Allergy Asthma and Clinical Immunology最新文献

Background: Hereditary angioedema (HAE) therapies have demonstrated improvements in clinical symptoms and health-related quality of life (HR-QoL) in patients with HAE. Specific causes for improvement in HR-QoL have not been sufficiently explored in Canada.

Objective: To understand patient perspectives on the burden of HAE and their experiences taking subcutaneous plasma-derived C1 inhibitor concentrate (SC-pdC1INH), and to investigate changes in HR-QoL domains which include physical, mental, emotional, functional, social, and medical well-being.

Methods: A qualitative research design was employed using telephone interviews from May to July 2023 and a quantitative self-administered Angioedema QoL questionnaire (AE-QoL), which has a recall period of 4 weeks. A conceptual map was generated from the interviews that illustrated HR-QoL domains most important to patients.

Results: This study included 20 patients (50% female; mean age of 51 years; 85% HAE Type 1/2). Patients reported more controlled HAE since starting SC-pdC1INH, with fewer attacks (85%) and even no/nearly no attacks (60%) in the past year. Patients reported emotional benefits (reduced stress/anxiety regarding potential attacks [75%], and increased confidence in managing HAE [95%]). Positive impacts also included increased productivity/less missed days from work/school (40%) and improved physical ability/well-being (50%). The total mean AE-QoL Score was 34 (range 0-87; SD 24.9), indicating a small effect of HAE on HR-QoL in the 4-week pre-interview period.

Conclusion: Overall, patients on long-term prophylaxis with SC-pdC1INH reported improvements in many HR-QoL domains, but most significantly relief of stress and anxiety associated with HAE, and improvement in social and physical well-being.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory condition, often treated with oral corticosteroids (OCS). OCS overexposure can increase the risk of adverse effects, highlighting the need for better treatment strategies including timely biologic therapy use. This study explored OCS use patterns in patients with severe CRSwNP in Canada pre-biologic initiation.

Methods: This retrospective, real-world study used IQVIA's Private Drug Plan (PDP) claims database to examine OCS use patterns 0-24 months pre-initiation of biologic therapy in patients with inferred CRSwNP in Canada (n = 747). Outcomes included OCS use patterns (proportions, claims per patient and by prescribing physician specialty, overexposure [≥ 1000 mg annually, prednisone-equivalent]), demographics, and stratified by comorbid asthma.

Results: Of 747 patients indexed from the PDP, 81.0% had ≥ 1 OCS claim(s), with a median (interquartile range [IQR]) of 3.0 (4.0) claims per patient. Median (IQR) total OCS dose over 24 months was 1020 (1420) mg; 41.5% of patients experienced OCS overexposure. OCS was primarily prescribed by general practitioners (35.9%) and otolaryngologists (32.8%). Patients had a median (IQR) age of 51 (18) years at index, 52.1% were male, and most were from Ontario (48.7%). OCS use was highest in patients with comorbid severe asthma.

Conclusions: This study highlights OCS overexposure in patients with CRSwNP pre-biologic initiation. Enhancing physician and patient awareness of appropriate OCS use and timely biologic initiation could reduce the risk of OCS-related adverse effects and improve CRSwNP management, benefiting long-term patient outcomes through shared decision-making. Trial registration GSK study number 221872.

Background:  X-linked agammaglobulinemia (XLA) is an inborn error of immunity resulting from mutations in the BTK gene. It is an X-linked inherited disease that almost exclusively affects males, while females are usually carriers of the disease. However, certain genetic conditions can lead to XLA disease expression in females. We report a 14-year-old girl who was diagnosed with XLA from a pathogenic BTK variant and skewed X chromosome inactivation (XCI).

