BackgroundChronic obstructive pulmonary disease (COPD) is driven by complex inflammatory processes in which neutrophil dysregulation plays a central role. Isonicotinylation (Kinic), a novel lysine acylation modification linked to cellular metabolism, has not yet been clearly associated with COPD.MethodsWe employed an artificial intelligence (AI)-driven, multi-omics framework. First, the Limma, WGCNA, and CIBERSORT algorithms were used to identify a Kinic- and neutrophil (KN)-associated shared molecular signature in the peripheral blood bulk profiles of COPD patients. Next, NMF and explainable machine learning identified molecular subgroups and developed a diagnostic model for COPD patients based on the KN-associated gene signature. In addition, a KN-associated pathogenic hub factor was identified, and its molecular and immune signatures in COPD were assessed using a cutting-edge analytical framework in spatial and temporal manners. An AI-based drug screening platform (DrugReflector) and molecular docking were used to identify therapeutic candidates. Finally, Lymphotoxin-beta (LTB) expression was validated in vitro using q-RT-PCR assays.ResultsWe identified a robust five-gene KN-associated signature that demonstrated diagnostic and patient-stratification potential in COPD. LTB was identified as an upregulated Kinic-associated hub gene mainly distributed in neutrophils and involved in the regulation of COPD pathogenesis. Notably, BRD-K97481123 was identified as a potential LTB-targeting compound for the treatment of COPD.ConclusionThis study unveils a novel KN-associated molecular axis in COPD pathogenesis, with LTB as a neutrophil-centric pathogenic factor. This axis provides a framework for patient stratification, offers a promising diagnostic biomarker, and identifies a potential therapeutic target, thereby linking a novel metabolic modification to neutrophilic inflammation in COPD.

Abstract Asthma is a heterogeneous chronic airway disease arising from a complex interplay of genetic susceptibility and environmental exposures. Key pathobiological features include dysregulated immune responses (particularly type 2 inflammation), structural airway remodeling, and mucus hypersecretion. Recent advances have illuminated mechanisms from epithelial “alarmin” cytokine release (TSLP, IL-33, IL-25) to downstream cellular networks involving Th2/Th17 lymphocytes, group 2 innate lymphoid cells (ILC2s), eosinophils, and mast cells. These pathways converge on bronchial hyperresponsiveness and airflow obstruction. Traditional therapy with inhaled corticosteroids and bronchodilators has improved asthma control, yet many patients, especially those with non–type 2-driven endotypes such as neutrophilic or obesity-related asthma, remain suboptimally controlled. This limitation has driven the development of precision medicine approaches that target specific cytokines and signaling cascades, including IgE, IL-5, IL-4/13, and TSLP, as well as intracellular signaling processes such as JAK–STAT. Parallel innovations in biomarkers such as FeNO, blood eosinophils, periostin, and multi-omics-based signatures facilitate patient stratification and prediction of treatment response. This comprehensive review synthesizes current knowledge from genetic and epigenetic foundations of asthma, through immunologic and neurogenic mechanisms, to translational advances in therapeutics from laboratory to clinic. We highlight the importance of endotyping and “treatable traits” such as eosinophilia, mucus plugging, or small-airway dysfunction in guiding individualized therapy. The emerging paradigm aims not only for symptom control but also for disease modification and remission, leveraging biomarkers and multidisciplinary approaches to achieve long-term asthma control in a broad patient population.

