Treatment Of Asthma Research Articles

Correlation of vitamin D serum level and quality of life in asthma patients

<p lang="hr-HR" align="JUSTIFY"><strong>Aim</strong> Moderate to severe asthma patients with sufficient and insufficient vitamin D serum level, respectively, were assessed with quality of life questionnaires before and after treatment with vitamin D added to their standard asthma treatment.<br /><strong>Methods</strong> Patients with moderate to severe asthma have been divided into two groups based on a serum level of vitamin D as sufficient or insufficient level of vitamin D, respectively. During 12 months, a total of 120 patients with sufficient level of vitamin D as well as 120 patients with insufficient level were given treatment with 2000 IU vitamin D for a three-month period. Quality of life of all patients was assessed by Asthma Control Test (ACT), Asthma Quality of Life (AQOL) and the physician's assessment expressed through the Global Evaluation of Treatment Effectiveness (GETE), which were performed before and after the treatment with Vitamin D.<br /><strong>Results</strong> Values of ACT and AQOL were higher after the treatment with vitamin D in both groups of patients. Values of GETE were lower after the treatment with vitamin D in both groups. All assessed components, psychological, physical, as well as the subjective feeling of control of the disease assessed by treating physicians, showed improvement after treatment.<br /><strong>Conclusion</strong> Adding vitamin D in the treatment regimen of moderate to severe asthma patients improves quality of life and general asthma treatment effectiveness.</p>

Timosaponin A-III Alleviates Asthma-Induced Airway Inflammation, Th17 Cell Differentiation, and STAT3/RORγt Pathway

ABSTRACT Introduction T helper 17 (Th17) cells have a significant effect in the pathogenesis of asthma, and signal transducer and activator of transcription 3 (STAT3) pathway activation is critical for Th17 cell differentiation. Timosaponin A-III (TA3) was reported to inhibit the STAT3 pathway. Here, we investigated whether TA3 improved asthma by inhibiting the STAT3 pathway. Methods Ovalbumin (OVA)-induced asthma murine models were developed, and TA3 (10 or 20 mg/kg) was gavage daily during OVA challenge. Murine naïve CD4+T cells were triggered for Th17 differentiation, and TA3 (5 or 10 μM) was used to treat cells during induction of Th17 differentiation. Results In vivo experiments showed that TA3 decreased airway inflammation, goblet cell and smooth muscle hyperplasia, α-smooth muscle actin and collagen deposition, Th17 differentiation, and STAT3/RORγt signaling activation in mice exposed to OVA. The inhibitory effect of TA3 on STAT3/RORγt signaling activation was also observed in in vitro experiments. Compared to positive control static (a specific inhibitor of STAT3), TA3 had a similar effect on Th17 differentiation. Discussion These findings indicate that TA3 may ameliorate Th17 cell differentiation by suppressing STAT3/RORγt signaling. Our data provide evidence of the potential benefits of TA3 for the treatment of asthma.

Potential drug targets for asthma identified through mendelian randomization analysis

BackgroundThe emergence of new molecular targeted drugs marks a breakthrough in asthma treatment, particularly for severe cases. Yet, options for moderate-to-severe asthma treatment remain limited, highlighting the urgent need for novel therapeutic drug targets. In this study, we aimed to identify new treatment targets for asthma using the Mendelian randomization method and large-scale genome-wide association data (GWAS).MethodsWe utilized GWAS data from the UK Biobank (comprising 56,167 patients and 352,255 control subjects) and the FinnGen cohort (including 23,834 patients and 228,085 control subjects). Genetic instruments for 734 plasma proteins and 154 cerebrospinal fluid proteins were derived from recently published GWAS. Bidirectional Mendelian randomization analysis, Steiger filtering, colocalization, and phenotype scanning were employed for reverse causal inference detection, further substantiating the Mendelian randomization results. A protein-protein interaction network was also constructed to reveal potential associations between proteins and asthma medications.ResultsUnder Bonferroni significance conditions, Mendelian randomization analysis revealed causal relationships between seven proteins and asthma. In plasma, we observed that an increase of one standard deviation in IL1R1[1.30 (95% CI 1.20–1.42)], IL7R[1.07 (95% CI 1.04–1.11)], ECM1[1.03 (95% CI 1.02–1.05)], and CD200R1[1.18 (95% CI 1.09–1.27)] were associated with an increased risk of asthma, while an increase in ADAM19 [0.87 (95% CI 0.82–0.92)] was found to be protective. In the brain, each 10-fold increase in IL-6 sRa [1.29 (95% CI 1.15–1.45)] was associated with an increased risk of asthma, while an increase in Layilin [0.61 (95% CI 0.51–0.73)] was found to be protective. None of the seven proteins exhibited a reverse causal relationship. Colocalization analysis indicated that ECM1 (coloc.abf-PPH4 = 0.953), IL-6 sRa (coloc.abf-PPH4 = 0.966), and layilin (coloc.abf-PPH4 = 0.975) shared the same genetic variation as in asthma.ConclusionA causal relationship exists between genetically determined protein levels of IL1R1, IL7R, ECM1, CD200R1, ADAM19, IL-6 sRa, and Layilin (LAYN) and asthma. Moreover, the identified proteins may serve as attractive drug targets for asthma, especially ECM1 and Layilin (LAYN). However, further research is required to comprehensively understand the roles of these proteins in the occurrence and progression of asthma.