Case presentation: A 14-year-old female Ukrainian refugee was referred to the respirology clinic at the Montreal Children's Hospital with an abnormal chest radiograph found during her immigration medical screening process in Canada. She was reported to be previously well until the age of 11 years when she was diagnosed with pneumonia following SARS-CoV-2 infection. She subsequently developed recurrent pneumonias, persistent productive cough, and chronic sinusitis with polyposis. Laboratory investigations showed severely reduced serum immunoglobulin G, A, and M concentrations of 0.78 g/L, < 0.10 g/L, and 0.21 g/L, respectively. Flow cytometry for lymphocyte subsets showed a complete absence of circulating B cells in peripheral blood. Next-generation sequencing panel for inborn errors or immunity revealed a heterozygous pathogenic variant in BTK (c.862C > T, p.Arg288Trp). Analysis of XCI revealed markedly skewed inactivation (99:1), resulting in predominant expression of the mutant pathogenic BTK allele. These findings support the clinical diagnosis of X-linked agammaglobulinemia manifesting in a female patient due to skewed XCI.

Conclusions: Female carriers of pathogenic mutations in BTK may develop clinically important disease as a result of extreme random X inactivation.

Cow's milk (CM) allergy is the most common food allergy in children, with cross-reactivity to goat and sheep milk (GSM) representing a common outcome due to high protein homology. However, isolated GSM allergy in CM-tolerant individuals is rare and poorly documented in the literature. We describe a 27-year-old male of Mediterranean origin who experienced two episodes of anaphylaxis after consuming sheep and goat cheese, despite regular CM consumption. Skin prick testing confirmed sensitization to GSM but not CM. This report contributes to the growing evidence of adult-onset isolated GSM allergy. Isolated GSM allergy typically presents later in life and may be underrecognized due to limited clinical awareness. We review the potential for species-specific mammalian milk protein allergy, likely mediated by structural differences in casein proteins. Clinicians should be cognisant to consider GSM sensitization in patients presenting with allergic reactions to dairy products, especially in multicultural populations with increasing GSM dietary exposure.

Asthma is a common chronic inflammatory disease in children. Pediatric asthma has a wide range of immunologic phenotypes and different treatment responses. Recent data from various studies suggest that the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a cytosolic multiprotein complex, has a central role in innate immunity, may be implicated in pediatric asthma pathogenesis, especially in the neutrophilic corticosteroid-resistant type. This review article investigates the mechanism of NLRP3 inflammasome activation as well as its role in airway inflammation and its expression in pediatric asthma based on sputum studies. The findings emphasize an association between elevated NLRP3 levels and poor asthma control. The need for novel treatments is important because Current using therapies such as corticosteroids and biologics demonstrate variable efficacy. According to data, their efficacy heavily depends on the underlying inflammatory phenotype. Biologics such as mepolizumab, benralizumab, and dupilumab are well known for their corticosteroid-sparing effects especially in cases of severe eosinophilic asthma. even though, their therapeutic benefits are limited when it comes to neutrophilic or steroid-resistant phenotypes. NLRP3 inhibitors are new, promising treatments which emerged recently and show potential capability in reducing airway inflammation in animal models. Furthermore, NLRP3-driven inflammation appears to play a role not only in asthma but also in inflammatory bowel disease and juvenile idiopathic arthritis, indicating a wider relevance for therapies that target the inflammasome pathway. Although promising data, application of this data in clinical practice is still challenging due to many causes, including diagnostic challenges, ethical considerations in trials involving children, and the lack of approved NLRP3 inhibitors for use in children. More research is required and essential to confirm that NLRP3 could be used as a biomarker or therapeutic target in pediatric asthma.

Background: Hereditary angioedema (HAE) attacks can be unpredictable, painful, and debilitating. Although studies described the burden of prophylactic HAE treatments on patient and caregiver health-related quality of life (HRQoL), few have explored the effects of injectable on-demand treatments on HRQoL.

Objective: To understand the impact of injectable on-demand HAE treatments on HRQoL.

Methods: Patients (aged ≥ 12 years) with ≥ 1 HAE attack in the prior 6 months and adult caregivers (aged ≥ 18 years) of patients of any age with HAE were recruited between July and October 2024 to complete a qualitative interview. Questions concerned on-demand injectable treatment use, impacts, and burden. Thematic analysis was used to identify key themes across responses.

