BACKGROUND:Common cold is one of the most prevalent illnesses affecting human health. Nasal symptoms are the most bothersome and characteristic manifestations, yet few safe and effective treatments are currently available. AIM:This phase 3, randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy and safety of bencycloquidium bromide (BCQB) nasal spray in nasal symptoms of common cold. METHODS:Participants with cold symptoms for ≤48 h and a rhinorrhea visual analogue scale (VAS) score ≥5 were enrolled. Participants were randomized 1:1 to receive either BCQB or placebo for 4 ± 1 days. Patients self-recorded VAS scores for rhinorrhea, sneezing, nasal congestion and itching daily. Efficacy and safety were assessed. RESULTS:A total of 480 patients were randomized and treated. The area under the curve (AUC) for rhinorrhea VAS scores over treatment period was significantly lower in the BCQB group than in the placebo group (13.01 ± 7.19 vs. 16.01 ± 8.00; P < 0.001). Daily improvement in the average rhinorrhea VAS score was significantly greater in the BCQB group from day 2 through day 4 (P < 0.005). BCQB also demonstrated significant efficacy for nasal congestion (AUC: 10.90 ± 7.42 vs. 13.63 ± 8.64; P < 0.001) and sneezing (AUC: 7.84 ± 7.18 vs. 9.30 ± 8.64; P = 0.046). The incidence of adverse events (AEs) was similar between the two groups, and no severe AEs were reported. BCQB was well-tolerated, with no systemic anticholinergic adverse effects observed. CONCLUSIONS:BCQB nasal spray is effective and safe for treating rhinorrhea, nasal congestion and sneezing associated with common cold. TRIAL REGISTRATION:The trial was registered at chictr.org.cn (ChiCTR2500107341).

Although the prevalence of allergic diseases has been rising in China since the late twentieth century, comprehensive nationwide epidemiological data covering all age groups and multiple allergic conditions remain scarce. To investigate the epidemiological patterns of eight major allergic diseases in China, including their national and regional prevalence, demographic distribution, and comorbidity profiles, the National Epidemiology Study of Asthma and Allergies in China (NESAAC) was a nationwide cross-sectional survey conducted from September 2010 to December 2015. A multistage stratified cluster sampling method was employed across seven geographical regions, covering 882 communities and 587 villages in 16 cities. Data were collected via face-to-face interviews using standardized questionnaires. Prevalence was calculated for three categories: lifetime symptoms, current symptoms (past 12 months), and physician-diagnosed history. Among the 121,023 participants analyzed, the current symptom prevalence of each specific disease was: allergic rhinitis (4.2%), asthma (0.9%), eczema (0.7%), drug allergy (0.6%), food allergy (0.4%), urticaria (0.4%), contact dermatitis (0.3%), and anaphylactic shock (0.02%). Geographic variations were notable, with the highest prevalence consistently observed in North, East, and South China. Urban residents had significantly higher prevalence than rural residents across all conditions except anaphylactic shock. Age distribution revealed eczema and food allergy predominance in children under 6 years, whereas asthma and drug allergy prevalence increased with age. Most conditions were more prevalent among females than males. Allergic rhinitis was not only the most common condition but also demonstrated the strongest comorbidity, particularly with asthma. This first nationwide, all-age survey underscores marked epidemiological variations in allergic diseases across China.

