Allergy Asthma and Clinical Immunology最新文献

Background: Penicillin allergy adversely impacts patient care, yet most cases do not have true allergies. Clinicians require efficient, reliable clinical tools to identify low risk patients who can be safely de-labeled. Our center implemented the FIRSTLINE electronic point-of-care decision support tool to help non-allergist practitioners risk stratify patients with penicillin allergy. We sought to explore the reliability and validity of this tool in relation to allergist assessment and actual patient outcomes. We additionally compared it with two other published stratification tools, JAMA and PENFAST, to assess ability to accurately identify low risk patients appropriate for direct oral challenge.

Methods: In this single-center, retrospective, observational study, 181 pregnant females with self-reported penicillin allergy between July 2019 to June 2021 at BC Women's Hospital, Vancouver, Canada were used to assess the reliability and validity of all three tools. Physician-guided history of penicillin use and symptoms were used for scoring. Results and recommendations were compared to actual patient outcomes after clinician decision for direct oral challenge or intradermal tests. We compared the performance of JAMA, PENFAST and FIRSTLINE.

Results: 181 patients were assessed. 176/181 (97.2%) patients were deemed not allergic. Each risk stratification tool labelled majority of patients as low risk with 88.4% of patients PENFAST 0-2, 60.2% of patients JAMA low risk, 86.7% of patients FIRSTLINE very low risk.

Conclusion: We demonstrate that our point-of-care electronic algorithm is reliable in identifying low risk pregnant patients, as compared to an allergist assessment. To our knowledge, this is the first study to provide direct comparison between multiple decision support tools using the same population, minimizing participant bias. Providing clinical algorithms to risk stratify patients, can enable healthcare professionals to safely identify individuals who may be candidates for direct penicillin oral challenges versus needing referral to specialists. This increases the generalizability and efficiency of penicillin allergy de-labeling.

Background: Oral immunotherapy (OIT) is an increasingly utilized management strategy for IgE-mediated food allergy. Despite promising efficacy and effectiveness, there is still a lack of data surrounding the reasons for discontinuation of OIT. The primary reason stated in the literature for discontinuation is adverse gastrointestinal effects. Social factors contributing to OIT discontinuation have not been well reported. We hypothesize that social considerations are significant contributors to treatment discontinuation.

Methods: We completed a retrospective chart review of 50 patients treated in community pediatric allergy practices who discontinued OIT out of 507 patients who were started on OIT between October 1, 2017-October 27, 2022. Reasons for discontinuation were identified and classified into five main categories: unsafe care decisions, anxiety, adverse effects of OIT, uncontrolled comorbidity and social factors. Categories were not exclusive.

Results: 507 patients were started on OIT, with data available for 50 patients who discontinued OIT, aged 10 months to 18 years and 2 months. The overall discontinuation rate was 9.8%, of which 40 patients (80%) discontinued during buildup, 9 patients (18%) discontinued during maintenance and one patient on two food OIT discontinued one food during buildup and one during maintenance (2%). Thirty-four patients (68%) had multiple reasons for discontinuing OIT. Social factors were the most common reason for discontinuation and were identified in 32 patients (64%). Twenty-four patients (48%) discontinued OIT due to adverse effects. Gastrointestinal symptoms were the most prevalent, while anaphylaxis contributed to discontinuation in 15 patients (30%). Anxiety led to discontinuation in 17 patients (34%).

Conclusions: Our data highlights the importance of social factors and anxiety in the success of OIT completion. Our results support the need to consider not only the patient's medical history, but also their social history and support networks when selecting patients who are good candidates for OIT to optimize the successful completion of OIT.

Background: Oral immunotherapy (OIT) has become the standard of care for children with food allergy (FA) and has substantially improved their quality of life. The effect of OIT on the quality of life in adults, however, has been studied to a much lesser degree.

Methods: Patients with food allergy aged ≥ 18 years who underwent OIT at Shamir Medical Center completed the Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) before and at the end of treatment. Adults with FA not undergoing OIT who completed the FAQLQ-AF at 2 time points, served as controls.

Results: A total of 44 adults, median age 23.4 years, who underwent OIT for milk (n = 19), egg (n = 2), peanut (n = 9), sesame (n = 6), and tree nuts (n = 8), and 11 controls were studied. The median OIT starting dose was 23.8 mg protein. 33 patients (75%) reached full desensitization within a median of 10.3 months. The FAQLQ-AF baseline scores were comparable between the study and control groups for all items except for Food Allergy related Health (FAH) item in which the study group had a significantly better score (p = 0.02). At the second time point, the study group had significantly better scores in all items (Allergen Avoidance and Dietary Restrictions (AADR), p = 0.02; and Emotional Impact (EI), Risk of Allergen Exposure (RAE), FAH and the Total Score, p < 0.01). The change in scores for the study group was significantly better, statistically and clinically, in AADR, p = 0.04; EI, p < 0.01; RAE, p = 0.01, and in the total score, p = 0.01.

