Association of MTOR gene polymorphisms with asthma and poor response to treatment in a Latin American population.

Quantitative morphometric analysis of asthmatic mouse lungs using micro-CT: A preclinical imaging study.

Seeds from Abelmoschus esculentus have strong anti-inflammatory properties and may effectively treat inflammatory diseases. This study explores the therapeutic potential of A. esculentus seed extract on bioactive components, hematological parameters, liver function tests, leukocytes, cytokines and histology in asthmatic mice. Mice were divided into six groups: The normal group, groups treated with A. esculentus (10, 15 and 20 mg/mL), a dexamethasone group (3 mg/mL) and an asthmatic control group. On days 1 and 14 after acclimation, all groups except the normal control received intraperitoneal injections of ovalbumin, followed by oral doses of A. esculentus (10, 15 and 20 mg/mL) or dexamethasone (3 mg/mL) during 15th to 26th day of the experiment. All treated groups were exposed to ovalbumin inhalation for three days afterward. The bioactive components in the acetonic extract were identified through Gas Chromatography-Mass Spectrometry (GC-MS) analysis. The primary bioactive compounds identified were fatty acids, flavonoids and phenolics. Mice given the extract showed improved liver enzyme levels, reduced leukocyte infiltration, alleviated airway constriction, lower cytokine levels (IgE, IL-4, IL-5, IL-10, IL-13 and IL-17A) and normalized blood indices. In conclusion, the seed extract of A. esculentus has significant potential to reduce asthma symptoms in the asthmatic mouse model.

Web-based cloud-computing Asthma Control Test differentiates uncontrolled asthma.

Asthma is a common respiratory disease in Canada, representing a significant burden on the health of the population and the healthcare system. While studies have attributed an association between obesity and asthma, understanding of this relationship remains underexplored in the Canadian population. This study aims to describe the association between BMI and current asthma in adults living across Canada. This study used cross-sectional data from the 2017-2018 Canadian Community Health Survey of individuals aged 18years and older who reported currently having asthma. Current asthma was defined as having been previously diagnosed with asthma and experiencing asthma symptoms or asthma attacks in the past 12months. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using log-binomial regression, modelling the association between BMI (underweight/normal weight (< 25kg/m2), overweight (25- < 30kg/m2), and obese (≥ 30kg/m2)) and current asthma, adjusting for relevant sociodemographic and health factors. Of the 7090 individuals with asthma in this study, 3627 (51.2%) experienced current asthma. The prevalence of current asthma was similar in overweight individuals (PR = 1.00, 95%CI 0.95, 1.05) when compared to those in the underweight/normal weight category, while individuals with obesity had a 5% higher prevalence (PR = 1.05, 95%CI 1.01, 1.10) when compared to those in the underweight/normal weight category. This study provides evidence for the association between obesity and an increased prevalence of current asthma among adults. Weight management, particularly for individuals with obesity, may be an important consideration in asthma control.

Prevalence of anemia and its association with asthma control in school-aged children: a cross-sectional study in Karachi, Pakistan (2025).

The effect of the CareAide® mobile application in adult outpatients with asthma: A randomised controlled trial.

Asthma is a heterogeneous condition and affected individuals show variable responses to available medications. An unmet need exists for add-on therapies that target novel molecular pathways, before patients escalate to biologics. Janus kinase 1 (JAK1) is implicated in multiple inflammatory cytokine pathways critical for the pathogenesis of asthma. Londamocitinib (AZD4604) is a highly specific, inhaled, JAK1 inhibitor with high potency to block multiple JAK1-dependent signalling pathways. AJAX is a phase 2a, randomised, double-blind, partially decentralised placebo-controlled study assessing the efficacy, safety and pharmacokinetics (PK) of londamocitinib in adults with moderate-to-severe asthma uncontrolled on medium-to-high-dose inhaled corticosteroid/long-acting β2-agonist. The primary endpoint is time to first CompEx Asthma event. Secondary endpoints include change from baseline in prebronchodilator forced expiratory volume in 1 s, chronic airways assessment test, six-item asthma control questionnaire, daily asthma symptom score, and morning and evening peak expiratory flow at weeks 4 and 12. In addition, assessment of the effect of londamocitinib on airway inflammation as measured by the fractional exhaled nitric oxide test; cough severity assessment; and the PK of londamocitinib in all participants after 4 and 12 weeks will also be evaluated. The study has received ethical approval from the appropriate ethic committee and will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines, and all applicable regulatory requirements. All participants will provide written informed consent prior to enrolment, with procedures in place to ensure comprehension and voluntary participation. Findings will be disseminated through peer‑reviewed publications and/or presentations at scientific conferences. Summary results will be posted on the trial registry and shared with participants and relevant patient groups in lay summaries.