Relationships between Chronic Cough and Asthma Control and Quality-of-Life in Patients with Severe Asthma: A 6-Month Longitudinal Analysis.

The prevalence and clinical implications of chronic cough (CC) in patients with severe asthma receiving asthma treatment remain relatively unknown. This study aimed to evaluate the relationships between CC and asthma control and quality-of-life (QoL) in patients with severe asthma through longitudinal analysis. Baseline and 6-month follow-up data from the Korean Severe Asthma Registry were analyzed. CC was defined as a cough visual analog scale (VAS) score of ≥40 at both baseline and 6-months. Demographic parameters and clinical outcomes were compared between patients with severe asthma and CC and those without CC. Generalized estimating equation (GEE) analysis was performed to identify associations of CC with asthma control and QoL scores. Of the total 286 participants with severe asthma, 116 (40.6%) were defined as having CC. Patients with CC had higher baseline cough and wheeze severity VAS scores (all P<0.001), poorer asthma control (P<0.001), and worse QoL (Severe Asthma Questionnaire [SAQ] and Euro-QoL 5-dimension [EQ-5D] index, all P<0.001), compared to those without CC. During follow-up, patients with CC were more frequently exposed to oral corticosteroids (58.6% vs. 38.6%, P=0.010) and experienced more frequent asthma exacerbations (48.3% vs. 28.6%, P=0.009) than those without CC. GEE analysis revealed that CC was independently associated with poor asthma control, lower SAQ scores, and lower EQ-5D index after adjusting for confounders. The presence of CC was associated with worse asthma control and QoL in patients with severe asthma. Further studies are warranted to better evaluate and manage CC in these patients.

Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Ginseng-Schisandra Chinensis decoction against asthma.

Ginseng-Schisandra chinensis (GSC) decoction has shown good efficacy in the treatment of asthma, but its t mechanism in the treatment of asthma is still not fully understood. This study aims to elucidate the therapeutic mechanism of GSC for AS by identifying the active components of GSC. The chemical composition of GSC was analyzed using UHPLC-MS/MS. The network pharmacology method combined with TCMSP and GeneCards database was used to identify potential targets and enriched pathways related to AS treatment. Use AutoDock for molecular docking to evaluate the binding affinity of active ingredients to core targets. Finally, the LPS-induced A549 cell inflammation model was used to evaluate the effect of GSC on the release of inflammatory cytokines. The main components in GSC, including ginsenosides (Rf, Rd, Rg2, Ro, Rg5, Rh1) and lignans (schisandrin A, B, schisandrol A, B, schisandrin ester A) were identified. Network analysis revealed 139 intersection targets and highlighted STAT3, TNF, EGFR, IL1B, and AKT1 as key targets, with the PI3K/AKT signaling pathway as the main pathway. Experimental results showed that GSC significantly reduced the levels of IL-1β, IL-6 and TNF-α in LPS-induced A549 cells (p < 0.01), indicating its powerful anti-inflammatory effect. GSC plays a role in treating asthma by targeting STAT3, TNF, IL-1β and AKT1, regulating the PI3K/AKT signaling pathway and inhibiting the release of inflammatory cytokines. These findings provide a basis for the clinical application of GSC.