Epithelial-mesenchymal transition (EMT) represents a key pathological mechanism underlying airway remodeling in asthma. However, the role of the circadian clock component PER2 in asthma-associated airway remodeling remains unclear. This study aimed to investigate the role of the circadian clock component PER2 in the pathogenesis of EMT in asthma and to elucidate the underlying molecular mechanism. PER2 expression on airway epithelial and association between of PER2 and lung function were determined using data from public databases. The wild-type (WT) and Per2 knockout (Per2⁻/⁻) mice was induced ovalbumin (OVA) to establish asthma model. Airway hyperresponsiveness (AHR), inflammation, mucus production, fibrosis, and EMT markers were assessed. Human bronchial epithelial cells (BEAS-2B) were stimulated with TGF-β1 to induce EMT, followed by PER2 overexpression. RNA sequencing, Western blot, immunofluorescence, and functional migration assays were employed. The Wnt/β-catenin agonist SKL2001 was used to rescue the phenotype. The role of melatonin was also investigated in vivo. Bioinformatic and clinical data identified PER2 as a key downregulated circadian gene in asthma, correlating with impaired lung function. Per2⁻/⁻ mice exposed to OVA exhibited exacerbated AHR, airway inflammation, mucus hypersecretion, subepithelial fibrosis, and enhanced EMT markers compared to WT mice exposed to OVA. RNA-seq and pathway analysis revealed that PER2 deficiency activated the Wnt/β-catenin pathway. In vitro, TGF-β1 downregulated PER2 expression. Overexpression of PER2 in cells suppressed TGF-β1-induced EMT, migration, and inhibited Wnt/β-catenin signaling activation. The protective effects of PER2 were partly reversed by the β-catenin agonist SKL2001. Finally, melatonin alleviated OVA-induced EMT by upregulating the PER2. This study demonstrates that the circadian clock component PER2 plays a critical protective role in inhibiting airway remodeling in asthma by suppressing EMT through the Wnt/β-catenin signaling pathway. Furthermore, melatonin exerts its therapeutic effects by upregulating PER2. Targeting the PER2 may represent a novel therapeutic strategy for mitigating airway remodeling in asthma.

ETHNOPHARMACOLOGICAL RELEVANCE:Danlong Oral Liquid (DLOL) is a proprietary Traditional Chinese Medicine (TCM) with documented clinical efficacy against asthma, yet its underlying mechanism of action remains incompletely understood. The bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) and its receptor S1PR2 signaling axis are critically implicated in asthma pathogenesis, particularly in driving airway smooth muscle cell (ASMC) remodeling, a key pathological feature of asthma. Despite this, the mechanistic involvement of DLOL in this specific pathway has not been explored. AIM OF THE STUDY:This study aimed to validate the effect of DLOL against asthma-associated airway remodeling and to elucidate whether its mechanism of action involves the modulation of the S1PR2/ROCK1/YAP signaling pathway in ASMCs. MATERIALS AND METHODS:The therapeutic effects and mechanisms of DLOL were investigated using a combination of in vivo and in vitro approaches. An in vivo rat model of allergic asthma was induced by ovalbumin (OVA) sensitization and challenge. We assessed airway hyperresponsiveness (AHR) and performed inflammatory cell counts in bronchoalveolar lavage fluid (BALF) using Wright-Giemsa staining. Lung histopathology was evaluated by Hematoxylin and Eosin (H&E) staining, Periodic Acid-Schiff (PAS) staining, and Masson's trichrome staining to assess inflammation, goblet cell hyperplasia, and collagen deposition. Levels of S1P and cytokines (IL-4, IL-5, IL-13) in BALF and serum, along with OVA-IgE in serum, were measured by enzyme-linked immunosorbent assay (ELISA). The protein and gene expression of key molecules in the S1PR2/ROCK1/YAP signaling pathway were analyzed by Western blotting (WB), immunohistochemistry (IHC), and Real-time quantitative polymerase chain reaction (RT-qPCR). For in vitro studies, primary rat ASMCs were stimulated with S1P. The impact of DLOL-containing serum (DL-CS) on proliferation was assessed using the Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assays. Cell migration and contraction were evaluated by scratch assay and collagen gel contraction assay, respectively. Underlying mechanisms were further examined by WB, RT-qPCR, and immunofluorescence (IF). RESULTS:DLOL administration significantly alleviated AHR, airway inflammation, and remodeling in a rat model of asthma. Mechanistically, DLOL downregulated the S1PR2/ROCK1/YAP signaling axis in lung tissues, inhibiting the expression of S1PR2, RhoA, and ROCK1, promoting YAP inactivation, and suppressing the downstream targets FOXM1 and CyclinD1. Consistently, DL-CS potently inhibited S1P-induced proliferation, migration, and contraction of ASMCs in vitro, further confirming its robust anti-remodeling activity. CONCLUSIONS:Our integrated findings demonstrate that DLOL alleviates allergic asthma and airway remodeling by inhibiting the S1PR2/ROCK1/YAP signaling pathway in ASMCs, thereby restraining their pro-remodeling phenotypes. This work not only provides a solid mechanistic basis for the clinical application of DLOL but also positions it as a promising multi-targeted therapy for asthma.