Objective. To study asthma control parameters and exacerbations characteristics in obese patients, as well as their associations with intestinal endotoxin (ET), fecal zonulin levels, along with clinical, laboratory and instrumental findings in this patient cohort. Materials and methods. The study included 143 individuals: 98 patients with asthma and obesity (Group 1 – mild asthma, (n = 47), Group 2 – severe asthma, (n = 51)) and 45 obese patients without asthma. All the patients underwent a comprehensive standard examination. Specific methods of study included measurements of intestinal endotoxin, fecal zonulin, and IgA levels. The IBM SPSS Statistics 26.0 software package was used for statistical analysis. A p-value of 0.05 was considered statistically significant. Results. New additional markers of uncontrolled asthma course in obese patients were identified: an intestinal endotoxin (ET) level ≥1.965 EU/ml (p = 0,034) and a fecal zonulin level ≥89.6 ng/ml (p 0,001). Asthma control in obese patients (as assessed by ACT-test) had statistically significant inverse associations with body mass index (BMI) (p 0.001), waist circumference (WC) (p 0.001), hip circumference (HC) (p = 0.001), the WC/HC ratio (p = 0.034), intestinal ET level (p 0.001), fecal zonulin level (p 0.001), and the number of metabolic syndrome (MS) components (p 0.001). Direct correlations were observed with forced vital capacity (FVC) (p 0.001) and forced expiratory level (FEV1) (p 0.001). In patients of Group 2 (severe asthma), statistically significant negative correlations were found between the presence of exacerbations, increased exacerbation frequency (2 or more per year), use of systemic glucocorticosteroids (SGCs) during exacerbations, and such parameters as AСT score (p = 0.008; p = 0.004; p 0.001), IgA level (p 0.001; p = 0.005; p 0.001), FVC (p = 0.003; p = 0.018; p 0.001), FEV1 (p 0.001; p = 0.001; p 0.001). Positive correlations were found with BMI (p 0.001), intestinal ET (p 0.001; p = 0.002; p 0.001) and fecal zonulin (p 0.001; p = 0.002; p 0.001). The number of MS components was positively correlated with both an increased frequency of asthma exacerbations (p = 0.034) and the need for SGCs to manage exacerbations (p = 0.006). Conclusions. Fecal zonulin and intestinal ET levels can be considered as additional markers for the risk of uncontrolled asthma in obese patients. An increase in these indicators is associated with the presence, frequency and severity of exacerbations.