Modern Possibilities of Usage Dupilumab in Children

Dupilumab is a genetically engineered immunobiological drug that has been increasingly used in recent years to treat bronchial asthma (BA), atopic dermatitis (AD) and eosinophilic esophagitis (EE) in children. The aim of the study is to analyze current literature data on the use of dupilumab in the treatment of BA, AD and EE in children. Despite the short history of dupilumab use in the pediatric population, its usage has shown promising results in the treatment of many conditions whose pathogenesis is T2 inflammation, primarily BA, AD and EE. It has demonstrated efficacy in patients with various clinical manifestations characterized by moderate to severe course or refractory to treatment, and has led to an improvement in the quality of life of patients. With the expansion of the use of dupilumab, there is more and more evidence of its usefulness in the treatment of other T-cell-mediated diseases.

Evaluating the Anti-inflammatory Potential of JN-KI3: The Therapeutic Role of PI3Kγ-Selective Inhibitors in Asthma Treatment.

Asthma is a chronic airway inflammatory disease of the airways characterized by the involvement of numerous inflammatory cells and factors. Therefore, targeting airway inflammation is one of the crucial strategies for developing novel drugs in the treatment of asthma. Phosphoinositide 3-kinase gamma (PI3Kγ) has been demonstrated to have a significant impact on inflammation and immune responses, thus emerging as a promising therapeutic target for airwayinflammatorydisease, including asthma. There are few studies reporting on the therapeutic effects of PI3Kγ-selective inhibitors in asthma disease. In this study, we investigated the anti-inflammatory and therapeutic effects of PI3Kγ-selective inhibitor JN-KI3 for treating asthma by utilizing both in vivo and in vitro approaches, thereby proving that PI3Kγ-selective inhibitors could be valuable in the treatment of asthma. In RAW264.7 macrophages, JN-KI3 effectively suppressed C5a-induced Akt phosphorylation in a concentration-dependent manner, with no discernible toxicity observed in RAW264.7 cells. Furthermore, JN-KI3 can inhibit the PI3K/Akt signaling pathway in lipopolysaccharide-induced RAW264.7 cells, leading to the suppression of transcription and expression of the classical inflammatory cytokines in a concentration-dependent manner. Finally, an ovalbumin-induced murine asthma model was constructed to evaluate the initial therapeutic effect of JN-KI3 for treating asthma. Oral administration of JN-KI3 inhibited the infiltration of inflammatory cells and the expression of T-helper type 2 cytokines in bronchoalveolar lavage fluid, which was associated with the suppression of the PI3K signaling pathway. Lung tissue and immunohistochemical studies demonstrated that JN-KI3 inhibited the accumulation of inflammatory cells around the bronchus and blood vessels, as well as the secretion of mucus and excessive deposition of collagen around the airway. In addition, it reduced the infiltration of white blood cells into the lungs. In summary, JN-KI3 shows promise as a candidate for the treatment of asthma. Our study also suggests that the inhibitory effects of PI3Kγ on inflammation could offer an additional therapeutic strategy for pulmonary inflammatory diseases.

Efficacy Assessment of Biological Treatments in Severe Asthma

Uncontrolled, severe asthma remains a significant clinical challenge, affecting a small proportion of asthma patients worldwide. Despite advancements in treatment options, a subset of patients continues to experience frequent exacerbations, uncontrolled symptoms, and impaired quality of life. The advent of biological therapies has revolutionized the management of severe asthma, offering targeted treatments that address specific inflammatory pathways. This review provides a comprehensive overview of the efficacy and response criteria of biological treatments in severe asthma, focusing on clinical, functional, and inflammatory markers used to help in the evaluation of the biologic treatment. Key response criteria include symptom control, reduction in exacerbations, improvement in lung function, and a reduction in or the discontinuation of oral corticosteroids. Biomarkers such as blood eosinophils and exhaled nitric oxide (FeNO) are essential tools in guiding treatment adjustments. Real-world studies underscore the importance of personalized treatment strategies, as variability in response to biological therapies can be significant. The emergence of tools such as the FEOS score and EXACTO questionnaire offer quantitative measures for assessing biological response and guiding clinical decisions. Additionally, predictive factors for better or poorer responses, such as pre-treatment lung function and comorbidities, like obesity and rhinosinusitis, are critical in patient selection. This review highlights the need for ongoing reassessments and potential modifications of therapy in cases of suboptimal response. Practical considerations for switching biological therapies are discussed, emphasizing the importance of tailoring treatments to individual patient profiles and disease phenotypes. With the continued development of personalized medicine, the outlook for patients with severe asthma is improving, selecting specific biomarkers to improve the selection of the biologic treatment.