Results: The 25 study participants from the US and UK (17 patients; 8 caregivers), who completed the interview, highlighted emotional and logistical reasons for delaying or forgoing injectable on-demand treatment, including fear of needles, portability, and complexity of administration. All participants described at least one negative impact on HRQoL, including anxiety and pain associated with treatment administration, disruption of daily activities or work/school days, and impacts on personal relationships. Adolescent patients reported greater impacts than adult patients. Although indicated for self-administration, some adult and all adolescent patients reported needing assistance with administration of their injectable on-demand treatment. All participants expressed interest in an oral on-demand treatment for reasons including portability, pain-free administration, and ability to treat attacks earlier.

Conclusion: This study highlights the unmet need for an on-demand treatment that allows for earlier, pain-free administration, ultimately increasing patient independence and improving HRQoL for both patients and caregivers.

Background: Japanese cedar pollinosis (JCP), which affects over 40% of the population and represents a major public health issue in Japan, has various treatment options, but limited clinical reports and high costs necessitate careful patient selection. This study aimed to evaluate the efficacy of omalizumab in treating JCP and identify key considerations for its appropriate clinical application.

Methods: We retrospectively analyzed 42 patients with JCP treated with omalizumab from 2021 to 2024. Treatment response was assessed using a 3-category patient-reported scale across all years. In a 2023-2024 subset (n = 23), quantitative total symptom score (TSS) data were available, allowing effect-size estimation and subgroup analyses.

Results: The study included 42 patients (30 men, 71.4%) aged 12-80 years (mean, 41.5 ± 17.2 years). Symptom improvement was observed in 38 patients (90%), including marked improvement in 23 (55%). Responders were younger (mean age 39.9 vs. 55.5 years) and had higher total IgE levels (251 vs. 211 IU/mL) than nonresponders. No significant correlation was observed between nasal eosinophil counts and treatment response. In the 2023-2024 subset (n = 23), TSS decreased significantly (mean paired difference - 2.61; p = 0.0010). Subgroup analyses suggested that CRSsNP cases tended to show insufficient improvement, while younger age and higher IgE levels were associated with better response trends.

Conclusions: Omalizumab significantly improved symptoms and QOL in patients with JCP. However, its high cost and the risk of nonresponse necessitate careful patient selection. Age and IgE levels may help guide treatment decisions, highlighting the importance of individualized strategies for severe JCP.

Objective: This study aimed to determine the prevalence of elevated serum Immunoglobulin E (IgE) levels among adult patients with asthma and to investigate the association between IgE levels and hospital admissions, ICU admissions, asthma control, and other clinical outcomes.

Methods: This was a retrospective single-centre study. Adult patients with a confirmed diagnosis of asthma between 28 February 2023 and 1 March 2024 at Al-Noor Specialist Hospital, Mecca, Saudi Arabia, were included. Patients were excluded if their records lacked spirometry or serum IgE data. Population characteristics were presented as frequency for categorical variables and median with interquartile range for continuous variables. Logistic regression analysis was used to identify predictors of severe asthma outcomes stratified by IgE levels.

Results: The study included 807 asthma patients, with a majority being females (68.9%) and a mean age of 48.2 years. A total of 311 patients (38.5%) had elevated serum IgE levels (> 100 IU). Patients with high IgE levels had significantly higher rates of hospital admission due to asthma (16.4% vs. 7.1%, p < 0.001) and ICU admission (4.2% vs. 1.2%, p = 0.008). They were also less likely to have controlled asthma (42.4% vs. 78.9%, p < 0.001) and more likely to report frequent acute care service visits (62.1% vs. 32.5%, p < 0.001). Logistic regression showed that elevated IgE levels were significantly associated with increased odds of hospital admission (OR = 2.6, 95% CI = [1.6-4.0], p < 0.001), ICU admission (OR = 3.5, 95% CI = [1.3-9.4], p = 0.011), uncontrolled asthma (OR = 0.2, 95% CI = [0.1-0.3], p < 0.001), and frequent ACS visits (OR = 0.3, 95% CI = [0.2-0.4], p < 0.001).

