-life origins of chronic obstructive pulmonary disease. In this review, he examines potential triggers or events that may cause people to develop reduced lung function.  To do so, he explores the impact of the potential role of genetics on lung function, parenteral factors such as exposure to cigarette smoke and preterm birth,  respiratory illness in early life, childhood asthma, air pollution and smoking during adolescence.  As noted by the author, acknowledging and when possible removing these triggers/events may pay great dividends with the reduction in the development of COPD.

2.) Innate immunity and asthma risk in Amish and Hutterite farm children.

Stein MM, Hrusch CL, Gozdz J, Igartua C, Pivniouk V et al. Innate immunity and asthma risk in Amish and Hutterite farm children. The New England Journal of Medicine 2016; 375(5): 411-421. (doi:10.1056/NEJMoa1508749)

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This is an amazing study that explores two US agricultural populations, the Amish and Hutterites. Interestingly, these two populations have very significant differences in childhood asthma prevalence, with the Amish having a prevalence of 5.2% while the Hutterites have a rate of 21.3% despite what appears to be similar agrarian environments. Although their lifestyles are very similar in many respects, their farming practices, are very disparate, with the Amish following traditional farming practices whereas the Hutterites rely upon industrialized farming practices.

To try to understand why this disparity in childhood asthma occurs, the authors explored environmental exposures, genetic ancestry, and immune profiles among 60 Amish and Hutterite children, measuring levels of allergens and endotoxins and assessing the microbiome composition of indoor dust samples. They also collected whole blood to measure serum IgE levels, cytokine responses, gene expression, and peripheral blood leukocytes were phenotyped with flow cytometry. Lastly, they examined the effects of dust extracts obtained from Amish and Hutterite homes on immune and airway responses through the use of a murine model of experimental allergic asthma.

The authors found that despite the similar genetic ancestries and lifestyles of Amish and Hutterite children, the prevalence of asthma and allergic sensitization was indeed four and six times higher in the Hutterite children, while the median endotoxin levels in Amish house dust was 6.8 times higher.  Further, the authors found very striking differences in the proportions, phenotypes, and functions of innate immune cells between the two groups of children. This is exemplified through the mouse model of experimental allergic asthma, in which intranasal instillation of dust extracts from Amish, but not Hutterite homes significantly inhibited airway hyperreactivity and eosinophilia.

In light of these results, the authors conclude that the Amish environment provides protection against asthma by “engaging and shaping the innate immune response”.

3.) Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective

Vickery BP, Berglund JP, Burk CM, Fine JP, Kim EH et al. Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective. Journal of Allergy and Clinical Immunology 2016; published online ahead of print, August 4. (doi: 10.1016/j.jaci.2016.05.027)


In this important study, the authors explored the hypothesis that targeting newly diagnosed young peanut-allergic children would provide the best opportunity to maximize the clinical effectiveness of OIT as an immunomodulatory/disease-modifying treatment by interrupting allergic priming before its full maturation and termed this approach early intervention oral immunotherapy (E-OIT).

To test this hypothesis, they performed a randomized, double-blinded clinical trial of low-dose (300 mg/d) and high-dose (3,000 mg/d) peanut E-OIT among recently diagnosed peanut-allergic children aged 9 to 36 months and compared outcomes to a control group of untreated peanut-allergic children. The primary end-point, sustained unresponsiveness at four weeks after stopping early intervention oral immunotherapy (4-SU), was assessed by double-blinded, placebo-controlled food challenge either upon achieving four pre-specified criteria or after three years of maintenance E-OIT.

Overall, 29 of 37 (78%) in the intent-to-treat analysis achieved 4-SU (300-mg arm, 17 of 20 [85%]; 3000 mg, 12 of 17 [71%], = 0 .43) over a median of 29 months. Per-protocol, the overall proportion achieving 4-SU was 29 of 32 (91%). Furthermore, peanut-specific IgE levels significantly declined in the E-OIT-treated children, who were 19 times more likely to successfully consume dietary peanut than matched standard-care controls, in whom peanut-specific IgE levels significantly increased (relative risk, 19.42; 95% CI, 8.7-43.7; P < .001). The authors conclude that treating peanut-allergic preschool children with OIT is feasible and may enhance long-term outcomes, which means that we may be able to provide some of our peanut allergic patients with some hope. 

4.) Hypersensitivity and immunologic reactions to biologics: opportunities for the allergist.

Khan DA. Hypersensitivity and immunologic reactions to biologics: opportunities for the allergist. Annals of Allergy, Asthma & Immunology 2016; 117(2): 115-120. (doi:10.1016/j.anai.2016.05.013)

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This is a wonderful review article that explores our understanding of both hypersensitivity as well as immune reactions to biologic agents, focusing on Omalizumab and Rituximab.  In this article, Dr. Khan provides a comprehensive commentary concentrating on issues that allergists must grapple within our care of patients receiving these agents.  He even includes potential skin test concentrations and desensitization protocols for those suffering from potential allergic reactions.

5.) Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

Bousquet J, Farrell J, Crooks G, Hellings P, Bel EH et al. Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5). Clinical and Translational Allergy 2016; 6(29). (doi:10.1186/s13601-016-0116-9)

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In light of the growing health and care service demands in Europe as a consequence of expansion of the aging population as well as chronic diseases, the European Commission DG Santé (Directorate General for Health and Food Safety) and DG CNECT (Directorate General for Communications Networks, Content and Technology) launched the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) to enhance European Union competitiveness and to “tackle” societal challenges through research and innovation.  One of the potential fixes is the   development and testing of innovative solutions as well as the implementation of the most successful pilots. As noted by the authors there is presently a multitude of good practices developed throughout the European Union which favor a comprehensive and multi-dimensional scaling-up strategy at European level.

Chronic respiratory diseases including a variety of diseases such as airway diseases (allergic and non-allergic asthma, rhinitis, rhinosinusitis, and COPD, occupational lung diseases, sleep apnoea syndrome, interstitial diseases, pulmonary vascular diseases and genetic diseases such as cystic fibrosis) are the pilot for chronic diseases of the EIP on AHA Action Plan B3. Several effective plans exist in Europe for chronic respiratory diseases, but presently they are rarely deployed to other regions or countries. There is an urgent need for scaling up strategies in order to (1) avoid fragmentation, (2) improve health care delivery across Europe, (3) speed up the implementation of good practices using existing cost-effective success stories and (4) meet the triple win of the EIP on AHA. The scaling up strategy of AIRWAYS ICPs confirms that the proposed strategy of the EIP on AHA is simple and easy to follow; it may be used as a model for the scaling up strategies of other projects of the EIP on AHA.