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Medical Journal Review

March 2023

WAO Reviews – Editors' Choice

The WAO Reviews editors, Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, select articles on a monthly basis for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases.

Epithelial barrier in the nasal mucosa, related risk factors and diseases
Zhang R, Zhang L, Li P et al
International Archives of Allergy and Immunology 2023 (1 February)

This review by Zhang examines the epithelial barrier of the nose. We know the importance of this barrier, as it is the first line of defense against risk factors and maintains homeostasis in the nasal mucosa. The composition of this barrier contains physical, chemical, immune, and microbiological barriers. Together, these barriers form the nasal defense against irritations. Risk factors from both internal and external environments can disrupt them. Furthermore, external risk factors contain allergen containing proteases, bacteria, virus, particulate matter, diesel exhaust particles, and cigarette smoke.

Considering the epithelial barrier's role in the nasal mucosa, several studies have focused on the treatment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) to restore the epithelial barrier. Among the therapeutic approaches, histone deacetylase (HDAC) inhibitor and corticosteroids are two of the more studied interventions. The underlying mechanism of HDAC inhibitor may be related to the transcription factor p63. And the protection of corticosteroids may be associated with the allergic disease susceptibility gene, protocadherin-1. Notably, manipulation of the microbiological barrier also has a positive effect on AR and CRS. Also in this review, the authors examine the utility of probiotics as well as several promising novel approaches that attempt to restore the defective barrier in nasal allergic diseases.

Associations between outdoor air pollutants and non-viral asthma exacerbations and airway inflammatory responses in children and adolescents living in urban areas in the USA: a retrospective secondary analysis
Altman MC, Kattan M, O’Connor GT et al
Lancet Planet Health 2023;7(1):e33-e44 (January)

Previous research has demonstrated that asthma prevalence and severity have markedly increased with urbanization, and children in low-income urban centers have among the greatest asthma morbidity. Not surprisingly, outdoor air pollution has been associated with adverse respiratory effects in children with asthma. However, the mechanisms by which air pollution exposure exacerbates asthma, and how these mechanisms compare with exacerbations induced by respiratory viruses, are poorly understood. Thus, the aim of this study was to investigate the associations between regional air pollutant concentrations, respiratory illnesses, lung function, and upper airway transcriptional signatures in children with asthma, with particular focus on asthma exacerbations occurring in the absence of respiratory virus.

To do so, the authors performed a retrospective analysis of data from the MUPPITS1 cohort and validated our findings in the ICATA cohort. The MUPPITS1 cohort recruited 208 children aged 6–17 years living in urban areas across nine US cities with exacerbation-prone asthma between Oct 7, 2015, and Oct 18, 2016, and monitored them during reported respiratory illnesses. The ICATA cohort was composed of 419 participants aged 6–20 years with persistent allergic asthma living in urban sites across eight US cities between Oct 23, 2006, and March 25, 2008.

The authors used air quality index values and air pollutant concentrations for PM2·5, PM10, O3, NO2, SO2, CO, and Pb from the US Environmental Protection Agency spanning the years of both cohorts, and matched values and concentrations to each illness for each participant and investigated the associations between regional air pollutant concentrations and respiratory illnesses and asthma exacerbations, pulmonary function, and upper airway transcriptional signatures by use of a combination of generalized additive models, case crossover analyses, and generalized linear mixed-effects models.

Of the 208 participants from the MUPPITS1 cohort and 419 participants from the ICATA cohort, 168 participants in the MUPPITS1 cohort (98 male participants and 70 female participants) and 189 participants in the ICATA cohort (115 male participants and 74 female participants) were included in their analysis. The authors found that increased air quality index values, driven predominantly by increased PM2·5 and O3 concentrations, were significantly associated with asthma exacerbations and decreases in pulmonary function that occurred in the absence of a provoking viral infection.

