Current Opinion in Allergy and Clinical Immunology最新文献

Purpose of review: Asthma is a mosaic of phenotypes shaped by complex host-environment interactions. Among these, the microbiome has moved to a central determinant of disease expression, and airway and gut microbiome should be seen as active players in asthma pathophysiology. This review critically examines how environmental exposures, including pollution, drugs, diet, and climate, remodel microbial ecosystems, and reprogram immune responses in adults with asthma, with emphasis on clinical translation.

Recent findings: Advances from multiomics, large-scale cohorts, and Mendelian randomization studies reinforce the concept of the gut-lung axis as a decisive modulator of asthma outcomes. Airway dysbiosis, often marked by Proteobacteria dominance, consistently correlates with poor asthma control, exacerbations, and steroid resistance. Environmental determinants of microbiome reshape erode immune tolerance. Microbial metabolites such as short-chain fatty acids act as molecular messengers capable of restoring epithelial and immune balance. These findings challenge the traditional inflammatory-centric view of asthma and demand broader mechanistic frameworks.

Summary: The microbiome should be considered a central piece of the puzzle in asthma research. Precision medicine in adult asthma will remain aspirational unless microbiome-informed biomarkers and interventions are embraced. Robust interventional studies are urgently needed to translate this promise into practice.

Purpose of review: Immediate hypersensitivity disorders, such as asthma, food intolerance, and anaphylaxis, have risen dramatically since the 20th century, marking a shift in the global disease burden. While mast cells have been associated with IgE-mediated disorders, they also play important roles in homeostasis. To prevent chronic inflammation and aberrant tissue remodeling, tight regulation of mast cells is essential in response to microorganisms, autoantigens, and environmental changes.

Recent findings: The surge in mast cell-mediated disorders and evidence of mast cell interactions with epithelial and neural networks have led to the epithelial barrier hypothesis. This hypothesis extends the protective role of the epithelium by highlighting its integrated communication with both the nervous and immune systems, proposing that dysregulated nerve-mast cell signaling at epithelial barriers contributes to the development of immediate hypersensitivity disorders - both allergic and nonallergic phenotypes. In turn, it offers new strategies for prevention and treatment, focusing on restoring barrier integrity and modulating neuroimmune pathways.

Summary: Clinical populations including hypermobility syndromes, such as certain Ehlers-Danlos syndrome variants and Job syndrome, exemplify the systemic consequences of disrupted epithelial barriers and chronic nerve-mast cell dysregulation. Accordingly, this review discusses the co-emergence of hypersensitivity and hypermobility syndromes as manifestations of immune-neuro-epithelial dysfunction in the context of modern environmental change.

Purpose of review: The expansion of the legal cannabis market has driven rapid, exponential growth in its workforce. Emerging evidence suggests that occupational exposures during cannabis production contribute to respiratory and allergic disease in cannabis workers.

Recent findings: There is a substantial burden of respiratory and allergic disease in cannabis production workers. Recent evaluations have demonstrated exposure to respiratory irritants and allergic sensitizers during cannabis production activities, though the cause of health symptoms among cannabis workers remains unknown. While some studies suggest that sensitization to cannabis plant allergens may drive disease, no epidemiological studies have quantitatively assessed the relationship between inhalation hazards and health outcomes in cannabis production workers.

Summary: Research is critically needed on the etiology of work-related respiratory and allergic disease within the cannabis industry. Although the specific cause of reported health effects is uncertain, recent findings provide sufficient preliminary evidence to justify swift action to safeguard this rapidly growing workforce.

Purpose of review: This review examines how environmental injustice contributes to disparities in allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. It focuses on the role of social, geographic, and economic inequities in shaping disease prevalence, severity, and access to care among underrepresented racial and ethnic communities.

Recent findings: Recent studies emphasize the persistent exposure of low-income and racially marginalized populations to environmental hazards such as air pollution, substandard housing, and climate-related changes, factors that are linked to increased prevalence and severity of allergic diseases. While environmental policies have led to overall improvements in air quality, disparities in exposure and outcomes persist. Emerging policies show promise in reducing these gaps through more equitable and inclusive approaches.