Background Type 2 inflammatory diseases (T2IDs) often coexist, but their shared genetic basis remains unclear. This study explores common genetic basis between asthma and other T2IDs and identifies pleiotropic loci and mechanisms.Methods: Using genome-wide association study (GWAS) summary statistics, we assessed genetic correlation between asthma and four T2IDs (allergic conjunctivitis [AC], allergic rhinitis [AR], pollen allergy [PA], atopic dermatitis [AD]) via cross-trait pleiotropy analysis, followed by functional, tissue-specificity, and multi-trait colocalization analyses. Results Significant genetic correlations were detected in all four trait pairs. Pleiotropy analysis under the composite null hypothesis (PLACO) identified 21 pleiotropic loci, with 2 colocalized (PP.H4 > 0.75). Notable pleiotropic loci were identified, such as 4q24 (MANBA, UBE2D3, and CISD2) and 19q13.2 (SNRPA, RAB4B, MIA-RAB4B, and EGLN). MAGMA revealed 49 candidate pleiotropic genes involved in synaptic structure/function and cellular organization. Tissue enrichment analysis, stratified LD score regression (S-LDSC), and summary data-based Mendelian randomization (SMR) analysis revealed that pleiotropic mechanisms play significant roles in the brain, spleen, whole blood, and EBV-transformed lymphocytes. Hyprcoloc implicated distinct lymphocyte subtypes in shared mechanisms between asthma and AD. Conclusions We identified shared genetic loci and gene sets between asthma and T2IDs, offering insights into genetic mechanisms and potential therapeutic targets.

BACKGROUND:Ensifentrine, a novel phosphodiesterase 3/4 inhibitor, was shown to significantly improve lung function and reduced COPD exacerbations in previous trials in Western populations. However, efficacy and safety data on its use in Chinese participants with COPD remain limited. RESEARCH QUESTION:Is nebulized ensifentrine effective and safe compared with placebo for the treatment of COPD in Chinese participants? STUDY DESIGN AND METHODS:A phase III, multicenter, randomized, double-anonymized, placebo-controlled trial was conducted between March 2023 and March 2025. The study enrolled participants with moderate to severe symptomatic COPD randomized to the ensifentrine group or the placebo group (5:3) over 24 weeks. Participants were stratified according to maintenance therapy and smoking status. The primary end point was lung function improvement measured by FEV1 area under the curve at 0 to 12 hours. Other end points included quality of life, symptoms, and exacerbations. RESULTS:Overall, 525 participants were included in the analysis, with 45.9% receiving concomitant maintenance therapy. Ensifentrine significantly improved average FEV1 area under the curve at 0 to 12 hours vs placebo (110 mL; 95% CI, 69-151 mL; P < .0001). Lung function improvement was consistent across clinically relevant subgroups, including participants with and without maintenance therapy, as well as participants with moderate and severe COPD. Ensifentrine significantly improved Transition Dyspnea Index score and showed improvements in Evaluating Respiratory Symptoms and St. George's Respiratory Questionnaire scores vs placebo. Ensifentrine treatment tended to reduce the rate of moderate to severe exacerbations and increased the time to first exacerbation. Adverse event rates were similar between the ensifentrine and placebo groups. INTERPRETATION:Ensifentrine was shown to significantly improve lung function and showed efficacy benefits in symptoms and quality of life improvement in Chinese individuals with COPD. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT05743075; URL: www. CLINICALTRIALS:gov.

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.

Background Type 2 inflammatory diseases (T2IDs) often coexist, but their shared genetic basis remains unclear. This study explores common genetic basis between asthma and other T2IDs and identifies pleiotropic loci and mechanisms. Methods: Using genome-wide association study (GWAS) summary statistics, we assessed genetic correlation between asthma and four T2IDs (allergic conjunctivitis [AC], allergic rhinitis [AR], pollen allergy [PA], atopic dermatitis [AD]) via cross-trait pleiotropy analysis, followed by functional, tissue-specificity, and multi-trait colocalization analyses. Results Significant genetic correlations were detected in all four trait pairs. Pleiotropy analysis under the composite null hypothesis (PLACO) identified 21 pleiotropic loci, with 2 colocalized (PP.H4 > 0.75). Notable pleiotropic loci were identified, such as 4q24 (MANBA, UBE2D3, and CISD2) and 19q13.2 (SNRPA, RAB4B, MIA-RAB4B, and EGLN). MAGMA revealed 49 candidate pleiotropic genes involved in synaptic structure/function and cellular organization. Tissue enrichment analysis, stratified LD score regression (S-LDSC), and summary data-based Mendelian randomization (SMR) analysis revealed that pleiotropic mechanisms play significant roles in the brain, spleen, whole blood, and EBV-transformed lymphocytes. Hyprcoloc implicated distinct lymphocyte subtypes in shared mechanisms between asthma and AD. Conclusions We identified shared genetic loci and gene sets between asthma and T2IDs, offering insights into genetic mechanisms and potential therapeutic targets.

