Allergy Asthma and Clinical Immunology最新文献

Background: Mastocytosis is driven by a clonal expansion of mast cells, commonly triggered by the KIT D816V mutation which is present in over 90% of adult patients. Individuals with indolent systemic mastocytosis (ISM) frequently experience recurrent anaphylaxis and mast cell mediator-related symptoms, leading to substantial morbidity. In rare cases, progression to more severe subtypes, such as smoldering systemic mastocytosis (SSM), can occur.

Case presentation: We describe one patient with ISM and another with ISM transitioning to SSM, both treated with the selective KIT D816V inhibitor avapritinib at a daily dose of 25 mg. Following initiation of avapritinib, both patients exhibited a marked reduction in serum tryptase levels and complete remission of maculopapular cutaneous mastocytosis. Additionally, joint pain, gastrointestinal symptoms, and neurocognitive complaints decreased. Sustained clinical improvement over follow-up periods of 9 and 12 months was consistently reflected in disease-specific patient-reported outcome measures (PROMs).

Conclusions: Regular clinical and laboratory monitoring, including serum tryptase and KIT D816V mutation assessment in peripheral blood, is essential in all ISM patients to detect early signs of disease progression. In refractory cases, avapritinib is a promising therapeutic option that can reduce mast cell burden, alleviate symptoms, and enhance overall quality of life.

Background: Allergic bronchopulmonary aspergillosis (ABPA) presents with a wide range of symptom severity, with severe disease manifestations being harder to control through conventional inhalers. While corticosteroids remain a standard treatment option, their use is often hindered by significant adverse side effects. This case series discusses a novel treatment of duo-administration of monoclonal antibodies for two patients that reduced their exacerbations, spared the use of steroids, and improved their quality of life.

Case presentation: Both patients were diagnosed with ABPA. Before the administration of treatment, they experienced almost monthly exacerbations and infections requiring constant systemic oral corticosteroids and antibiotics. After the implementation of successive concomitant monoclonal antibody treatments, absolute eosinophil levels were brought down to normal levels, and the monthly exacerbations were eliminated.

Conclusion: This case series describes a novel approach for ABPA therapy that holds potential in improving patient outcomes for those with severe ABPA. Duo biologic therapy may improve disease control and reduce corticosteroid reliance in patients with refractory ABPA by targeting multiple mechanistic pathways of inflammation. Mepolizumab with Omalizumab offers a potential treatment strategy to reduce exacerbation frequency and severity and has minimal adverse effects.

Background: Food allergy imposes considerable financial costs on families, but few programs are available in Canada to offset these costs. To fill this gap, we developed, piloted, and evaluated a program designed to address the financial burden of food allergy.

Methods: The current study employed the use of an unblinded, crossover design. Participating families who began the study in the case condition received biweekly deliveries of food packages for 2 months, while those in the control condition received recipes and educational materials. Following the initial study period, the groups entered a one-month washout period and the conditions were reversed. During both conditions, an adult member of each participating family ("caregivers") responded to a quantitative cost measure and completed a qualitative interview. Quantitative data were analysed using a series of linear mixed models. Qualitative data were analysed using thematic analysis.

Results: A total of 14 participants were randomized to a sequence using Stata. However, 5 participants were dropped from the final quantitative sample due to a failure to complete one or more set of quantitative measures. Caregivers included in the final quantitative sample were 32.1 years old, on average, overwhelmingly female (89%), and had annual, after-tax, household income of $52,660.00 (SD=$23,188.92; CAD). Target children were largely under six years old (89%) and were evenly split between boys (44%) and girls (44%). Milk (67%), peanut (67%), and egg (67%) allergies were most common. Quantitative results revealed participants had non-significantly lower indirect costs in the food delivery condition ($724.56 vs. $797.83), largely because of lower food preparation costs ($561.41 vs. $656.15). In contrast, participants reported non-significantly higher direct costs when they were receiving the food packages ($678.47 vs. $655.56). Findings from the qualitative interviews suggest that this increase may reflect the fact that participants purchased more expensive grocery items in response to the cost savings afforded by the program.

Conclusions: Participants derived several benefits from the program, but more research is needed to better understand how to maximize the impact of programs like NOURISH-US and to identify families most in need of financial support.

Background: Since 2015, our nasal allergen challenge (NAC) protocol has been used to investigate the pathophysiology of allergic rhinitis (AR) with various allergens. However, we have yet to publish a comprehensive examination of the pathophysiology associated with AR to ragweed pollen.

