Allergy and asthma proceedings最新文献

Background: Immediate hypersensitivity reactions (IHR) to ciprofloxacin can be caused by Mas-related G-protein coupled receptor X2 (MRGPRX2) as well as immunoglobulin E (IgE)-dependent mechanisms. When considering the complexity of the Patho mechanism, there are doubts with regard to the adequacy of conventional basophil activation test (BAT) in diagnosing fluoroquinolone-induced IHR. Our aim was to present a BAT method that relies on specifically evaluating the basophils expressing MRGPRX2 to increase the diagnosis rate of ciprofloxacin-induced MRGPRX2-mediated IHR. Methods: CD63 and MRGPRX2 expressions were analyzed with and without ciprofloxacin stimulation on basophils from patients and healthy controls by using flow cytometry. The net percentage of upregulation (net%) of MRGPRX2 and CD63 on basophils were statistically analyzed. Results: Fourteen patients with confirmed IHR to ciprofloxacin and age- and gender-matched 12 healthy controls were analyzed. The median (interquartile range) age of the patients was 39.5 years (33.5-51.5 years) and 92.9% were women. The median (interquartile range) net% expression of CD63 on basophils, MRGPRX2 on basophils, and CD63 on MRGPRX2⁺ basophils after ciprofloxacin stimulation was all higher in patients (18.1 [5.8-25.3], 3.7 [3.0-5.4], and 13.9 [7.8-28.8], respectively) compared with healthy controls (6.6 [3.8-11.4], 2.4 [0.6-3.7], and 1.3 [0.4-8.9], respectively) (p = 0.027, p = 0.042, and p = 0.001, respectively). Receiver operating characteristic analysis showed that the net% of CD63 expression on MRGPRX2⁺ basophils had a greater area under the curve to predict ciprofloxacin IHR than did the net% of CD63 expression on basophils. A net% > 10.3% of CD63 expression on basophils showed a sensitivity of 71.4% and a specificity of 75.0%, whereas a net% > 3.9% of theCD63 expression on MRGPRX2⁺ basophils showed a sensitivity of 100% and a specificity of 75.0%. The proposed method diagnosed four more patients compared with the conventional BAT. Conclusion: Analysis of our data indicated that the determination of MRGPRX2 together with CD63 in basophils improves the in vitro diagnosis of ciprofloxacin IHR with a better sensitivity compared with conventional BAT.

Background: Hereditary angioedema (HAE) attacks substantially impair health-related quality of life (HRQoL). Current World Allergy Organization and the European Academy of Allergy and Clinical Immunology guidelines goals include complete control and normalization of patients' lives. Garadacimab (anti-activated factor XII monoclonal antibody) reduced the mean attack rate after first administration in the pivotal phase III (VANGUARD; NCT04656418) and ongoing long-term phase III open-label extension (OLE) (NCT04739059) studies. Objective: To report exploratory HRQoL data from the interim analysis of the phase III OLE study (data cutoff February 13, 2023). Methods: Patients ages ≥12 years and with HAE received garadacimab 200 mg subcutaneously once monthly in the OLE study. The patient population comprised patients who were garadacimab naive (received placebo in the previous phase III study and newly enrolled patients) and patients who received garadacimab in previous phase II/III studies. The Angioedema Quality of Life (AE-QoL) questionnaire, Treatment Satisfaction Questionnaire for Medication version II (TSQM II), and Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire were administered at baseline and every 3 months during the OLE study. AE-QoL and TSQM II scores were evaluated in comparison with minimal clinically important differences (MCID). Results: Overall, 90 patients who were garadacimab naive and 71 patients with previous garadacimab exposure received garadacimab in the phase III OLE study. The mean ± standard deviation AE-QoL total score improved by 34.2 ± 18.8 points in patients who were garadacimab naive and by 2.3 ± 13.1 points further to the reduction experienced in patients with previous garadacimab exposure. The AE-QoL MCID was met by 92.1% of patients who were garadacimab naive; 81.6% of patients with previous garadacimab exposure experienced stable AE-QoL scores or further improvements per MCID. TSQM II scores were improved from day 1 with garadacimab and sustained to month 12. Improvements in WPAI:GH scores were consistent with AE-QoL and TSQM II. Conclusion: Garadacimab elicited clinically meaningful long-term improvements in HRQoL, work productivity, and treatment satisfaction in patients with HAE, which brought them closer to complete disease control and normalization of life.Clinical trial NCT04739059, clinicaltrials.gov.