Objectives: Information on the safety and efficacy of chaishituire granules (CSTR) for treating influenza is limited. We evaluated the safety and efficacy of CSTR in shorteningthe disease and fever course and improvingthe traditional Chinese medicine (TCM) syndrome score in influenza treatment. Methods: This multi-center, randomized, positive-drug, parallel-controlled study involved 17 hospitals across China and 221 patients with influenza aged 14-75 years. These patients met the syndrome differentiation criteria for "Wind-Heat Invading the Wei-Exterior". Patients in the CSTR group received CSTR and oseltamivir phosphate dummy capsules, whereas those in the oseltamivir control group received oseltamivir phosphate capsules and CSTR dummy granules. The primary outcomes were the time to complete remission of fever and the main clinical symptoms. The secondary outcomes were the time to elicit antipyretic effects, acetaminophen use, TCM syndrome score, remission rate of main clinical symptoms, single symptom area under the curve (AUC), and the incidence of complications or severe/critical diseases. Results: The TCM syndrome score, single symptom AUC, incidence of complications and severe/critical disease, time to complete remission of fever, main clinical symptoms, and initiation of antipyretic effects were evaluated. However, CSTR demonstrated a more rapid action and superior efficacy in alleviatingsore throat compared to oseltamivir. The incidence of adverse reactions was similar between the groups. Conclusions: CSTR could be an alternative therapy for influenza virus infections.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis characterized by high clinical heterogeneity. The conventional binary classification based on antineutrophil cytoplasmic antibody (ANCA) status inadequately captures this heterogeneity and provides limited guidance for individualised treatment decisions. This study aimed to identify and validate clinical-biological endophenotypes in EGPA using unsupervised machine learning methods based on multidimensional real-world clinical data, to inform precision medicine approaches. In this retrospective single-centre observational study, we included 205 patients diagnosed with EGPA between January 2015 and December 2023 at China-Japan Friendship Hospital. Comprehensive data on demographics, clinical manifestations, laboratory tests, imaging features, and treatment information were systematically collected. Consensus clustering combined with K-means algorithm was applied to identify patient subgroups based on 14 core features, including peripheral blood eosinophil count, fractional exhaled nitric oxide (FeNO), serum total IgE, C-reactive protein (CRP), ANCA status, and multi-system involvement. Principal component analysis was used for dimensionality reduction and visualisation. Differences in clinical characteristics, laboratory parameters, imaging patterns, and treatment responses were compared among the subgroups. An online prediction tool was developed and validated based on the clustering results. Consensus clustering analysis identified three stable endophenotypes (optimal cluster number k = 3). Subgroup 1 (n = 78, 38.0

Background:There is limited information available on patients with asthma in hospitals in China. We investigated their clinical and phenotypic characteristics and management. Methods:The China Asthma Data Registry Project (CHART) study is a multicentre, hospital-based, prospective, observational study in which patients were recruited from outpatient clinics. This analysis used baseline cross-sectional data from patients with asthma (≥12 years) enrolled at 58 tertiary hospitals in China between 25 March 2018 and 11 July 2019. Results:A total of 20 683 patients with asthma (56.2% female, 15.0% patients with active tobacco use) were enrolled. Overall, 22.8% had uncontrolled asthma, 39.5% had partially controlled asthma. Furthermore, 45.3% experienced ≥1 exacerbation annually, including 31.7% who required hospitalisation, with only 21.4% having previously used inhaled corticosteroids (ICSs) in the past year. Cough (80.0%) was the most common symptom, followed by wheezing (70.7%), with 14.6% having cough-predominant asthma and 11.4% having cough-variant asthma. Multivariate logistic regression revealed that cough severity independently predicted poor control, irrespective of airflow limitation or inflammatory status. The association was stronger in ICS users than in nonusers across all cough severity metrics: a visual analogue scale (VAS) score ≥40 (aOR 3.88-5.47 versus 2.49-2.94), a cough evaluation test (CET) score ≥12 (aOR 11.15-20.91 versus 3.97-5.55), and a Leicester Cough Questionnaire (LCQ) score <15 (aOR 6.15-13.66 versus 2.45-3.18). Conclusions:We found significant suboptimal control, a high prevalence of cough-related phenotypes, frequent exacerbations and hospital admissions in patients with asthma attending hospitals. This underscores the need to prioritise the assessment and treatment of cough in asthma.

