Journal of Asthma and Allergy最新文献

As a vital component of the immune system, macrophages play a critical role in the progression of asthma. The two classic polarization states of macrophages, M1 and M2, exhibit distinct functions. M1-polarized macrophages eliminate pathogens through the secretion of pro-inflammatory cytokines, while M2-polarized macrophages secrete anti-inflammatory factors to facilitate tissue repair. However, in asthma, the activation of M1 macrophages is often associated with excessive inflammatory responses, whereas M2 macrophages contribute to airway remodeling and chronic inflammation. These processes collectively exacerbate airway inflammation and remodeling, thereby aggravating asthma symptoms. Reactive oxygen species (ROS), as crucial signaling molecules, have been shown to regulate macrophage polarization and promote both M1 and M2 polarization states. This review summarizes the primary endogenous and exogenous sources of ROS in asthma and elaborates on the mechanisms by which ROS influence M1/M2 polarization of macrophages. Endogenous ROS arise chiefly from NOX2, xanthine oxidase, peroxisomes and mitochondria, whereas ozone and fine particulate matter are major exogenous sources. ROS activate MAPK, NF-κB and NLRP3 cascades, boosting IL-1β, IL-6 and IL-27 release by M1 cells, while low NOX2 flux or mitochondrial H₂O₂ supports STAT6-dependent ARG1 expression and drives an M2 program. Additionally, we discuss the impact of different macrophage polarization states on asthma pathophysiology and the potential applications of macrophage-modulating agents in asthma treatment, particularly those targeting ROS-mediated polarization pathways. ARG1 rich M2 cells convert L-arginine into proline, fostering collagen deposition; Ym1/2, Fizz1 and CD206 correlate with airway remodeling and declining lung function. Emerging antioxidant and macrophage-polarization strategies that selectively modulate ROS show promise in rebalancing M1/M2 responses and attenuating airway hyper-responsiveness. This review provides new insights into the interplay between ROS and macrophage polarization and highlights the potential for developing therapies aimed at modulating macrophage polarization via ROS regulation.

Background: The emergency room (ER) approach for patients with asthma exacerbations (AEs) should be based on a comprehensive, multidisciplinary approach to ensure effective and timely care. This study aims to analyze the compliance level of recommended indicators, as defined in a consensus document, for the management of AEs in the ER using available electronic medical records.

Methods: An open-label, observational, non-interventional, retrospective study of adult patients treated in hospital ER for AEs was conducted at La Paz University Hospital and Salamanca University Hospital. Data were collected from medical records regarding a set of predefined measures and variables concerning asthma severity, ER stay, and subsequent discharge.

Results: During 2019, a total of 1,019 patients accounted for 1,089 AEs were evaluated. Clinical variables predominantly included historical data, such as previous hospitalizations, Intensive Care Unit admissions, and prior exacerbations, which were recorded in 45.8% of medical records. Auscultation details were extensively documented (99.8%), yet respiratory rate (25.4%) and spirometry (less than 10%) were notably lower. Regarding discharge planning, 69.6% of patients had a defined care plan, and 59.5% received Inhaled Corticosteroids plus Long-Acting Beta-Agonists combination treatment at discharge. Medical referrals resulted in 25.5% being referred for specialized care and 87.2% to primary care. 13.3% had a specific post-discharge care timeframe.

Conclusion: This study highlights significant variability in the documentation and adherence to recommended indicators for AE management in the ER. Moreover, discharge planning and follow-up care were suboptimal. These findings underscore the need for improved standardization and implementation of evidence-based protocols in emergency asthma care.

Purpose: Severe asthma is frequently accompanied by comorbidities such as chronic rhinosinusitis, nasal polyps, allergies, and gastroesophageal reflux disease (GERD). With increasing age, non-communicable conditions such as cardiovascular diseases and multimorbidity become more prevalent. This study aimed to analyze the prevalence of comorbidities and their impact on asthma-related outcomes over a two-year period using data from the Swiss Severe Asthma Registry (SSAR).

