Annals of Allergy Asthma & Immunology最新文献

Background: Most of the Fractional exhaled Nitric Oxide (FeNO)'s physiological production occurs in small airways, but the relationship between FeNO and small airway disease (SAD) in asthma is scant.

Objective: To investigate the relationship between asthma control, changes of FeNO in relation to airway bronchodilation (BD), and SAD.

Methods: Baseline conventional spirometry, impulse oscillometry (IOS), and FeNO pre- and post-bronchodilation (salbutamol 400 mcg) were tested on consecutive community-treated adult asthmatic patients. Results were stratified by FeNO response (ΔFeNO), being FeNO "responder" if an increase >10% post-BD compared to the basal values were registered, and "non-responder" if ≤10%.

Results: When measured, post-BD FeNO>25ppb was found in an additional 31.5% of patients. Of the 92 patients included, 61% were classified as FeNO "responders" and 39% as "non-responders". A significant moderate-to-strong correlation was observed between ΔFeNO and R5R20, a functional marker of SAD (R=0.52, p<0.0001), while correlations between spirometry markers and ΔFeNO were not significant (p> 0.05). Both R5R20 and ΔFeNO inversely correlated with asthma control (<0.0001). By means of the causal mediation analysis modelling, the effect of asthma control on ΔFeNO was mediated by SAD; with a strong indirect effect of asthma control on ΔFeNO mediated by SAD (β value:-7.04, 95%CI:-11.80; -3.53, p<0.0001), without a significant direct effect (β value:-4.96; 95%CI:-9.15; +0.11; p=0.056).

Conclusion: Changes in FeNO values pre-/post-BD can improve the identification of patients with "Th2 high" asthma. The relationship between ΔFeNO and asthma control is mainly mediated by SAD, highlighting its contribution in determining asthma control in real-life.

Background: Epinephrine is the first-line treatment for anaphylaxis and is administered through intramuscular or subcutaneous injection. AQST-109, a sublingual film containing the prodrug epinephrine, was developed as an alternative delivery method for treating severe allergic reactions, including anaphylaxis.

Objective: To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine after the administration of AQST-109 with those of epinephrine delivered by manual intramuscular injection and epinephrine autoinjectors.

Methods: Data were integrated from 2 randomized, open-label, phase I crossover trials that evaluated the PK and PD of epinephrine in 54 healthy volunteers. They had no previous medical conditions and were delivered either AQST-109 12 mg or 0.3 mg EpiPen, 0.3 mg generic EpiPen, 0.3 mg Auvi-Q, and 0.3 mg manual intramuscular injection.

Results: AQST-109 yielded comparable epinephrine PK and exposure to both manual intramuscular injections and epinephrine autoinjectors. The median time to maximum concentration (Tmax) for AQST-109 was 15 minutes, compared with EpiPen (10 minutes), generic EpiPen (15 minutes), Auvi-Q (30 minutes), and manual intramuscular injection (50 minutes). There was also an early, rapid, and consistent increase in systolic blood pressure, diastolic blood pressure, and heart rate after the administration of AQST-109.

Conclusion: AQST-109 delivered epinephrine with PK and PD results within the bracketed range of approved intramuscular products. AQST-109 has promise as an innovative, needle-free, nondevice, portable, and orally delivered alternative for first-line treatment of type I allergic reactions, including anaphylaxis.

Background: Loss-of-function FLG mutation (FLGmut) carriers are at an increased risk of developing atopic dermatitis (AD), characterized by earlier onset and more severe disease. AD is driven by a complex interplay between skin barrier function, T_H2 and T_H2-dominant immune dysregulation, and dysbiosis. Results from the Short-Term Topical Application for Prevention of Atopic Dermatitis study suggest 2 early initiating AD pathogenetic pathways: an FLGmut-related skin barrier deficiency pathway and an immune function-related inflammatory pathway. The Short-Term Topical Application for Prevention of Atopic Dermatitis study suggested that early preventative intervention with specialized emollients for barrier function augmentation may benefit newborns with FLGmut. This requires early identification of FLGmut carriers, for which noninvasive Raman spectroscopic determination of natural moisturizing factor (NMF) levels in the stratum corneum of the thenar eminence provides a surrogate marker.

Objective: To identify strategies for early identification of infants with FLGmut.

Methods: FLG sequencing was performed on 253 infants, and NMF concentrations were measured in the stratum corneum of the palmar eminence (pSC-NMF) using noninvasive Raman spectroscopy at 6 time points after birth. Furthermore, the pSC-NMF concentrations were obtained from both parents of 150 infants.

