Allergy最新文献

Background: 15-oxo-eicosatetraenoic acid (15-oxo-ETE), is a product of arachidonic acid (AA) metabolism in the 15-lipoxygenase-1 (15-LOX-1) pathway. 15-oxo-ETE was overproduced in the nasal polyps of patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). In this study we investigated the systemic biosynthesis of 15-oxo-ETE and leukotriene E₄ (LTE₄) and assessed their diagnostic value to identify patients with N-ERD.

Methods: The study included 64 patients with N-ERD, 59 asthmatics who tolerated aspirin well (ATA), and 51 healthy controls. A thorough clinical characteristics of asthmatics included computed tomography of paranasal sinuses. Plasma and urinary 15-oxo-ETE levels, and urinary LTE₄ excretion were measured using high-performance liquid chromatography and tandem mass spectrometry. Repeatability and precision of the measurements were tested.

Results: Plasma 15-oxo-ETE levels were the highest in N-ERD (p < .001). A receiver operator characteristic (ROC) revealed that 15-oxo-ETE had certain sensitivity (64.06% in plasma, or 88.24% in urine) for N-ERD discrimination, while the specificity was rather limited. Modeling of variables allowed to construct the Aspirin Hypersensitivity Diagnostic Index (AHDI) based on urinary LTE₄-to-15-oxo-ETE excretion corrected for sex and the Lund-Mackay score of chronic rhinosinusitis. AHDI outperformed single measurements in discrimination of N-ERD among asthmatics with an area under ROC curve of 0.889, sensitivity of 81.97%, specificity of 87.23%, and accuracy of 86.87%.

Conclusions: We confirmed 15-oxo-ETE as a second to cysteinyl leukotrienes biomarker of N-ERD. An index based on these eicosanoids corrected for sex and Lund-Mackay score has a similar diagnostic value as gold standard oral aspirin challenge in the studied group of patients with asthma.

Background: Registries can yield important insights on allergen immunotherapy (AIT) outcomes in daily clinical practice. However, systematic recordings of adverse events (AE) due to AIT in real-life are lacking.

Methods: The Allergen Immunotherapy Adverse Events Registry (ADER) is a prospective, multicenter registry on real-life AIT safety. Data on adults (>18 years old) with respiratory allergies receiving AIT with mites, pollens, epithelia, and/or molds were retrieved and analyzed from ADER. The frequency, characteristics and risk factors of AE were investigated. The MedDRA terminology was used to record AE.

Results: A total of 1545 individuals with a mean age of 33 ± 10 years receiving 1815 AIT courses (n = 1060 sublingual (SLIT); n = 755 subcutaneous (SCIT)) in centers from eight countries were included. Patients had allergic rhinitis (65%) or, asthma only (3.7%) or rhinitis with asthma (31.2%). Grass was the most frequent specific sensitizer (60.7%), followed by mites (45.5%), birch pollen (20.6%), epithelia (16.1%), and molds (8%). There were 296 AE recorded in 115 patients (7.4%). A higher frequency of AE occurred during up-dosing (59%) compared to maintenance. Severe reactions were rare (0.2%), all in the context of SCIT. After 6 weeks of maintenance only one moderate AE was recorded. The most frequently reported symptoms were from the respiratory system and the skin. Having asthma, doing SCIT, AIT with mugwort, cat, or birch were associated with higher risk for AE while the use of allergoids induced lower risk.

Conclusion: In real life clinical practice, AIT-associated AE occur in a minority of patients, while severe reactions are rare. The presence of asthma and use of SCIT are risk factors, while the use of modified allergens lowers the risk.

Background: Neuropilin-1 (NRP1) is expressed on the surface epithelium of respiratory tract and immune cells, demonstrating its possible function in regulating the immune response in airway disease. However, its role in patient with chronic rhinosinusitis (CRS) remains unknown. This study aimed to elucidate the role of NRP1 in CRS with nasal polyps (CRSwNP).

