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Medical Journal Review

July 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.

Exposure frequency, intensity, and duration: What we know about work-related asthma risks for healthcare workers from cleaning and disinfection
Wilson AM, Ogunseye O, Fingesi T et al
Journal of Occupational and Environmental Hygiene 2023; Published online ahead of print (6 July)

In this review the authors explore the current evidence related to three exposure assessment concepts: frequency, intensity, and duration (latency) for cleaning and disinfection exposures in healthcare and subsequent work-related asthma risks. Three databases were searched: Embase, PubMed, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database. Data were extracted related to three main components of risk assessment. They found that the latency periods for occupational asthma were exponentially distributed, with a mean waiting time (1/λ) of 4.55 years. No extracted concentration data were above occupational exposure limits except for some formaldehyde and glutaraldehyde concentrations. Data from included sources also indicated some evidence for a dose-response relationship regarding increased frequency yielding increased risk, but this relationship was unclear due to potential confounders (differences in role/task and associated exposure) and the healthy worker effect. The authors stress that more data are needed to understand how demographic variables; and task, role, as well as chemical type vary this distribution. Furthermore, they note that contributions of latency to risk will inform work-related asthma monitoring efforts and risk perception research that has the potential for connecting exposure intensity, frequency, and duration to probabilities of work-related asthma outcomes.

LMAN1 is a receptor for house dust mite allergens
Miller MH, Swaby LG, Vailoces VS et al
Cell Reports 2023;42(3):112208 (3 March)

The development of therapies with the potential to change the allergic asthmatic disease course will require the discovery of targets that play a central role during the initiation of an allergic response, such as those involved in the process of allergen recognition. In attempt to better understand potential targets in house dust mites (HDM), Miller and colleagues utilized the glycocapture technique to screen for house dust mite (HDM) receptors and identified LMAN1 as a candidate. They verified the ability of LMAN1 to directly bind HDM allergens and demonstrated that LMAN1 is expressed on the surface of dendritic cells (DCs) and airway epithelial cells (AECs) in vivo. Overexpression of LMAN1 downregulates NF-kB signaling in response to inflammatory cytokines or HDM. HDM promotes binding of LMAN1 to the FcRg and recruitment of SHP1. They also found that peripheral DCs of asthmatic individuals show a significant reduction in the expression of LMAN1 compared with healthy controls. These findings have potential implications for the development of therapeutic interventions for atopic disease.

Mechanisms of allergen immunotherapy and potential biomarkers for clinical evaluation
Sahiner UM, Giovannini M, Escribese MM et al
Journal of Personalized Medicine 2023;13(5):845 (17 May)

Allergen-immunotherapy (AIT) is an efficacious and disease-modifying treatment option for IgE-mediated diseases, including allergic rhinitis, insect venom allergy, food allergy, and allergic asthma. AIT gives rise to clinical immunotolerance which may last for years after the treatment cessation. As highlighted in this review, while AITs efficacy is well established, we are not certain of its mechanism of action, but proposed routes include suppression of allergic inflammation in target tissues and stimulation of the production of blocking antibodies, especially IgG4 and IgA. These mechanisms are followed by a reduction of underlying allergen-specific Th2 cell-driven responses to the allergens. Tolerance induction takes place through the desensitization of effector cells and stimulation of regulatory T cells that show their effects by mechanisms involving cell-cell cross-talk, but also other mechanisms, e.g., by the production of immunomodulatory cytokines such as, e.g., IL-10 and TGF-beta. The authors of this review note that there is a need for clinical biomarkers of value in selecting responders and optimizing patient care during AIT, as well as a deeper understanding of underlying mechanistic processes which could improve AIT’s future outcomes.

Finding the Right Biological: Eosinophil Subset Differences in Asthma and COPD
Freeman CM, Curtis JL, Hastie AT
American Journal of Respiratory and Critical Care Medicine 2023; Accepted article, published online ahead of print (13 June)

In this editorial accompanying a recent article by Cabrera Lopez et al., the authors note that the paper provides important new insights into differences in the roles of eosinophils between COPD versus asthma, finding higher inflammatory Eos (high expression of the IL-5 receptor alpha chain [IL5Rα, CD125]) proportions in participants with asthma compared to participants with COPD (25% vs. 0.5%) matched for age, sex, and FEV1%. The editorial stresses that future studies should not simply count eosinophils, but should characterize subsets of eosinophils. Furthermore, they point out that clinical trials of both existing and novel biologics would benefit from in-depth eosinophil phenotyping to identify the best participants for personalized therapies.

Diversity of B cell populations and Ig repertoire in human lungs
Aihara F, Wang Y, Belkina AC et al.
Journal of Immunology 2023; Published online ahead of print (14 June)

The human lung carries a unique microbiome adapted to the air-filled, mucous-lined environment, specifically having an immune system capable of recognizing harmful populations while preventing reactions toward commensals. B cells in the lung play a key role in pulmonary immunity, generating Ag-specific Abs, as well as cytokine secretion for immune activation and regulation. In this study, Aihara and colleagues compared B cell subsets in human lungs versus circulating cells by analyzing patient-paired lung and blood samples, finding a significantly smaller pool of CD19+, CD20+ B cells in the lung relative to the blood. CD27+, IgD2, class-switched memory B cells (Bmems) composed a larger proportion of the pool of pulmonary B cells. The residency marker CD69 was also significantly higher in the lung. Furthermore, that authors also sequenced the Ig V region genes (IgVRGs) of class-switched Bmems that do, or do not, express CD69, finding the IgVRGs of pulmonary Bmems to be as heavily mutated from the unmutated common ancestor as those in circulation. Overall, their results show the unique proportion of B cell subsets within the lung. The IgVRGs of pulmonary Bmems are as diverse as those in blood, and progenies of Bmems retain the ability to gain or lose residency.

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