Allergy Asthma and Clinical Immunology最新文献

Background: An epidemiological association among asthma, blood eosinophil level and chronic rhinosinusitis (CRS) is well established, but whether consistent genetic relationships exist, and whether this reflects a shared genetic etiology between CRS and asthma or blood eosinophil level remains unclear.

Methods: Data from CRS patients (N = 1,255) and healthy controls (N = 1,032) were reviewed retrospectively to investigate associations between clinical characteristics and CRS. Data from white blood cells in the UK biobank (N = 173,480), asthma in the Trans-National Asthma Genetic Consortium (127,669) and CRS (N = 272,922) or nasal polyps (N = 264,107) in the FinnGen consortium were used to conduct genetic study, including linkage disequilibrium score regression analysis to detect genetic associations between aforementioned variables, Mendelian randomization (MR) analysis to investigate causal relationships of asthma and blood eosinophil levels on CRS, and Bayesian co-localization to consolidate MR findings and to identify shared genetic signals.

Results: We found that blood eosinophil count, blood eosinophil percentages and asthma shared positive and causal genetic correlations with CRS (all q < 0.0001) and CRS with nasal polyps (CRSwNP) (all q < 0.0001) in both our observational and genetic study. Through colocalization analysis, 4 loci are shared among asthma, CRS and CRSwNP, 7 loci are shared among blood eosinophil count, CRS and CRSwNP, 2 loci are unique to blood eosinophil count and CRS, and 3 loci are unique to blood eosinophil count and CRSwNP.

Conclusions: These findings contribute to understanding CRS etiology, and provide insights for intervention and treatment target for CRS comorbid with asthma or high blood eosinophil levels.

Background: The goal of on-demand treatment for hereditary angioedema attacks is to halt attack progression to minimize morbidity and mortality. Four on-demand treatments have been approved thus far (ecallantide, icatibant, recombinant human C1 esterase inhibitor [rhC1INH], and plasma-derived C1INH). Results from the sebetralstat phase 3 KONFIDENT trial (NCT05259917) have been reported. To put these results into context without head-to-head trials, an indirect treatment comparison (ITC) was conducted to facilitate comparisons of efficacy and safety across treatment options.

Methods: Based on a systematic literature review and feasibility assessment, only the pivotal trial for intravenous rhC1INH (NCT01188564) reported necessary data for a comparable primary efficacy endpoint (time to beginning of symptom relief) to enable an ITC with oral sebetralstat. Bayesian fixed-effects network meta-analyses models were conducted to indirectly compare the efficacy and safety outcomes of sebetralstat and rhC1INH (NCT01188564, NCT00225147, NCT00262301). A matching-adjusted indirect comparison (MAIC) of efficacy was performed, adjusting for baseline attack severity and demographic characteristics.

Results: The fixed-effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and rhC1INH 50 IU/kg (hazard ratio [95% credible interval], 0.96 [0.42-2.15] to 1.19 [0.58-2.45]). After adjusting for baseline attack severity, the MAIC showed numerically favorable results with sebetralstat compared with rhC1INH, regardless of whether baseline demographics were matched. The fixed-effects model found no significant differences in treatment-related treatment-emergent adverse events. All sensitivity analyses returned consistent results.

Conclusions: This ITC found no significant differences in time to beginning of symptom relief and overall treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH.

Food oral immunotherapy (OIT) is an option for the treatment of immunoglobin E (IgE)-mediated food allergy that involves administering gradually increasing doses of an allergenic food over time (under medical supervision) with the goal of desensitizing an individual to the food allergen. Current Canadian clinical practice guidelines for OIT recommend this form of therapy as an option in patients with food allergy. The intervention should be prioritized in the infant and toddler population, in which it is particularly well tolerated and can lead to sustained unresponsiveness (also sometimes referred to as remission). In this article, we provide an overview of OIT and discuss the role non-allergist clinicians can play in caring for patients undergoing OIT.

Background: Contact allergens typically trigger localised reactions, but systemic Type I hypersensitivity from skin contact reactions are rare.

Case presentation: We present the case of a 69-year-old non-atopic male who developed anaphylaxis following the application of moisturizer to an area of chemical burns. Skin testing showed a strong positive result to moisturizer. Whilst not all ingredients were available for testing, phenoxyethanol was thought to be the likely culprit agent based on literature review and a weakly positive skin test result.