OBJECTIVE:Severe steroid-resistant asthma (SSRA) is characterized by persistent neutrophilic airway inflammation and limited glucocorticoid efficacy. Dysregulated macrophage polarization toward the pro-inflammatory M1 phenotype contributes to SSRA pathogenesis. The voltage-gated potassium channel Kv1.3 regulates immune cell activation, but its role in asthma-related macrophage polarization remains unclear. METHODS:We analyzed KCNA3 (Kv1.3-encoding gene) expression in alveolar macrophages from asthma patients (GSE2125 dataset). An OVA/LPS-induced SSRA mouse model was established and treated with the Kv1.3 inhibitor Margatoxin (MgTX), clarithromycin (CLA), or dexamethasone (DEX). Airway hyperresponsiveness (AHR) and lung pathology were evaluated. Macrophage phenotypes and STAT signaling were analyzed by flow cytometry, immunofluorescence, and Western blotting. Bone marrow-derived macrophages (BMDMs) were polarized in vitro with or without MgTX. RESULTS:KCNA3 expression was significantly elevated in alveolar macrophages from asthma patients. In SSRA mice, MgTX and CLA outperformed DEX in reducing AHR, inflammation, and collagen deposition. Kv1.3 inhibition upregulated M2 markers (Arg-1, FIZZ1) and downregulated the M1 marker iNOS, and was associated with enhanced STAT3 phosphorylation (p-STAT3/STAT3 ratio increased ∼2.5-fold). In vitro, MgTX promoted BMDM M2 polarization through selective STAT3 activation without affecting STAT6. CONCLUSION:Kv1.3 negatively correlates with STAT3 pathway activity, suggesting a potential inhibitory role in macrophage M2 polarization, which may contribute to sustained inflammation in SSRA. Pharmacological Kv1.3 inhibition is associated with restored macrophage balance and STAT3 activation, highlighting its potential as a novel therapeutic target for steroid-resistant asthma.

Rationale:Asthmatic cough may not respond well to corticosteroids. The underlying mechanisms and heterogeneity of cough variant asthma (CVA) remain poorly understood. The objectives of the present study were to explore airway immunological mechanisms and identify molecular endotypes in CVA by analysing sputum transcriptomics, clinical and pathophysiological characteristics. Methods:RNA sequencing and cytokine measurement were performed on sputum samples from newly diagnosed patients with CVA (n=72), classic asthma (CA) (n=28) and healthy controls (HC) (n=28). Patients with CVA were treated and followed-up for 6 months. Results:The majority of differentially expressed genes in CVA versus HC overlapped with those identified in CA versus HC. However, the type 2 immunity co-expression network in CVA was lower than that in CA. Based on sputum transcriptomics profiles, two endotypes of CVA were identified: mixed-inflammatory CVA (n=40) and pauci-inflammatory CVA (n=32). Mixed-inflammatory CVA showed higher inflammation-related gene set signatures compared to both pauci-inflammatory CVA and HC. Mixed-inflammatory CVA also showed elevated levels of eosinophils, neutrophils, type 2, type 1 and type 3 cytokines in sputum compared to HC. Conversely, pauci-inflammatory CVA had slightly elevated sputum eosinophils, but no significant gene signatures and cytokine differences compared to HC. During 6 months' follow-up, pauci-inflammatory CVA showed a trend of less complete resolution in cough (56.2% versus 80.0%, p=0.0553) compared to mixed-inflammatory CVA. Kaplan-Meier analysis found significantly higher cough persistence in pauci-inflammatory versus mixed-inflammatory CVA. Conclusions:CVA exhibits overlapping but distinct airway transcriptomics profiles compared to CA. Two distinct molecular endotypes are identified in CVA, presenting different clinical and pathophysiological features.

