Allergy and asthma proceedings最新文献

Perioperative anaphylaxis is a serious entity with high morbidity and mortality. Perioperative anaphylaxis can be caused by any of the multitude of medications and substances used in anesthesia and surgery, and the most common causes include neuromuscular blocking agents, antibiotics, antiseptics, latex, and dyes. The differential diagnosis of perioperative anaphylaxis is wide from both an immunologic and a nonimmunologic standpoint. The majority of the intraoperative anaphylaxis reactions are thought to be immunoglobulin E (IgE) mediated; however, other primary non-IgE-mediated mechanisms can also be present. Clinical manifestations can vary from mild cutaneous exanthema to cardiac arrest. Tryptase can be helpful in identifying perioperative anaphylaxis. In this article, we present the case of a 75-year-old man who had a cardiac arrest without skin symptoms perioperatively during coronary artery bypass surgery. We describe the presentation, strategic evaluation, and subsequent management with recommendations for future surgery based on his evaluation and the identified culprit. Subsequent surgery was later completed. Understanding the clinical presentation, key components of testing, and recommendations for future management of perioperative anaphylaxis are invaluable skills that the allergist can provide for the patient and the anesthesia and surgery teams.

Background: Despite the use of long-term prophylaxis (LTP) for hereditary angioedema (HAE), the risk of having an attack remains and patients with HAE and on LTP may still experience attacks that can be life threatening. However, the behavioral patterns and perspectives surrounding HAE attack management by patients on LTP are not fully understood. Objective: This survey aimed to better understand and compare the behavioral patterns and perspectives, including attitudes and perceptions associated with on-demand treatment among patients on LTP versus those using on-demand therapy only. Methods: People living with HAE were recruited by the US Hereditary Angioedema Association to complete a 20-minute online survey between September 6 and October 19, 2022. Participants were stratified by treatment (50% using LTP [+on-demand therapy], 50% on-demand therapy only). Results: Respondents included 107 patients with HAE (mean age, 41 years [range, 16-83 years]). Patients using LTP reported treating a mean ± standard deviation 84.8% ± 23.8% of their HAE attacks compared with a mean ± standard deviation 75.6% ± 27.5% for patients with on-demand only treatment. Similar percentages of patients on LTP versus patients on-demand only reported always carrying on-demand treatment when away from home (35% versus 38%) and modifying their daily lives to minimize the occurrence of HAE attacks, which included avoiding potential triggers (42.9% versus 45.5%). Conclusion: Although patients on LTP treat a higher percentage of their attacks compared with patients with on-demand only treatment, both groups reported similar behaviors in terms of carrying on-demand treatment when away from home and modifying their daily lives to minimize the occurrence of HAE attacks. These findings highlight the importance of understanding patient perspectives and behaviors in the management of HAE.

Since its first description more than a decade ago, our understanding of the clinical impact of hereditary alpha-tryptasemia has continued to evolve. First considered to be a genetic disorder with a subset of patients having a syndromic presentation composed of connective tissue abnormalities, symptoms of autonomic dysfunction, and findings of mast cell activation, we now know that hereditary alpha-tryptasemia is a common genetic trait and modifier of mast cell-mediated reactions. More recent studies have shown some previously held associations with congenital hypermobility and postural orthostatic tachycardia syndrome (POTS) to be lacking, and illuminated previously unappreciated associations with clonal and nonclonal mast cell disorders. With the discovery of heterotetrameric tryptases and demonstration of their unique functional activities, the importance of tryptase gene composition in general has begun to take focus. Hereditary alpha-tryptasemia exists at the end of a spectrum of alpha-tryptase expression and as a natural overexpression model of this protein, brought to the fore the potential of tryptase genotyping as a genetic biomarker for anaphylaxis severity. These data and future studies hold the promise of enhancing our understanding of the role that tryptases play in health and disease.