Background: Value-based health care in the field of allergy/immunology must be informed by multiple factors, including costs (direct and indirect), outcomes, and the patient experience. Objective: We review features that define value-based health care and discuss a perspective that considers cost-effective care beyond the quality-adjusted life year (QALY). Methods: A narrative review and synthesis of the literature was leveraged to advance an understanding of health-care delivery that considers shared decision-making, health-economic outcomes, and the patient experience. Results: The patient and family experience of health and wellness must be considered carefully when interpreting health-economic evaluations. Health-state utilities consider trade-offs for wellness under conditions of risk and are used to inform QALYs for a myriad of disease states. Cost-effectiveness of medical therapies relates to trade-offs that are considered for populations, but these metrics can be translated holistically to inform health-care decisions for patients if considered contextually. In the case of food allergy, omalizumab would likely not be cost-effective on an individual level (incremental cost-effectiveness ratio, $573,698/QALY), but for those individuals with a high utility impairment, or, if considered from the perspective of a family unit, may be a more attractive therapy from a health-economic point of view. Conclusion: The balance between health and disease is such that there is always more disease than can be treated at any given moment, and both money and time can only be spent once. Because choice is inevitable, health-economic analysis can help inform clinical care. Still, translating population-level cost-effectiveness to individuals is challenging and decisions must be tailored to each patient and context.

Background: The cost-effectiveness of school environmental remediation in asthma is not known. The School Inner City Asthma Intervention Study (SICAS2) was a randomized controlled trial that assessed school integrated pest management (IPM) and classroom high efficiency particulate air (HEPA) filtration on asthma morbidity in urban schools. Objective: The objective was to evaluate the cost-effectiveness of SICAS2. Methods: We conducted a cost-effectiveness analysis from a societal perspective that compared four interventions: IPM, HEPA, IPM + HEPA, and no intervention. Quality-adjusted life years (QALY) were derived from the EuroQol-5 Dimension-Youth and EuroQol-5 Dimension-3 levels instruments. Total costs (2021 U.S. dollars) included intervention cost, cost of caregiver productivity impacted by child school absenteeism, and health-care utilization costs (e.g., emergency department visits). The evaluation period was based on a mean follow-up time of 166 days. Sensitivity analyses were performed by using cost estimates 50% above and below initial cost benchmarks. Results: A total of 154 SICAS2 participants were included. Intervention costs per student were $12.21 (IPM + HEPA), $7.27 (IPM), and $4.94 (HEPA). Sequential analyses revealed that IPM + HEPA was the most cost-effective option, with an incremental cost-effectiveness ratio of $19,667 per QALY. Sensitivity analyses demonstrated stability, with variability in probability estimates not exceeding 10%. Conclusion: IPM + HEPA demonstrated good value to society, which reflected the low cost and the economic impact of missed school days. This intervention may have a pronounced benefit for historically minoritized and marginalized children in urban schools who are disproportionately exposed to air pollution and indoor allergens. The SICAS2 intervention may offer a cost-effective tool to target proximal causes of disparities even in the most resource-limited schools.

Background and Aims: Asthma, overweight/obesity, and cancer are closely related major public health problems. This study aimed to investigate the interaction between asthma and overweight/obesity on the cancer risk. Methods: We analyzed data from the National Health and Nutrition Examination Survey 2005-2018. Participants ages ≥ 20 years with information on asthma status, body mass index (BMI), and cancer diagnosis were included. Multivariate logistic regression models adjusted for relevant covariates were used to examine the associations among asthma, overweight/obesity, and cancer risk. In addition, we assessed the additive interaction between asthma and overweight/obesity on the cancer risk by using measures, including the relative excess risk due to interaction (RERI), attributable proportion of interaction (AP), and synergy index (S). Results: In total, 26,320 participants met the inclusion criteria. Asthma was associated with an increased risk of cancer (odds ratio [OR] 1.37 [95% confidence interval {CI}, 1.17-1.59]), whereas overweight/obesity (BMI ≥ 25 kg/m²) was also significantly associated with an elevated cancer risk (OR 1.97 [95% CI, 1.32-2.94]). Notably, a significant interaction between asthma and overweight/obesity was observed in relation to the cancer risk (RERI 0.49 [95% CI, 0.02-0.96]; AP 0.20 [95% CI, 0.04, 0.37]; S 1.53 [95% CI, 1.01-2.32]). Conclusion: Our findings demonstrated a synergistic interaction between asthma and overweight/obesity on the cancer risk. The combined effect of asthma and overweight/obesity on the cancer risk exceeded the sum of their individual effects.