Summary: Environmental injustice is a key driver of health disparities in allergic diseases and asthma. Structural inequities continue to place marginalized communities at higher risk of harmful exposures and adverse health outcomes. Addressing these disparities requires collaboration between policymakers, healthcare workers, researchers, and affected communities.

Purpose of review: To summarize the effects of type 2 (T2) cytokine-targeting therapies on respiratory infection risk in patients with allergic diseases, with a focus on the interplay between epithelial barrier restoration and immune rebalancing.

Recent findings: T2 inflammation, driven by IL-4, IL-13, IL-5, and IgE, disrupts epithelial integrity and impairs mucosal defenses, increasing susceptibility to infections. Biologics targeting these pathways restore barrier function and modulate immune responses, promoting Th1/Th17-mediated antimicrobial activity. Dupilumab improves epithelial integrity and Th1/Th17 activity, with post hoc analyses from QUEST and SINUS-52 showing fewer respiratory infections compared to placebo. IL-13-specific therapies (tralokinumab, lebrikizumab) reduce excessive Th2 signaling and effector T-cell transdifferentiation, supporting mucosal homeostasis and low infection rates. IL-5-targeted biologics (mepolizumab, benralizumab) decrease eosinophil-mediated tissue injury without significantly increasing respiratory infections, despite theoretical concerns regarding antiviral defense. Omalizumab enhances Th1 antiviral pathways while reducing IgE-mediated inflammation, preserving infection control.

Summary: T2-modulating biologics not only control allergic inflammation but also restore epithelial and immune homeostasis, contributing to maintained or reduced respiratory infection risk. These therapies represent a dual benefit of barrier repair and immune rebalancing. Further studies are warranted to evaluate long-term infection outcomes in high-risk populations.

Purpose of review: Asthma management is ongoing a paradigm shift from symptom control and exacerbation prevention toward the more comprehensive goal of clinical remission. This review is timely because biologic therapies, precision medicine, and improved understanding of immunopathological mechanisms have made remission a realistic therapeutic goal. By integrating clinical, functional, and biological outcomes, remission offers a more comprehensive framework for assessing long-term disease control.

Recent findings: Recent evidence demonstrate that biologic drugs, such as Mepolizumab, Omalizumab, Dupilumab, Benralizumab, and Tezepelumab, allow clinical remission to be achieved in many patients affected by severe asthma particularly those who show a phenotyping polarized toward T2-High. Lifestyle change, particularly weight loss and smoking cessation, early intervention, and the use of allergen immunotherapy may increase the chances of achieving remission. Real-world data confirm that remission rates vary depending on the definition applied, going from clinical to complete remission, highlighting the lack of a universally shared definition of remission and the need for standardized criteria.

Summary: Clinical remission in asthma is now a feasible target. Achieving this goal requires a multidimensional approach that integrates biologics, early treatment, comorbidity management, and lifestyle interventions. Standardized definitions and biomarkers are essential to guide therapeutic decisions and predict long-term outcomes.

Purpose of review: This review explores patients' perspective on allergen immunotherapy (AIT) for respiratory allergy, addressing awareness, motivations, adherence challenges, perceived benefits and risks, and the importance of education and shared decision-making. It also summarizes the data on patient-reported outcomes, considers the role of patient associations, and outlines future directions for enhancing adherence and advancing patient-centered care.

Recent findings: AIT is the only treatment capable of modifying the natural course of allergic diseases, providing lasting benefits in terms of symptom reduction, quality of life (QoL), and asthma control. Despite its efficacy and safety, AIT remains underused due to several factors, including cost, misinformation, patient skepticism, and adherence challenges. Limited reimbursements further restrict access.