BACKGROUND:Few studies have explored the association between circadian syndrome (CircS) and lung health. OBJECTIVE:To assess the relationship between CircS and lung health. METHODS:This prospective cohort study enrolled 6252 adults. Multivariable logistic and linear regression models were employed to examine the association between CircS and the prevalence of chronic lung disease, respiratory symptoms, and lung function, as appropriate. Receiver operating characteristic curve analysis was used to compare the predictive power of the number of metabolic syndrome (MetS) and CircS components for lung health. Kaplan-Meier survival and multiple Cox regression analyses were used to assess the relationship between CircS and all-cause mortality. The effects of CircS on health-related quality of life (HQL) and health care use were also evaluated. RESULTS:Participants with CircS were significantly associated with a higher prevalence of asthma, chronic bronchitis, cough, wheeze, phlegm production, and exertional dyspnea. The number of CircS components demonstrated better predictive power for the prevalence of asthma, chronic bronchitis, emphysema, cough, wheeze, phlegm production, and exertional dyspnea than the number of MetS components. Higher numbers of CircS components were significantly associated with decreased forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), worse HQL, and increased health care use. Longitudinally, participants with CircS exhibited a higher risk of all-cause mortality than those without CircS. CONCLUSIONS:Our results support the claim of that CircS is a better predictor of lung health than the MetS in adults in the United States. Elevated CircS levels are associated with poorer lung function, increased health care use, worse HQL, and a higher risk of mortality.

BACKGROUND:Different types of T helper cells play an important role in disease severity and treatment response in patients with asthma. The potassium channel Kv1.3 is a type of potentially therapeutic target in T-cell-mediated inflammatory diseases. OBJECTIVE:This study aimed to explore the potential of Kv1.3 as a therapeutic target for asthma and to assess the efficacy of the Kv1.3 inhibitor PAP-1 in the treatment of asthma. METHODS:Kv1.3 expression on CD4+T cells was determined using data from public databases. CD4+T cells were isolated from peripheral blood samples obtained from healthy individuals and patients with asthma. The mouse models of OVA-induced asthma and Kv1.3 knockout were established. The underlying mechanism was investigated using mouse splenic CD4+T cells and BEAS-2B cells. OVA-induced asthmatic mice were treated with the Kv1.3 selective blocker PAP-1. RESULTS:Based on public data, we determined the distribution of Kv1.3 on CD4+T cells, its up-regulation in asthma, and its correlation with Th17/Treg balance. Upregulation of Kv1.3 in CD4+T cells was associated with enhanced activation of these cells and airway inflammation in patients and mice with asthma, accompanied by increased IL-17A levels in alveolar lavage fluid. Conversely, Kv1.3 deficiency significantly attenuated airway inflammation, lowered IL-17A levels in bronchoalveolar lavage fluid, and inhibited airway epithelial-mesenchymal transition in asthmatic mice. Furthermore, treatment with the Kv1.3 selective blocker PAP-1 attenuated inflammation in lung tissues and prevented airway remodeling in OVA-induced asthmatic mice. CONCLUSIONS:Kv1.3 expression on CD4+ T cells was correlated with IL-17A-associated airway inflammation and remodeling in asthma, which may be regarded as a potential diagnostic marker and therapeutic target for asthma. TRANSLATIONAL SIGNIFICANCE:Based on our study, Kv1.3 expression on CD4+T cells was correlated with IL-17A-associated airway inflammation and remodeling in asthma, which may be regarded as a potential diagnostic marker and therapeutic target for asthma. The treatment with the Kv1.3 selective blocker PAP-1 attenuated inflammation in lung tissues and prevented airway remodeling in OVA-induced asthmatic mice. Our discoveries offer novel perspectives for a better understanding of IL-17A-associated airway remodeling in asthma. The development of drugs targeting Kv1.3 holds application value for IL-17A-associated asthma.

AIM:Chronic Obstructive Pulmonary Disease (COPD) is a common chronic airway disease that can lead to decreased lung function in patients. It places a heavy economic burden on patients and society. Traditional Chinese medicine (TCM) and Western medicine have played important roles in managing COPD. We aimed to develop an evidence-based guideline for treating COPD with Chinese and Western Medicine. METHODS:We formed a guideline panel of multidisciplinary experts. The clinical questions were identified based on two rounds of issue solicitation and expert demonstration. We searched the literature for direct evidence on the management of COPD and assessed its certainty-generated evidence using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. The recommendations and their strengths were formulated using the Delphi method. RESULTS:Our guideline covers aspects of the diagnosis and treatment of COPD such as principles and commonly used medications for both traditional Chinese medicine and Western medicine, complications, and the high-risk populations. 9 clinical questions and 35 recommendations were identified, which covered the combinations of YuPingFeng granule, Buzhong Yiqi decoction, Gushen Dingchuan Pill, Bufei Huoxue Capsules, Runfei cream, Bailing Capsule, Tanyin Pills, etc., and nonpharmacological therapy of TCM such as combined acupoint application, electroacupuncture, and Chinese exercise techniques (Tai Chi, Baduanjin), etc. Recommendations were either high or low or in the form of ungraded consensus-based statements. CONCLUSIONS:This is a comprehensive and systematic evidence-based guideline and we hope it can systematically and effectively guide clinicians in managing COPD and improve overall medical care.

