Journal of Asthma and Allergy最新文献

Purpose: Mas-related G-protein-coupled receptor member X2 (MRGPRX2) is a key receptor in mast cell activation and plays a critical role in mediating pseudo-allergic reactions. However, its role in allergic rhinitis (AR) remains poorly understood. Therefore, we investigated the correlation between plasma MRGPRX2 and symptoms in AR patients.

Patients and methods: A total of 116 patients with typical AR symptoms and positive skin prick test results and 100 healthy controls were recruited. Plasma MRGPRX2, total and specific IgE, and histamine were measured. AR patients who tested negative for both total IgE and sIgE were defined as IgE-negative. Symptom severity was evaluated using a questionnaire combining the Total Nasal Symptom Score (TNSS) and the Visual Analog Scale (VAS). TNSS assessed nasal (sneezing, rhinorrhea, congestion, itching), each scored from 0 (none) to 3 (severe). The VAS ranged from 0 cm (no symptoms) to 10 cm (most severe).

Results: Plasma MRGPRX2 levels were significantly elevated in patients with AR compared with healthy controls (P<0.001) and demonstrated good discriminative performance (AUC=0.92, P<0.001). Moreover, patients with moderate to severe AR had significantly higher plasma MRGPRX2 levels than those with mild AR (P<0.001). A significant positive correlation was also observed between plasma MRGPRX2 levels and VAS scores (ρ=0.37, P<0.001). This correlation was stronger in the IgE-negative AR group (ρ=0.61, P<0.001) compared with the IgE-positive group (ρ=0.25, P=0.027) (Z=2.25, P=0.024). Notably, plasma MRGPRX2 levels were positively correlated with TNSS only in IgE-negative AR patients (ρ=0.38, P=0.016), whereas no significant correlation was observed in the IgE-positive group (ρ=0.17, P=0.238).

Conclusion: Plasma MRGPRX2 levels are elevated in patients with AR and are positively correlated with disease symptoms, particularly in IgE-negative cases. MRGPRX2 may serve as a novel biomarker to improve the classification and management of AR, especially in patients exhibiting allergic symptoms despite clinically insignificant IgE levels.

Cough-variant asthma (CVA), a distinct asthma phenotype characterized by chronic cough as the predominant symptom, presents unique clinical and pathophysiological features. The development of accurate murine models is essential for elucidating its underlying mechanisms and evaluating therapeutic interventions. While animal models remain indispensable tools for studying human disease pathogenesis, current bronchial asthma models inadequately recapitulate CVA-specific pathology. Notably, CVA represents the most common etiology of chronic cough in children and shares core pathogenic mechanisms with classic asthma-including chronic airway inflammation, airway hyperresponsiveness (AHR), and remodeling. Despite established protocols for typical asthma modeling, standardized CVA-specific models are lacking. This review synthesizes current methodologies for establishing CVA murine models, evaluates modeling success criteria, and analyzes commonly employed sensitizers/induction approaches. We further examine physiological, immunological, and molecular assessment parameters, proposing a comprehensive evaluation framework based on inflammatory cell profiles, AHR, and cytokine expression. Such standardization is critical for advancing precision in CVA model development.

Background: The comorbidity of allergic rhinitis (AR) and functional constipation (FC) in preschool children represents an emerging clinical entity; yet its underlying microbial mechanisms remain inadequately elucidated. This study sought to comprehensively characterize the gut microbiota (GM) profile and functional alterations in children with concurrent AR and FC (ARFC), with specific emphasis on the gut-nasal axis.

Methods: In this cross-sectional analysis, fecal samples from 32 ARFC, 22 AR, and 21 healthy control (HC) children underwent 16S rRNA gene sequencing (V3-V4 regions). Microbial α-and β diversity, taxonomic composition, functional pathways, and correlations with clinical parameters were systematically analyzed.