Background: Atopic dermatitis (AD), a common chronic inflammatory skin disorder is characterized by a complex pathology with skin-barrier abnormalities, immune dysregulation, and microbial dysbiosis. Patients' quality of life is often negatively impacted by persistent pruritus, sleep disturbance, and recurrent skin infections. In addition, patients may have comorbid atopic as well as nonatopic diseases. Objective: The objective was to help clinicians better manage AD by using new therapies and new indications, including a topical (Janus kinase [JAK]) inhibitor as well as monoclonal antibodies and oral JAK inhibitors, have been approved for AD. Methods: This review presents highlights from the American College of Allergy, Asthma and Immunology AD Yardstick Update, which incorporates Expert Commentary, and from the Joint Task Force (JTF) AD 2023 Guidelines that use Grading of Recommendations, Assessment, Development, and Evaluation methodology. Results: Practical pearls from the AD Yardstick Update Expert Commentary are presented, along with results from systematic reviews and meta-analyses that addressed specific recommendations on the role of (1) dilute bleach baths, (2) dietary avoidance and/or elimination diets, (3) allergen immunotherapy, (4) topical treatments, and (5) systemic treatments, informing the JTF 2023 AD Guidelines. These guidelines are noteworthy for addressing patient values and preferences. Conclusion: The AD Yardstick Update Expert Commentary and JTF 2023 AD Guidelines provide timely, practical, and trustworthy information to help clinicians manage patients with AD.

Background: The United States Pharmacopeia (USP) Chapter 797 provides critical standards for compounding sterile preparations to ensure patient safety and medication efficacy. The latest revision, effective November 1, 2023, introduces updates particularly relevant to the compounding of allergenic extracts, which emphasizes stringent compliance measures. Objective: This article aims to review the key updates to USP Chapter 797, outline the compliance requirements for personnel and facilities, and offer strategies for staying current with these practice guidelines, leveraging resources from professional organizations such as American College of Allergy, Asthma, and Immunology and American Academy of Allergy, Asthma, and Immunology. Methods: An extensive review of the updated USP Chapter 797 guidelines was conducted, along with supplementary research from professional resources and literature to provide a comprehensive overview of the new standards and best practices for compliance. Results: The updated USP Chapter 797 mandates comprehensive training and competency testing for compounding personnel, facility maintenance and documentation standards, and robust quality assurance protocols to minimize contamination and ensure the efficacy of compounded allergenic extracts. Key requirements include enhanced personnel hygiene and garbing requirements, facility maintenance protocols, and detailed documentation practices. Conclusion: Staying current with USP Chapter 797 and practice guidelines is crucial for allergists and immunotherapy practitioners to ensure high standards of patient care and safety. By understanding the key updates, complying with personnel and facility requirements, leveraging professional resources, and adopting standardized practices, health-care providers can effectively navigate the evolving regulatory landscape. Continuous education and adherence to quality assurance protocols will further support compliance and enhance patient outcomes in allergen immunotherapy.

Background: Unconfirmed penicillin allergies over time lead to poor health outcomes and increased health-care cost. Health disparities (HD) can create barriers in optimizing penicillin allergy care. Objective: The objective was to characterize HDs in our primary care-led amoxicillin challenge (PLAC) delabeling pathway within a universal coverage health care system. Methods: In three outpatient clinic sites, 41,104 patients were screened, and 1,749 patients were discovered to have penicillin allergies. Of the 1,749 patients with penicillin allergy, 336 (ages 4 months to 76 years) were determined to be candidates for PLAC. A retrospective chart review was completed after 1 year of PLAC implementation to compare demographic characteristics and HD core categories (neighborhood living type, economic stability, background education status, and access to care) between those who completed and those who did not complete their PLAC appointment. All candidates underwent the same PLAC protocol and had universal health coverage that reduced health cost. Results: Of 336 PLAC candidates (45.8%), 154 presented for their PLAC appointment and had their penicillin allergy removed without adverse outcomes. One hundred and eighty-two candidates (54.2%) did not complete a PLAC appointment and retained their penicillin allergy label. Candidates who did not complete their PLAC appointment were older (p = 0.001) and white (p = 0.006), and did not identify as officers (p = 0.04). There was no significant difference in neighborhood type or gender between the groups. In candidates ages ≥ 19 years, those without proactively scheduled appointments more commonly (p < 0.001) did not complete their PLAC appointment; whereas proactive scheduling increased delabeling from 5.8% to 91.3% in candidates ages ≥ 19 years. Of the 199 candidates with proactively scheduled PLAC appointments, those with less perceived economic stability and background education status (enlisted members) were more likely not to attend their PLAC appointment (p < 0.001). Conclusion: Results of our study suggest that our PLAC protocol provides a foundation of decreased HDs to successfully delabel patients at low risk of penicillin allergy when scheduling appointments for all and controlling for health-care cost.