BackgroundEvidence for the benefits of resveratrol (Res) in the treatment of asthma is progressively accumulating. However, the full spectrum of its molecular targets and the precise mechanisms remain incompletely characterized.MethodTargets of Res were obtained from Swiss Target Prediction, TCMCP, and DrugBank. Targets of asthma were obtained from DisGeNET, Therapeutic Target Database, GeneCards, and DrugBank. Intersecting target genes were identified by using jvenn. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analyses were performed using the R package clusterProfiler in R version 4.4.0. Protein–protein interaction networks were constructed using Cytoscape 3.9.1 software. Molecular docking validation of the binding capacity between Res and targets was performed using AutoDock Vina and visualized in PyMOL version 3.0.4. ELISA and Western blotting were used to verify the reliability of Res effects on the top five targets in both house dust mite (HDM)-induced asthma mouse model and BEAS-2B cell model.ResultsAfter the intersection of the 236 Res targets and the 2,382 asthma targets, 120 targets for Res against asthma were obtained. The top five therapeutic targets based on weighted degree score were TNF, IL6, STAT3, TP53, and IL1B. GO enrichment analysis identified 2,595 significant terms, associated with 2,402 biological processes, followed by 153 molecular functions and 40 cellular components. KEGG enrichment analysis identified 107 relevant pathways, including “apoptosis,” “TNF signaling pathway,” and “MAPK signaling pathway.” Molecular docking showed that Res had a strong binding affinity toward the top five targets with binding energies less than −5.8 kcal/mol. Res treatment normalized the dysregulated expression of TNF-α, IL-6, STAT3, p53, and IL-1β both in vitro and in vivo.ConclusionRes may target TNF-α, IL-6, STAT3, p53, and IL-1β to act as a therapeutic agent for asthma. These findings reveal the potential therapeutic targets for Res against asthma and provide theoretical bases for the clinical application of Res.

BACKGROUND:Few studies have explored the role of furan exposure plays in chronic respiratory diseases and mortality. OBJECTIVE:To access the relationship of furan exposure to chronic respiratory diseases and mortality. METHODS:This study involves 5261 adults over 20 years old from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Blood furan levels were employed to quantify furan exposure. Multinomial survey-weighted regressions were utilized to analyze the associations between furan exposure and the prevalence of asthma alone, COPD alone, and ACO. Multiple Cox regression was employed to evaluate the association between furan exposure and all-cause and respiratory mortality. RESULTS:After adjusting for covariates, log10-transformed blood furan levels (LBFL) were independently associated with an increased risk of the prevalence of asthma alone, COPD alone, and ACO (aOR = 2.086, 95 % CI = 1.005-4.332, P = 0.049; aOR = 6.503, 95 % CI = 3.471-12.185, P < 0.001; aOR = 10.739, 95 % CI = 2.250-51.246, P = 0.003). For every one-unit increase in the LBFL, the odds of asthma were 1.086 higher, COPD were 5.503 higher, ACO were 9.739 higher. Longitudinally, LBFL were positively correlated with all-cause and respiratory mortality (HR = 1.997, 95 % CI = 1.015-3.931, P = 0.045; HR = 4.979, 95 % CI = 1.053-23.541, P = 0.043). CONCLUSIONS:Exposure to furan revealed a positive association with greater odds of asthma, COPD, and ACO. An elevated blood furan also was associated with increased all-cause and respiratory mortality.

BACKGROUND:Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management.METHODS:Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring.RESULTS:In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01).CONCLUSIONS:The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.

Severe asthma is a complex and heterogeneous chronic airway inflammatory disease. Current treatment strategies are increasingly focused on disease classification, facilitating the transition towards personalized medicine by integrating biomarkers and monoclonal antibodies for tailored therapeutic approaches. Several approved biological agents, including anti-immunoglobulin E (IgE), anti-interleukin (IL)-4, anti-IL-5, and anti-thymic stromal lymphopoietin (TSLP) monoclonal antibodies, have demonstrated significant efficacy in reducing asthma exacerbations, eosinophil counts, improving lung function, minimizing oral corticosteroid usage, and enhancing patients' quality of life. The utilization of these biological agents has brought about profound transformations in the management of severe asthma. This article provides a comprehensive review on biomarkers and biological agents for severe asthma while emphasizing the increasing importance of further research into its pathogenesis and novel treatment modalities.

