Allergy最新文献

In the last decades, critical advancements in research technology and knowledge on disease mechanisms steered therapeutic approaches for chronic inflammatory diseases towards unprecedented target specificity. For allergic and chronic lung diseases, biologic drugs pioneered this goal, acquiring on the way-through the clinical use of monoclonal antibodies-a deeper understanding of how inflammatory and immune pathways are configured in disease-specific patterns. In this biomarker-driven approach, synthetic small molecule drugs (SMDs) were perceived as lagging behind in innovation for their relative lack of specificity. This was, however, mostly due to a shift in focus towards biologics rather than true obsolescence of SMDs. In the same timeframe, in fact, advances in structural biology and medicinal chemistry, bioinformatics and artificial intelligence held steadily SMDs' innovation and relevance. The use of kinase inhibitors, well established in the treatment of cancer and rheumatological diseases, is now approved for some allergic skin diseases and is approaching asthma and COPD with several clinical trials; moreover, new therapeutics targeting mast cell receptors and molecules involved in innate immunity are entering preclinical and clinical testing. Alongside, the portfolio of biologics is harboring the expansion of RNA therapeutics, which gained global recognition during the COVID-19 pandemic due to RNA vaccines. Different types of RNA therapeutics, including those based on different non-coding RNAs, are advancing to agency approval and market, thanks to improvements in molecule stability and delivery systems. In summary, the evidence presented in this position paper illustrates that precision medicine is becoming a goal shared between synthetic SMDs and biologics, both protein/antibody-based and RNA therapeutics. We review the current state, unmet needs and opportunities within this evolving landscape, highlighting how small molecular species, both synthetic as SMDs and biologic in nature as RNA, can contribute to the precision medicine approach along with protein and antibody-based biologics and cell therapies.

Background: Our previous study demonstrated that laundry detergents induce group 2 innate lymphoid cell-driven eosinophilic airway inflammation by disrupting airway epithelial barriers and promoting IL-33 release, and that detergent residues are present in nearly all household dust. However, their impact on allergen-induced airway inflammation remains unclear.

Methods: C57BL/6 background mice were intranasally primed four times with ovalbumin (OVA) or house dust mite (HDM) allergens in the presence or absence of a commercial laundry detergent. Following priming, mice were challenged with the same antigen for 3 consecutive days and sacrificed the day after the final challenge. Bronchoalveolar lavage fluid (BALF) and sera were analyzed by ELISA. Lungs were evaluated histologically and analyzed by qPCR.

Results: Mice intranasally primed with antigen in the presence of detergent exhibited eosinophilic airway inflammation upon antigen challenge, accompanied by increased IL-5 and IL-13 levels in the BALF. Intranasal administration of detergent and antigen also stimulated antigen-specific IgE production. These detergent- and allergen-induced type 2 responses were significantly suppressed in Il33^-/- and Il13^-/- mice. Administration of an anti-IL-4 receptor α chain antibody during the challenge phase reduced eosinophil counts in the BALF and antigen-specific IgE levels in the serum. By contrast, anti-IL-33 antibody treatment during the challenge phase did not affect eosinophilic airway inflammation or antigen-specific IgE production.

Conclusions: Laundry detergents promote sensitization to co-inhaled allergens and exacerbate eosinophilic airway inflammation and antigen-specific IgE responses via IL-33 and IL-13. These findings suggest that detergents can act as adjuvants that facilitate airway sensitization.

Chronic rhinosinusitis (CRS) and asthma are prevalent conditions that often coexist. These diseases share common inflammatory mechanisms, such as T-helper cell 2 (T2)-high inflammation, driven by interleukin (IL)-4, IL-5, and IL-13 cytokines. The frequent comorbidity between CRS, especially CRS with nasal polyps (CRSwNP), and asthma exacerbates disease severity, impairs quality of life, and complicates treatment. Patients with NSAID-exacerbated respiratory disease (N-ERD) represent a severe phenotype of this disease, characterized by the coexistence of CRSwNP, asthma, and NSAID hypersensitivity, which poses unique therapeutic challenges. This EAACI Task Force explores the shared risk factors, including genetic predispositions, epithelial barrier dysfunction, microbiome dysbiosis, underlying CRS, and asthma. It also evaluates current therapeutic strategies such as biologics, aspirin therapy after desensitization (ATAD), and endoscopic sinus surgery (ESS). Biologics have shown their effectiveness and safety in the treatment of asthma and CRS. Dupilumab, mepolizumab, depemokimab, and omalizumab have emerged as transformative therapies, particularly for patients with severe type 2 inflammation. Tezepelulumab is effective for both T2-high and T2-low asthma and CRSwNP. Itepekimab has shown its effect in asthma and is under investigation for CRSwNP. Omalizumab is effective in allergic asthma and CRSwNP. ATAD provides an additional disease-modifying approach for N-ERD, though patient adherence and tolerability remain critical challenges. ESS significantly improves asthma control, reduces medication use, and enhances sinonasal outcomes, particularly in severe asthma cases; however, these patients often need recurring surgeries. Despite these advances, treatment outcomes vary based on individual phenotypes and endotypes, underscoring the need for personalized approaches. The report highlights gaps in the literature, such as the lack of head-to-head trials comparing biologics, ATAD, and surgery. Future research should focus on refining treatment algorithms, identifying biomarkers for treatment selection, and assessing long-term outcomes to optimize care for patients with CRS, asthma, and N-ERD.