To compare the efficacy and safety of oral montelukast and inhaled tiotropium as add-on drugs to inhaled corticosteroids (ICS) in children with partly controlled/uncontrolled asthma. This open-label, parallel-group, non-inferiority, randomized controlled trial was conducted over two-year period in the pediatrics department of a tertiary care teaching institute. Children aged 6 to 14 y with partly controlled/uncontrolled asthma, despite being on step 2 or 3 of treatment as per Global Initiative for Asthma (GINA) 2021, were enrolled. The primary outcome was proportion of children with ACT/c-ACT score >19 at 3 mo. The secondary outcomes were proportion with ACT/c-ACT score >19 at 6 mo, change in lung function and quality of life score, asthma exacerbations, need for rescue therapy, and steroid use during the follow-up at 3 and 6 mo. All adverse events were recorded. A total of 152 participants were enrolled. At 3-mo follow up, 47/73 (64.4%) and 33/66 (50%) children in the montelukast and tiotropium arms respectively, had an Asthma Control Test/ Childhood Asthma Control Test (ACT/c-ACT) score >19. The difference was not statistically significant and the non-inferiority comparison of tiotropium to montelukast was inconclusive. There was no significant difference in any of the secondary outcomes at 3 or 6 mo. One child in the montelukast group developed neuropsychiatric symptoms. No other significant adverse events were noted. Non-inferiority of tiotropium to montelukast at 3 mo, when added to ICS in children with partly controlled/uncontrolled asthma, with respect to asthma control, was not proven in this trial. No significant difference was noted at 6 mo.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent, often Type 2-mediated inflammatory disease that markedly impairs quality of life. While dupilumab provides rapid improvement, there is limited evidence on long-term outcomes beyond 2 years, and the clinical impact of dosing-interval extension remains unclear. We therefore set out to evaluate long-term real-world outcomes of dupilumab therapy in CRSwNP and assess the effectiveness and safety of dosing-interval extension after achieving disease control. This retrospective single-center cohort included 224 adults with CRSwNP (37% with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease) treated with dupilumab for up to 4.5 years with outcomes modeled to 5 years. Longitudinal changes in polyp size, symptom burden, olfaction, asthma control, and Type 2 biomarkers were analyzed using mixed-effects models. Outcomes were then compared between patients who maintained standard 2-week dosing and those who voluntarily extended dosing intervals after achieving stable control. Dupilumab led to significant improvements in polyp burden, olfactory function, and quality of life peaking within 6 months, with sustained benefit through 5 years according to longitudinal modeling. Forty percent of patients extended dosing intervals without loss of efficacy and reported fewer treatment-related adverse events. Overall, 16% experienced side effects, most commonly musculoskeletal complaints, followed by skin reactions and injection site reactions. Long-term dupilumab therapy provided durable disease control and excellent safety. Personalized dosing-interval extension maintained efficacy and reduced treatment burden, supporting its potential role in optimizing long-term management of CRSwNP, especially in patients with troublesome side effects.

BackgroundSevere asthma is associated with poor asthma control, leading to poor outcomes. However, few studies have evaluated asthma control status in patients with severe asthma in the biologic era. This study aimed to evaluate baseline asthma control in patients with severe asthma using phase 2 of the Korean Severe Asthma Registry (KoSAR-2).MethodsAdult subjects meeting the international consensus definition of severe asthma were prospectively enrolled from 41 hospitals in Korea (March 2022 to June 2023). Data on demographics, comorbidities, lung function, inflammation and healthcare utilisation were collected. Using asthma control test (ACT) scores, patients were classified into a well-controlled asthma group (ACT ≥20) and poorly controlled asthma group (ACT <20).ResultsAmong 594 severe asthma patients, 51.9% had poorly controlled asthma. Multivariable analysis showed that medical aid (adjusted odds ratio (aOR)=5.515, 95% confidence interval (CI) 2.614–13.110, p<0.001), being underweight (aOR=4.129, 95% CI 1.081–20.192), forced expiratory volume in 1 s <60% predicted (aOR=1.854, 95% CI 1.090–3.175) and prior exacerbations (aOR=3.400, 95% CI 1.987–6.012) were associated with poorly controlled asthma, while T2 inflammation was associated with well-controlled asthma (aOR=0.560, 95% CI 0.316–0.977). However, biologic use was not associated with asthma control status.ConclusionsAbout half of patients with severe asthma in KoSAR-2 had poorly controlled asthma at baseline. While poor socioeconomic status reflected by medical aid was a key factor underlying poor asthma control, T2 inflammation was associated with better asthma control in severe asthma. These findings underscore the importance of both clinical management and socioeconomic support to improve asthma control outcomes.

