Last year brought a significant advance in asthma management, unyielding to the pressure of the pandemics. Novel key findings in asthma pathogenesis focus on the resident cell compartment, epigenetics and the innate immune system. The precision immunology unbiased approach was supplemented with novel tools and greatly facilitated by the use of artificial intelligence. Several randomised clinical trials and good quality realworld evidence shed new light on asthma treatment and supported the revision of several asthma guidelines (GINA, Expert Panel Report 3, ERS/ATS guidelines on severe asthma) and the conception of new ones (EAACI Guidelines for the use of biologicals in severe asthma). Integrating asthma management within the broader context of Planetary Health has been put forward. In this review, recently published articles and clinical trials are summarised and discussed with the goal to provide clinicians and researchers with a concise update on asthma research from a translational perspective.

Improved understanding of the contribution of immune-inflammatory mechanisms in allergic diseases and asthma has encouraged development of biologicals and small molecules specifically targeting the innate and adaptive immune response. There are several critical points impacting the efficacy of this stratified approach, from the complexity of disease endotypes to the effectiveness in real-world settings. We discuss here how these barriers can be overcome to facilitate the development of implementation science for allergic diseases and asthma.

Purpose of review Allergic diseases are prototypic examples for gene × environment-wide interactions. This review considers the current evidence for genetic and epigenetic mechanisms in allergic diseases and highlights barriers and facilitators for the implementation of these novel tools both for research and clinical practice. Recent findings The value of whole-genome sequencing studies and the use of polygenic risk score analysis in homogeneous well characterized populations are currently being tested. Epigenetic mechanisms are known to play a crucial role in the pathogenesis of allergic disorders, especially through mediating the effects of the environmental factors, well recognized risk modifiers. There is emerging evidence for the immune-modulatory role of probiotics through epigenetic changes. Direct or indirect targeting of epigenetic mechanisms affect expression of the genes favouring the development of allergic diseases and can improve tissue biology. The ability to specifically edit the epigenome, especially using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, holds the promise of enhancing understanding of how epigenetic modifications function and enabling manipulation of cell phenotype for research or therapeutic purposes. Summary Additional research in the role of genetic and epigenetic mechanisms in relation to allergic diseases’ endotypes is needed. An international project characterizing the human epigenome in relation to allergic diseases is warranted.

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Purpose of review Allergen immunotherapy (AIT) is a well-known disease-modifying intervention for allergic diseases. Its benefit in allergic asthma, ranging from prevention to facilitating asthma control, is yet to be clarified. Recent findings In 2017, following several well-designed randomised controlled trials (RCTs) with house-dust mites (HDM) sublingual (SLIT) tablets in asthma, global initiative for asthma (GINA) guidelines highlighted the need to treat the allergic component of asthma. In 2019, the European Academy of Allergy and Clinical Immunology published the first comprehensive guidelines for HDM AIT in allergic asthma, formulating separate recommendations for subcutaneous, SLIT drops, and SLIT tablets. Significant steps were undertaken in understanding the mechanisms of allergic asthma, facilitating the stratified approach for selecting responders and in translating the immune-modulation effect in achieving long-term control of the chronic inflammation in asthma. Summary Currently existing guidelines recommend AIT as a therapeutic option in controlled or partially controlled HDM allergic asthma. Limited data are available for pollen, molds and pets, as well as for the severe allergic asthma population. The challenge for the future research will be to clarify the subendotypes of allergic asthma responding to AIT, the mechanisms facilitating its’ preventive and disease-modifying effect, the optimal duration of the treatment, and route of administration.

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Allergen immunotherapy (AIT) is considered the only disease-modifying treatment available at present for allergic disorders. Its main benefits include improvement of symptoms, decreased need for pharmacotherapy, prevention of new sensitizations and sustained effect after AIT completion. The key pillars of AIT-induced tolerance include a shift from Th2 to Th1 response, an increase of regulatory T and B cells, pro-inflammatory effector cell downregulation and IgE suppression, in addition to IgG4, IgA and IgD induction. AIT may also induce trained immunity, characterized by a durable decrease in group 2 of innate lymphoid cells (ILCs) and increased ILC1 and ILC3s. Understanding the immune mechanisms of AIT is essential for validating biomarkers for the prediction of AIT response and for achieving AIT success.

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