Results: The ARFC group exhibited significant GM dysbiosis, including elevated α-diversity (Shannon index: 5.2 ± 0.3 vs HC 4.5 ± 0.4; P = 0.014) and distinct β-diversity (PERMANOVA P = 0.001). Taxonomic analysis revealed elevated enrichment of Proteobacteria (7.92% vs HC 1.94%; P = 0.001) and depletion of Bacteroidetes (40.06% vs HC 50.72%; P = 0.049). Pathogen genera, including Klebsiella and Escherichia/Shigella, were elevated, while butyrate-producing genera (Faecalibacterium and Ruminococcus) were reduced. Paradoxically, Bifidobacterium abundance was higher in ARFC than AR (4.21% vs 1.80%; P = 0.018), suggesting a potential compensatory immunomodulatory response. Functional prediction indicated impaired carbohydrate and lipid metabolism alongside enhanced xenobiotic degradation. Haemophilus abundance positively correlated with constipation severity (ρ = 0.52 and P = 0.008) and rhinorrhea severity (ρ = 0.56 and P = 0.003).

Conclusion: ARFC comorbidity is characterized by a distinct GM signature featuring pathogenic expansion, metabolic dysfunction, and compensatory Bifidobacterium enrichment, which may modulate immune responses. Loss of butyrate-producing bacteria may disrupt the gut-nasal axis, highlighting potential microbial and therapeutic targets for integrated therapeutic strategies in this dual symptom condition. These findings provide a foundation for microbiota-based interventions targeting both allergic and gastrointestinal manifestations.

Purpose: Airway mucus plugs are driven by eosinophilic inflammation and considered an important treatable trait in severe asthma. However, whether mepolizumab, an antibody that suppresses the interleukin-5 pathway and eosinophilic inflammation, can remove mucus plugs remains unclear. The purpose of this study is to evaluate whether mepolizumab treatment could reduce the extent of mucus plugs on computed tomography (CT), and whether changes in mucus plugs were associated with changes in symptoms and pulmonary function following the treatment.

Patients and methods: This retrospective study included consecutive patients with severe asthma who underwent an asthma control test (ACT), spirometry, and chest CT before and after treatment with mepolizumab at three Japanese hospitals. The mucus plug score (MPS) and total airway count (TAC) were quantified by CT.

Results: Thirty-one (15 male) patients were included in this analysis. Their baseline (pre-mepolizumab) median age, ACT, CT-measured MPS, and TAC were 67 years, 19 points, 7 points, and 232, respectively. Baseline MPS was significantly correlated with forced expiratory volume in one second (FEV1) and TAC (R= -0.39 and R= -0.71, respectively). After treatment with mepolizumab (median 466 days later), median ACT and MPS were 23 points and 1 point, respectively, significantly improved from baseline (both P<0.001). Changes in MPS were significantly correlated with changes in ACT and FEV1 (R= - 0.47 and R= - 0.68, respectively). Furthermore, a higher baseline MPS was significantly associated with greater changes in ACT and FEV1 (R= 0.41 and R= 0.47, respectively).

Conclusion: In this study, mepolizumab treatment coincided with a decrease in MPS, although a direct causal relationship could not be established. Nevertheless, the observed associations between higher baseline MPS and ACT improvement suggest the potential utility of MPS as a biomarker for biological treatment.

Background: Evidence suggests a bidirectional relationship between asthma and sepsis, but the mechanisms are unclear. This study explores the co-diagnostic genes and molecular links between asthma and sepsis using Mendelian Randomization (MR) and bioinformatics methods, and further validates the findings through clinical data, aiming to identify potential therapeutic targets and drugs.

Methods: Protein Quantitative Trait Loci (pQTL) data from an Icelandic population were used for two-sample MR analysis. Differential expression analysis identified common genes. Gene Ontology and KEGG enrichment analyses explored biological functions. Receiver Operating Characteristic (ROC) curves validated gene performance, and immune cell infiltration was analyzed using CIBERSORT. Drug targets were predicted using DrugSigDB and validated by molecular docking. Clinical data of the three groups of people were collected, and baseline analysis, ROC curve analysis, and comparison of the expression levels of CXCL8 were carried out.

Results: At the genetic level, 435 genes related to asthma and 1,385 genes related to sepsis were identified, with 141 common genes. Further findings showed that there were 247 differentially expressed genes in asthma and 2,878 differentially expressed genes in sepsis, and 65 common differentially expressed genes were enriched in immune and inflammatory pathways. The key gene CXCL8 exhibited excellent diagnostic performance and was closely related to immune cell subsets. Based on the research results, ten potential therapeutic drugs were screened, and seven of them were verified by molecular docking. Clinical sample testing results show that CXCL8 is closely related to asthma and sepsis.

Conclusion: CXCL8 may be a biomarker for both asthma and sepsis. Immune cells like monocytes, macrophages, and T cells may drive comorbid progression. Potential drug candidates were identified, offering new insights for future research on these diseases.

