Annals of Allergy Asthma & Immunology最新文献

Background: Obesity is a risk factor for poor asthma control. Previous research suggests that patients with asthma and obesity have reduced responsiveness to corticosteroids. Recent studies indicate that body fat percentage may be more strongly associated with obesity-related diseases compared with body mass index. However, the relationship between body fat percentage and asthma, particularly regarding steroid sensitivity, remains unclear.

Objective: This study aimed to investigate the association between body fat percentage and steroid sensitivity in patients with asthma and elucidate the potential mechanisms underlying this association.

Methods: Adult patients with asthma were enrolled and categorised into high body fat percentage (HBF) and control (CONT) groups. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples. These cells were cultured with dexamethasone followed by stimulation with tumour necrosis factor (TNF-α) to assess the half-maximal inhibitory concentration of dexamethasone (IC50-Dex). Serum adipocytokines and oxidative stress markers were also measured. The effects of metformin on steroid sensitivity and oxidative stress in PBMCs were evaluated ex vivo.

Results: The HBF group exhibited significantly higher IC50-Dex values than the CONT group. In the HBF group, IC50-Dex correlated with the number of acute exacerbations per year and serum oxidative stress marker levels. Treatment with metformin significantly reduced both IC50-Dex and oxidative stress marker levels in the HBF group.

Conclusion: Oxidative stress associated with increased body fat may contribute to impaired steroid sensitivity in patients with asthma. Metformin may improve steroid sensitivity by reducing oxidative stress, suggesting a potential therapeutic approach in this patient population.

Excessive anxiety regarding the potential for accidental and fatal cross-contamination is very common among patients and families with food allergy and contributes significantly to burden, reduced quality of life, and poorer management. In their landmark paper published nearly a decade ago, Dinakar and colleagues recommended that food allergists incorporate proximity food challenges such as smelling or touching an allergen into regular clinical practice to improve patient knowledge regarding safety and relative risk and reduce anxiety. Such proximity challenges are akin to the exposure tasks routinely employed to treat anxiety in cognitive-behavioral therapy (CBT), the first-line psychosocial intervention for anxiety disorders. Exposure is a highly evidence-based therapy technique where patients - guided and encouraged by their providers - directly and strategically confront a feared object, situation, or activity. Anxiety eventually diminishes and erroneous beliefs are corrected when exposures happen repeatedly in the absence of the feared negative outcome. Following a summary of the history and evidence-base for exposure in both the psychiatric and food allergy literature, we review several considerations related to conducting in-office proximity challenges. Topics include in-office assessment of food allergy anxiety and medically unnecessary avoidance; choosing appropriate, individualized proximity challenges based on patient presentation; and practical considerations in carrying out in-office proximity challenges to maximize benefits to anxious patients.

Background: Protease-activated receptor 2 (PAR-2) and IL-13 receptor α1 (IL-13Rα1) play major roles in type 2 inflammation. However, most of the literature was limited to allergic asthma.

Objective: This study examined how these receptors contribute to upper respiratory tract inflammation and explored potential therapeutic targets in patients with eosinophilic chronic rhinosinusitis (eCRS).

Methods: Using protein interaction analysis, animal experiments, and human tissue samples, we assessed the effects of exposure to house dust mite (HDM) allergen on PAR-2 and IL-13Rα1 activation and inflammatory markers, as well as the impact of the PAR-2 antagonist GB88. A fluorescent multiplex staining kit was used along with specific antibodies to label and detect proteins in the immunofluorescence tissue samples.

Results: Close relationship between PAR-2 (F2RL1), SPI-1, IL-13Rα1, and RNASE2 (EDN) was noted in protein interaction analysis. HDM exposure significantly activated PAR-2 and IL-13Rα1 in nasal epithelial cells, leading to Th2 cytokine release (IL-25, IL-33 & TSLP) and elevation of eosinophil proteins (ECP and EDN) that intensify upper respiratory tract inflammation. The PAR-2 antagonist GB88 reduced HDM allergen-induced PAR-2 and IL-13Rα1 expression, STAT-6 phosphorylation, and eosinophil infiltration, and decreased inflammatory markers. PAR2/SPI-1/ IL-13Rα1 was validated in IHC and IF analysis of human chronic rhinosinusitis specimens.

Conclusion: The PAR-2/IL-13Rα1 pathway is a promising target for treating upper respiratory tract inflammation. PAR-2 inhibitors could reduce inflammation and improve the outcomes of upper respiratory tract diseases, like eCRS.