Efficacy and Safety of Specific Immunotherapy Combined with Biologics in Allergic Rhinitis and Asthma: A Systematic Review and Network Meta-Analysis.

Allergic diseases are common clinical diseases. Although allergen-specific immunotherapy (AIT) and biologics have been widely recognized, the clinical efficacy, safety, advantages and disadvantages of the combined application have not yet been sufficiently recognized. We aimed to investigate the efficacy and safety of AIT combined with biologics in patients with allergic rhinitis and asthma. PubMed, EMBASE, the Cochrane Library, and Web of Science were systematically searched to identify RCTs investigating AIT combined with biologics for treating allergic rhinitis and asthma. The relevant outcome indicators, including incidences of emergency drugs use, severe nasal symptoms, severe adverse effects (AEs), local reactions at the site of administration, headache, and general AEs, were collected and extracted. Routine and network meta-analyses were conducted using RevMan-5.4 and STATA-MP-14 to assess efficacy and safety. Eight RCTs and a retrospective study involving 1494 patients aged 5 to 65 years with allergic rhinitis and asthma were included in this review. ① Routine meta-analysis revealed that AIT combined with biologics was significantly better than control treatment (placebo, AIT or biologics) in terms of the incidence of emergency drugs use, severe nasal symptoms, and severe AEs (P=0.0002; P=0.01; P=0.02). However, the differences in the incidence of local reactions at the site of administration, headache and general AEs were not significant. ② In the network meta-analysis, compared with AIT or placebo alone, AIT combined with biologics observably reduced the incidence of emergency drugs use and severe nasal symptoms (OR=0.32, 95% CI 0.14-0.73; OR=0.41, 95% CI 0.26-0.63). Furthermore, AIT combined with biologics yielded an evidently lower incidence of serious adverse reactions than AIT alone (OR=0.42, 95% CI 0.23-0.74). The combined application of AIT and biologics has promising prospects in the clinical treatment of allergic rhinitis and asthma due to the improvement of both clinical efficacy and safety. SYSTEMATIC REVIEW REGISTRATION (PROSPERO #CRD42024496277).

Exploring Asthma Mechanism of Belamcanda Chinensis by "Dose-effect Weighted Coefficient" Network Pharmacology and Experiment Validation.

Asthma is a chronic inflammatory disease of the airways that seriously endangers human health. Belamcanda chinensis (BC), a traditional Chinese medicine, has been used to counteract asthma as it has been shown to possess anti-inflammatory and regulatory immunity properties. The study aimed to investigate the mechanisms of action of BC in the treatment of asthma; a "dose-effect weighted coefficient" network pharmacology method was established to predict potential active compounds. Information on the components and content of BC was obtained by UPLC-QEOrbitrap- MS spectrometry. Based on BC content, oral bioavailability, and molecular docking binding energy, dose-effect weighting coefficients were constructed. With the degree greater than average as the index, a protein-protein interaction (PPI) database was used to obtain the core key targets for asthma under dose-effect weighting. GO function and KEGG pathway analyses of the core targets were performed using DAVID software. Finally, MTT and ELISA assays were used to assess the effects of active components on 16HBE cell proliferation. The experimental results using the 16HBE model demonstrated BC to have a potential protective effect on asthma. Network pharmacology showed SYK, AKT1, and ALOX5 to be the main key targets, and Fc epsilon RI as the promising signaling pathway. Eight components, such as tectoridin, mangiferin, luteolin, and isovitexin were the main active compounds, Finally, we analyzed the LPS-induced 16HBE proliferation of each active ingredient. Based on the activity verification study, all five predicted components promoted the proliferation of 16HBE cells. These five compounds can be used as potential quality markers for asthma. This study provides a virtual and practical method for the simple and rapid screening of active ingredients in natural products.