Introduction: We previously showed that individuals without a prior history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness and underlying eosinophilic (T2) inflammation, features suggestive of undiagnosed early-stage asthma. Improving our understanding of the inflammatory processes that contribute to asthma onset is essential, as it may ultimately lead to earlier detection, timely intervention and improved long-term outcomes.

Purpose: This study aimed to evaluate several key inflammatory biomarkers in this well-characterized population and examine their associations with clinical presentation to identify early signs of asthma.

Patients and methods: This retrospective, observational cohort sub-study included Canadian adults with respiratory symptoms and normal pre- and post-bronchodilator spirometry. Demographics and clinical data were extracted from study files. Plasma and serum levels of biomarkers associated with T2 airway inflammation and epithelial shedding, including IL-4, IL-5, IL-13, IL-25, IL-33, eotaxin, eotaxin-3, TARC, periostin and TNF-α, were measured using ELISA and multiplex electrochemiluminescent assays. Airway hyperresponsiveness was defined as a PC₂₀ <16 mg/mL, and T2 airway inflammation as sputum eosinophils >2% and/or FeNO >25 ppb.

Results: Among 128 adults (mean age ±SD: 58.0 ±13.9 years, 52% women), 45 (35%) had T2 airway inflammation. Most biomarker levels were low or undetectable, with substantial inter-individual variability. No significant differences in biomarker levels were observed between individuals with and without airway hyperresponsiveness or T2 airway inflammation. Eotaxin levels negatively correlated with post-bronchodilator FEV₁/FVC ratio (r=-0.18, P=0.0433), and eotaxin-3 positively correlated with FeNO (r=0.18, P=0.0482).

Conclusion: This panel of clinically accessible T2 biomarkers may not reliably reflect early pathophysiological signs of asthma in symptomatic adults with normal spirometry. Longitudinal follow-up of this cohort, along with the integration of airway sampling, may provide further insight into the role of these biomarkers in asthma development and progression.

Purpose: This study aims to evaluate the link between sleep disorders and patients with severe asthma enrolled in the Severe Asthma Network Italy (SANI) registry. We investigated the prevalence and the overall disease burden sleep disorders in severe asthmatics, identifying their clinical features, risks factors and treatable traits.

Patients and methods: We performed a retrospective analysis using data from the SANI registry, stratifying patients based on the presence or absence of sleep disorders at their baseline visit, to gather their clinical, functional, and demographic information.

Results: About 26.1% of severe asthmatics have concomitant sleep disorders, especially overweight patients. Severe asthmatic patients with sleep disorders have significantly more frequent rhinitis, chronic rhinosinusitis with (CRSwNP and without nasal polyps (CRSsNP), gastroesophageal reflux disease (GERD), cardiovascular disease (CVD) and type II diabetes. These patients more frequently use intranasal corticosteroids and show higher exacerbation rate needing systemic corticosteroids. They show less severe lung function impairment but worse asthma control and quality of life, increased asthma-related hospital admission and number of unscheduled medical visits. Multivariate analysis shows that overweight, moderate-to-severe rhinitis, CRSwNP, CRSsNP, GERD and CVD are independent risk factors for sleep disorders.

Conclusion: Sleep disorders are a common and relevant feature among patients with severe asthma. The two diseases influence each other worsening the severity of symptoms, quality of life and overall healthcare burden. These data suggest that, treating comorbidities, including sleep disorders, might result in a better management of asthma and so a better health outcome.

Purpose: Pulmonary rehabilitation (PR) is a well-established non-pharmacological intervention for patients with asthma. While PR improves asthma control and exercise capacity, its impact on airway inflammation remains unclear. Fractional exhaled nitric oxide (Fe_NO) is a biomarker of type 2 airway inflammation, yet its response to PR has not been extensively studied. Therefore, aim of this study was to investigate diurnal variations in Fe_NO and how Fe_NO develops during PR in asthmatic patients with different levels of Fe_NO.

Patients and methods: This prospective, single-center study investigated Fe_NO changes in asthma patients undergoing a comprehensive three-week inpatient PR program. The study observation period covered 15 consecutive days of FeNO measurements. Patients were divided into three subgroups according to their initial Fe_NO measurement: low (<25 ppb), intermediate (25-50 ppb) and high (>50 ppb). Fe_NO was measured three times a day, along with assessments of asthma control, lung function, blood eosinophils and exercise capacity before and after PR.