Summary: The patient's perspective is crucial in AIT, as it directly impacts adherence and treatment outcomes. Allergic rhinitis and asthma significantly reduce the QoL, especially when poorly controlled, but their burdens are often underestimated. Adherence to AIT depends on multiple factors including age, physician engagement, perceived efficacy, convenience, education, and socioeconomic status. Effective communication, shared decision-making, and tailored education enhance long-term compliance, while financial barriers and lack of reimbursement remain significant obstacles. Patient-reported outcome measures (PROMs) are essential tools for assessing symptom burden, disease control, and QoL, supporting clinical decisions and research. Validated PROMs, as well as combined symptom-medication scores, help personalize care and are increasingly integrated into digital platforms for real-time monitoring. Respiratory patient associations play a vital role in promoting education, empowerment, and advocacy, enhancing adherence and access to care.

Purpose of review: Many patients with inborn errors of immunity (IEI) reach the reproductive age these days. This systematic review focuses on possible complications during pregnancy in women with IEI.

Recent findings: The total number of pregnancies reported was 2531 in seven cohort studies. A total number of 97 pregnancies was described in case reports. Based on the cohort studies, there was an increased prevalence of preterm births (10.4-13%), caesarean sections (14-18%) and low neonatal weight at birth (4.5-16.5%) in women with IEI compared to control groups (P < 0.05). There was no difference in the prevalence of ectopic pregnancies, terminated pregnancies, gestational diabetes, spontaneous abortions and stillbirths in women with IEI compared to control populations based on the available cohort studies. Case reports showed infections in women with IEI were associated with premature delivery of the infant and an emergency caesarean section. Furthermore, women with IEI who previously experienced pregnancy complications, had uncomplicated pregnancies after immunoglobulin replacement therapy (IGRT).

Summary: There was a higher prevalence of preterm births, caesarian sections and low neonatal birth weight in pregnant women with IEI compared to control groups. Treatment of antibody deficiencies may lower the risk of pregnancy complications.

Purpose of review: Clinical data are reviewed pertaining to depemokimab, the first extended life anti-IL5 mAb, for treating severe eosinophilic asthma. This molecule was engineered through amino acid modification (YTE mutation) of the Fc region. This modification increases Fc receptor affinity and enables antibody recycling, thereby greatly extending serum half-life and will allow a dosing duration of 26 weeks.

Recent findings: Phase 1 and 3 clinical studies have demonstrated that depemokimab maintains drug concentrations and reduces peripheral eosinophils over a single 26-week dosing interval. A 52-week double-blinded, placebo-controlled (DBPC) Phase 3 study of patients with severe eosinophilic asthma demonstrated that depemokimab reduced annualized asthma exacerbations by 54% compared with placebo, the primary efficacy outcome. No significant differences between active and placebo arms were detected for secondary endpoints (e.g., symptoms, FEV1 and quality of life). Results of a noninferiority study comparing depemokimab, benralizumab and mepolizumab are pending. In a DBPC trial of chronic rhinosinusitis with nasal polyps (CRSwNP), depemokimab was also effective in reducing nasal polyp endoscopy scores and nasal obstruction.

Summary: Depemokimab could offer patients with severe persistent asthma a more convenient add-on treatment option than existing shorter acting biologics and thereby improve overall adherence.

Purpose of review: Omalizumab was approved by the U.S. Food and Drug Administration (FDA) to reduce allergic reactions from accidental exposures to food allergens in 2024. This review examines the current state of play including the most relevant studies supporting this approval and ongoing research regarding the use of omalizumab for food Allergy.

Recent findings: The OUtMATCH trial demonstrated omalizumab's effectiveness in increasing the reaction threshold to multiple foods in patients with multiple food allergy. New evidence from stage 3 of OUtMATCH suggests that omalizumab can further allow dietary consumption of allergenic foods. Ongoing studies are evaluating omalizumab's role compared to oral immunotherapy (OIT) and in combination with OIT.

Summary: Omalizumab represents an important treatment option for patients and families affected by food allergy. Significant progress has been made in understanding the drug's effects as a monotherapy and as an adjunct to OIT. As new evidence continues to emerge, the optimal use of omalizumab in managing food allergy will be further clarified.