Recent Advances and New Therapeutic Goals in the Management of Severe Asthma.

Asthma is characterized by chronic airway inflammation as its primary pathological condition, which leads to various respiratory symptoms due to airway narrowing, with type 2 inflammation playing a central role. Asthma treatment, primarily centered on inhaled corticosteroids, aims to suppress type 2 inflammation and improve airway narrowing. However, severe asthma that cannot be controlled with high-dose inhaled corticosteroids or other asthma medications remains a clinical issue. The availability of multiple biological agents has recently improved the management of severe asthma. In addition, the concept of clinical remission has emerged as a treatment goal, further clarifying the objectives of asthma management. However, despite these advancements, the treatment of severe asthma driven primarily by non-type 2 inflammation remains a major challenge, and new biologics are currently being developed to address this issue.

Effects of the combination of Epimedium brevicornum Maxim, Ligustrum lucidum Ait and Dexamethasone on asthmatic rats by endogenous glucocorticoid pathway.

The theory of traditional Chinese medicine (TCM) believes that kidney deficiency is the fundamental cause of chronic refractory asthma, accompanied by pathological changes such as airway remodeling and a reduction of endogenous glucocorticoid (GC) synthesis. The combination of Epimedium brevicornum Maxim (EB) and Ligustrum lucidum Ait (LL) is frequently used in TCM for kidney tonifying and the alleviation of asthma symptoms. This approach is based on Pei-Ben formula, a renowned treatment for asthma developed by the distinguished Shanghai Practitioner, Professor Huiguang Xu, over 30 years of clinical experience. Long-term use of exogenous GC in the treatment of asthma lead to the inhibition of endogenous GC synthesis and further hypothalamic-pituitary-adrenal (HPA) axis function. Our previous experiments confirmed that the combination of Epimedium brevicornum Maxim and Ligustrum lucidum Ait (EL) with dexamethasone (Dex) enhances kidney Yin and Yang, boosts endogenous GC levels, and improves airway remodeling and HPA axis function in asthmatic rats. However, the underlying mechanism remains unclear. This study aimed to investigate the regulatory effect of EL with Dex on endogenous GC pathway in asthmatic rats. We employed an ovalbumin (OVA)-induced asthma rat model and an OVA-induced asthma rat model with Metyrapone (Met, an inhibitor of endogenous GC synthesis) intervention to evaluate the effects of Dex, EL and their combination (EL+Dex) on asthma treatment. The assessment included the lung histopathology, GC receptors (GR) countent and GC-GR binding in bronchoalveolar lavage fluid (BALF), corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), cortisol (COR), interleukin 6 (IL-6), and immunoglobulin E (IgE) in serum, GC metabolites in urine, and hydroxysteroid dehydrogenase (HSD) 11B1, HSD11B2, cytochrome P450 family 11 subfamily B member 1 (CYP11B1) and steroidogenic factor 1 (SF1) in lung, liver, and adrenal gland. In the OVA-induced asthma model, we found that endogenous GC synthesis was suppressed in both the asthma group and the Dex group. The combination of EL and Dex could enhance HPA axis function, increase protein expression of key endogenous GC synthesis factors (HSD11B1, HSD11B2 in lung; CYP11B1, SF1 in adrenal; HSD11B2, CYP11B1 in liver), and improve the level of endogenous GC synthesis. In the OVA-induced asthma model with Met intervention, we observed a highly significant endogenous suppression in both the asthma+Met group and the Dex group. Additionally, the use of EL, either alone or in combination with Dex, demonstrated a significant effect in improving HPA axis function and enhancing the protein expression of key endogenous GC synthesis factors (HSD11B1, HSD11B2 in lung; HSD11B1, HSD11B2, CYP11B1, SF1 in adrenal; HSD11B1 in liver). In both asthma models, the combination of EL and Dex could relieve the pathological changes of airway inflammation and airway remodeling, and enhance GC-GR binding capacity. This study reveals that the combined use of EL and Dex could improve airway inflammation and airway remodeling in asthma through enhancing HPA axis function, endogenous GC synthesis, and GC-GR binding, offering a promising therapeutic strategy for asthma management.