BackgroundTo investigate the longitudinal association between baseline cold spells and the risk of incident chronic lung disease (CLD) among middle-aged and elderly adults in China, and to characterize its spatial distribution and multifactorial context.MethodsUsing national data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2020), Cox proportional hazards models, logistic regression, stratified analysis and sensitivity analyses were employed to analyze the impact of nine differently defined cold spell indicators on the risk of new-onset CLD in adults aged ≥45 years. Geographically Gaussian process regression (GGPR) mapped spatial disease distribution, and GeoShapley decomposition quantified factor contributions.ResultsIn Cox models, baseline cold spell exposure was associated with a modestly elevated risk of incident CLD (fully adjusted hazard ratios [HRs] ranged from 1.10 to 1.13). This positive association was further supported by logistic regression analyses (fully adjusted odds ratios [ORs]: 1.11–1.13) and sensitivity analyses. After correction for multiple comparisons, urban residence, higher education, and cancer history modified the association. Spatial prediction models (GGPR) identified northern China as a consistent high-risk region across all nine cold spell definitions (validation AUC: 0.7077–0.7129). Notably, GeoShapley analysis revealed that air pollutants and geographic coordinates contributed more substantially to spatial prediction than did cold spell exposure, indicating that regional background factors dominate the spatial patterning of CLD risk.ConclusionHigher baseline cold spell exposure was associated with a modestly increased risk of incident CLD among Chinese adults aged ≥45 years, with northern China identified as a consistent high-risk region. The independent longitudinal association of cold spells, though not dominant in spatial prediction models, highlights their potential role as an environmental trigger warranting further investigation.

The epithelial barrier in different organs is the first line of defense against environmental insults and allergens, with type 2 immunity serving as a protective function. Genetic factors, and biological and chemical insults from the surrounding environment altered regulate epithelial homeostasis through disruption of epithelial tight junction proteins or dilated intercellular spaces. Recent studies suggest that epithelial barrier dysfunction contributes to pathologic alteration in diseases with type 2 immune dysregulation including (but not limited to) atopic dermatitis, prurigo nodularis, asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. In this review, we summarized current understanding of dysfunction of barrier and its interaction with type 2 inflammation across different organs, and discussed the role of epithelial barrier disruption in the pathogenesis of type 2 inflammation. In addition, recent progresses of emerging barrier restorative therapies are reviewed.

PURPOSE:Clinical remission (CR), an emerging treatment goal in asthma, was assessed by a post hoc analysis of a phase 3 study of mepolizumab in severe asthma with an eosinophilic phenotype (SA-EP). METHODS:Asthmatic patients aged ≥ 12 years, with a blood eosinophil count of ≥ 150 cells/µL at screening (or ≥ 300 cells/µL in the previous year), receiving fluticasone propionate ≥ 500 µg/day or equivalent plus ≥ 1 controller medication, and experiencing ≥ 2 exacerbations in the previous year were randomised to receive add-on mepolizumab or placebo every 4 weeks for 52 weeks. CR was assessed using both 3- and 4-component definitions (at 1 year, no maintenance oral corticosteroids, no clinically significant exacerbations, and asthma control questionnaire-5 [ACQ-5] score ≤ 1.5 for both, plus change from baseline in pre-bronchodilator forced expiratory volume in 1 second ≥ 0 mL for 4-component definition). RESULTS:At week 52, 41.6% (62/149) of mepolizumab-treated patients and 21.2% (32/151) of placebo-treated patients met the 4-component definition (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.59-4.41; P < 0.001), with a difference of 20.4% (95% CI, 9.1%-31.2%), and 54.4% (81/149) of mepolizumab-treated patients and 32.5% (49/151) of placebo-treated patients met the 3-component definition (OR, 2.48; 95% CI, 1.55-3.96; P < 0.001), with a difference of 21.9% (95% CI, 10.5%-32.7%). Baseline characteristics potentially associated with CR in the mepolizumab group were lower ACQ-5 score and lower St George's Respiratory Questionnaire scores. CONCLUSIONS:A higher proportion of Chinese SA-EP patients treated with mepolizumab achieved CR compared to those receiving placebo. Certain baseline characteristics are potentially predictive of CR. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03562195.