Background: Idiopathic non-mast cell angioedema (INMA) is a rare disease typified by recurrent attacks of cutaneous and subcutaneous swelling. Every attack carries the potential for severe morbidity and, in the case of laryngeal involvement, mortality. Whereas therapies approved for hereditary angioedema (HAE) have been used in the care of patients with INMA, little is known with regard to their efficacy for the treatment of this disease. Objective: The objective was to gather evidence from global experts, ranking their assessment of on-demand therapy (ODT) and long-term prophylactic (LTP) treatment efficacy for INMA. Methods: A survey was developed and distributed to international experts invited to attend a 2023 symposium. INMA was diagnosed by standardized criteria. Linkert scales were used to rate the efficacy for ODT and LTP therapy. Enrollment was closed after 1 month and the data were analyzed. Results: Surveys were distributed to 31 experts from 16 countries with a 77% response rate (n = 24) reporting on 300 patients with INMA. Efficacy rankings of ODT were the following: icatibant (14 experts with 93 treated patients), 46.2% high and 38.7% moderate; and plasma-derived C1 inhibitor (C1INH) (13 experts with 31 treated patients), 32.3% moderate and 45.2% mild. Efficacy rankings of LTP were the following: antifibrinolytics (11 experts with 52 treated patients), 23.1% high and 38.5% moderate; lanadelumab (5 experts with 19 treated patients), 21% high and 79% moderate; and subcutaneous C1INH (3 experts with 19 treated patients), 21.1% moderate and 79.0% mild. LTP efficacy was also recorded for berotralstat and progestin. Conclusion: Icatibant (ODT) and either antifibrinolytics or lanadelumab (LTP) were ranked as the most efficacious treatments for the patients with INMA (among medications with at least five treated patients) by the expert physicians. Progestins, berotralstat, and plasma derived C1INH each demonstrated a favorable prophylactic effect; however, broader experience will be required to formulate overall recommendations.

Background: Standardized quality (SQ) house-dust mite (HDM) sublingual immunotherapy tablets (10,000 Japanese allergy units [JAU], equivalent to 6 SQ-HDM in Europe and the United States) are licensed for the treatment of HDM-induced allergic rhinitis (AR) without age restriction, based on 52-week administration clinical trials. There are no large-scale data on the administration of 10,000 JAU for > 1 year in actual clinical practice. Objective: To examine the safety and effectiveness of 10,000 JAU during use for up to 3 years at real-world clinical sites in Japan. Methods: This survey was a multicenter, observational, prospective study. We assessed the safety and effectiveness of the long-term administration of 10,000 JAU as well as effectiveness after its discontinuation in patients with HDM AR with an observation period of 3 years. Results: The safety analysis included 815 patients, and the effectiveness analysis included 768 patients. Adverse reactions that occurred in 144 patients (17.67%) were mainly site-related events that occurred early in the dosing period. Serious adverse reactions were dyspnea and anaphylactic reaction in one patient each, and both patients recovered. With regard to effectiveness, compared with scores before the administration of SQ-HDM, nasal symptom scores decreased, depending on the administration period, from 6 months to 3 years. Overall, 67.34% of the patients had improved quality of life after 6 months, and this improvement continued after 12 months. The proportion of patients with "improved and slightly improved" of overall improvement exceeded 90% after 2 years. Treatment discontinuation because "symptoms disappeared" occurred in 24.42% of the patients at 3 years. Patients who discontinued 10,000 JAU (n = 39) had a sustained improvement in nasal symptom scores compared with baseline, even 1 year after discontinuing treatment. Conclusion: The real-world safety and effectiveness of 10,000 JAU SQ-HDM sublingual immunotherapy tablets were confirmed in Japanese patients with HDM AR. No new safety and effectiveness precautions were required.

