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Medical Journal Review

September 2022

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.

Respiratory syncytial virus prevention within reach: The vaccine and monoclonal antibody landscape
Mazur NI, Terstappen J, Baral R et al
The Lancet Infectious Diseases 2022;S1473-3099(22):00291-2

Respiratory syncytial virus is the second most common cause of infant mortality and a major cause of morbidity and mortality in older adults (aged >60 years). Efforts to develop a respiratory syncytial virus vaccine or immunoprophylaxis remain highly active. The authors of this review note that 33 respiratory syncytial virus prevention candidates are in clinical development using six different approaches: recombinant vector, subunit, particle-based, live attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. Nine candidates are in phase 3 clinical trials. Understanding the epitopes targeted by highly neutralizing antibodies has resulted in a shift from empirical to rational and structure-based vaccine and monoclonal antibody design. The authors note that an extended half-life monoclonal antibody for all infants is likely to be within one year of regulatory approval. Live-attenuated vaccines are in development for older infants (aged >6 months), while subunit vaccines are in late-stage trials for pregnant women to protect infants, vector, subunit, and nucleic acid approaches are being developed for older adults.

Microbiome, metabolism, and immunoregulation of asthma: An American Thoracic Society and National Institute of Allergy and Infectious Diseases Workshop Report
Kozik AJ, Holguin F, Segal LN et al
American Journal of Respiratory Cell and Molecular Biology 2022;67(2):155-163

This report presents the proceedings from a jointly sponsor workshop (American Thoracic Society and National Institute of Allergy and Infectious Disease), titled “Microbiome, Metabolism and Immunoregulation of Asthma” that was held virtually May 13 and 14, 2021. This was an interdisciplinary group of experts with backgrounds in asthma immunology, microbiome science, metabolomics, computational biology, and translational pulmonary research. The main purpose of this panel was to identify key scientific gaps and needs to further advance research on microbial and metabolic mechanisms that may contribute to variable immune responses and disease heterogeneity in asthma. Discussions focused on several topics, including: 1) immune and microbial mechanisms of asthma pathogenesis in murine models, 2) the role of microbes in pediatric asthma exacerbations, 3) dysregulated metabolic pathways in asthma associated with obesity, 4) metabolism effects on macrophage function in adipose tissue and the lungs, 5) computational approaches to dissect microbiome–metabolite links, and 6) potential confounders of microbiome–disease associations in human studies. This report explored identification of specific knowledge gaps, challenges, and suggested directions for future research. These include questions surrounding mechanisms by which microbiota and metabolites shape host health versus an allergic or asthmatic state; direct and indirect influences of other biological factors, exposures, and comorbidities on these interactions; and ongoing technical and analytical gaps for clinical translation.

European guideline (EuroGuiDerm) on atopic eczema: Part I – systemic therapy
Wollenberg A, Kinberger M, Arents B et al
Journal of The European Academy of Dermatology and Venereology 2022;36(9):1409-1431

This evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual resulting from four consensus conferences held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users, and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment used in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab, and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib). The second part of this guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant, and breastfeeding patients.

BSACI guideline for the diagnosis and management of pollen food syndrome in the UK
Skypala IJ, Hunter H, Krishna MT et al
Clinical & Experimental Allergy 2022;52(9):1018-1034

Pollen food syndrome (PFS) is a very prevalent food allergy affecting pollen-sensitized children and adults. Sufferers experience allergic symptoms when consuming raw plant foods, due to the homology between the pollen allergens and unstable proteins in these foods. The triggers involved can vary depending on the pollen sensitization, which in turn is affected by geographical location. The British Society of Allergy and Clinical Immunology (BSACI) Standards of Care Committee (SOCC) identified a need to develop a guideline for the diagnosis and management of PFS in the United Kingdom (UK). Guidelines produced by the BSACI use either the GRADE or SIGN methodology; but, due to a lack of high-quality evidence these recommendations were formulated using the SIGN guidelines, which is acknowledged to be less robust than the GRADE approach.

The authors stress that the correct diagnosis of PFS ensures the avoidance of a misdiagnosis of a primary food allergy, such as peanut or tree nut allergy or confusion with another plant food allergy to non-specific lipid transfer proteins. The characteristic foods involved, and rapid-onset oropharyngeal symptoms, means that PFS can often be diagnosed from the clinical history alone. However, reactions involving tree nuts, peanuts and soya milk or severe/atypical reactions to fruits and vegetables may require additional diagnostic tests. Management of this illness involves avoidance of known trigger foods, which may appear to be simple, but can be highly problematic if coupled with a pre-existing food allergy or for individuals following a vegetarian/vegan diet. The authors note that immunotherapy to pollens is not an effective treatment for PFS, and although oral or sublingual immunotherapy to foods seems more promising, large, controlled studies are needed before these therapies can be recommended for this illness. While the typically mild symptoms of PFS can lead to an erroneous perception that this condition is always easily managed, it should be noted that severe reactions can occur, and anxiety about the onset of symptoms to new foods can have a profound effect on patients’ quality of life.

Allergic and eosinophilic asthma in the era of biomarkers and biologics: Similarities, differences and misconceptions
Oppenheimer J, Hoyte FCL, Phipatanakul W et al
Annals of Allergy Asthma & Immunology 2022;129(2):169-180

Severe asthma is associated with substantial personal and economic burden; maintaining disease control is the key management goal. Increased understanding of asthma heterogeneity and development of type 2 (T2)-targeting biologics has substantially advanced disease management and outcomes; however, despite both being driven by T2 inflammation, allergic and eosinophilic asthma have different treatment recommendations. In this review, the authors examine the literature regarding similarities and differences between allergic and eosinophilic asthma and highlight where misconceptions may arise. The authors note that severe allergic and eosinophilic asthma are both driven by T2 inflammation with eosinophils playing a cardinal role. Despite this overlap, treatment recommendations differ based on asthma classification. T2 cytokine gene expression is a reasonably well-established research tool, but not a well-established biomarker in clinical practice, unlike blood eosinophil counts, fractional exhaled nitric oxide, and IgE; the clinical relevance of IgE as a predictive biomarker remains unclear. Asthma classifications that can be easily characterized at the patient level to ensure accurate diagnosis, predict disease trajectory, and treatment response are required. The authors suggest that the current dichotomy of allergic and eosinophilic asthma classifications is likely too simplistic, given the similar eosinophil-mediated disease pathophysiology in both classifications and better understanding may aid in defining responders more precisely with personalized medicine approaches.

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