Background:Type 2 (T2) inflammatory respiratory diseases encompass a range of conditions characterized by inflammation affecting the airways and lung parenchyma, with their pathogenesis rooted in T2 inflammation. Biological treatments that mitigate T2 inflammation revolutionize the therapeutic landscape for these respiratory diseases. However, there are decision-making difficulties in terms of the target population, timing of initiation, and type selection for biological targeted therapy. Methods:Search strategies were focused on relevant issues related to T2 inflammatory respiratory diseases from PubMed with search date from 2014 to 2024. The quality of evidence and grading recommendations were assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Consensus was achieved through two rounds of anonymous voting with a strong recommendation demanding at least 70% approval from the participants. Results:A total of 370 basic research results and clinical evidence-based medical data were collected and reviewed. The latest research advances, clinical evidence, and expert insights relating to the use of biological treatments aiming at T2 inflammation in respiratory diseases and their co-morbidities were discussed rigorously and iteratively by an expert panel, and a consensus report with recommendations is presented. Conclusions:This consensus outlines the pathogenesis, assessment of T2 inflammation, biological therapies targeted at T2 inflammation, and management strategies for T2 inflammatory respiratory diseases and their comorbidities. It will serve as a valuable guide for clinicians in China, empowering them to diagnose and manage these conditions more effectively.

PURPOSE:The objective of this trial was to evaluate the efficacy and safety of anti-IgE monoclonal antibody (CMAB007) in Chinese patients with inadequately controlled moderate or severe asthma with increased total IgE level despite medium or high dose inhaled corticosteroids (ICS)/long acting β₂-agonist (LABA) treatment. METHODS:This was a multicenter, randomized, placebo controlled, double blinded, phase 3 trial. Eligible patients with moderate or severe asthma with increased total IgE level (60-1,500 IU/mL) receiving optimal ICS-LABA were randomly assigned to receive CMAB007 or placebo treatment at a 2:1 ratio for 24 weeks. The primary efficacy endpoint was asthma exacerbation (AE) rate, the key second endpoints were asthma control test (ACT) score, pulmonary function and safety. RESULTS:A total of 392 patients were included in the efficacy analysis. AE rate was 0.45 with CMAB007 and 0.66 with placebo (hazard ratio, 0.68; 95% confidence interval, 0.49, 0.96; P = 0.030). The proportions of patients showing an increase of at least 3 points from baseline in ACT scores were greater in the CMAB007 group than in the placebo group at Week 8 (49.8% vs. 36.9%, P = 0.018), Week 16 (59.4% vs. 42.9%, P = 0.003) and Week 24 (60.2% vs. 47.0%, P = 0.019). Greater improvement of pre-bronchodialteor forced expiratory volume in 1 second was achieved in the CMAB007 group at 4 weeks (11.40% vs. 5.03%, P = 0.006), 8 weeks (16.27% vs. 6.57%, P = 0.003), 12 weeks (16.51% vs. 6.60%, P = 0.002) and 16 weeks (20.18% vs. 7.42%, P = 0.002). The incidence of adverse events was similar between the CMAB007 (77.2%) and placebo groups (75.2%). CONCLUSIONS:CMAB007 reduces AE and improves asthma control, lung function and quality of life without additional safety concern in Chinese patients having moderate to severe asthma with increased total IgE level. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03468790.

