Journal of Asthma and Allergy最新文献

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.

Purpose: Biologic (antibody) therapy is a safe, effective, and guideline-recommended treatment for patients with severe and otherwise uncontrolled asthma. The number of older individuals with asthma is increasing but there is a lack of data on the use of biologics in this cohort. Therefore, this study reports the characteristics of older individuals receiving biologic therapy for severe asthma.

Patients and methods: This study was a retrospective data analysis conducted at two centers in Germany.

Results: Eighty-eight patients were included (52 aged 50-59 years and 36 aged ≥60 years). There was a high rate of comorbidities and associated pharmacological therapy use. Nearly half (49%) of participants were current or ex-smokers and 29% had chronic obstructive pulmonary disease. The older age group (≥ 60 years) had significantly more cardiovascular comorbidities, more comorbidities overall, and a worse diffusion capacity compared with the group aged 50-59 years. Baseline lung function parameters, and the change in lung function after 6 months of biologic therapy, did not differ significantly between the two age groups. Participants aged ≥60 years used self-injection less than those aged 50-59 years.

Conclusion: These data help to characterize the specific population of older people receiving biologic therapy for severe asthma, and showed a high rate of comorbidities, polypharmacy, and poor diffusion capacity in this group.

Purpose: Asthma is a chronic inflammatory airway disease that impacts millions of people worldwide. Understanding and reporting its prevalence and characteristic symptoms are essential for a comprehensive investigation of the disease.

Patients and methods: This study aimed to assess the prevalence of asthma and asthma-related symptoms across Iraq. A cross-sectional study was conducted using the European Community Respiratory Health Survey (ECRHS) questionnaire. A questionnaire was created using Google Forms and distributed through various social networking sites.

Results: A total of 1131 participants were included in the study from different rural and urban Iraqi communities. The prevalence of physician-diagnosed asthma was 10.5%. The most commonly reported asthma symptom was waking due to an attack of coughing, reported by 60.9% of participants, followed by shortness of breath triggered by dust or fumes (45.9%) and waking due to shortness of breath (36.6%). Our results indicated that being a male, having allergic rhinitis and a family history of asthma is more like to have asthma according to physician diagnosis. Also, a significant association was found between asthma and having allergic rhinitis, food allergies, drug allergies and family history of asthma with asthma according to ECRHS.

Conclusion: This study highlights the prevalence of asthma and its associated symptoms among adults in Iraq, using the ECRHS questionnaire. The findings highlight the need for improved awareness, early diagnosis, and targeted interventions, particularly for high-risk groups such as older adults, smokers, and those with allergies. Further research is needed to explore environmental and genetic factors contributing to asthma prevalence in the region.

Background: Systemic corticosteroid use in type 2 inflammation-associated diseases including asthma, atopic dermatitis, allergic rhinitis, and chronic rhinosinusitis has been associated with adverse outcomes, and corticosteroid-sparing treatments are available.

Objective: Assess temporal changes in systemic corticosteroid use and the impact of type 2 inflammation multimorbidity (eg multiple concurrent type 2 inflammation-associated diseases) and specialist assessment on systemic corticosteroid exposure.

Methods: Using nationwide databases, all Danish adults with asthma, atopic dermatitis, allergic rhinitis, or chronic rhinosinusitis, based on hospital diagnoses or redeemed prescriptions between 1997 and 2021 were included in an open, serial cross-sectional cohort.

Results: Over 25 years, a total of 2,151,209 Danish adults were included. Of those with a single diagnosis (type 2 inflammation monomorbidity),13.9% had asthma, 19.2% allergic rhinitis, 52.9% atopic dermatitis, and 14.0% chronic rhinosinusitis. In terms of type 2 inflammation multimorbidity, 75.1% of included individuals had one, 21.3% two and 3.5% three diagnoses, respectively. Overall, 9.6% of type 2 monomorbid individuals redeemed systemic corticosteroids, with asthma (16.5%) and atopic dermatitis (6.0%) having the highest and lowest prevalence of use. Systemic corticosteroid use peaked in 2006 (10.6%) and was lowest in 2020 (7.2%). Exposure > 5 mg prednisolone/day was constant around 15% overall among users. Type 2 inflammation multimorbidity was associated with increases in systemic corticosteroid use at 9.6%, 16.0% and 20.9% for one, two and three diagnoses, respectively. A median referral delay of 4.1 [8.1] years from first systemic corticosteroid redemption to specialist assessment was seen. Specialist assessment led to a 64.9% reduction in median annual systemic corticosteroid exposure overall.

Conclusion: In type 2 inflammation associated diseases, systemic corticosteroid use remains common despite the introduction of corticosteroid-sparing treatments. Timely referrals to specialist assessment could reduce the overall systemic corticosteroid exposure.

Background: Due to the inability of children with allergies to exhibit appropriate clinical symptoms, pediatricians often face the challenge of accurately diagnosing allergic diseases in children. Identifying the distribution of allergens is essential for the effective diagnosis and treatment of allergic diseases.