To evaluate the prevalence of uncontrolled asthma in children and its association with parental knowledge. This cross-sectional study was conducted at the paediatric clinic of the Aga Khan University Hospital, Karachi, Pakistan, from July 2024 to December 2024. Asthmatic children aged 4-16 years and their accompanying parents (at least one) were enrolled in the study with consent. Uncontrolled asthma was determined using the Childhood Asthma Control Test, with a score of less than 19. Parental asthma knowledge was assessed using the Asthma Knowledge Questionnaire. Multivariable logistic regression analysis was used to adjust for potential confounding factors and identify markers of suboptimal control among children with asthma. A total of 170 children were enrolled in the study, 99 (58.2%) were male, and the mean age was 8.00 ± 2.97 years. The mean age at the time of asthma diagnosis was 3.77 ± 2.59 years. There were 110 (64.7%) children who had controlled asthma, and 60 (35.3%) had uncontrolled asthma. Inhaler use was more frequent among children with uncontrolled asthma (76.7% vs 57.3%). Emergency department visits in the past year (75.0% vs 51.8%), intensive care unit (ICU) admissions (48.3% vs 27.2%) and pet exposure (28.3% vs 15.5%) were significantly higher in the uncontrolled group. The mean parental knowledge scores in both groups did not differ significantly (56.77±7.36 vs 55.00±7.43) and were inadequate in both groups. In multivariable analysis, children with good asthma control have fewer emergency department visits, while inhaler use (reliever or controller) is more common in poorer control. This study concludes that parental asthma knowledge was inadequate and not associated with asthma control in children. Emergency department visits, ICU admissions and pet exposure were more common among children with poor asthma control.

Maintenance and Reliever Therapy in Pediatric Asthma: A Concise Review of Recent Evidence-Part II.

Optimal control and dynamical transmission of asthma due to smoking populations: Incorporating medical and public health measures

β2-adrenergic signaling promotes airway smooth muscle relaxation and limits the release of pro-inflammatory mediators by immune cells. The rs1042713 polymorphism encodes a glycine-to-arginine substitution (Arg16Gly) that enhances β2-receptor downregulation. We investigated the association of this polymorphism with the risk of severe eosinophilic asthma and its impact on the long-term effectiveness of mepolizumab and clinical remission. Genotypes from 102 patients with severe eosinophilic asthma receiving mepolizumab were compared with those from 31 individuals with mild asthma and 20 healthy controls. The severe-asthma cohort was followed for up to 24 months, and clinical data were collected at baseline and after 3, 6, 12, and 24 months of treatment. Analyses were stratified by Arg/Arg, Arg/Gly, and Gly/Gly genotypes. Each additional Arg16 allele increased the odds of severe eosinophilic asthma by 2.61-fold (95% CI 1.48-4.59; p = 0.0001) relative to mild asthma and by 3.61-fold (95% CI 1.78-7.35; p < 0.0001) relative to healthy controls. Over 24 months of mepolizumab treatment, Arg/Arg patients had an increased risk of exacerbations (HR 2.3 [95% CI 1.03-5.20]; p = 0.0414) and poorer asthma control compared with Gly/Gly patients (ACT ≥ 20: 72.4% vs. 100%, p = 0.0308). Gly/Gly patients also experienced less decline in lung function. By month 24, each additional Gly16 allele increased the odds of achieving clinical remission by 2.86-fold (95% CI 1.20-6.81; p = 0.0170), defined as no annual exacerbations, no OCS, and ACT ≥ 20, and by 3.06-fold (95% CI 1.34-6.96; p = 0.0080) when including an FEV1 decline ≤ 5% from baseline. The Arg16 allele of the rs1042713 polymorphism increases the risk of severe eosinophilic asthma and may reduce the long-term efficacy of mepolizumab, whereas the Gly16 allele appears to confer better outcomes and higher remission rates.