Oral administration of Limosilactobacillus reuteri VHProbi® M07 alleviates ovalbumin-induced allergic asthma in mice.

Asthma is characterized by chronic airway inflammation, persistent cough, wheezing, and dyspnea. This study aimed to evaluate the efficacy of Limosilactobacillus reuteri VHProbi® M07 (M07) administration in alleviate the asthma severity in a mice model. In vitro studies confirmed that M07 can survive and proliferate within the gastrointestinal tract. BALB/c mice were administered M07 both before and after ovalbumin (OVA) challenge. Serum levels of OVA-specific immunoglobulin (Ig) E and IgG1, inflammatory cells and cytokines in bronchoalveolar lavage fluid were assessed, along with histopathological examination of lung tissue. Compared to the placebo (PLA) group, mice treated with M07 exhibited significantly lower levels of OVA-specific IgE and IgG1 (P < 0.01). The counts of eosinophils and neutrophils were also significantly reduced in both the pretreated (PRE) group and post-treated (POS) group compared with the PLA group (P < 0.01). Histological analysis of lung tissues verified the protective effects of M07 against inflammation, demonstrating reduced infiltration of inflammatory cells. Additionally, mice in the PRE and POS groups showed significantly increased levels of IL-10 (P < 0.01), and significantly decreased levels of IL-5, IL-13, MCP-1, eotaxin, and tumor necrosis factor-α (P < 0.01). Oral administration of M07 mitigated key features of inflammatory responses in the OVA-induced mice asthma model. These findings suggest that M07 holds therapeutic potential for the treatment of allergic asthma.

Total alkaloids in Fritillaria cirrhosa D. Don alleviate OVA-induced allergic asthma by inhibiting M2 macrophage polarization

Fritillaria cirrhosa D. Don (FCD) is a traditional Chinese medicine used to treat respiratory disorders, known for its effects in clearing heat, moistening the lungs, resolving phlegm, and relieving cough. Additionally, the total alkaloids extracted from FCD can alleviate asthma symptoms and reduce airway inflammation. However, no studies have investigated the effects of total alkaloids on lung macrophages. This study explored whether the total alkaloids of FCD (TAs-FCD) reduce M2 macrophage polarization and, consequently, attenuate airway remodeling in asthmatic mice. This study further elucidated its mechanism of action in treating allergic asthma. The extracted TAs-FCD was analyzed for its composition using UPLC-Q-TOF/MS. Network pharmacology was employed to identify the active ingredients and potential mechanisms of TAs-FCD in the treatment of allergic asthma. A mouse model of ovalbumin-induced allergic asthma was established, adopted, and validated through in vivo experiments. Hematoxylin-eosin staining (H&E), immunohistochemistry (IHC), immunofluorescence staining (IF), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and real-time fluorescence quantitative polymerase chain reaction (q-PCR) were used to investigate the role of TAs-FCD in inhibiting M2 macrophage polarization in the context of allergic asthma. A total of 66 active ingredients were screened from 116 compounds using SWISSADME. The targets of these 66 compounds were predicted by SwissTargetPrediction, resulting in 808 unique drug targets after excluding duplicates. Additionally, 1756 targets related to allergic asthma were identified from the DisGeNET, Genecard, and OMIM databases. This led to 267 cross-targets between the active ingredient targets and allergic asthma targets, including interleukin (IL)-1β, tumor necrosis factor (TNF), and STAT3. Animal experiments demonstrated that TAs-FCD improved histopathological injury in mouse lungs, reduced peri-airway collagen fiber accumulation, airway mucus secretion, and airway smooth muscle proliferation. TAs-FCD also lowered IL-1β, TNF-α and IL-4 levels in lung tissues and alleviated airway inflammation. Furthermore, TAs-FCD significantly reduced levels of Arg1 and CD206, which are closely associated with M2 macrophages, and downregulated the expression of p-STAT3 and p-JAK2. TAs-FCD may inhibit M2 macrophage polarization by regulating the JAK2/STAT3 pathway, thereby alleviating airway remodeling and inflammation in allergic asthmatic mice.

