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Medical Journal Review

August 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.

Country-wide medical records infer increased allergy risk of gastric acid inhibition
Jordakieva G, Kundi M, Untersmayr E, Pali-Scholl I, Reichardt B, Jensen-Jarolim E
Nature Communications 2019;10(1):3298. doi: 10.1038/s41467-019-10914-6.
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In this epidemiologic study by Jordakieva and colleagues, the authors report a relationship between gastric acid-suppression and the development of allergic symptoms. Previous animal studies have demonstrated that gastric acid suppression promotes allergy in mechanistic experiments and observational human studies, but whether gastric acid inhibitors increase allergy incidence at a population level had not previously been studied. Thus, the authors examined the use of anti-allergic medication following prescription of gastric acid inhibitors through analysis of data from health insurance records covering 97% of the Austrian population between 2009 and 2013 on prescriptions of gastric acid inhibitors, anti-allergic drugs, or other commonly prescribed (lipid-modifying and antihypertensive) drugs as a control. They found that rate ratios for anti-allergic drugs following gastric acid-inhibiting drug prescriptions are 1.96 (95%CI:1.95–1.97) in the overall Austrian dataset. Furthermore, this association was more significant in women, and it occurred in all assessed gastric acid-inhibiting substances. Finally, the ratios increased from 1.47 (95%CI:1.45–1.49) in subjects <20 years, to 5.20 (95%-CI:5.15–5.25) in> 60 year olds.

Home environment: respiratory and allergic phenotypes from birth to age six in the PELAGIE cohort
Apel K, Costet N, Chapron A, Cordier S, Monfort C et al.
NPJ Primary Care and Respiratory Medicine 2019;29(1):29. doi: 10.1038/s41533-019-0141-y.
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In this study by Apel and colleagues, the authors explored respiratory and allergic phenotypes from birth to 6 years of age, focusing on environmental determinants. Data on respiratory and allergic health outcomes and domestic environmental exposure were collected for 935 mother-infant pairs from a longitudinal mother-child cohort based on mothers, included before 19 weeks of gestation in Brittany between 2002 and 2006. Information was obtained by self-administered questionnaires completed by parents at inclusion, delivery, and when the child was 2 and 6 years old. Kml3D clustering was used to describe profiles of children who shared similar trajectories of symptoms as phenotypes, and association with environmental determinants was estimated by polytomous logistic regression. The investigators found 5 phenotypes: a reference group characterized by low symptom levels (31.1%), a transient cough phenotype (36.5%), an eczema/cough phenotype (12.3%), a wheeze/cough phenotype (11.8%), and a mixed phenotype (8.0%). The wheeze/cough profile was associated with postnatal exposure to glues used in renovation activities (aOR 2.3 [1.2–4.7]), and the mixed phenotype with postnatal exposure to paint (aOR 2.1 [1–4.5]). The authors note that several of the exposures associated with respiratory/allergic phenotypes observed in this study are avoidable, and if their findings are confirmed by further research, home-based environmental counseling could be a possible prevention target.

Cough rhythms in asthma: Potential implication for management
Lodhi S, Smith JA, Satia I, Holt KJ, Maidstone RJ, Durrington HJ
JACI: In Practice 2019;7(6):2024-2027. doi: 10.1016/j.jaip.2018.12.020.
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It is well known that increasing nocturnal cough signals worsening asthma and treatment escalation. In this study Lodhi and colleagues analyzed hourly cough frequency data in adults with mild/moderate asthma recorded over 24 hours using the VitaloJAK cough monitor and compared this data with that found in healthy controls. Data from 92 individuals with asthma and 44 healthy participants were analyzed. Both groups were well matched for sex, body mass index, and smoking pack-years.  Participants with asthma were significantly younger (23 years [21-27] compared with 38 years [29-51]) and had a lower percent predicted FEV1. Participants with asthma had significantly greater cough frequency than healthy participants over 24 hours (27 [12-67] vs 3.5[1-19.75] coughs/24 h respectively; P<.0001). Analysis of hourly cough frequency data revealed a similar shaped graph for both healthy individuals and patients with asthma, with significantly more coughs occurring during the day than at night in both groups (P<.0006 healthy; P<.0001 asthma).

Those with nocturnal cough were more likely to use an inhaled corticosteroid (ICS) (P=.02) as well as higher daily doses of ICS (P=.02). Univariate logistic regression analysis found that nocturnal cough was associated with higher odds of ICS use (odds ratio [OR], 2.87;95% CI, 1.17-7.00;P=.021) and daily ICS dose (OR, 1.00;95% CI, 1.00-1.01;P=.042). Multivariate logistic regression analysis confirmed the significance of daily ICS dose (OR, 1.00;95% CI, 1.00-1.01;P=.031). Overall, this indicates that patients with asthma with nocturnal cough use more frequent and increased doses of ICS and have poorer asthma control. Despite this escalated therapy, these patients are still coughing, implying that currently used asthma treatments may not be effective in treating the component of cough. This is an important finding, as commonly used asthma symptom questionnaires place emphasis on nocturnal symptoms as a marker of worsening asthma and often lead to escalation in ICS, yet this therapy may not be effective in controlling the underlying cough symptom.

Promoting trust between patients and physicians in the era of artificial intelligence
Nundy S, Montgomery T, Wachter RM
JAMA 2019; published online ahead of print (15 July). doi: 10.1001/jama.2018.20563.
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The authors of this JAMA “viewpoint” note that health care artificial intelligence (AI) holds enormous potential to transform the health care system. This includes not only how patients access care but also how physicians and patients make decisions. Health care AI is likely to affect relationships between physicians and patients, but it need not automatically erode trust between them. The authors stress that by reaffirming the foundational importance of trust to health outcomes and engaging in deliberate system transformation, the benefits of AI could be achieved while strengthening patient-physician relationships.

Eosinophilic disorders: Evaluation of current classification and diagnostic criteria, proposal of a practical diagnostic algorithm
Leru PM
Clinical and Translational Allergy 2019;9:36. doi: 10.1186/s13601-019-0277-4.
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Interest in eosinophilic disorders has increased during the last two decades, with great progress being made regarding our understanding of molecular mechanisms, refining diagnostic criteria, classification and evaluation of therapeutic options. Despite these gains, there are still many gaps and difficulties in evaluating eosinophilic syndromes and diseases in medical practice. The disease prognosis depends mainly on the cause and mechanism of eosinophilia, severity of organ dysfunction, and accurate diagnosis and response to treatment. Besides primary hypereosinophilic syndromes and secondary or reactive eosinophilias, many associated or idiopathic forms have been described, making this topic extremely complex. An important aim in our field is for experts to agree upon a clear and practically useful classification as well as a better characterization of various phenotypes and endotypes of eosinophilic diseases, and to identify novel biomarkers and more effective therapies. In this review Leru explores the recent data regarding definition, classification, and diagnosis criteria of eosinophilic diseases and proposes a revised and updated diagnostic algorithm.