Conclusion: Products such as moisturizers can rarely trigger anaphylaxis, especially when applied to damaged skin which may favor systemic absorption. This case highlights the need for careful consideration of cosmetic application when discerning culprit allergens.

Background: When a member of a family has been diagnosed with hereditary angioedema (HAE) before a child is born, the question of early diagnosis arises. Indeed, the first attacks may occur at birth. Early diagnosis is complicated by biological issues. Due to the immaturity of the complement system, C1 Inhibitor (C1 INH) and C4 levels can be low at birth, generally in the range of 60 to 100% of adult reference values. Like most complement proteins, their levels generally normalize after one year of life. However, this is not always the case, and we report two counter-examples here.

Case presentation: A woman with well-documented HAE due to type II C1 INH deficiency gave birth to two children 4 years apart. Functional C1 INH assays performed at 8 and 7 months of age returned normal C1 INH inhibitory activity. However, a genetic exploration revealed the presence of the mother's pathogenic gene variant in both children. Subsequent monitoring of C1 INH activity at 3 and 4 years of age confirmed a pathological reduction in C1 INH inhibitory activity.

Conclusion: For the early detection of HAE in children, these cases lead us to recommend genetic testing for the index parent's pathological variant rather than reliance on results of C1 INH assays.

Asthma is one of the most common respiratory disorders in Canada, however, many Canadians with asthma remain poorly controlled. In most patients, control can be achieved through appropriate therapy, including: inhaled corticosteroids (ICS), combination ICS/long-acting beta₂-agonists (LABA), "triple therapy" with ICS/LABA/long-acting muscarinic receptor antagonist (LAMA), and biologic therapies. The medical management of severe asthma, in particular, has changed dramatically with the incorporation of biologics in asthma treatment plans. Allergen-specific immunotherapy represents a potentially disease-modifying therapy for many patients with asthma; it must only be prescribed by physicians with appropriate training in allergy. Other essential components of asthma management include: regular monitoring of asthma control and risk of exacerbations; patient education and written asthma action plans; assessing barriers to treatment and adherence to therapy; adequate management of comorbidities (e.g., allergic rhinitis) and reviewing inhaler device technique. This article provides a review of current literature and guidelines for the appropriate diagnosis and management of asthma in adults and children.

Background: Our previous 2007 study reported a 19.4% rate of biphasic anaphylaxis in Kingston, Ontario. Since then, few updates have been published regarding the etiology and risk factors of biphasic anaphylaxis. This study aimed to describe the incidence of and predictors of biphasic anaphylaxis in a single centre through a retrospective evaluation of patients with diagnosed anaphylaxis.

Methods: From November 2015 to August 2017, all patients who presented to the emergency department at two hospital sites in Kingston given a diagnosis of "allergic reaction," "anaphylaxis," "drug allergy," or "insect sting allergy," were evaluated. Patients were contacted sometime after ED discharge to obtain consent and confirm symptoms and timing of the reaction. A trained allergist determined if criteria for anaphylaxis were met and categorized the reactions as being uniphasic, biphasic, or non-anaphylactic biphasic. A full medical review of the event ensued, and each type of anaphylactic event was statistically compared.

Results: Of 138 anaphylactic events identified, 15.94% were biphasic reactions, 79.0% were uniphasic, and 5.07% were classified alternatively as a non-anaphylactic biphasic reaction. The average time of a second reaction was 19.0 h in patients experiencing biphasic reactivity. For biphasic anaphylaxis, the symptom profiles of second reactions were significantly less severe (p = 0.0002) compared with the initial reaction but significantly more severe than non-anaphylactic biphasic events (p < 0.0001).No differences of management were identified between events.

Conclusion: The incidence of biphasic reactions in this cohort was 15.94% and the average second-phase onset was 19.0 h. In biphasic reactivity, it appears that the symptom profile second reaction is less severe compared to the first reaction.

The field of medicine is constantly changing and, as healthcare providers, we are fortunate to be practicing in a time when patients are living longer and novel therapeutic options continue to evolve. However, these new advances may be associated with adverse effects that practitioners need to be aware of. Some of these impair the immune system leading to secondary immunodeficiencies (SID) that increase host susceptibility to infections and other complications. The causes and consequences of these SID are extremely broad, and a detailed review is beyond the scope of this article. The goal of this primer is to provide a general overview and understanding of common conditions and therapies leading to SID, as well as a guide to the assessment and management of patients with SID.