Tryptase is currently the most specific mast cell biomarker available in clinical laboratories. Tryptase levels in peripheral blood contribute to the diagnostic, prognostic and therapeutic evaluation of three clinical categories: (1) immediate hypersensitivity reactions including the life-threatening systemic form known as anaphylaxis, (2) clonal mast cell diseases and other myeloid malignancies, including as a biomarker for efficacy of chemotherapeutic agents targeting mast cell survival, and (3) hereditary α-tryptasemia (HαT), a genetic trait found in 4 - 8% of general population associated to increased risk of severe immediate hypersensitivity reactions. Rapidly evolving pathophysiology knowledge and management guidelines impact tryptase use in clinical practice, explaining the need for frequent updates. Such updates often lack context on the pathophysiology and methods regarding mast cells and tryptase, thus hampering the practicing clinician's ability to get the full picture from tryptase test results. Here, we provide the practicing physician with the 2025 state-of-the-art recommendations on tryptase use and interpretation in clinical practice, also exposing their basic, clinical and technical foundations. Successive additions to mast cells and tryptase research are summarized and revisited in the light of today's knowledge. The review sections are titled to reflect matter-of-fact questions arising in clinical practice. Currently unmet needs of tryptase use and selected lines of ongoing research expected to influence clinical practice in the near future are also presented.

Background: Severe asthma presents a major challenge to healthcare and negatively affects the quality of life of the patients. Understanding on the factors predicting the development of severe asthma is limited.

Objective: This study aimed at characterizing patients with severe asthma and establishing risk factors for the development of severe asthma in a Finnish sample with a nationwide coverage of population, healthcare and drug register data.

Methods: We used data from January 1st, 2014 to December 31st, 2020. Pooled data over the years were used to identify characteristics of patients with severe asthma. Annual data were used in machine learning methods and logistic regression to identify factors predicting the development of severe asthma.

Results: Analysis of pooled data including 242,164 individuals showed that patients with severe asthma were more often women, slightly older, multimorbid and had higher body mass index values compared to patients with non-severe asthma. They also had higher use of non-asthma-related medications, manifesting as polypharmacy. Annual data from 6,908 patients showed that the most significant predictors of the development of severe asthma were being aged 51-60 (odds ratio (OR) 3.90 [95% confidence interval (CI): 3.42-4.47], chronic sinusitis (OR 2.48 [95% CI: 2.12-2.89]) and higher blood eosinophil counts (≥600 cells/μl, OR 2.10 [95% CI: 1.56-2.28]). Increases in all medications (non-asthma and asthma medications) were observed in the year before the onset of severe asthma.

Conclusion: The results provide a clinically relevant risk factor profile for early identification of the patients at risk of developing severe asthma.

Background: While fatal food-induced anaphylaxis is rare, adolescence is the period of highest risk. However, we lack strong estimates of the incidence of food allergic reactions among adolescents.

Objective: To estimate the incidence of food allergic reactions and anaphylactic reactions among adolescents with food allergy who have a prescription for epinephrine.

Methods: As part of a cohort study that was embedded in a randomized trial to promote safe food allergy management, we followed adolescents ages 15-19 years with food allergy and a current prescription for epinephrine for a period of 15 months in 2019-2020. At monthly intervals, participants were asked, via text message check-in, whether they had experienced a food allergic reaction due to accidental exposure to food allergens in the past month.

Results: Among the cohort of 131 adolescents, 112 answered at least one of the 15 monthly check-ins. Together, these respondents contributed 742 person-months of follow-up data out of a total possible 1,680 person-months. Over the 15-month study period, the incidence of food allergic reactions among adolescents with food allergy was 34.0 events per 100 person-years (95% CI: 21.0, 51.9). The incidence of food allergic reactions meeting the criteria for anaphylaxis was 16.2 events per 100 person-years (95% CI: 7.8, 29.7).

Conclusion: Data on the incidence of food allergic reactions can help set expectations for safe food allergy management for adolescents and their families and can help inform discussions between patients, families, and physicians regarding different treatment options available and their associated risks and benefits.

Background: Sublingual immunotherapy (SLIT) is a safe, effective therapy for the treatment of food allergy. Studies demonstrating SLIT efficacy have primarily used pharmaceutical glycerinated food extracts for the administration of food allergens, which may limit accessibility due to extract cost and availability.

Objective: To develop novel sample protocols and resources for the preparation of grocery-sourced real food SLIT solutions, which could help more clinicians incorporate food SLIT into their practice and increase accessibility to this treatment. Secondly, to describe our site's experience with real food SLIT implementation.

Methods: Three- and five-dose build-up protocols were developed using powdered or liquid-based forms of food allergens, with a maintenance dose of 2-4 mg protein/day. Patient adherence and satisfaction data were collected via online surveys. After 1-2 years of daily real food SLIT maintenance dosing, patients were offered a low-dose oral food challenge (OFC) (cumulative dose, 330-340 mg protein).

Results: Sample protocols for real food SLIT were developed for 31 foods, including peanut, cow's milk, cashew, egg, and sesame. At our site, 305 patients have undergone or are currently undergoing real food SLIT. Of 162 satisfaction survey respondents, 99% (n=160) were satisfied or very satisfied with their care. Adherence surveys showed that 82% of respondents (n=105/128) reported consistently taking their SLIT dose. Among a subset of 33 patients, 57 low-dose OFCs were performed, of which 70.1% (n=40) were successful.

Conclusion: Grocery-sourced real food SLIT solutions present another food SLIT option that may expand the feasibility and accessibility of this safe and effective food allergy immunotherapy.