Methods: Nineteen ragweed pollen allergic and 12 healthy (nonallergic) control participants from Kingston, Ontario, Canada, completed the NAC to ragweed pollen extract out-of-season. Total nasal symptom score (TNSS) and percent fall in peak nasal inspiratory flow (PNIF) were collected up to 48 h post-exposure. Nasal fluid and serum samples were collected post-exposure, and white blood cell differential counts, serum ragweed-specific and total immunoglobulin-E (IgE), and nasal cytokine concentrations were analyzed. Statistical tests were performed using GraphPad Prism 10.4.0.

Results: The mean TNSS and percent PNIF fall from baseline were significantly higher in participants with ragweed pollen allergy compared to nonallergic controls up to 24 h (P ≤ 0.05) and 12 h (P ≤ 0.05) post-NAC, respectively. Nasal eosinophils significantly increased in allergic participants at 6 h (P = 0.0010) and 24 h (P = 0.0049), while peripheral blood eosinophil percentages decreased significantly at 6 h compared to baseline (P = 0.0499). The specific to total IgE ratio for allergic participants significantly increased 1 h and 24 h (P = 0.0022 and P = 0.0034, respectively) post-NAC, with a decrease at 6 h compared to both 1 h and 24 h (P = 0.0224 and P = 0.0316, respectively). Allergic and nonallergic participants had significantly different cytokine profiles, particularly IL-4, IL-5, IL-6, IL-13, MIP-1β, and TNF-α.

Conclusions: This study confirms the effectiveness of our NAC protocol in eliciting clinical and biological responses in ragweed-allergic participants, particularly highlighting eosinophil activity, IgE, and cytokine dynamics. Future research should investigate the roles of specific IgE, IL-4, and eosinophil activation in allergic inflammation. Additionally, this NAC study population provides a strong foundation for examining the nasal microbiome in AR. Longitudinal studies exploring the relationship between allergic responses and microbiome shifts could offer deeper insights into the underlying mechanisms of disease.

Background: The use of in vivo and ex vivo diagnostic tools for delayed hypersensitivity reactions (DHRs) associated with iodinated contrast media (ICM) is currently ill-defined.

Objective: To evaluate the role of in vivo and ex vivo diagnostic tools for DHRs occurring >6 h following intravenous low-osmolality ICM.

Methods: We conducted a prospective, multicenter, international cohort study. The patients were recruited from two tertiary care adult allergy clinics, Austin Health, Australia and the McGill University Health Centre, Canada. Eligible participants were adults who reported a DHR after receiving ICM. In vivo testing (skin testing and intravenous challenge) was performed to identify an alternative agent. Ex vivo testing using interferon-γ enzyme-linked ImmunoSpot assay was performed in four Australian patients to explore its diagnostic performance.

Results: The culprit ICM was identified by dIDT in 17/20 (85%) while in 3/20 (15%) a challenge was necessary to confirm delayed hypersensitivity. All patients with a positive dIDT to iohexol were positive to iodixanol (15/15; 100%) while 3/4 (75%), 3/4 (75%), 4/6 (67%), and 3/5 (60%) were positive to iopromide, ioversol, iopamidol, and iobitridol, respectively. Overall, 7/20 (35%) patients tolerated a challenge with an alternative ICM. The IFN-γ release assay was negative for the implicated ICM in 4 patients with confirmed DHR through a positive dIDT.

Conclusion: dIDT allowed confirmation of T cell-mediated allergy to the implicated ICM in 85% of patients with a strong clinical suspicion of DHR and identification of non-cross-reactive ICM in 35% of patients. The IFN-y ELISpot was not useful in the four patients tested.

In recent years, the use of monoclonal antibodies directed against interleukin-5 (anti-IL-5) and its receptor alpha (anti-IL-5R) has proven to be an effective therapeutic option for patients with severe asthma by reducing the number of eosinophils, which may promote disease remission. This study aimed to evaluate clinical improvement and remission in patients with severe asthma treated with anti-IL-5 and anti-IL-5R antibodies over a period of 12 months. A cohort study was conducted with 49 patients diagnosed with severe eosinophilic asthma and who did not respond to conventional treatment. During follow-up, medical control was performed every 3 months using spirometry, eosinophil counts, quality of life scales, and disease control. The results revealed an improvement in FEV1 after 3 months of treatment, with statistical significance at 12 months in patients treated with anti-IL-5 and at 9 months in those treated with anti-IL-5R. In addition, better perceptions of asthma control and quality of life were observed, with significant differences at 6 and 12 months. Correlations between spirometry and ACT, ACQ, and AQLQ reflect a progressive recovery of well-being and function. Finally, the remission rate was 41.1% with anti-IL-5 treatment and 47.3% with anti-IL-5R treatment after one year of follow-up. These findings support the efficacy of anti-IL-5 and anti-IL-5R treatment in improving severe asthma control and patients' quality of life, suggesting their key role in disease remission.