Methods: Sinonasal biopsy specimens were immunohistochemically stained to investigate NRP1 expression. Double immunofluorescence, immunoblotting, and real-time polymerase chain reaction were performed to evaluate NRP1 in primary human nasal epithelial cells (hNECs). An NRP1 inhibitor was administered to a murine nasal polyp (NP) model.

Results: NRP1 was highly expressed in the epithelium in patients with CRSwNP compared to nasal tissue from controls and CRS without NP patients. NRP1 and vascular endothelial growth factor were upregulated in hNECs under hypoxia. Treatment with NRP1 inhibitor (EG00229) reduced the secretion of interleukin (IL)-1β, IL-6, IL-8, and IL-33 cytokines, as well as inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E2 in hNECs. We found that NRP1 was highly expressed in the airway epithelium in the murine NP model. The group treated with the NRP1 inhibitor had significantly fewer nasal polypoid lesions and reduced accumulations of immune cells.

Conclusions: These findings reveal that NRP1 is upregulated in CRS and NP epithelium, and the inhibition of NRP1 may lead to a reduction in NP growth and immune cell infiltration. Our results suggest that NRP1 inhibition could be a novel possibility for treating nasal polyposis.

Background: Infantile colic is a common condition with limited knowledge about later clinical manifestations. We evaluated the role of the early life gut microbiome in infantile colic and later development of atopic and gastrointestinal disorders.

Methods: Copenhagen Prospective Studies on Asthma in Childhood₂₀₁₀ cohort was followed with 6 years of extensive clinical phenotyping. The 1-month gut microbiome was analyzed by 16S rRNA sequencing. Infantile colic was evaluated at age 3 months by interviews. Clinical endpoints included constipation to age 3 years and prospectively diagnosed asthma and atopic dermatitis in the first 6 years of life, and allergic sensitization from skin prick tests, specific Immunoglobulin E, and component analyses.

Results: Of 695 children, 55 children (7.9%) had infantile colic. Several factors were associated with colic including race, breastfeeding, and pets. The 1-month gut microbiome composition and taxa abundances were not associated with colic, however a sparse Partial Least Squares model including combined abundances of nine species was moderately predictive of colic: median, cross-validated AUC = 0.627, p = .003. Children with infantile colic had an increased risk of developing constipation (aOR, 2.88 [1.51-5.35], p = .001) later in life, but also asthma (aHR, 1.69 [1.02-2.79], p = .040), atopic dermatitis (aHR, 1.84 [1.20-2.81], p = .005) and had a higher number of positive allergic components (adjusted difference, 116% [14%-280%], p = .012) in the first 6 years. These associations were not mediated by gut microbiome differences.

Conclusions: We link infantile colic with risk of developing constipation and atopic disorders in the first 6 years of life, which was not mediated through an altered gut microbiome at age 1-month. These results suggest infantile colic to involve gastrointestinal and/or atopic mechanisms.

Background: The field of drug development is witnessing a remarkable surge in the development of innovative strategies. There is a need to develop technological platforms capable of generating human data prior to progressing to clinical trials.

Methods: Here we introduce a new flexible solution designed for the comprehensive monitoring of the natural human skin ecosystem's response to immunogenic drugs over time. Based on unique bioengineering to preserve surgical resections in a long survival state, it allows for the first time a comprehensive analysis of resident immune cells response at both organ and single-cell levels.

Results: Upon injection of the mRNA-1273 COVID-19 vaccine, we characterized precise sequential molecular events triggered upon detection of the exogenous substance. The vaccine consistently targets DC/macrophages and mast cells, regardless of the administration route, while promoting specific cell-cell communications in surrounding immune cell subsets.

Conclusion: Given its direct translational relevance, this approach provides a multiscale vision of genuine human tissue immunity that could pave the way toward the development of new vaccination and drug development strategies.