Results: Babies are born with little to no NMF. In the first days after birth, NMF levels rapidly increase and 65% of newborns with FLG wild type already reach pSC-NMF concentrations, which excludes them as FLGmut carriers with high specificity. At 2 weeks of age, FLGmut carriers could be distinguished from newborns with FLG wild type with high sensitivity (97%) and specificity (97%). In addition, parent pSC-NMF concentrations offer the possibility to exclude their newborn as FLGmut carriers with high specificity.

Conclusion: Noninvasive Raman spectroscopy enables the accurate early identification of infants with FLGmut.

Background: Allergic rhinitis (AR) is a prevalent chronic inflammatory condition that significantly impacts patient quality of life and poses a substantial public health burden. Recent advancements in metabolomics have facilitated a deeper understanding of the metabolic pathways involved in AR, offering potential for new biomarkers and therapeutic targets.

Objective: This article aims to conduct a systematic review and meta-analysis of clinical studies summarizing the metabolomic profiles of allergic rhinitis (AR) to gain deeper insights into the metabolic changes and pathological processes underlying AR.

Methods: A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science databases up to October 2024. A qualitative review of the screened studies was performed, followed by meta-analyses of metabolites reported in at least two studies. High-impact targets, pathways, and their associations were identified using bioinformatic analyses.

Results: A total of 21 studies, encompassing 84 metabolites associated with AR, met the inclusion criteria. Seven metabolites consistently exhibited upregulation in AR across multiple studies and were included in the meta-analysis. Pathway enrichment analyses revealed significant involvement of pathways such as "Valine, leucine, and isoleucine biosynthesis" and "Linoleic acid metabolism" in AR pathogenesis. The metabolite-pathway-gene network analysis highlighted key functional connections between metabolites, pathways, and immune response genes.

Conclusion: This comprehensive analysis indicates that differential metabolites may play pivotal roles in AR pathogenesis, offering potential biomarkers and therapeutic targets. Further studies are necessary to validate these findings and elucidate the complex metabolic pathways involved in AR.

Background: Some patients with severe asthma have overlapping allergic and eosinophilic phenotypes and may be eligible for anti-eosinophilic or anti-IgE biologics.

Objective: This post hoc sub-analysis assessed real-world mepolizumab effectiveness in patients with overlapping allergic and eosinophilic phenotypes, using 1-year data from the international, prospective REALITI-A study.

Methods: The clinically significant asthma exacerbation (CSE) rate was assessed 1 year prior to (pre-treatment) and following (follow-up) mepolizumab treatment, stratified by baseline total IgE levels (tIgE; <60, 60-<190, 190-<550, and ≥550 kU/L), atopic status (yes/no/unknown), prior omalizumab use (yes/no), geographic baseline omalizumab eligibility (eligible/non-eligible), and baseline tIgE level and blood eosinophil count (BEC) threshold combinations (<81 or ≥81 kU/L and <300 or ≥300 cells/µL).

Results: Overall, 822 patients were included. CSEs occurred in 760 (93%) patients pre-treatment and 398 (49%) during follow-up. CSE rate (RR[95% CI]) was reduced in follow-up across all tIgE subgroups (<60 [n=173]: 0.31[0.25, 0.37]; 60-<190 [n=176]: 0.30[0.25, 0.36]; 190-<550 [n=170]: 0.26[0.20, 0.33]; ≥550 kU/L [n=155]: 0.28[0.23, 0.35]) and irrespective of atopic status (yes [n=422]: 0.29[0.26, 0.33]; no [n=52]: 0.33[0.23, 0.47]; unknown [n=348]: 0.28[0.24, 0.32]), prior omalizumab use (yes [n=151]: 0.37[0.30, 0.45]; no [n=671]: 0.27[0.24, 0.30]) or eligibility (eligible (n=349): 0.29[0.25, 0.34]; non-eligible [n=191]: 0.32[0.27, 0.38]). Furthermore, the CSE rate was reduced across all tIgE (kU/L) and BEC (cells/µL) combinations (<81/<300 [n=53]: 0.34[0.24, 0.47], <81/≥300 [n=103]: 0.33[0.26, 0.41], ≥81/<300 [n=98]: 0.36[0.28, 0.47], ≥81/≥300 [n=249]: 0.26[0.22, 0.31]).

Conclusion: Mepolizumab demonstrates real-world effectiveness in reducing exacerbations in patients with severe asthma and an eosinophilic phenotype, regardless of any overlapping allergic phenotype.