Background: Cat allergen is the second most common cause of perennial allergic rhinitis. Despite its prevalence (~ 20% of the population), many patients continue to suffer from persistent symptoms due to constant exposure to cat allergens that reduce treatment efficacy. Modelling of the disease can improve our understanding of its onset and progression. The Specialized Particulate Control Environmental Exposure Unit (SPaC-EEU) is a controlled allergen challenge facility that has recently undergone a successful technical validation for cat dander exposure, measuring Felis domesticus 1 (Fel d 1). We then sought to perform a clinical validation with cat-allergic and non-allergic participants.

Methods: This study consisted of 3 visits. Recruited participants attended a Screening visit where eligibility was assessed, and a skin prick test (SPT) was completed. Successfully screened cat-allergic and non-allergic participants were invited back for the Allergen Exposure visit. They attended one of two 3-hour cat dander exposure Sessions in the SPaC-EEU, due to space limitations, with a target Fel d 1 concentration of 70 ng/m³. Fel d 1 concentrations were collected using air sampling cassettes and processed using a Fel d 1-specific ELISA. Real-time particle counts were monitored using a laser particle counter (LPC). Participants recorded symptom scores at time points from baseline up to 24 h post-onset of allergen exposure. Participants returned to the research site for a 24-hour Follow-up visit. Allergic participants completed a cat exposure and Quality of Life questionnaire.

Results: Forty-six (31 cat-allergic and 15 non-allergic) participants completed this study. Allergic participants had significantly larger (p < 0.0001) SPT wheals to cat hair than non-allergic controls. Twenty-five participants attended the first Session (mean Fel d 1 = 35.7 ng/m³), and 21 participants attended the second Session (mean Fel d 1 = 102.3 ng/m³). No significant differences in symptom and safety scores were observed between Sessions, hence participants' data were pooled. Allergic participants experienced significantly elevated (p < 0.05) Total Nasal Symptom Scores and Total Rhinoconjunctivitis Symptom Scores from 15 min to 24-h post-onset of allergen exposure and significantly decreased (p < 0.05) percent change in Peak Nasal Inspiratory Flow from 1 to 3 hours, compared to non-allergic controls. Mean Quality of Life scores were different between phenotypes, unimpacted by whether or not one lived with a cat.

Conclusion: The SPaC-EEU can safely produce clinically relevant nasal symptoms in only cat-allergic participants, highlighting its use for modelling cat allergen-induced allergic rhinitis.

Background: Allergic rhinoconjunctivitis (ARC), asthma and eczema carry a substantial morbidity. These conditions often co-exist within the same individual and their prevalence can differ based on age, ethnicity and gender.

Objectives: Using a UK primary care database, we estimated the trends in prevalence over the last decade for ARC, asthma and eczema and associated risk factors.

Methods: Longitudinal cohort analysis of the health improvement (THIN) database between 1st Jan 2010 and 1st Jan 2019. Logistic regression analysis was used to explore risk factors for diagnosis of these conditions.

Results: An average of 4.17 million records per year were analysed, 19.4% were children and 49.75% were male. There was an increase in prevalence of ARC, asthma and eczema amongst adults during the study period, whereas ARC and asthma prevalence amongst children has fallen. By 2018, 1:8 adults and 1:14 children had ARC; asthma was diagnosed in 1:7 adults and 1:10 children whereas eczema was diagnosed in 1:6 adults and 1:4 children respectively. There were regional discrepancies in allergy prevalence across the UK. Caucasians generally had the highest rates of asthma and lower rates of ARC compared with other ethnic groups. Having other allergies substantially increases the odds of having asthma, eczema and ARC.

Conclusion: The population burden of ARC, asthma and eczema in the UK is substantial. These conditions are often associated with other allergies and can, therefore, be complex to manage. These data support calls for improvement of pathways of care for allergy patients in the UK.