Furthermore, individual pollutants were significantly associated with altered gene expression in coordinated inflammatory pathways, including PM2·5 with increased epithelial induction of tissue kallikreins, mucus hypersecretion, and barrier functions and O3 with increased type-2 inflammation.

Overall, these findings suggest that air pollution is an important independent risk factor for asthma exacerbations in children living in urban areas and is potentially linked to exacerbations through specific inflammatory pathways in the airway.

Benchmarking omics-based prediction of asthma development in children
Wang XW, Wang T, Schaub D et al
Respiratory Research 2023;24(1):63 (26-February)

It is well known that asthma is a heterogeneous disease with high morbidity. Advancement in high-throughput multi-omics approaches has enabled the collection of molecular assessments at different layers, providing a complementary perspective of complex diseases such as asthma. While numerous computational methods have been developed for the omics-based patient classification or disease outcome prediction in other illnesses, systematic benchmarking of those methods using various combinations of omics data for the prediction of asthma development is still lacking.

Thus, the goal of this study was to investigate the computational methods in disease status prediction using multi-omics data by systematically benchmarked 18 computational methods using all the 63 combinations of six omics data (GWAS, miRNA, mRNA, microbiome, metabolome, and DNA methylation) collected in The Vitamin D Antenatal Asthma Reduction Trial (VDAART) cohort. The authors evaluated each method using standard performance metrics for each of the 63 omics combinations finding that overall Logistic Regression, Multi-Layer Perceptron, and MOGONET display demonstrated superior performance, and the combination of transcriptional, genomic and microbiome data achieves the best prediction. They also found that including the clinical data can further improve the prediction performance for some but not all the omics combinations.

The authors conclude that omic combinations can reach the optimal prediction of asthma development in children with certain computational methods demonstrating superior performance compared with other methods. This is the beginning of a new age of further precision in our care of asthmatic patients.

Allergic march in children: The significance of precision allergy molecular diagnosis (PAMD@) in predicting atopy development and planning allergen-specific immunotherapy
Knyziak-Mędrzycka I, Majsiak E, Cukrowska B
Nutrients 2023;15(4):978 (15-February)

In this paper, Knyziak-Medrzycka et al explore the literature regarding the allergic march, which they described with age. The classic allergic march typically begins in infancy manifesting in the form of atopic dermatitis and food allergy. As immune tolerance develops over time, these conditions may resolve by the age of 3–5 years; however, they may evolve into allergic illnesses, including allergic rhinitis and bronchial asthma. Traditional diagnostic assessments, such as skin prick testing or serum allergen-specific immunoglobulin E (sIgE) level testing, are conducted to introduce effective treatment. Recently the utilization of precision allergy molecular diagnosis (PAMD@), which assesses sIgE against allergenic molecules has been introduced. This recent technology helps more accurately evaluate the patient’s allergy profile, which helps create more precise dietary specifications and personalize allergen-specific immunotherapy. The focus of this review highlights possible predictors regarding the allergic march and the means of controlling it, based on PAMD@ results.

New Indications of Biological Drugs in Allergic and Immunological Disorders: Beyond Asthma, Urticaria, and Atopic Dermatitis
Russo D, Di Filippo P, Di Pillo S et al
Biomedicines 2023;11(2):236 (17-Jan)

Asthma, chronic urticaria, and atopic dermatitis are some of the most common allergic illnesses affecting children. Recent advances in the understanding of their specific intracellular molecular pathways have led to the approval of monoclonal antibodies which target specific inflammatory molecules associated with the illness, to control symptoms and improve quality of life. Less is known about other allergic and immunologic disorders such as rhinosinusitis with nasal polyps, eosinophilic esophagitis, anaphylaxis, and food allergy. With the increasing evidence regarding the molecular mechanisms underlying their pathogeneses it is now possible to find, in the pediatric population, new indications for existing biological drugs, such as omalizumab and dupilumab, as well as novel compounds with even more specificity. In this review, the authors explore the latest evidence regarding the safety, and efficacy of biologic agents to treat allergic and immunologic diseases in children.

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