Conclusions: OIT significantly improves quality of life of adults with FA. This finding adds important support for providing OIT in this population.

Primary immunodeficiency diseases (PIDs), also referred to as inborn errors of immunity, constitute a group of genetic conditions that affect the immune system. The current standard of care for patients with PIDs is lifelong immunoglobulin replacement therapy, delivered by intravenous (IVIG) or subcutaneous (SCIG) infusion. Immune globulin subcutaneous (human) 20% solution stabilized with glycine (Ig20Gly) is indicated as a replacement therapy for PIDs in adults and children of any age in Europe and in patients aged 2 years and above in the USA. Typically, Ig20Gly is administered using an infusion pump; however, delivery of Ig20Gly by manual administration has recently been approved in Europe. Practical recommendations on the use of Ig20Gly manual administration are lacking; this review therefore aims to provide guidance for use of this method of administration. Additionally, we summarize the infusion parameters, safety, patient-reported outcomes, and economic benefits associated with Ig20Gly manual administration. Manual administration of Ig20Gly was shown to permit faster rates of infusion than administration via infusion pump. Patients typically infused at two or fewer infusion sites with manual administration of Ig20Gly. Safety and tolerability profiles were similar for Ig20Gly manual administration and administration by infusion pump. Overall, there were comparable levels of patient satisfaction with manual administration and infusion pump, with patient preference deemed to be a key determinator of success for either method of administration. Economic studies identified cost savings for the healthcare system through manual administration compared with IVIG or SCIG infusion by infusion pump because of the reduced equipment costs and nurse support. For infusion of Ig20Gly by manual administration, a syringe and butterfly needle are used; patients are advised to start infusion at 1-2 mL/min to prevent discomfort. Overall, manual administration of Ig20Gly offers an effective and well-tolerated alternative to administration by infusion pump.

Objective: The aim of this study was to investigate the influence of osthole (OS) on asthma-induced airway epithelial cell apoptosis and inflammation by restraining Th2 differentiation through suppressing TSLP/NF-κB.

Methods: An asthma mouse model and an inflammation cell model were constructed with ovalbumin (OVA) and lipopolysaccharide (LPS), respectively. CD4 + T cells were treated with IL-4 to induce Th2 differentiation. Model mice were treated with OS (15,40 mg/kg) for 7 days, and 10 µg/mL OS was added to cell treatment groups. The levels of relevant indices were detected by RT‒qPCR, HE and Masson staining, Western blotting, ELISA and flow cytometry.

Results: In a mouse asthma model, TSLP expression was elevated, and the NF-κB pathway was activated. Therefore, OS could restrain the apoptosis and inflammation of airway epithelial cells. Downstream mechanistic studies revealed that OS can suppress Th2 differentiation by restraining the level of TSLP and NF-κB nuclear translocation, thus facilitating the proliferation of airway epithelial cells, restraining their apoptosis and inflammation, and alleviating airway inflammation in asthmatic mice.

Conclusion: OS can inhibit Th2 differentiation by inhibiting the TSLP and NF-κB pathways, which can reduce the apoptosis and inflammation of airway epithelial cells caused by asthma.

PF-06817024 is a humanized antibody against interleukin-33 that has the potential to inhibit type 2 inflammation. An exploratory analysis of the pharmacodynamics and clinical effects of single and repeat doses of PF-06817024 was assessed in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and patients with moderate-to-severe atopic dermatitis (AD), respectively, as part of a Phase 1, first-in-human study. Rhinosinusitis symptoms were improved, and nasal polyps were decreased in size following treatment with PF-06817024 in patients with CRSwNP. In patients with AD, PF-06817024, in aggregate, reduced disease severity and improved symptoms, as demonstrated by greater percentage decrease from baseline in Eczema Area and Severity Index (EASI) scores and reduced pruritus numerical rating scores, compared with placebo. The efficacy in AD appeared to be bimodal with a sub-group of participants exhibiting high levels of improvement (EASI75 and EASI90) for a sustained period of time after dosing. In patients with CRSwNP, a consistent trend of decrease in eosinophil levels was observed in the PF-06817024 group, compared with placebo. Further research would be needed to confirm the clinical benefit and safety of PF-06817024 as a treatment for allergic diseases. Trial registration ClinicalTrials.gov, NCT02743871. Registered 15 April 2016, https://clinicaltrials.gov/study/NCT02743871?term=NCT02743871&rank=1 .