Conclusions: Elevated serum IgE levels are significantly associated with poorer asthma control, increased hospital admissions, and higher ICU admission rates. Stratifying asthma patients based on IgE levels may help identify high-risk individuals and guide management strategies through a targeted approach.

Background: Emerging evidence suggests that specific allergen molecules may influence the clinical phenotype of anaphylaxis in children, but robust data are scarce. This study aimed to rigorously test the molecule-phenotype association in a large pediatric cohort and to determine the relative influence of the sensitizing molecule versus patient age on symptom presentation.

Methods: A retrospective analysis was conducted on 184 pediatric patients (0-18 years) hospitalized for anaphylaxis. Molecular allergen-specific immunoglobulin E (IgE) profiles were determined using the ALEX² test. Symptom frequencies across different organ systems were analyzed in relation to allergen molecules and age groups using Cochran's Q and Pearson's χ2 tests.

Results: The most frequent molecular triggers were Ara h 2 (18.79%), Gal d 1 (9.09%), and Ana o 3 (9.09%). While significant differences in symptom distribution were observed within individual allergen molecules (p < 0.05), no molecule-specific symptom pattern was identified. In contrast, age significantly influenced respiratory symptom prevalence, with a higher frequency in older children compared to infants (p = 0.003). A similar trend was observed for gastrointestinal symptoms (p = 0.051).

Conclusions: In pediatric anaphylaxis, patient age is a more significant determinant of clinical presentation, particularly for respiratory symptoms, than the specific sensitizing allergen molecule. This suggests that clinical risk stratification and management strategies in children should prioritize age-related factors over specific molecular sensitization profiles.

An increasing number of patients are presenting to allergists with concerns about mast cell activation syndrome (MCAS), often in the context of persistent, unexplained, multisystem symptoms. This review aims provide a practical, stepwise approach to the diagnosis and management of MCAS, based on the consensus criteria established by the European Competence Network on Mastocytosis-American Initiative on Mast Cell Diseases, an international consortium of leading experts in mast cell disorders endorsed by major scientific organizations. The first step is to evaluate whether the clinical presentation is consistent with MCAS, recognizing that the prototypical presentation is idiopathic anaphylaxis. Symptoms should be severe, episodic, typical of mast cell activation, and involve at least two organ systems. The next step is to exclude secondary causes of mast cell activation, particularly cofactor-dependent food allergy and nonsteroidal anti-inflammatory drug hypersensitivity. Objective evidence of mast cell activation must then be obtained, preferably by identifying an acute increase in serum tryptase (on a sample drawn within four hours of an episode) compared to baseline. Alternatively, urinary metabolites of mast cell mediators can be assessed by comparing baseline values with those obtained 3-6 h post-event. Importantly,elevated baseline values in serum tryptase or urinary metabolites are not diagnostic of MCAS, nor do normal values exclude the diagnosis. In patients with idiopathic anaphylaxis, evaluation for a clonal mast cell disorder is recommended. This includes measuring baseline serum tryptase, testing for the KIT p.D816V mutation in peripheral blood (using high-sensitivity assays, if available), and calculating a mast cell clonality prediction score. A bone marrow biopsy should be considered for those with a high probability of mast cell clonality. Management includes instructing patients to treat acute episodes with an epinephrine auto-injector, particularly when anaphylaxis criteria are met. For patients with recurrent episodes, prophylactic therapy may be initiated, starting with H1-antihistamines and stepping-up as needed. While most patients have a favourable clinical course, some may require multiple medications to prevent or attenuate episodes. Future research should focus on validating and refining diagnostic and therapeutic strategies. In clinical practice, expanding access to key diagnostic tools-such as urinary mediator assays, sensitive KIT mutation testing, and tryptase genotyping-would facilitate and improve care of those patients.