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Medical Journal Review

January 2021

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, and John J. Oppenheimer, MD - FACAAI - FAAAAI, WAO Reviews Editor. 

Asthma and COVID-19: Do we finally have answers?
Eger K, Bel EH
European Respiratory Journal 2020; in press

In this paper, Eger and Bel explore the impact of asthma on COVID 19. While it is well known that older age, obesity, cardiovascular disease, and diabetes are risk factors of poor COVID-19 outcome, much controversy surrounds asthma’s impact. The focus of this manuscript was 2 papers published in the same edition of the ERJ (Choi et al and Izquierdo et al). In summary, these large-scale studies confirmed previous findings regarding risk for asthma patients to develop (severe) COVID-19 – specifically that asthmatics appear to be slightly more susceptible to contracting COVID-19, but severe disease progression does not seem to be related to medication use, including asthma biologics, but rather linked to older age and co-morbidities. The authors stress the fact that often when examining studies of COVID-19 and asthma, potential bias factors have not been considered, leaving many questions unanswered. Furthermore, large-scale, multinational real-life studies with detailed information on asthma phenotype and medication usage in patients with a confirmed diagnosis of COVID-19 would be ideal to aid us in resolving these questions.

The Metabolomics of Childhood Atopic Diseases: A Comprehensive Pathway-Specific Review
Schjødt MS, Gürdeniz G, Chawes B
Metabolites 2020;10(12):511

Asthma, allergic rhinitis, food allergy, and atopic dermatitis are common childhood diseases with several different underlying mechanisms, i.e., endotypes of disease. In this review, the authors stress that metabolomics has the potential to identify disease endotypes, which could beneficially promote personalized prevention and treatment. They do a wonderful job of reviewing the metabolomics literature in children with atopic diseases, focusing on tyrosine and tryptophan metabolism, lipids (particularly, sphingolipids), polyunsaturated fatty acids, microbially derived metabolites (particularly, short-chain fatty acids), and bile acids. Specifically, tyrosine, 3-hydroxyphenylacetic acid, N-acetyltyrosine, tryptophan, indolelactic acid, 5-hydroxyindoleacetic acid, p-Cresol sulfate, taurocholic acid, taurochenodeoxycholic acid, glycohyocholic acid, glycocholic acid, and docosapentaenoate n-6 were identified in at least two studies as being impactful. They stress that altered metabolic pathways highlight some of the underlying biochemical mechanisms leading to these common childhood disorders, which in the future could provide utility in clinical practice. Much further work on this topic is still needed.

Helicobacter pylori and skin disorders: a comprehensive review of the available literature
Guarneri C, Ceccarelli M, Rinaldi L, Cacopardo B, Nunnari G, Guarneri F
European Review for Medical and Pharmacological Sciences 2020;24(23):12267-12287

Helicobacter pylori is a Gram-negative bacterium identified for the first time about 30 years ago and commonly considered as the main pathogenic factor of gastritis and peptic ulcer. Since then, it was found to be associated with several gastrointestinal and extra-gastrointestinal diseases, including skin disorders such as chronic urticaria, rosacea, lichen planus, atopic dermatitis, psoriasis, pemphigus vulgaris, vitiligo, primary cutaneous MALT-type lymphoma, sublamina densa-type linear IgA bullous dermatosis, primary cutaneous marginal zone B-cell lymphomas, and cutaneous T-cell pseudolymphoma. The aim of this review is to summarize the available studies regarding the topic and draw possible conclusions. The authors found that, overall, further clinical and laboratory studies are needed to assess the real plausibility and relevance of these associations, as well as the possible role of Helicobacter pylori with the underlying pathogenic mechanisms.

Allergy prevention: An overview of current evidence
Royal C, Gray C
Yale Journal of Biology and Medicine 2020;93(5):689-698

There has been a rapid rise in allergic disorders worldwide, which has resulted in increased research into the determinants of allergy development in attempt to identify factors that may be manipulated to mitigate risk. Present literature demonstrates that an opportune window in immunological development appears to exist in early life, whereby certain exposures may promote or prevent the development of an allergic disposition. Furthermore, factors that affect the composition and diversity of the microbiome in early life may also be impactful. In this review, the authors explore the current literature and recommendations relating to exposures that may prevent allergy development or promote tolerance. They note several risk factors, including delivery by caesarean section, omission of breastfeeding, vitamin D insufficiency, and environmental exposures, such as cigarette smoke exposure, all increase the risk of an allergic predisposition. Likewise, they note several protective factors, including dietary diversity during pregnancy, lactation, and in infancy is protective. They also note that recommendations for food-allergen exposure have shifted from delayed introduction to early introduction as a tolerance-inducing strategy. Supplements such as probiotics and vitamins during pregnancy and infancy have yet to produce conclusive results for allergy prevention. Finally, they note that emollient use in infancy has not been shown to be protective against eczema or food allergy.

The airways microbiome of individuals with asthma treated with high and low doses of inhaled corticosteroids
Martin MJ, Zain NMM, Hearson G, Rivett DW, Koller G et al
PLoS One 2020;15(12):e0244681

Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, but evidence suggests a link between ICS usage and increased rates of respiratory infections. In this study, Martin and colleagues assessed the composition of the asthmatic airways microbiome in patients taking low and high dose ICS and the stability of the microbiome over a 2-week period. Sputum from each subject underwent DNA extraction, amplification and 16S rRNA gene sequencing of the bacterial component of the microbiome. Nineteen subjects returned for further sputum induction after 24 h and 2 weeks. A total of 5,615,037 sequencing reads revealed 167 bacterial taxa in the asthmatic airway samples, with the most abundant being Streptococcus spp. No significant differences in sputum bacterial load or overall community composition were seen between the low- and high-dose ICS groups; however, Streptococcus spp. showed significantly higher relative abundance in subjects taking low-dose ICS (p = 0.002). Furthermore, Haemophilus parainfluenzae was significantly more abundant in subjects on high-dose fluticasone propionate compared to those on high-dose budesonide (p = 0.047). There were no statistically significant changes in microbiota composition over a 2-week period. The authors note that the clinical implications for patients are not known, but suggest that this does provide a possible explanation for the increased risk of pulmonary infection seen in asthma and COPD, particularly with FP.  More research is needed.

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