Patients and methods: We included 234 patients with baseline data and 2 years of follow-up visits from the SSAR. Patient's asthma control (ACT), quality of life (QoL), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide (DLCO) and fraction expiratory nitric oxide (FeNO) and their association to comorbidities were analyzed longitudinally using general estimation equations (GEEs) with log link function.

Results: Over the study period, ACT and QoL scores significantly improved, and the frequency of exacerbations declined. The prevalence of the examined comorbidities remained stable. However, the presence of chronic obstructive pulmonary disease (COPD) was significantly associated with lower ACT scores, reduced QoL, and impaired pulmonary function (all p < 0.05). GERD was also linked to lower ACT and QoL (p < 0.05), while depression was associated with a significant decrease in DLCO (p < 0.05).

Conclusion: Our findings underscore the strong impact of comorbidities-particularly COPD, GERD, and depression-on asthma control, quality of life, and lung function in patients with severe asthma. These results highlight the need for integrated, multidisciplinary management strategies targeting comorbid conditions to improve overall asthma outcomes. Further research should explore these subgroups in more detail to guide personalized treatment approaches.

Recurrent pulmonary infections (RPIs) represent a common yet clinically complex entity, primarily triggered by aspiration or the presence of foreign bodies. They are notoriously insidious and challenging to detect clinically. These infections typically involve the invasion of bacteria, viruses, or fungi, leading to inflammation and damage of lung tissue. The development of RPIs may also arise from the interplay of multiple factors. Due to their inherent complexity and association with poor prognosis, RPIs constitute a significant cause of mortality stemming from pulmonary infections. Understanding the risk factors associated with RPIs secondary to foreign body aspiration is crucial for effective clinical management. This narrative review synthesizes current knowledge on the pathogenesis, diagnosis, management, and prevention of RPIs caused by foreign body aspiration. We emphasize the heightened vulnerability of pediatric and elderly populations. The review delineates characteristic clinical presentations and outlines appropriate diagnostic modalities. Furthermore, it provides perspectives on antimicrobial therapy and the critical importance of foreign body removal. The synthesis aims to inform future research directions, preventive strategies, and therapeutic approaches, ultimately seeking to improve patient outcomes and mitigate the risk of recurrent infections.

Purpose: Asthma is the most common chronic disease among adolescents, yet disparities exist in its diagnosis and management across racial and gender groups. This study aims to assess asthma knowledge, awareness, and healthcare access among adolescents, with a focus on racial and gender disparities. The goal is to identify gaps in asthma education and knowledge, as well as other barriers that may contribute to the underdiagnosis of asthma within these groups.

Patients and methods: This cross-sectional survey included adolescents aged 10-18 years, with responses collected through Qualtrics. A total of 90 participants were selected, with no restrictions based on asthma status. Written informed consent was obtained from parents of participants under 18, while participants who were 18 years old provided their own written consent in accordance with IRB guidelines. Participants' knowledge of asthma symptoms, triggers, and healthcare access was assessed using multiple-choice and Likert scale questions. Data were analyzed for demographic differences in asthma knowledge and healthcare access across racial and gender groups.

Results: The study found that asthma education was minimal, with only 8% of participants reporting prior formal asthma education. Despite this, 53.4% of participants considered themselves knowledgeable about asthma, 59.5% could identify three or more asthma symptoms, and 50.6% identified more than three triggers. Racial disparities were evident, with Asian adolescents having a significantly lower asthma diagnosis rate compared to other racial groups (6.5% vs 47.4%, P<0.01), a lower rate of self-reported asthma knowledge (45.1% vs 64.9%, P=0.08), and lower odds of finding healthcare access "extremely easy" (OR=0.179, 95% CI: 0.076-0.455, P=0.00018). Although there was no difference in the rate of previous asthma diagnoses, males were more likely to seek medical help compared to females (OR=2.55, 95% CI: 1.037-6.268, P=0.032).

