BackgroundHypercytokinemia is a major contributor of tissue damage and mortality in severe influenza. However, most studies rely on static, single-time-point measurements, providing limited insight into the evolving inflammatory response. The prognostic relevance of longitudinal cytokine trajectories remains poorly defined.MethodsWe conducted a multi-cohort analysis of 186 patients from three public datasets to identify cytokines with influenza-severity-dependent expression patterns. We then analyzed a longitudinal cohort of 33 patients with severe influenza who underwent serial cytokine measurements, using linear mixed-effects models to identify the top 10 severity-associated cytokines. Integrating both analyses, we defined a core cytokine panel and a composite core panel score. Prognostic value was assessed using time-varying Cox regression and landmark analyses, with comparisons against clinical predictors, including LODS scores and CRP, as well as sensitivity analyses adjusting for diabetes.ResultsA core panel of six pro-inflammatory cytokines (IL-8, IL-6, G-CSF, MCP-1, TNF-α, and MIP-1α) was identified. Non-survivors showed distinct longitudinal trajectories of the core panel score, characterized by a progressive increase over the disease course. Paired sputum analyses suggested that these systemic cytokine signatures partially reflected pulmonary inflammation. Baseline core panel scores were not significantly associated with mortality (HR 3.29, 95% CI 0.95-11.38; P = 0.059), whereas time-varying monitoring showed better model fit (AIC 29.34 vs 34.85). Core panel scores remained associated with mortality in analyses accounting for LODS scores, baseline CRP, and diabetes. Landmark analysis further suggested that updated core panel scores may provide increasing prognostic information over time compared with baseline assessment, with delta AUC increasing from near zero at day 5 to 0.24 by day 17 after ICU admission.ConclusionsDynamic monitoring of a core cytokine panel may provide greater prognostic information than single-time-point assessment in severe influenza, although these findings require validation in larger independent cohorts. Longitudinal inflammatory profiling may help refine risk stratification and provide a framework for future precision studies.

Background: Inactivated vaccines have been widely used in China and many low- and middle-income countries, but real-world evidence on the protective effectiveness of heterologous mRNA boosters after a SinoPharm primary regimen during Omicron waves in Chinese populations remains limited. This study aimed to evaluate the real-world infection protection effectiveness of a SinoPharm primary regimen with mRNA boosters during the 2022 Omicron (BF.7 and BA5.2 variants) wave in Macao, China. Methods: An online survey conducted for two days among Macao residents towards the end of the 2022 Omicron wave gathered 4,879 responses (61.7% female, n=3,010). Among the participants, 83.2% (n=4,052) reported receiving the SinoPharm primary vaccination regimen, while 20% (n=827) reported receiving mRNA boosters; 71.4% of respondents reported confirmed infections, with an average duration of 5.4 days testing positive. Logistic and Ordinary Least Squared regressions were utilized to analyze the infection risk and the number of days testing positive. Results: When compared to those who received a three-dose inactivated vaccine, those with one-dose mRNA booster shows a significantly lower likelihood of confirmed infection [odds ratio (OR) =0.421, P<0.01]. In the event of an infection, they also experienced a decreased likelihood of developing fever (OR =0.290, P<0.01), and fewer sick days (-0.931, P<0.05). Conclusions: Heterologous vaccination is recommendable for both the Chinese population and other low-to-middle-income countries that have predominantly adopted inactivated vaccines as their primary regimen. Future studies are needed to examine the long-term effects, which could not be assessed in this survey.