Introduction: Real-world evidence that compares the treatment patterns of targeted long-term prophylaxis (LTP) for hereditary angioedema (HAE), including berotralstat, lanadelumab, and subcutaneous (SC) plasma-derived C1 inhibitor (pdC1-INH) is limited. Objective: The study aimed to assess adherence and persistence after initiation of berotralstat, lanadelumab, or SC-pdC1-INH. Methods: Electronic health records linked to claims data was used to select patients ages ≥ 12 years, initiating one of three LTPs between June 22, 2017, and September 12, 2023, with mutually exclusive cohorts assigned hierarchically in reverse order of their U.S. Food and Drug Administration approval date. Patients were required to have ≥ 12 months of continuous enrollment before and after the LTP initiation date. Demographics and baseline clinical characteristics were captured. Primary study measures were adherence, defined as the mean proportion of days covered (PDC), and persistence, defined as having no gap in treatment ≥ 45 days after the LTP initiation date. A subgroup analysis was conducted among patients with two or more claims for their index LTP. A sensitivity analysis was performed by reassigning cohorts based on the first claim for qualifying LTP after June 22, 2017. Results: The main analysis included 357 patients (90 on berotralstat, 189 lanadelumab, and 78 SC-pdC1-INH). Overall, 46% to 51% of the patients had LTP experience. Adherence (mean PDC) was similar between treatments at 0.73, 0.78, and 0.74 for berotralstat, lanadelumab, and SC-pdC1-INH, respectively. Proportions of patients persistent on index LTP after 12 months were similar across LTPs: 61%, 58%, and 53% for berotralstat, lanadelumab, and SC-pdC1-INH, respectively. The findings of the subgroup and sensitivity analyses supported the main analysis. Conclusion: Adherence and persistence rates for all three LTP treatments were uniformly high. Berotralstat adherence and persistence were comparable with those observed after lanadelumab or SC-pdC1-INH initiation in the main analysis, among patients with two or more claims for their index LTP, and among cohorts assigned based on the first claim for qualifying LTP.

Background: The diagnosis and management of anaphylaxis in pediatric populations can be a particularly formidable challenge due to its variable definitions and atypical symptom presentation, which can often masquerade as other conditions. This complexity often leads to delays in early recognition and timely intervention. Most pediatric anaphylaxis guidelines emphasize the importance of identifying and avoiding triggers, ensuring accurate dosing and prompt administration of epinephrine to prevent severe complications. There is also growing scientific interest in strategies to intervene early in food allergy development to prevent allergies and protect infants and children from severe allergic reactions. Objective: This report aimed to review key aspects of the pathophysiology, epidemiology, management, and prevention of anaphylaxis in the pediatric population. Also, approved treatment modalities and future research to treat and prevent anaphylactic reactions are discussed. Methods: A review of the medical literature was conducted by using terms that included anaphylaxis, severe allergic reaction, pediatric, prevalence, desensitization, and immunotherapy. Results: Food allergies remain the leading trigger of pediatric anaphylaxis, followed by Hymenoptera venom, whereas drug allergies are less common in children compared with adults. A review of the literature underscores the importance of recognizing early signs and symptoms of anaphylaxis, particularly in preverbal infants, of identifying and eliminating key triggers and of prompt epinephrine administration in the immediate management of pediatric anaphylaxis. Advances in oral immunotherapy and other treatments (e.g., biologics) provide new management options. Notably, anti-immunoglobulin E therapy with omalizumab has shown substantial protection against reactions to accidental food exposure in children as young as 1 year old and with food allergy. Conclusion: This report explores critical aspects of anaphylaxis that affect allergic diseases in infants and children. Gaining a deeper understanding of age-specific triggers and the diverse symptoms of anaphylaxis will significantly enhance diagnosis, treatment, and prevention strategies, ultimately improving the timeliness of interventions. Recent approvals of novel therapies for food allergies, along with promising developments for future treatment and prevention of anaphylaxis in pediatric populations, hold exciting potential for better management of these conditions.