Conclusion: This study highlights significant gaps in asthma education, perception of healthcare access, and healthcare seeking behaviour particularly among Asian adolescents and females, and underscores the need for targeted interventions to address racial and gender disparities in asthma diagnosis and care.

Background: Atopic dermatitis (AD), a chronic inflammatory skin condition, affects up to 20% of children and 10% of adults globally, driven by a type 2 immune response via IL-4 and IL-13 through IL-4Rα. The rs1801275 variant in IL-4Rα gene, a glutamine-to-arginine substitution (Q576R), increases AD severity and atopic comorbidities. This study examines rs1801275's prevalence and clinical impact in Vietnamese population.

Methods: A cross-sectional study (January-May 2021) with 113 AD patients (Hanifin and Rajka criteria) and 213 healthy controls has been conducted. Demographics, clinical features, and SCORAD severity were assessed via questionnaires and dermatologist evaluations. rs1801275 variant was genotyped using allele-specific real-time PCR. Frequencies were compared, and associations with AD severity were analyzed using Fisher's Exact Test, Kruskal-Wallis test, and logistic regression, adjusting for age and sex.

Results: Allele frequencies (A: 82.74% vs 79.58%; G: 17.26% vs 20.42%) and genotypes of AD patient and control groups, respectively, showed no significant difference (p = 0.315), indicating no link to AD susceptibility. However, the G allele was associated with higher SCORAD severity in the dominant model (AG+GG vs AA: median 40 vs 30.5, p = 0.010; OR 4.67, p = 0.005) and additive model (p = 0.023), with a dose effect (AA: 30.5, AG: 39, GG: 49.65). Age group independently predicted severity (OR 2.31-2.43, p < 0.05).

Conclusion: The rs1801275 variant correlates with increased severity in G allele carriers, per SCORAD, in dominant model. These findings support personalized AD management in Vietnam, though larger studies are needed for GG genotypes.

Rational: Asthma severity assessment is essential for asthma management. Transcriptomics contributes substantially to asthma pathogenesis. Then, this study aimed to explore asthma severity-associated transcriptomics profile and promising biomarkers for asthma severity prediction.

Methods: In discovery cohort, induced sputum cells from 3 non-severe and 3 severe asthma patients were collected and analyzed using RNA-seq. Multivariate analysis was performed to explore asthma severity-associated transcriptomics profile and differential expressed genes (DEGs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used for pathway enrichment analysis. Subsequently, based on the previous study and clinical experience, the mRNA expressions of 6 overlapped asthma severity-associated DEGs and C3 in induced sputum cells and serum C3 were verified in validation cohort.

Results: Distinct asthma severity-associated transcriptomics profile was identified in induced sputum cells in discovery cohort. Then, 345 DEGs were found, of which 38 terms and 32 pathways were enriched using GO and KEGG, respectively. In validation cohort, the mRNA expressions of ZNF331, CD163, MACC1, ADAMTS2, and C3 were increased, and RYR1 and NRXN3 were decreased in induced sputum cells in severe asthma. Meanwhile, the AUC of ROC was 0.890 for serum C3 in asthma severity prediction, with the best cut-off of 1.272 g/L.

Conclusion: Collectively, this study provides the first identification of the association between induced sputum cells transcriptomics profile and asthma severity, indicating the potential value of transcriptomics for asthma management. The study also reveals the promising value of serum C3 for predicting asthma severity in clinical practice.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease of the nose and paranasal sinuses. Asthma is a common coexisting condition, associated with more severe sinus disease and reduced quality of life. Treating patients with uncontrolled CRSwNP and coexisting asthma is currently challenging.

Objective: To compare baseline characteristics and disease burden in patients with CRSwNP with and without coexisting asthma in AROMA.

Methods: AROMA is a prospective global registry study recruiting adult patients with severe CRSwNP who initiate dupilumab and follows them for up to 36 months. All patients entering the registry were assessed for baseline demographics and disease characteristics.