Allergic rhinitis (AR) is a prevalent disease in Canada that affects both children and adults. Several guidelines for the management of AR have been published by professional allergy societies worldwide. However, there are regional differences in the clinical management of AR, and regulatory approval of some AR pharmacotherapies varies among countries. Thus, six research questions specific to the treatment of AR in Canada were identified for this focused practice parameter. Reviews of the literature published since 2016 were conducted to obtain evidence-based support for the responses of the Work Group to each research question. In response to research question 1 "In patients with symptoms indicative of AR, is serum-specific IgE sufficient to identify candidates for immunotherapy or is a skin prick test mandatory?" the Work Group concluded that either sIgE testing or skin prick test are acceptable for diagnosing AR and guiding immunotherapy. In response to research question 2 "When taking into account the preferences of the patient and the prescriber (stakeholder engagement) should second-generation oral antihistamine (OAH) or intranasal corticosteroid (INCS) be first line?" the Work Group concluded that existing guidelines generally agree on the use of INCS as a first-line therapy used for AR, however, patient and provider preferences and considerations can easily shift the first choice to a second-generation OAH. In response to research question 3 "Is a combination intranasal antihistamine (INAH)/INCS formulation superior to INCS plus OAH? Do they become equivalent after prolonged use?" the Work Group concluded that that the combination INAH/INCS is superior to an INCS plus OAH. However, there was insufficient evidence to answer the second question. In response to research question 4 "Do leukotriene receptor antagonists (LTRA) have a greater benefit than OAH in AR for some symptoms to justify a therapeutic trial in those who cannot tolerate INCS?" the Work Group concluded that LTRAs have inferior, or at best equivalent, daytime or overall symptom control compared with OAH, but LTRAs may improve nighttime symptom control and provide benefits in patients with AR and concomitant asthma. In response to research question 5 "Should sublingual immunotherapy (SLIT) tablets be considered first-line immunotherapeutic options over subcutaneous immunotherapy (SCIT) based on the evidence of efficacy?" the Work Group concluded that the choice of SLIT or SCIT cannot be made on efficacy alone, and differences in other factors outweigh any differences in efficacy. In response to research question 6 "Based on efficacy data, should ALL patients seen by an allergist be offered SLIT or SCIT as a treatment option?" the Work Group concluded that the efficacy data suggests that SLIT or SCIT should be used broadly in patients with AR, but other clinical concerns also need to be taken into consideration.

Background: Hereditary angioedema (HAE) is characterized by debilitating attacks of tissue swelling in various locations. While guidelines recommend the importance of early on-demand treatment, recent data indicate that many patients delay or do not treat their attacks.

Objective: This survey aimed to investigate patient behavior and evaluate the key factors that drive on-demand treatment decision-making, as reported by those living with HAE.

Methods: People living with HAE were recruited by the US Hereditary Angioedema Association (HAEA) to complete a 20-minute online survey between September 6, and October 19, 2022.

Results: Respondents included 107 people with HAE, 80% female, 98% adults (≥ 18 years). Attack management included on-demand therapy only (50%, n = 53) or prophylaxis with on-demand therapy (50%, n = 54). Most patients (63.6%) reported that they did not carry on-demand treatment at all times when away from home. The most common reason for not carrying on-demand treatment when away from home was 'prefer to treat at home' (72.1%). Overall, 86% of respondents reported delaying on-demand treatment, despite recognizing the initial onset of an HAE attack and despite 97% of patients agreeing that it is important to recover quickly from an HAE attack. Reasons for non-treatment or treatment delay included 'the attack is not severe enough to treat' (91.9% and 88.0%, respectively), 'cost of treatment' (31.1% and 40.2%, respectively), anxiety about refilling the prescription for on-demand treatment quickly (31.1% and 37.0%, respectively), the pain (injection or burning) associated with their on-demand treatment (18.9% and 28.3%, respectively), the lack of a suitable/private area to administer on-demand treatment (17.6% and 27.2%, respectively), lack of time to prepare on-demand treatment (16.2% and 16.3%, respectively), and a 'fear of needles' (13% and 12.2%, respectively). Survey findings from the patient perspective revealed that when on-demand treatment was delayed, 75% experienced HAE attacks that progressed in severity, and 80% reported longer attack recovery.

Conclusions: Survey results highlight that decision-making regarding on-demand treatment in HAE is more complicated than expected. The burden associated with current parenteral on-demand therapies is often the cause of treatment delay, despite acknowledgment that delays may result in progression of HAE attacks and longer time to recovery.