Angioedema is nonpitting swelling that involves the deeper subcutaneous and submucosal layers of tissue. Angioedema can be classified as histaminergic, bradykinin mediated, or idiopathic in etiology. Bradykinin-mediated angioedema presents without urticaria, whereas histaminergic angioedema is usually associated with urticaria (i.e., chronic spontaneous urticaria and angioedema) but manifests with isolated angioedema in ∼20% of patients and clinically overlaps with idiopathic angioedema. Bradykinin-mediated angioedema most commonly occurs in hereditary angioedema (HAE) with or without C1-esterase inhibitor (C1-INH) (HAE-C1INH) deficiency, acquired C1-INH deficiency, and angiotensin-converting enzyme (ACE) inhibitor angioedema. HAE is a life-threatening genetic autosomal dominant disorder most commonly due to a mutation in the serpin family G member 1 (SERPING1) gene, which leads to a deficiency in C1-INH, although multiple new genetic mutations have also been described in HAE with normal C1-INH (HAE-nl-C1INH) level. Clinically, patients have edema that can lead to life-threatening laryngeal edema and asphyxiation. HAE-nl-C1INH describes patients with similar symptoms to those with HAE-C1INH deficiency but have normal C1-INH function and are distinguished by various genetic mutations and a family history of angioedema. Acquired C1-INH deficiency also mimics HAE with symptoms but is due to circulating anti-idiotypic antibodies, leading to either C1-INH consumption or inactivation. Patients are often diagnosed with underlying malignant, lymphoproliferative, or autoimmune disorders. ACE-inhibitor angioedema classically presents with facial, tongue, and oral cavity swelling not associated with pruritus accompanied by normal laboratory studies. Treatment involves stopping the ACE inhibitor though recurrence can occur for a few weeks to months after discontinuation. Idiopathic angioedema is the largest category and is diagnosed when patients experience angioedema without an identifiable etiology with nl-C1INH function and no family history of angioedema. Idiopathic angioedema is further characterized into histaminergic or nonhistaminergic angioedema, depending on the response to high-dose antihistamines. Given the considerable impact of angioedema, physicians and patients must collaborate to craft personalized management strategies. For those with HAE, short- and long-term prophylaxis and on-demand therapy must be considered.

Background: Antibiotic allergy in children is often misdiagnosed. The criterion standard for confirming drug allergy is the drug provocation test (DPT) based on the patient's history and clinical findings. Objective: This study aimed to assess whether the characteristics and the severity grades of the index reaction can accurately predict DPT outcomes in children with suspected antibiotic allergy. Methods: A retrospective study was conducted from 2014 to 2024, which included children with immediate-type index and provocation reactions. Data included age, type, duration, severity grades of reactions, and suspected antibiotic. Reactions were graded by using the Brown scoring system. Statistical analyses included the Spearman correlation and kappa coefficient. Results: Seventy-three children with negative skin test results underwent DPT in this study. Urticaria was the most common reaction, which occurred in 46.6% of index and 57.5% of provocation reactions. Brown's grading showed 64 grade 1, 5 grade 2, 3 grade 3, and 1 ungraded index reactions. The Brown grading showed 64 grade 1, 5 grade 2, and 3 grade 3 reactions, and 1 ungraded index reaction. For provocation, 64 grade 1, 6 grade 2, 1 grade 3, and 2 were ungraded. There was moderate agreement between the index and provocation reaction types (kappa = 0.348; p < 0.001). A significant agreement was found between urticaria in the index reaction and anaphylaxis during the DPT (kappa = 0.173; p = 0.009). Moderate agreement was also observed for index and provocation anaphylaxis (kappa = 0.480; p < 0.001). In addition, a positive correlation was noted between the severity of the index and provocation reactions (Spearman = 0.460; p < 0.001). Conclusion: The severity and characteristics of index reactions provide valuable insight into the outcome of DPT. The Brown grading system is a valuable tool for predicting DPT outcomes, including severe reactions. Urticaria and anaphylaxis during the index reaction may be predictors of severe outcomes in DPT and should be closely monitored. Understanding the characteristics and severity of the index reaction and incorporating them into clinical practice may facilitate the prediction of DPT outcomes, guide clinical decision-making, improve diagnostic accuracy, and enhance patient safety.