Allergy Asthma and Clinical Immunology最新文献

Background: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare but potentially life-threatening hypersensitivity reaction characterized by skin rash, fever, lymphadenopathy, hematologic abnormalities, and organ involvement. Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is used to treat ovarian, fallopian tube, or primary peritoneal cancer. Although niraparib is associated with cutaneous toxicities, no severe cutaneous adverse reactions (SCARs) have been reported until now.

Case presentation: We present a case of DRESS syndrome in a 73-year-old woman with high-grade serous ovarian cancer treated with niraparib. After 20 days of therapy, she developed a widespread maculopapular rash. Despite discontinuation of niraparib and treatment with corticosteroids, she exhibited pruritus, facial edema, lymphadenopathy, eosinophilia, and impaired liver and renal function. A RegiSCAR score of 6 confirmed the diagnosis of DRESS. Patch testing to niraparib 1% in DMSO was positive when performed nine weeks after DRESS resolution.

Conclusions: This is the first reported case of DRESS by hypersensitivity due to niraparib. This case highlights the importance of recognizing DRESS as a potential adverse reaction to niraparib and the efficacy of early corticosteroid intervention. Further research is needed to understand and mitigate the risk.

Introduction: Asthma inhalers are significant contributors of greenhouse gas emissions. However, less is known about the potentially avoidable carbon footprint i.e. medication wastage and oversupply. We aimed to analyse dispensing patterns and carbon footprints of asthma inhalers, quantify medication wastage, and identify determinants of medication oversupply.

Methods: We reviewed the asthma-related dispensation records from 2015 to 2019, in an anonymised, cluster-wide repository linking electronic medical, pharmacy and administrative records, containing patient and visit details on demographics, comorbidities, GINA step, and site of care. Medication wastage, a visit-level measure, was defined as the number of inhalers dispensed in excess of the quantity required during each refill interval. Medication oversupply, a patient-level aggregated measure defined by medication possession ratio (MPR) > 1.2, where MPR equals total dispensed days (summed across all maintenance inhalers) divided by the follow-up period. All analyses were performed using R Studio.

Results: 205,337 inhaler units were dispensed over the study period, contributing an estimated 1,541,591 kgCO2e. The most frequently prescribed inhalers were SABA MDIs (79,007 units; 38.5%), followed by ICS-LABA MDIs (46,335 units; 22.6%), ICS MDIs (36,635 units; 17.8%), ICS-LABA DPIs (33,730 units; 16.4%), and ICS DPIs (9,630 units; 4.7%). ICS-LABA MDIs remained the greatest contributor of carbon footprint, with annual carbon emissions nearly doubling from 114,476 kgCO2e in 2015 to 214,575 kgCO2e in 2019. A total of 6,427 canisters were dispensed in excess of refill intervals, accounting for 46,798 kgCO2e. Beclomethasone MDIs accounted for the majority of wasted inhalers. In a multinomial regression analysis, patients receiving care in primary care settings were significantly more likely to be oversupplied medications compared to those in specialist care (OR 1.93, 95% CI 1.49-2.51).

Conclusion: ICS-LABA MDIs are the predominant source of inhaler-related carbon footprint, with additional contribution from excessive dispensation of inhalers.

Background: Unverified drug allergy labels are common and associated with significant patient harm, yet infrastructure and testing practices vary across clinical settings in Canada.

Objective: To characterize variability in drug allergy management among allergists in Canada and identify setting-specific barriers to drug allergy testing and desensitization.

Methods: We developed a peer-reviewed 40-item survey, distributed via the Canadian Society of Allergy and Clinical Immunology, to assess practice patterns, testing modalities, and perceived barriers among allergists. Descriptive statistics and Fisher's exact test were used to evaluate responses by practice setting.

Results: Sixty-six allergists responded (30% estimated response rate), with 48.4% solely practicing in community clinics and 21.9% solely in hospital-based clinics. While 87.9% performed some form of drug allergy testing, hospital-based allergists were significantly more likely to perform intradermal (81.1% vs. 48.7%, p = 0.004) and patch testing (38.2% vs. 8.8%, p = 0.009), as well as non-oral drug challenges (63.6% vs. 20.0%, p = 0.0005). Common barriers included a lack of nursing support and inadequate reimbursement.

Conclusion: Drug allergy management practices vary substantially across Canada, with drug allergy testing being more frequently performed by allergists practicing in hospital-based clinics than by those in community-based clinics. Findings support the need for equitable access to testing infrastructure and system-level investments in improving drug allergy testing services.

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.