Background: Remission of asthma can occur as part of the natural history of the disease; however, the use of biologics can result in disease remission in some patients. Objective: In this post hoc analysis of the RELIght study, we aimed to evaluate clinical remission in real life among patients treated with mepolizumab, to detect possible differences between "remitters" and "nonremitters," and to evaluate possible predictors of remission. Methods: Clinical remission was defined as the absence of asthma exacerbations, discontinuation of oral corticosteroids (OCS), achievement of asthma control (Asthma Control Test [ACT] ≥ 20), and stable or improved lung function. Results: A total of 146 patients were evaluated; remission was achieved in 40 (27.4%) and 29 (22%) after 12 and 24 months, respectively. At 12 months, the patients in remission had a better baseline ACT score (17.0 [14.0-19.0] versus 15.0 [12.0-17.0]; p = 0.027), were more rarely using OCS (35% versus 62.2%; p = 0.004), and required a lower baseline dose of OCS (5.0 mg/day [5.0-10.0 mg/day] versus 10.0 mg/day [5.0-15.0 mg/day]; p = 0.042) at baseline, whereas, at 24 months, they less frequently carried a baseline diagnosis of gastroesophageal reflux disease (GERD) (10.3% versus 32%; p = 0.031) and used lower doses of OCS at baseline (5.0 [1.0-5.0] versus 10.0 [5.0-15.0]; p = ≤0.001) versus nonremitters; 52.5% of patients had sustained remission, whereas 42.5% experienced relapse. These patients more frequently had GERD versus patients with sustained remission (52.9% versus 4.8%; p = 0.002). Finally, regression analysis has shown that GERD was the only predictor of relapse. Conclusion: Remitters had better asthma control and needed lower doses or no maintenance OCS at baseline, whereas GERD seems to be an important factor that affects remission and relapse.Clinical trial NCT04084613, www.clinical trials.gov.

Background: Allergen immunotherapy (AIT) is currently the most effective immunologic form of treatment for patients with atopic allergic diseases commonly used by allergist/immunologists to reduce allergic symptoms by gradually desensitizing the immune system to specific allergens. Currently, the primary mechanism of AIT emphasizes the crucial role of immune regulation, which involves a shift from a T-helper type 2 (Th2) cell response, which promotes allergy, to a T-regulatory (Treg) cell population, which inhibits the allergic inflammatory response through the production of immunosuppressive cytokines interleukin 10 and transforming growth factor β, which play pivotal roles in suppressing the allergic reaction. In a series of previous in vitro and in vivo experiments, we have demonstrated the capacity of synthetic methylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) moieties as well as methylated genomic DNA ODN motifs from Bifidobacterium longum subspecies infantis to activate Treg cell differentiation in contrast to the unmethylated ODN moiety, which promotes proinflammatory responses driven by Th17-mediated responses. Objective: The purpose of the present study was to continue exploring the reciprocally related effects of methylated and unmethylated forms of DNA motifs from B. longum subspecies infantis on inflammation, specifically focusing on evaluating their capacity to alleviate allergic symptoms in a murine allergic disease model. Results: We show that methylated CpG moieties (ODNA) inhibit inflammation by stimulating Treg cells whereas unmethylated CpG moieties (ODNB) promote inflammation through Th1/Th17 pathways. Conclusion: Analysis of our data confirms and extends our previous research on the mechanisms by which methylated and unmethylated forms of DNA motifs influence inflammation. Specifically, the findings demonstrate that methylated CpG moiety (OVA + ODNA) inhibits inflammation by stimulating Treg cells, whereas unmethylated CpG moiety (OVA + ODNB) promotes inflammation through Th1/Th17 pathways. Consequently, these effects were shown to alleviate or to exacerbate allergic symptoms in a murine model of allergic disease. These results set the stage for future clinical trials and studies in humans to explore the therapeutic potential of targeting CpG motifs in the treatment of allergic diseases.