Journal of Asthma and Allergy最新文献

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.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multi-organ autoimmune disease characterized by eosinophilic infiltration of peripheral blood and tissues, and necrotizing granulomatous inflammation of small and medium-sized blood vessels. In the prodromal stage of EGPA, patients may present with features of refractory asthma, with the involvement of other organs occurring later when the diagnosis of EGPA is made. The difficulty of early diagnosis makes treatment difficult.

Methods: We retrospectively describe patients (N=13) who attended the asthma clinic at the First Affiliated Hospital of Guangzhou Medical University between 2008 and 2024. The disease course was categorized into three stages: asthma, lung-limited or lung-dominant EGPA (L-EGPA), and systemic EGPA (S-EGPA). Patients with severe eosinophilic asthma served as controls. We evaluated baseline demographic, as well as organ involvement, complication, laboratory findings, lung function, high-resolution computed tomography (HRCT), and treatment across different disease stages. A case-crossover design and Bayesian conditional logistic regression were employed to evaluate the impact of medication use on disease progression.

Results: We identified a group of EGPA patients who exhibited consistent disease progression to transit from asthma to L-EGPA, and eventually to S-EGPA. These stages exhibit distinct clinical and imaging features, with significantly elevated eosinophilic inflammatory markers in induced sputum or blood being a hallmark of L-EGPA. This distinction may aid in differentiating refractory asthma from L-EGPA.

Conclusion: In conclusion, the L-EGPA phase may represent a distinct stage in EGPA development that is often challenging to distinguish from refractory asthma. Characterizing this phase and identifying specific biomarkers could facilitate earlier diagnosis and treatment, potentially improving patient outcomes-a hypothesis that warrants further validation.

Purpose: To evaluate the Achieving Clinical Audits with Electronic Records (ACAER) program in supporting primary care providers in quality improvement initiatives across asthma and COPD.

Patients and methods: This observational cohort study included individuals aged ≥12 years with documented diagnosis of asthma or COPD, receiving asthma or COPD therapy, at high risk of exacerbation and hospitalization. Data were derived from the intervention, linked patient questionnaires completed as part of practice evaluation and quality improvement, and routine primary care electronic medical records (EMR) within the Optimum Patient Care Research Database Australia (OPCRDA). Changes in exacerbation rates and maintenance treatment were evaluated.

Results: 7512 asthma and 6526 COPD patients were evaluated with EMR collection. A subset of 1327 asthma patients and 629 COPD patients were classified as active and high-risk. Patient questionnaires and evaluation reports were sent out between 29 October 2019 and 21 September 2021, the intervention period. For those at risk during the entire study period (2018-2023; N=1276), 48.4% and 59.3% of patients in the high-risk asthma and COPD populations, respectively, had maintenance therapy change in the first year post-intervention. Exacerbation rates fell after the intervention period in the high-risk asthma (74.8 to 32.4 per 1000 per month) and COPD (122.9 to 91.2 per 1000 per month) populations. High-risk asthma patients had increasing rates of exacerbations in the 2 years prior to the intervention period (linear trend: 2.79 exacerbations per 1000 per month [1.34, 4.24]; p=0.001), which declined and remained stable after the intervention (p=0.87; up to 2023). Exacerbation rates for high-risk COPD patients were stable pre-intervention (p=0.29). Post-intervention rates initially declined and then showed a marginal non-statistically significant increase (p=0.28).

Conclusion: Our findings support the potential for the ACAER asthma and COPD program to drive treatment change and improve long-term outcomes in high-risk patients in primary care settings.

Background: Viral-induced wheezing, a common respiratory issue in children, is characterized by wheezing triggered by viral infections. This study aims to evaluate parental knowledge, perceptions, and practices regarding viral-induced wheezing in Jordan.

Methods: A cross-sectional survey was conducted with 510 parents, recruited from schools and online platforms.

Results: The study found that 32.1% of parents had good knowledge about viral-induced wheezing, and 73.5% were aware that it could resolve in children over time. Parents of children with asthma, allergic rhinitis, or atopy were more informed about viral-induced wheezing. Regression analysis showed a significant association between children's recurrent upper respiratory tract infections and parental knowledge. During wheezing episodes, the majority of parents (91.8%) administered medications, and 80.1% used herbal remedies.

Conclusion: Parents of children with frequent upper respiratory tract infections exhibited greater knowledge related to wheezing management. Enhancing parental education may contribute to improved symptom recognition and management. These findings underscore the need for targeted educational initiatives and future longitudinal studies to explore the long-term impact of parental knowledge on respiratory outcomes.