Experiences of Oral Corticosteroid Use and Adverse Effects: A National Cross-Sectional Survey of People with Asthma

Experiences of Oral Corticosteroid Use and Adverse Effects: A National Cross-Sectional Survey of People with Asthma

Explore Alteration of Lung and Gut Microbiota in a Murine Model of OVA-Induced Asthma Treated by CpG Oligodeoxynucleotides.

We sought to investigate the impact of CpG oligodeoxynucleotides (CpG-ODN) administration on the lung and gut microbiota in asthmatic mice, specifically focusing on changes in composition, diversity, and abundance, and to elucidate the microbial mechanisms underlying the therapeutic effects of CpG-ODN and identify potential beneficial bacteria indicative of its efficacy. HE staining were used to analyze inflammation in lung, colon and small intestine tissues. High-throughput sequencing technology targeting 16S rRNA was employed to analyze the composition, diversity, and correlation of microbiome in the lung, colon and small intestine of control, model and CpG-ODN administration groups. (1) Histopathologically, both lung and intestinal tissue in asthmatic mice exhibited significant structural damage and inflammatory response, whereas the structure of both lung and intestinal tissue approached normal levels, accompanied by a notable improvement in the inflammatory response after CpG-ODN treatment. (2) In the specific microbiota composition analysis, bacterial dysbiosis observed in the asthmatic mice, accompanied by enrichment of Proteobacteria found to cause lung and intestinal epithelial damage and inflammatory reaction. After CpG-ODN administration, bacterial dysbiosis was improved, and a notable enrichment of beneficial bacteria, indicating a novel microecology. Meanwhile Oscillospira and Clostridium were identified as two biomarkers of the CpG-ODN treatment. (3) Heatmap analysis revealed significant correlations among lung, small intestine, and colon microbiota. CpG-ODN treatment can ameliorate OVA-induced asthma in mice. One side, preserving the structural integrity of the lung and intestine, safeguarding the mucosal physical barrier, the other side, improving the dysbiosis of lung and gut microbiota in asthmatic mice. Beneficial bacteria and metabolites take up microecological advantages, regulate immune cells and participate in the mucosal immune response to protect the immune barrier. Meanwhile, Oscillospira and Clostridium as biomarkers for CpG-ODN treatment, has reference significance for exploring precise Fecal microbiota transplantation treatment for asthma.

Trends in prescribing montelukast in patients with asthma in real-life: Results from the Turkish adult asthma registry.

Montelukast, a leukotriene receptor antagonist (LTRA) approved for the treatment of asthma and allergic rhinitis, is widely used, though real-world data on its application in asthma management remain limited. This registry-based study evaluated the use of montelukast in adult asthma patients, examining demographic and disease characteristics, asthma control status, asthma phenotypes, presence of atopy, and treatment regimens. Among 2053 patients analyzed, 61.76% (n = 1268; mean age: 46.2 ± 14.3 years), predominantly females (~76%), received montelukast. Montelukast users showed higher rates of allergic rhinitis (P < 0.001), hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) (P = 0.008), and chronic rhinosinusitis (P = 0.008). Montelukast group also had higher atopy and total IgE levels and tended to be more eosinophilic. Montelukast was commonly preferred in allergic, eosinophilic, NSAID-exacerbated respiratory disease, and severe asthma phenotypes (P < 0.001). Patients receiving Steps 4 and 5 treatments are more likely to be prescribed montelukast (P < 0.001). Montelukast usage was higher among patients with uncontrolled asthma [ACT< 20 (OR:1.29, 95%CI:1.052-1.582, P = 0.014)]. In addition, logistic regression analyses identified the main factors associated with increased montelukast use as; female gender (OR:1.33, 95%CI:1.041-1.713, P = 0.02), presence of atopy (OR:1.46, 95%CI:1.157-1.864, P = 0.002), comorbid allergic rhinitis (OR:2.12, 95%CI:1.679-2.293, P < 0.001), and severe asthma (OR:2.18, 95%CI:1.712-2.784, P < 0.001). These findings reveal that montelukast use is prevalent among asthma patients, particularly in females, middle-aged adults, and those with comorbid allergic rhinitis, uncontrolled asthma, or specific asthma phenotypes, underscoring the factors that influence its prescription in asthma management.

