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Medical Journal Review

September 2019

WAO Reviews – Editors' Choice

The Editors’ Choice comes to you from Juan Carlos Ivancevich, MD, WAO Web Managing Editor, and summary author, John J. Oppenheimer, MD, FACAAI, FAAAAI, WAO Reviews Editor. They select articles for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases, and whenever possible, for their accessibility to everyone.

Severe exacerbations in moderate-to-severe asthmatics are associated with increased pro-inflammatory and type 1 mediators in sputum and serum
Ghebre MA, Pang PH, Desai D, Hargadon B, Newby C et al.
BMC Pulmonary Medicine 2019; 19(1): 144. doi: 10.1186/s12890-019-0906-7.
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In this study, the authors examined the sputum and serum inflammatory profiles of both adults and children with moderate-to-severe asthma during both stable disease and an exacerbation. From this, they developed receiver-operator characteristic curves (ROC) to identify mediators that distinguish between stable disease and exacerbation events. The mediators that were significantly increased at exacerbations versus stable disease were sputum IL-1β, IL-6, IL-6R, IL-18, CXCL9, CXCL10, CCL5, TNFα, TNF-R1, TNF-R2, and CHTR, and serum CXCL11. The strongest discriminators of an exacerbation in adults – ROC area under the curve (AUC) – were sputum TNF-R2 0.69 (95% CI: 0.60 to 0.78) and IL-6R 0.68 (95% CI: 0.58 to 0.78). Sputum TNF-R2 and IL-6R were also discriminatory in children (ROC AUC 0.85 [95% CI: 0.71 to 0.99] and 0.80 [0.64to 0.96] respectively). The authors conclude that asthma exacerbations are associated with increased pro-inflammatory and Type 1 immune mediators.

Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations
Price DB, Bosnic-Anticevich S, Pavord ID, Roche N, Halpin DMG et al
Clinical and Translational Allergy 2019;9:41. doi: 10.1186/s13601-019-0282-7.
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Price and colleagues evaluated the relationship of blood eosinophil count (BEC) and FeNO both as complementary and independent biomarkers of severe asthma exacerbations, by performing an observational study derived from data of the Optimum Patient Care Research Database. This database was comprised of a population of patients (18–80 years) with valid continuous data for 1 year before FeNO reading, filled ≥1 inhaled corticosteroid prescription, and had a BEC recorded ≤5 years before FeNO reading. They found that the combination of high FeNO and high BEC was associated with significantly increased severe exacerbation rates in the year preceding FeNO reading, suggesting that combining FeNO and BEC measurements may identify asthma patients at risk of exacerbations.

Mobile technology in allergic rhinitis: Evolution in management or revolution in health and care?
Bousquet J, Ansotegui IJ, Anto JM, Arnavielhe S, Bachert C et al
Journal of Allergy and Clinical Immunology: In Practice 2019; published online ahead of print (21 August). doi: 10.1016/j.jaip.2019.07.044.
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In this article, an expert panel examined the role of mobile technology in allergic rhinitis.  They conclude that mHealth  apps represent  an  important evolution in  health  and  care  for  AR  allowing collection of real world evidence  regarding  patients’  behaviors  and  practices.  The authors note that this technology will have a profound impact on future guidelines and care pathways in AR and should be transposable to other chronic illnesses.

Randomized immunotherapy trial in dual-allergic patients using “active allergen placebo” as control
Wagenmann M, Worm M, Akboga Y, Karjalainen M, Hohlfeld JM
Allergy 2019;74(8):1480-1489. doi: 10.1111/all.13842.
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As placebo control in allergen immunotherapy (AIT) trials are plagued by ethical and blinding concerns, Wagenmann and colleagues performed a trial design with an “active allergen placebo,” as proposed by ARIA‐GA2LEN, to investigate in a double‐blind trial the efficacy and safety of AIT in dual‐allergic patients (grass and birch pollen) using active untargeted treatments as controls. To do so, they randomized 95 patients to receive either grass (N = 47) or birch AIT (N = 48) and exposed the subjects to both allergens in an allergen challenge chamber (ACC) before and after 9 months of AIT. Targeted (ACC‐allergen = AIT‐allergen) and untargeted (ACC‐allergen ≠ AIT‐allergen) treatment effects were assessed. They found that AIT significantly reduced the mean (95% confidence interval) area under the curve of total nasal symptom score (targeted effects) by −13.55 (−17.56, −9.54; P < 0.001) after grass and −9.81 (−14.13, −5.50; P < 0.001) after birch AIT. Differences in targeted vs untargeted effects between AIT groups (utility of control group) were statistically significant for both grass (P = 0.02) and birch (P = 0.02) allergens. Targeted vs untargeted differences within‐treatment groups (specificity of ACC measurement) were significant for grass AIT (P < 0.001) but not significant for birch AIT group (P = 0.24). Specific immunoglobulin G4 to both allergens increased significantly (P < 0.001) after targeted treatment, while remaining unchanged for un‐targeted treatments. This study reinforces the specificity of AIT and that untargeted treatment groups could serve as controls in future AIT trials.

A biodiversity hypothesis
Haahtela T
Allergy 2019; 74(8):1445-1456. doi: 10.1111/all.13763.
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This is a very interesting review of the biodiversity hypothesis, which states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. It is known that we are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, air‐ways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. It is believed that adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders, in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. It is feared that loss of immunoprotective factors derived from nature is a new kind of health risk poorly acknowledged until recently. The author stresses that the biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation, and he concludes that natural environments are dependent on planetary health, which should be a priority among health professionals.

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