Asthma, a chronic inflammatory disease, has a high disability rate, which greatly increases the disease burden. T cells are pivotal in the pathogenesis of asthma, and Treg cells, due to their role in maintaining immune system balance, represent a promising avenue for therapeutic intervention. Initial weighted correlation network analysis (WGCNA) analysis of asthma-related datasets indicates that N-glycosylation plays a critical role in asthma development. The establishment of an OVA-sensitized asthma model, along with the isolation of naive CD4+ T cells and subsequent in vitro induction of Treg cell differentiation, further underscores the significance of N-glycosylation in the Treg cell differentiation of asthma-related Treg cells. Employing immunofluorescence, flow cytometry, and Western blot techniques revealed that SIRT3-SUMO is instrumental in regulating N-glycosylation-mediated Treg cells development. Mechanistically, overexpression and deSUMOylation of SIRT3 enhance the expression levels of CPT1 and VLCAD to promote fatty acid oxidation (FAO), thereby increasing intracellular acetyl-CoA concentrations. Acetyl-CoA subsequently facilitates the synthesis of N-glycosylation substrates via the hexosamine biosynthetic pathway (HBP), promoting Treg cell differentiation. Ultimately, our in vivo experiments demonstrate that SIRT3-SUMO modulates asthma progression by influencing Treg cells differentiation; thus, augmenting Treg cells populations can inhibit Th2-type and non-Th2-type asthmatic developments. These findings elucidate mechanisms underlying Treg cell differentiation and provide theoretical foundations for targeted therapies aimed at enhancing Treg cells for asthma management.

Objectives The impact of anti-fibrotic medications on pulmonary fibrosis caused by COVID-19 remains inconclusive and lacks systematic investigation. This study assessed the efficacy of anti-fibrotic drugs in addressing post-COVID-19 lung fibrosis. Methods We searched PubMed, Web of Science, Embase, and the Cochrane Library until June 15, 2024. The meta-analysis was performed using Review Manager. Heterogeneity was evaluated utilizing I2 statistic, and publication bias was assessed via funnel plots. Results The study (CRD42024552847) included 7 trials with 496 participants. No significant differences were observed in chest CT score (SMD= -0.60, 95% CI: -1.33 to 0.12, P= 0.10), length of hospital stay (MD= -1.34, 95% CI: -4.39 to 1.70, P= 0.39), and mortality (OR= 0.91, 95% CI: 0.50 to 1.64, P= 0.75) between anti-fibrosis and standard treatment groups. Notable improvements in pulmonary function were observed with anti-fibrotic drugs, as indicated by FEV1%pred (MD= 23.95, 95% CI: 12.24 to 35.67, P< 0.0001) and FEV1/FVC (MD= 18.17, 95% CI: 11.96 to 24.38, P< 0.00001). Conclusions Anti-fibrotic medications may help reduce fibrotic lesions and improve pulmonary function in post-COVID-19 pulmonary fibrosis, but their practical use is currently based more on theory than on solid medical evidence. Currently, in clinical practice, the use of anti-fibrotic drugs in these patients primarily relies on empirical treatment. Further clinical studies are imperative to bolster its credibility for future applications.

BACKGROUND:Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE:To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS:MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting β2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/μL; <300/μL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS:Of 695 patients randomized, 473 had baseline bEOS ≥300/μL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/μL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS:MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Type 2 diabetes mellitus (T2DM) is a widespread metabolic condition with a high global morbidity and mortality rate that affects the whole body. Their primary consequences are mostly caused by the macrovascular and microvascular bed degradation brought on by metabolic, hemodynamic, and inflammatory variables. However, research in recent years has expanded the target organ in T2DM to include the lung. Inflammatory lung diseases also impose a severe financial burden on global healthcare. T2DM has long been recognized as a significant comorbidity that influences the course of various respiratory disorders and their disease progress. The pathogenesis of the glycemic metabolic problem and endothelial microangiopathy of the respiratory disorders have garnered more attention lately, indicating that the two ailments have a shared history. This review aims to outline the connection between T2DM related endothelial cell dysfunction and concomitant respiratory diseases, including Coronavirus disease 2019 (COVID-19), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