Asthma is a heterogeneous disease characterized by chronic inflammatory changes in the airways and reversible airflow limitation. Persistent airflow limitation (PAL) asthma, as a common phenotype of asthma, is usually defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio lower than 0.7 after bronchodilator in asthmatic patients. Recent research has indicated a correlation between PAL asthma and more frequent asthma exacerbations. A total of 1322 asthma patients were retrospectively assessed, and finally, 441 asthma patients were included in the study. Among them, 217 patients were diagnosed with non-PAL asthma, and 224 patients were PAL asthma. The differences in basic information, clinical manifestations, lung function, and laboratory test indicators between the PAL asthma and non-PAL asthma groups were compared. A clinical prediction model for PAL asthma based on patient demographics was established using logistic regression analysis. Comparing the demographic data of patients with PAL and non-PAL asthma, it was observed that PAL asthma was more common in elderly smoking males. Patients with PAL asthma had a higher severity of asthma, poorer control, and lower life quality compared to non-PAL asthma. In terms of lung function, patients with PAL asthma mainly exhibited obstructive ventilatory impairment, small airway dysfunction, diffusion dysfunction, and increased residual volume. Notably, after bronchodilators, patients with PAL asthma showed a significantly lower rate of improvement in small airway function compared with non-PAL asthma. Logistic regression analysis showed gender, smoking index, and Asthma Control Test (ACT) score were independent risk factors for PAL asthma. Linear regression analysis showed small airway function was closely associated with ACT score. PAL asthma was poorly controlled, leading to a diminished quality of life. The limited improvement in small airway function after bronchodilator in PAL asthma suggested that targeting small airway dysfunction may hold significant value in the treatment of PAL asthma. This retrospective study (441 asthma patients) found that PAL asthma is more common in elderly males, with smoking index and ACT score as its independent risk factors. PAL patients have poor small airway function and limited improvement after bronchodilators, suggesting targeting small airways may effective for PAL asthma treatment.

Vitamin D attenuates PCSK9-driven phenotypic switch of vascular smooth muscle cells and neointimal hyperplasia via SIRT6 activation.

The Impact of Treatable Traits on Clinical Remission in Patients with Asthma.

Epithelial barrier dysfunction is a pivotal feature of asthma, and it also commonly occurs in other inflammatory conditions such as atopic dermatitis (AD) and ulcerative colitis (UC). However, the core regulatory mechanisms underlying epithelial barrier dysfunction-especially whether shared mechanisms exist across these diseases-remain unclear. Gene expression profiles of patients with asthma, AD, and UC were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the limma package. Common DEGs among the three diseases were identified via a Venn diagram, followed by correlation analysis with junction molecules to screen for key genes. Interaction networks (protein-protein, transcription factor-gene, miRNA-gene, chemical-gene) of the key genes were constructed, and their correlations with asthma clinical features [Asthma Control Questionnaire (ACQ) score, Inhaled Corticosteroid (ICS) dose, lung function parameters] were analyzed. The effects of the key genes on epithelial barrier function were assessed in airway, epidermal, and intestinal epithelial cells. A total of eight common DEGs exhibited consistent upregulation in the epithelial tissues of patients with asthma, AD, and UC. Four key genes-CDC7, PXDN, TCN1, and TIMP1-were identified; they were upregulated in the epithelium of all three diseases, significantly elevated in IL-13-stimulated airway epithelial cells, and negatively correlated with junction molecules that were downregulated in the three diseases. Furthermore, the expression of these key genes was associated with the severity of asthma. Correlation analysis between key gene expression and asthma clinical features revealed that PXDN expression was significantly negatively correlated with the lung function parameter FEV1 (forced expiratory volume in 1 s), while TCN1 expression showed a significant negative correlation with FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity). Chemical-gene interaction analysis revealed that benzo[a]pyrene could induce the expression of these four key genes. Subsequent experiments confirmed that stimulation of airway epithelial cells with benzo[a]pyrene significantly upregulated the expression of these key genes. Finally, targeting these key molecules was found to alleviate the IL-13-induced reduction in CLDN1 expression in airway epithelial cells. In invitro collagen-coated transwell assays, knocking down either CDC7 or TCN1 significantly attenuated IL-13-induced epithelial barrier disruption in airway, epidermal, and intestinal epithelia. Our findings confirm that targeting CDC7 and TCN1 facilitates the improvement of barrier function in airway epithelial cells, epidermal keratinocytes, and intestinal epithelial cells invitro, thereby providing promising therapeutic targets for diseases characterized by epithelial barrier dysfunction.