Results: As of February 2023, the study had enrolled 303 patients, with 210 (69.3%) patients reporting coexisting asthma. Of the patients with asthma, 11.0% reported ongoing oral/systemic corticosteroid use at baseline, and 29.0% had at least 1 severe asthma exacerbation in the year before screening.

Conclusion: More than two-thirds of adults with CRSwNP who initiated dupilumab in AROMA have coexisting asthma. Of these patients, one-third reported at least 1 severe asthma exacerbation in the past year.

Background: Bronchial asthma is a chronic inflammatory condition that affects the lungs and causes airway narrowing. Multiple genetic and environmental factors contribute to bronchial asthma. The complex interactions between these factors play a vital role in the susceptibility to and severity of asthma. Several genetic factors are associated with the prevalence and severity of bronchial asthma. Among these genes, ARG1 rs2781666 polymorphism has been found to be associated with bronchial asthma prevalence worldwide. Furthermore, increased serum arginase activity has been reported in patients with asthma, suggesting an association with bronchial asthma phenotypes.

Purpose: To determine the frequency of ARG1 rs2781666 polymorphism among Jordanians, we compared plasma arginase activity and ARG1 rs2781666 polymorphism in asthmatic patients and non-asthmatic volunteers, and analyzed the distribution of rs2781666 genotypes among asthma severity groups.

Patients and methods: Four hundred and twenty-four asthmatic and non-asthmatic Jordanian subjects visiting the Jordan University Hospital were genotyped for ARG1 rs2781666 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method and were examined for serum arginase activity using an arginase activity assay.

Results and conclusions: There was a significant association between ARG1 rs2781666 G/T polymorphism and bronchial asthma frequency and severity. The GT genotype and T allele frequencies were significantly higher in asthmatic patients than in non-asthmatic patients. In addition, comparison between the ARG1 rs2781666 genotype distribution and asthma severity revealed that the TT genotype was more frequent in the severe asthma group. Furthermore, a comparison of plasma arginase activity between the asthmatic and non-asthmatic groups revealed that arginase activity was significantly higher in asthmatic patients than in non-asthmatic patients. In addition, the results showed a positive association between elevated plasma arginase activity and rs2781666 G/T in asthmatic patients compared to that in non-asthmatic subjects.

Background: Asthma is a chronic, heterogeneous disease driven by inflammatory phenotypes, primarily eosinophilic asthma (EA) and neutrophilic asthma (NEA). While allergen triggers are well-known, the role of the airway microbiome and metabolites in asthma exacerbations remains poorly understood.

Methods: We recruited 64 participants (24 EA, 20 NEA, 20 healthy controls [HC]) for the discovery cohort, with validation in an external cohort (10 EA, 8 NEA, 8 HC). Induced sputum samples were analyzed using 16S rRNA sequencing to profile bacterial composition and non-targeted metabolomics to assess airway metabolites. Random forest models identified diagnostic markers, validated in the external cohort.

Results: Significant shifts in airway microbiota were observed, particularly between NEA and HC, and between EA and NEA. Four bacterial general-Stenotrophomonas, Streptococcus, Achromobacter, and Neisseria-were consistently identified across groups. Veillonella was more abundant in NEA vs HC, while Achromobacter was enriched in NEA vs EA, indicating distinct microbial signatures. Metabolomic profiling revealed distinct pathways: pyrimidine metabolism (EA vs HC), tryptophan metabolism (NEA vs HC), and arachidonic acid metabolism (EA vs NEA). Microbial-metabolite correlations indicated microbiota-driven metabolic activity. Biomarker candidates were validated in the external cohort.

Conclusion: The airway microbiota and metabolites are intricately linked to asthma exacerbations, with distinct patterns between EA and NEA. These findings highlight their potential as diagnostic biomarkers and therapeutic targets for personalized asthma management.