Results: Sixty-two patients were included. Only patients in the high Fe_NO group (n=22) showed a significant 40% decrease in Fe_NO from pre to post PR (93±29 ppb to 56±27 ppb, p<0.001), independent of medication changes. Fe_NO levels of patients with low (17±8 ppb to 16±10 ppb) and intermediate levels (39±12 ppb to 30±10 ppb) remained unchanged. Asthma control and exercise capacity improved across all three subgroups, with the greatest gains observed in patients with initially high Fe_NO. No significant Fe_NO changes occurred in the low and intermediate Fe_NO groups.

Conclusion: PR significantly reduced Fe_NO levels in asthma patients with high baseline Fe_NO, suggesting an anti-inflammatory effect beyond pharmacological treatment. These findings highlight the role of PR as a complementary strategy in asthma management, particularly for patients with persistent airway inflammation despite optimized medication. Further randomized trials are needed to confirm these results and explore long-term effects.

Purpose: Bananas are one of the most widely consumed fruits globally, particularly in Thailand. However, banana fruits have been recognized as allergenic, with the WHO/IUIS currently listing six identified banana allergens. This study investigates the proteome and allergenome of crude protein extracts from Musa 'Kluai Hom Thong' bananas.

Patients and methods: Proteins were separated using two-dimensional gel electrophoresis (2DE) and characterized through 2DE-IgE immunoblotting with sera from 20 banana-allergic patients. Reactive protein spots were analyzed using LC-MS/MS, and proteins were identified via database searches against UniProt-Musaceae.

Results: A total of 559 proteins were identified, with 35 reactive protein spots detected across the sera samples, corresponding to 19 distinct proteins. Notably, none of these proteins have been previously reported as banana allergens, categorizing them as potential novel allergens. Among these, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pathogenesis-related (PR) proteins are notable, as they are major allergens in other fruits and organisms.

Conclusion: Nineteen IgE-reactive proteins were identified from Musa 'Kluai Hom Thong', with GAPDH and PR proteins proposed as candidate novel allergens associated with systemic reactions and cross-reactivity. Future multi-center studies incorporating functional assays are needed to validate their clinical relevance and diagnostic potential.

Objective: This study investigated age-related variations in airway hyperresponsiveness (AHR) based on pulmonary function, fractional exhaled nitric oxide (FeNO), total immunoglobulin E (IgE), eosinophils, basophils, neutrophils, monocytes, and lymphocytes.

Methods: A total of 1,500 patients treated at the Second Hospital of Shanxi Medical University from 2021 to July-September 2023 were enrolled and stratified into four age groups. General information, smoking history, pulmonary function, FeNO (including FeNO50, FeNO200, and CaNO), and blood biomarkers (total IgE, eosinophils, basophils, neutrophils, monocytes, lymphocytes) were collected. Intergroup comparisons and correlation analyses were performed.

Results: Pulmonary function: The positive rate of bronchial provocation test and the decline rate of FEV1 were higher in adolescents and the elderly, exhibiting a "U-shaped" distribution. FEV1, FVC, MEF50, and MEF25 increased with age until 18 years old and then declined. FEV1/FVC showed an overall decline with age. Exhaled nitric oxide test: The positive rate of type 2 inflammation in small airways showed a "U-shaped" distribution. CaNO was highest in the elderly group, overall displaying a "U-shaped" trend. No age-related differences were observed in FeNO50 and FeNO200. Laboratory indicators: Eosinophils, total IgE, and lymphocytes decreased with age. Basophils were highest in the young adult group. Neutrophils were lower in adolescents and higher in the elderly. Monocytes were elevated in both adolescent and elderly groups.

Conclusion: AHR is more prominent in adolescents and the elderly, showing a "U-shaped" age distribution. Adolescents exhibited Th2-type inflammation (mainly eosinophil-driven), while the elderly showed non-Th2-type inflammation (mainly neutrophil- and monocyte-driven). Pulmonary function peaks in young adulthood and declines more rapidly after middle age, with small airway obstruction worsening in the elderly. The elevated CaNO in the elderly group dissociated from decreased blood eosinophils, suggesting localized eosinophilic inflammation or impaired migration, potentially indicating an eosinophil non-dependent inflammatory phenotype.