Background Few studies have explored the role of furan exposure plays in aggravating asthma. Objective To access the relationship of furan exposure to asthma. Methods This is a prospective cohort study, involving 7,047 adults over 20 years old from the National Health and Nutrition Examination Survey 2007–2012. Blood furan levels were employed to quantify furan exposure. Multivariate survey-weighted regressions were utilized to analyze the associations between furan exposure, the prevalence of asthma. Mediation analyses for furan exposure and asthma prevalence were conducted. Multiple Cox regression was employed to evaluate the association between furan exposure and asthma prognosis. Results Asthmatics have higher blood furan levels than non-asthmatics (P < 0.001). After adjusting for covariates, log10-transformed blood furan levels (LBFL) were independently associated with an increased risk of asthma prevalence (adjusted odds ratio [aOR] = 2.40, 95% confidence interval [CI] = 1.21–4.78, P = 0.014). There was a significant positive linear relationship between LBFL and risk of asthma (P for linear = 0.0003). In mediation analyses, FEV1 was identified as mediators in the above relationships, with mediated proportions of 32.73%. Longitudinally, multiple Cox regression analysis demonstrated that LBFL were positively correlated with respiratory mortality in asthma (HR = 27.88, 95% CI = 4.19-185.69, P < 0.0001). Conclusions Exposure to furan revealed a positive association with greater odds of asthma, and lung function was identified as an important mediator. An elevated LBFL also is associated with an increased health care use, worse HQL, and prognosis of asthma.

Ethnopharmacological relevance Danlong oral liquid (DLOL) is a traditional Chinese proprietary medicine commonly used to treat chronic respiratory diseases, including bronchial asthma and chronic obstructive pulmonary disease. However, the therapeutic effects and pharmacological mechanisms of DLOL in improving airway remodeling remain unclear. Aims of the study This study utilizes in vivo and in vitro experiments, serum pharmacological analysis, and network-based pharmacology approaches to investigate the effects and mechanisms of DLOL on airway remodeling and epithelial-mesenchymal transition (EMT) in asthma. Methods An asthma model was established through ovalbumins (OVA) sensitization and challenge in BALB/c mice to observe the effects of DLOL on airway hyperresponsiveness (AHR), inflammation, remodeling, and molecular markers of EMT. The absorbed chemical prototype constituents of DLOL were analyzed using Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), and targets for asthma and airway remodeling were predicted using a network pharmacology approach. Key biological processes and signaling pathways were analyzed. Additionally, TGF-β1 was used to induce EMT in BEAS-2B cells. TGF-β1 and DLOL-containing serum were screened to determine the optimal time and concentration in BEAS-2B cells using CCK8 assays. The cell scratch assay was used to assess cell migration, while immunofluorescence and immunohistochemistry were employed to evaluate protein expression levels. Results DLOL improved AHR in asthmatic mice, reduced inflammatory cell infiltration in lung tissue, decreased airway wall and smooth muscle thickness, and reduced collagen deposition. It also down-regulated mesenchymal markers (N-cadherin, vimentin, α-SMA) and key remodeling factors (TGF-β1, MMP9), while up-regulating the epithelial marker E-cadherin. A total of 17 absorbed chemical prototype constituents were identified, predicting 54 core targets involved in airway remodeling. Following Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the key targets were found to be associated with the regulation of cell migration, cell-cell adhesion, and cell adhesion molecular processes, with the PI3K-Akt signaling pathway likely playing a critical role. Cellular experiments confirmed that DLOL-containing serum inhibited TGF-β1-induced EMT in BEAS-2B cells and suppressed the phosphorylation of Akt and GSK-3β. Conclusion This study identifies, for the first time, the serum medicinal chemistry of DLOL using UPLC-MS. Combining network pharmacology, in vivo and in vitro experiments, it elucidates the effects and potential mechanisms of the drug on airway remodeling and EMT. DLOL may offer a novel therapeutic approach for asthma-related airway remodeling.