IL-17A-producing group 3 innate lymphoid cells (ILC3s) have been found to participate in the development of various phenotypes of asthma, however, little is known about how ILC3s mediate neutrophilic airway inflammation. Elevated IL-1β has been reported in neutrophilic asthma (NA) and IL-1β receptor is highly expressed on lung ILC3s. Therefore, we hypothesize that IL-1β aggravates neutrophilic airway inflammation via provoking IL-17A-producing ILC3s. We sought to determine the pathological roles of the IL-1β-ILC3-IL-17A axis in neutrophilic airway inflammation. Lung ILC subsets were measured in eosinophilic asthma (ovalbumin [OVA]/Alum) and NA (OVA/lipopolysaccharides [LPS]) murine models. Rag2-/- (lacking adaptive immunity), RORc-/- (lacking transcription factor RORγt), Rag2-/- RORc-/- (lacking adaptive immunity and ILC3s), and ILCs depletion mice were used to verify the roles of ILC3s in neutrophilic airway inflammation by measurement of CXCL-1, IL-17A, IL-22 and neutrophil counts in bronchoalveolar lavage fluid (BALF), detection of Muc5ac in lung tissues, and quantification of IL-17A-producing ILC3s after treatment of anti-IL-17A or recombinant IL-1β (rIL-1β) and its monoclonal antibody. NLRP3, Caspase 1 and their induction of IL-1β were detected in lung tissues of OVA/LPS-induced mice. The OVA/LPS model was characterized by an enrichment of airway neutrophilia, lung RORγt+ ILC3s and Th17 cytokines (IL-17A and IL-22) and neutrophilic chemokine C-X-C motif (chemokine) ligand 1 (CXCL-1), compared to the phenotypic features of airway eosinophilia, GATA3+ ILC2s and type-2 cytokines in OVA/Alum model. The concentration of CXCL-1 and neutrophil counts in BALF were decreased by anti-IL-17A. RORγt deficiency led to a decrease in IL-17A and CXCL-1 levels and neutrophil counts in BALF. ILC depletion in Rag2-/- mice ameliorated OVA/LPS-induced IL-17A, IL-22, CXCL-1 and airway neutrophil counts. IL-17A-producing ILCs and BALF neutrophil counts were significantly lower in Rag2-/- RORc-/- mice than those in Rag2-/- mice. IL-1β was highly expressed in BALF and bronchial epithelial cells (BECs) in OVA/LPS model, and administration of rIL-1β substantially aggravated airway inflammation and promoted upregulation of RORγt+ and IL-17A-producing lung ILC3s, which were reversed by anti-IL-1β. NLRP3 and Caspase 1 expressions were enhanced by OVA/LPS, and their inhibitors abolished the OVA/LPS-induced IL-1β in BECs. ILC3s play a pathogenic role in the pathogenesis of NA, which is triggered by IL-1β via promoting IL-17A production of lung ILC3s.

Patients with neutrophil-mediated asthma have poor response to glucocorticoids. The roles and mechanisms of group 3 innate lymphoid cells (ILC3s) in inducing neutrophilic airway inflammation and glucocorticoid resistance in asthma have not been fully clarified. ILC3s in peripheral blood were measured by flow cytometry in patients with eosinophilic asthma (EA) and non-eosinophilic asthma (NEA). ILC3s were sorted and cultured in vitro for RNA sequencing. Cytokines production and signaling pathways in ILC3s after IL-1β stimulation and dexamethasone treatment were determined by real-time PCR, flow cytometry, ELISA and western blot. The percentage and numbers of ILC3s in peripheral blood was higher in patients with NEA compared with EA, and negatively correlated with blood eosinophils. IL-1β stimulation significantly enhanced CXCL8 and CXCL1 production in ILC3s via activation of p65 NF-κB and p38/JNK MAPK signaling pathways. The expression of neutrophil chemoattractants from ILC3s was insensitive to dexamethasone treatment. Dexamethasone significantly increased phosphorylation of glucocorticoid receptor (GR) at Ser226 but only with a weak induction at Ser211 residues in ILC3s. Compared to human bronchial epithelial cell line (16HBE cells), the ratio of p-GR S226 to p-GR S211 (p-GR S226/S211) was significantly higher in ILC3s at baseline and after dexamethasone treatment. In addition, IL-1β could induce Ser226 phosphorylation and had a crosstalk effect to dexamethasone via NF-κB pathway. ILC3s were elevated in patients with NEA, and associated with neutrophil inflammation by release of neutrophil chemoattractants and were glucocorticoid (GC) resistant. This paper provides a novel cellular and molecular mechanisms of neutrophil inflammation and GC-resistance in asthma. Trial registration The study has been prospectively registered in the World Health Organization International Clinical Trials Registry Platform (ChiCTR1900027125)

