Journal of Allergy and Clinical Immunology最新文献

Background: Evidence suggests that school factors influence the prevalence of allergic diseases in students. However, little is known about how such factors affect the health of teachers.

Objective: We sought to compare the prevalence of allergic and respiratory conditions among teachers from urban, suburban, and rural schools.

Methods: Electronic survey data were collected from a random sample of prekindergarten through grade 12 teachers in Massachusetts. Comparisons were made between teacher demographics and allergic respiratory symptoms.

Results: Of the 398 respondents, median (SD) age was 45 (12.32) years; 71.8% of teachers taught in suburban schools, 76.6% were female, and 87.1% were White, similar to teacher demographics collected by the Massachusetts Department of Higher Education. Although there were more female teachers, male teachers more frequently reported adverse breathing symptoms, such as wheezing (P = .007). Over half of rural teachers (54.54%) experienced respiratory symptoms such as disrupted sleep due to coughing compared to 34.61% of suburban schoolteachers (P = .03). Almost half (48.26%) of public schoolteachers experienced exercise-induced chest pain compared to 37.03% of private schoolteachers (P = .05). A higher proportion of urban schoolteachers with asthma commonly missed school as a result of food allergy compared to suburban and rural schoolteachers with asthma (P = .02). In teachers undiagnosed with asthma, associations existed between school absences and nighttime awakening due to trouble breathing (P < .0001), persistent cough (P = .002), and sore throat (P < .0001) CONCLUSIONS: Rural and public teachers reported proportionately more respiratory symptoms compared to suburban and private teachers, suggesting disparities. Future studies addressing evidence-based solutions are needed.

Background: Deficiency of adenosine deaminase (ADA or ADA1) has broad clinical and genetic heterogeneity. Screening techniques can identify asymptomatic infants whose phenotype and prognosis are indeterminate, and who may carry ADA variants of unknown significance.

Objective: We systematically assessed the pathogenic potential of rare ADA missense variants to better define the relationship of genotype to red blood cell (RBC) total deoxyadenosine nucleotide (dAXP) content and to phenotype.

Methods: We expressed 46 ADA missense variants in the ADA-deficient SØ3834 strain of Escherichia coli and defined genotype categories (GCs) ranked I to IV by increasing expressed ADA activity. We assessed relationships among GC rank, RBC dAXP, and phenotype in 58 reference patients with 50 different genotypes. We used our GC ranking system to benchmark AlphaMissense for predicting variant pathogenicity, and we used a minigene assay to identify exonic splicing variants in ADA exon 9.

Results: The 46 missense variants expressed ∼0.001% to ∼70% of wild-type ADA activity (40% had <0.05% of wild-type ADA activity and 50% expressed >1%). RBC dAXP ranged from undetectable to >75% of total adenine nucleotides and correlated well with phenotype. Both RBC dAXP and clinical severity were inversely related to total ADA activity expressed by both inherited variants. Our GC scoring system performed better than AlphaMissense in assessing variant pathogenicity, particularly for less deleterious variants.

Conclusion: For ADA deficiency, pathogenicity is a continuum and conditional, depending on the total ADA activity contributed by both inherited variants as indicated by GC rank. However, in patients with indeterminate phenotype identified by screening, RBC dAXP measured at diagnosis may have greater prognostic value than GC rank.

Background: Peanut allergy (PA) is one of the most prevalent food allergies with a lack of favorable safety/efficacy treatment. A cucumber mosaic virus-like particle expressing peanut allergen component Ara h 2 (VLP Peanut) has been developed as a novel therapeutic approach for PA.

Objective: We assessed the tolerogenic properties and reactivity of VLP Peanut.

Methods: Whole blood and peripheral blood mononuclear cells were collected from 6 peanut-allergic children. Modulation of dendritic cells (DCs), T cells, and B cells, stimulated with VLP Peanut, Ara h 2, and whole peanut extract in vitro, were assessed by quantitative real-time PCR and flow cytometry, respectively. Basophil and skin reactivity in response to VLP Peanut was assessed by basophil activation test and skin prick test, respectively.

Results: VLP Peanut showed beneficial biochemical properties, fit for use in clinical studies. VLP Peanut induced IFN-γ⁺ T_H1 (P < .05) while having reduced capacity to elicit proliferation of T_H2, allergen-specific T_H2, and IL-4⁺-T follicular helper cells. Moreover, VLP Peanut is associated with upregulation of DC1-associated genes (MX1) compared to Ara h 2 and whole peanut extract. VLP Peanut was the most prominent at inducing IL-10⁺ regulatory B cells (P < .05). Unbiased clustering analyses identified metaclusters of T and B cells targeted by VLP Peanut. Finally, VLP Peanut had reduced capacity to elicit high- and low-affinity IgE receptor-mediated responses compared to Ara h 2 or whole peanut extract (all P < .05). Finally, in an open-label first-in-human cohort of 6 peanut-allergic adults, administration of increasing concentration of VLP Peanut through skin prick test was tolerated and demonstrated no development of skin reactivity.

Conclusions: VLP Peanut displayed tolerogenic properties by modulating DCs, T cells, and B cells in vitro. Preliminary findings of skin reactivity using VLP Peanut in 6 peanut-allergic adults was safe and well tolerated in an open-label phase 1 study.

Clinical trial identifier: PROTECT, NCT05476497.

Background: Previous randomized controlled trials have established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up.

Objective: This population-based cohort study aimed to explore the long-term safety and effectiveness of dupilumab in patients with COPD.

Methods: The study included US patients with COPD who were seen between April 2017 and August 2024. Patients initiating dupilumab and therapies that incorporated long-acting β₂-agonist (LABA) inhalers were included. Patients with asthma or lung cancer were excluded. The risk of outcomes occurring after initiation of dupilumab versus LABA-containing therapies was measured. For detailed methods, please see the Methods section in this article's Online Repository at www.jacionline.org.

Results: A total of 1521 dupilumab initiators and 1521 propensity score-matched patients who were receiving LABA-based therapies were included. Receiving dupilumab was associated with lower all-cause mortality (hazard ratio [HR] = 0.53, 95% CI = 0.43-0.65), fewer emergency department visits (HR = 0.78, 95% CI = 0.69-0.89), and lower acute exacerbation rates (HR = 0.59, 95% CI = 0.53-0.65). Dupilumab was also associated with reductions in the requirement for short-acting β₂-agonists (HR = 0.48, 95% CI = 0.43-0.52) and short-acting muscarinic antagonists (HR = 0.43, 95% CI = 0.37-0.49) for symptom control. Additionally, dupilumab decreased rates of subsequent pneumonia (HR = 0.65, 95% CI = 0.50-0.86), and COPD-relevant comorbidities, including new-onset heart failure (HR = 0.69, 95% CI = 0.53-0.90) and new-onset anxiety (HR = 0.70, 95% CI =0.53-0.93).

Conclusions: In patients with COPD, dupilumab was associated with a lower mortality rate, fewer emergency department visits, and a reduced risk of acute exacerbations, respiratory symptoms, and respiratory infections. More studies are needed to validate the efficacy of dupilumab among patients with COPD of various severities.