Recent advances in research on common targets of neurological and sex hormonal influences on asthma.

Asthma is currently one of the most common of respiratory diseases, severely affecting the lives of patients. With the in-depth study of the role of the nervous system and sex hormones on the development of asthma, it has been found that the nervous system and sex hormones are related to each other in the pathway of asthma. To investigate the effects of sex hormones and the nervous system on the development of asthma. In this review, we searched for a large number of relevant literature to elucidate the unique mechanisms of sex hormones and the nervous system on asthma development, and summarized several common targets in the pathways of sex hormones and the nervous system on asthma. We summarize several common important targets in the pathways of action of sex hormones and the nervous system in asthma, provide new directions and ideas for asthma treatment, and discuss current therapeutic limitations and future possibilities. Finally, the article predicts future applications of several important targets in asthma therapy.

Combination Inhaled Corticosteroid and Short-acting Beta2 Agonist (ICS-SABA) Use for Older Adults With Asthma

The first combination inhaled corticosteroid and short-acting beta2 agonist (ICS-SABA) was approved by the Food and Drug Administration (FDA) in 2023 for as-needed treatment or prevention of bronchoconstriction and to reduce the risk of asthma exacerbations in patients 18 years of age and older. The recently approved product contains an ICS-albuterol combination. The 2024 Global Initiative for Asthma (GINA) guidelines recommend as-needed ICS-formoterol as the preferred asthma reliever therapy; however, a GINA alternative recommendation is the use of ICS whenever an as-needed (SABA) is used. There is no difference in as-needed asthma treatment recommended by the GINA guidelines in older adults, and there has been minimal study in older adults. Because of limited guidance on the use of the ICS-SABA reliever inhaler in older adults, the purpose of this review is to evaluate the DENALI and MANDALA studies and the potential role of ICS-SABA in older adults. The mean ages in both studies were 50 years. The MANDALA primary outcome result was a statistically significant lower risk of severe exacerbations in the ICS-SABA reliever group compared with the as-needed albuterol (ALB) group at 24 weeks. In the MANDALA older adults subgroup analysis, there was not a statistically significant difference in the ICS-SABA reliever group compared with the as-needed ALB-alone group but the results favored ICS-SABA. The DENALI primary outcome results were a greater change from baseline in forced expiratory volume in the first second (FEV1) area under the curve averaged over 12 weeks with albuterol/budesonide (ALB-BUD) 180/160 ug compared with budesonide alone and placebo and a greater change from baseline in trough FEV1 with ALB-BUD 180/160 ug and 180/80 ug than ALB-alone and placebo. Because of minimal adverse effects in both trials and the benefits in preventing asthma exacerbations reported in the MANDALA trial, it is important to assess and recommend that older adults with asthma receive inhaled corticosteroid with their reliever asthma inhaler.

Antiviral and Immunomodulatory Effects of Zafirlukast Against Flaviviruses via Inhibition of the TNF Signaling Pathway.

The two most clinically important members of the flavivirus genus, Zika virus (ZIKV) and dengue virus (DENV) pose a significant public health challenge. They cause a range of diseases in humans, from hemorrhagic to neurological manifestations, leading to economic and social burden worldwide. Nevertheless, there are no approved antiviral drugs to treat these infections. Zafirlukast is an orally available Food and Drug Administration (FDA) approved drug for the prophylaxis and treatment of chronic asthma. It is a leukotriene receptor antagonist (LTRA) with high selectivity of the cysteinyl leukotriene-1 receptor (CYSLTR1) that acts as an immune modulator. Thus, we evaluated the antiviral potential of Zafirlukast against ZIKV and DENV in SK-N-SH cells. We showed that Zafirlukast exhibited potent antiviral activity against ZIKV, which could be linked to Zafirlukast's immune blockade of TNF signaling pathways and its downstream signaling pathways such as MAPK and ERK1/2. In addition, our results showed that Zafirlukast also counteracts ZIKV-induced changes in key genes involved in cellular lipid metabolism. Thus, these findings highlight the translational potential of optimizing Zafirlukast as a therapeutic agent for the treatment of ZIKV and DENV.