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Medical Journal Review

November 2018

WAO Reviews – Editors' Choice

The Editors select articles for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases, and whenever possible they seek articles that everyone can access freely. 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.

MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world evidence
Bousquet J, Arnavielhe S, Bedbrook A, Bewick M, Laune D et al
Clinical and Translational Allergy 2018; 8:45. DOI:10.1186/s13601-018-0227-6. eCollection 2018.

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With the rise in mHealth (apps running on mobile smart devices), these authors have advanced the ARIA guidelines to a care pathways approach suited to real-life using mobile technology in allergic rhinitis and asthma by developing the Mobile Airways Sentinel networK (MASK) as a novel tool to obtain real-life data regarding rhinitis and asthma multi-morbidity and to help patients and physicians to improve shared decision making. Through their initial study they have demonstrated that MASK can be used for multiple purposes, in a friendly manner, in order to improve the control of allergic diseases in a cost-effective approach. Further research using this tool is planned.

Estimates of the global burden of ambient PM 2.5, ozone, and NO2 on asthma incidence and emergency room visits
Anenberg SC, Henze DK, Tinney V, Kinney PL, Raich W et al
Environmental Health Perspectives 2018; 126(10): 107004. DOI:10.1289/EHP3766

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It long has been known that ambient air pollution exacerbates asthma among populations and may also contribute to new-onset asthma. In this study Anenberg and colleagues relied upon epidemiological studies to examine associations between air pollutants and both asthma exacerbation and incident asthma to estimate the number of asthma emergency room visits and new onset asthma cases globally attributable to fine particulate matter (PM2:5), ozone, and nitrogen dioxide (NO2) concentrations. Through their analysis they estimated that 9-23 million and 5-10 million annual asthma emergency room visits globally in 2015 could be attributable to ozone and PM2:5, respectively, representing 8-20% and 4-9% of the annual number of global visits, respectively. They suggest that anthropogenic emissions were responsible for ∼37% and 73% of ozone and PM2:5 impacts, respectively. Remaining impacts were attributable to naturally occurring ozone precursor emissions (e.g., from vegetation, lightning) and PM2:5 (e.g., dust, sea salt), though several of these sources are also influenced by humans. The largest impacts were estimated in China and India.

Early IL-10 producing B-cells and coinciding Th/Tr17 shifts during three year grass-pollen AIT
Zissler UM, Jakwerth CA, Guerth FM, Pechtold L, Aguilar-Pimentel JA et al
EBioMedicine 2018; 36:475-488. DOI:10.1016/j.ebiom.2018.09.016

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As allergists, we are all too aware that we need to better understand the mechanism of action as well as biomarkers that translate into clinical efficacy with use of allergy immunotherapy. In this paper Zissler and colleagues rely upon an observational allergy cohort to phenotype 32 grass-pollen allergic patients with hayfever undergoing allergen-specific immunotherapy (AIT) for over three years and controls using local and systemic samples for ex vivo FACS, nasal transcriptomes and in vitro phleum-stimulation at critical time windows six hours after therapeutic allergen administration and during peak-season responses. They found that the up-dosing phase was marked by increased IL-10+ B-cells with allergen-specific PD-L1 up-regulation, while effector Th1/Th17 cells and CCR6+IL-17+FoxP3+T-cells decrease. The conversion phase demonstrated Th17 recovery in the absence of Th2 cells. The tolerance-mounting phase/after three years of treatment was characterized by induction of Tregs while Th2 and phleum-specific Th17 responses decrease. Notably, high ratios of circulating Breg/Th17 following initial AIT correlate significantly with clinical improvement after three years. Through this exploratory data, the authors hypothesize that differential shifts in the hierarchy of tolerance occur in three distinct phases of AIT characterized by conversion of regulatory against pro-inflammatory mechanisms, of which the Breg/Th17 ratio after initial treatment emerges as potential early prediction of AIT efficacy.

Overdiagnosis of penicillin allergy leads to costly, inappropriate treatment
Rubin R
JAMA 2018; 320(18):1846-1848. DOI:10.1001/jama.2018.14358

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This AMA “News and Analysis” is a wonderful article reinforcing the importance of confirming penicillin allergy in those believing they are allergic. The author notes that while approximately 10% of US residents have been labeled as allergic to penicillin, studies suggest that as few as 10% of people who report they’re allergic to the antibiotic really are. Furthermore, avoidance of beta-lactam antibiotics may result in greater costs and potential side effects as a result of the use of alternative antibiotics. The author concludes by stating that “delabeling people mistakenly thought to be allergic to penicillin is safe and cost-saving”. This is a great paper to give to primary care physicians, as well as patients. It reinforces the utility of allergy evaluation to rule out beta lactam allergy.

B lymphocyte-induced maturation protein 1 (Blimp-1), a negative regulator of TH9 development, orchestrates the resolution of airway inflammation in patients with allergic asthma
Finotto S
Journal of Allergy and Clinical Immunology 2018; published online ahead of print (4 September). DOI:https://doi.org/10/1016/j.jaci.2018.07.039

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This editorial by Finotto provides an excellent discussion of the pathogenetic role of TH9 cells in asthma. The mechanism that controls TH9 differentiation has been recently elucidated, including that downstream of IL-4, signal transducer and activator of transcription 6 (STAT6) suppresses the TH1- specific transcription factor T-box expressed in T cells (Tbet). In this editorial, the author focuses on recent work by Benevides et al., who describe a new TH9 inhibitory role of the transcription factor B-lymphocyte induced maturation protein 1 (Blimp-1). Although the mechanism on how Blimp-1 inhibits IL-9 remains to be fully elucidated, she stresses that further studies examining Blimp-1 as a potential anti-inflammatory factor for allergic asthma should be undertaken.