Methods: We investigated the distribution of 28 allergens among 12,292 suspected allergic children in Shenzhen, whose serum-specific IgE was subjected to relevance analysis with influencing factors.

Results: The results showed the overall allergen distribution was 66.36%. Mite, cow's milk, and egg white were the most prevalent allergens. Indoor allergens are significantly higher than outdoor allergens. There was extensive cross-reactivity among homologous species of allergens such as crustacean allergens, plant-derived allergens, etc. A 14KDa profilin as a common ingredient is suspected to be the main cause of the cross-reactivity among these plant-derived allergens. The frequencies of mite, cow's milk and egg white showed different trends with growing age, indicating that the frequencies of allergens are age-related. Various mechanisms of immune systems of children mature at different ages. We found that the proportion of mite sensitivity was highest in children with allergic rhinitis and conjunctivitis, while the proportion of cow's milk and egg white sensitivity was higher in children with allergic dermatitis such as eczema and urticaria.

Conclusion: Age and cross-reactivity play important roles in diagnosing allergies in children. Children at different ages exhibit varying sensitivities to different types of allergens, and identifying cross-reactions helps to comprehensively understand children's allergic status. Pediatricians can develop corresponding prevention and management measures based on allergen results and clinical symptoms.

Purpose: This study aimed to investigate the associations of anaemia status and body mass index (BMI) with asthma severity in adult subjects.

Methods: The study included 300 adults who had asthma and admitted to King Abdulaziz Medical City from about 2017 to 2022. The subjects' demographic data, BMI, anaemia status, and number of asthma-related hospital admissions were analyzed. Associations between anaemia, BMI, and asthma severity were investigated within a cross-sectional comparative design. Anaemia status as well as BMI variations may have an impact on the frequency of asthma-related hospitalizations.

Results: Most subjects in the study were female (74.3%) and over the age of 65. Mild anaemia was the most common condition (41.7%), and (42.3%) of subjects were classified as obese and (22.7%) were overweight. Age was found to be a significant factor in asthma-related hospital admissions (p-value = 0.0002), however sex was not significant. Subjects with mild or moderate anaemia and those who were obese had a higher frequency of asthma-related hospital admissions. Furthermore, the study revealed significant differences in the mean number of asthma-related hospital admissions among the different BMI and anaemia status categories. Subjects with severe obesity had a significantly greater number of asthma-related hospital admissions with a mean of 2.21 compared with the other BMI groups (p-value= 0.029). Subjects with mild anaemia had a significantly greater number of asthma-related hospital admissions with a mean of 2.07 than those with severe anaemia (p-value=0.04). These results highlight the importance of considering comorbid conditions in the clinical assessment and management of asthma.

Conclusion: These findings highlight that anemia and BMI abnormalities can complicate asthma management. Health care professionals should be aware of these factors when assessing severity and developing treatment plans. Further research is needed to explore the underlying mechanisms and evaluate interventions targeting anaemia and BMI to improve outcomes.

Introduction: Asthma causes airway inflammation, leading to symptoms that impair patients' quality of life, making it a significant global public health issue. Inhaled corticosteroids (ICS) with long-acting beta-agonists therapy (LABA) is commonly used to manage moderate to severe asthma. For patients unresponsive to ICS with LABA, omalizumab may be added to improve asthma control. Understanding transcriptomic expressions is crucial as it provides insights into the molecular mechanisms underlying treatment. However, the impact of omalizumab on transcriptomic expressions remains unclear. Therefore, this study aims to investigate the transcriptomic expression profiles and clinical outcomes between patients receiving ICS with LABA therapy and those adding omalizumab.

Materials and methods: This is a prospective, real-world study that enrolled 26 participants, divided into three groups: Group 1, ICS with LABA (n=10); Group 2, ICS with LABA plus omalizumab (n=12); and Group 3, healthy controls (n=4). Assessments included transcriptomic expression profiles, and bioinformatics analysis, IgE, airborne allergen test, pulmonary function test, blood tests, and asthma control test (ACT).

Results: ACT scores were significantly higher in Group 1 and 2 compared to Group 3. IgE levels, dust mite sensitivity, and dynamic pulmonary function changes after bronchodilator administration were notably higher in Group 2. In these patients, down-regulated genes included those related to immune response, NOD-like receptor signaling, RIG-I signaling, IL-17 signaling, and antioxidant activity. Conversely, up-regulated genes were found in the cGMP-PKG signaling pathway, cardiomyopathy-related pathways, and voltage-gated calcium channel activity.

Conclusion: Patients receiving ICS with LABA plus omalizumab still exhibited more dynamic airway changes and higher IgE levels. Downregulation of immune and inflammatory pathways suggests its potential as an add-on treatment for severe asthma. However, upregulated genes were observed in the cGMP-PKG signaling pathway, cardiomyopathy-related pathways, and voltage-gated calcium channel activity.