Abstract Background ICS-based maintenance treatment was the basic treatment of asthma. Nevertheless, data of real-world study of ICS-based maintenance treatment on asthma outcome was limited. Methods Based on a national survey on asthma control and disease perception (CARN-2015-01 study), we analysed the impact of ICS-based maintenance treatment on asthma outcome: asthma control, annual incidence of asthma exacerbation hospitalization and emergency department visit in China. Results Altogether 3875 asthmatic outpatients were recruited. 66.7% (2583/3875) asthma patients chose ICS-based maintenance treatment as daily maintenance treatment. After adjusting for confounding factors (age, height, weight, BMI, smoking status, comorbidities, etc), ICS-based maintenance treatment was associated with better asthma control level [OR = 0.542, 95%CI (0.476, 0.617)], higher annual incidence of asthma exacerbation hospitalization [OR = 1.501, 95%CI (1.271, 1.773)] and higher annual incidence of emergency department visits [OR = 1.272, 95%CI (1.074, 1.507)]. In subgroup analysis, in well-controlled asthma patients, there was no statistical difference on annual incidence of asthma exacerbation hospitalization and emergency department visits. In partly controlled asthma patients, patients with ICS-based maintenance treatment have significantly higher annual incidence of asthma exacerbation hospitalization (31.9% vs. 22.5%, P < 0.001) and higher annual incidence of emergency department visits (24.1% vs. 19.1%, P = 0.013). In uncontrolled asthma patients, patients with ICS-based maintenance treatment have significantly higher annual incidence of asthma exacerbation hospitalization (44.7% vs. 28.5%, P < 0.001) but showed no statistical difference on annual incidence of emergency department visits (39.0% vs. 32.4%, P = 0.051). Conclusions ICS-based maintenance treatment was associated with better asthma control level, higher annual incidence of asthma exacerbation hospitalization and higher annual incidence of emergency department visits. During the process of ICS-based maintenance treatment, improvement of symptom control might be prior to the decrease of exacerbation risk.

Objective: To evaluate the influencing factors of poor treatment adherence in patients with uncontrolled asthma in China. Methods: From April 2017 to April 2018, all asthma patients with uncontrolled asthma and poor compliance in 32 third-class hospitals in 28 provinces and cities of China mainland included in the "National Mobile Asthma Assessment and Management Project" were selected as the subjects. A total of 923 patients were enrolled in the study including 388 males and 535 females. By analyzing the baseline data of the patients at the initial visit when enrolled, the influencing factors of poor adherence of adult asthma was analyzed by inter-group comparison and χ2 test. Results: Poor compliance in asthma was related to the following factors: age from 59 to 68 years old, course of disease more than 20 years, low education level, non-local follow-up, having obstructive ventilation dysfunction and low awareness of the disease[P values were 0.026(t=1.20), 0.004(t=3.97), 0.001(t=4.92), 0.003(t=3.98), 0.032(t=1.22) and 0.001(t=4.99), respectively]. Totally, 243 patients (26.33%) answered all the questions about asthma correctly. Their medication adherence rating scale (MARS-A) scores were significantly higher than those who answered incompletely correctly (36.23±5.85 vs. 31.77±5.74, P=0.001). Conclusions: The adherence of adult asthma patients was affected by individual and external environment factors. Clinicians should choose individualized methods based on the characteristics of patients. Patient education should be strengthened to improve patients' awareness of the disease at the same time.