Background:Florensocatib (formerly known as HSK31858) is a novel reversible inhibitor of dipeptidyl peptidase 1. We sought to determine the efficacy and safety of florensocatib in decreasing exacerbation frequency in Chinese adults with bronchiectasis. Methods:The HOPE-BE trial was a phase 3, randomised, placebo-controlled trial which determines the efficacy and safety of high-dose florensocatib (40 mg once daily) versus placebo in Chinese adults with bronchiectasis who had two or more exacerbations within the past year. Patients were randomly assigned in a 2:1 ratio to receive florensocatib 40 mg or matching placebo once daily for 52 weeks. We recorded demographics, medical history, bacterial infection status and quality-of-life and performed spirometry at baseline. Results:We randomised 700 patients who were enrolled from 67 sites in mainland China between September 2024 and November 2025. 60.4% of patients were female. 559 (79.9%) and 141 (20.1%) of patients, respectively, had two and three or more exacerbations in the past year. The median (interquartile range) of 24-h sputum weight was 14.8 (29.3) g, and the median (interquartile range) of sputum purulence score was 5.0 (2.0). 192 (27.4%) patients were culture positive to Pseudomonas aeruginosa, and demonstrated significantly higher 24-h sputum volume and purulence score, and lower lung function and quality-of-life scores. Significant geographical variations were seen regarding comorbidity, blood eosinophil counts and sputum bacteriology. Conclusion:The baseline demographic characteristics of the HOPE-BE trial may provide important clues to future therapeutic efficacy assessment in adults with bronchiectasis.

Multiciliated cells (MCCs) are essential for airway innate defense through mucociliary clearance, yet the diversity of MCCs in the healthy human airway remains poorly defined, hindering the understanding of their dysfunction in chronic respiratory diseases. In this study, we first profiled multiple anatomical regions of the healthy airway, including the turbinate, nasal sinus, nasopharynx, trachea, proximal bronchi, distal bronchi, and bronchioles. Morphological evaluation of MCCs revealed a progressive proximal-to-distal decline in their coverage, ciliary length, and axonemal diameter in the lower respiratory tract. Single-cell RNA sequencing further identified five distinct MCC subtypes whose distribution exhibited marked heterogeneity across airway anatomical regions. At the molecular level, proximal bronchial MCCs exhibited enrichment of antioxidant pathways with up-regulation of NQO1 and TXN compared with bronchiolar MCCs, a finding validated by spatial transcriptomics and immunofluorescence. Organoid experiments functionally confirmed that bronchiolar organoids accumulated significantly higher levels of reactive oxygen species than bronchial organoids upon cigarette smoke extract stimulation. In diseased conditions (nasal polyps, asthma, and COPD), we identified 22 commonly up-regulated and 4 commonly down-regulated genes in MCCs relative to matched control regions, pointing to shared injury features across chronic respiratory diseases. Moreover, we discovered that FTO and IRF9 were significantly up-regulated in MCCs from COPD patients but markedly down-regulated in those from asthma patients, highlighting disease-specific ciliary alterations. This atlas delineates the regional morphological and molecular landscape of airway MCCs, identifies the antioxidant deficiency of distal MCCs as a previously unrecognized feature, and reveals novel targets for therapeutic intervention in chronic respiratory diseases.

Pneumonia remains a leading cause of global mortality, posing particular diagnostic challenges in resource-limited settings. While traditional methods, such as X-ray and computed tomography, provide detailed anatomical information, they require specialized equipment, involve radiation exposure, and are not portable for rapid screening. To overcome the limitation of single-site analysis in capturing spatially heterogeneous pneumonia, we developed a framework that integrates respiratory sounds from six lung regions. On a dataset of 108 patients, our subject-wise five-fold cross-validation demonstrates that multi-site analysis significantly improves performance across both deep learning and traditional machine learning models. The results demonstrate that multi-site models significantly outperform single-site alternatives, with the Audio Spectrogram Transformer achieving 78.08% accuracy, 89.00% specificity, 78.56% precision, and 80.13% recall in pneumonia detection under the six-site configuration. For severity assessment, VGG16 attained the highest specificity of 66.50% in the ternary classification task. These findings confirm that spatial integration of respiratory acoustic signatures enables more comprehensive pulmonary assessment than single-location analysis, while highlighting the complementary strengths of different algorithmic approaches for specific clinical tasks. This work establishes validated methodological foundations for intelligent auscultation systems, with future efforts directed towards multi-center validation and integration into clinical workflows.

Background Mepolizumab is clinically beneficial for patients with severe asthma with an eosinophilic phenotype (SA-EP) but lacks randomised controlled trial efficacy data in those on medium-dose inhaled corticosteroids (ICS). This analysis assessed mepolizumab's efficacy in a subgroup of patients on medium-dose ICS from a Chinese phase 3 trial ( NCT03562195 ). Methods Eligible SA-EP patients had received daily ≥500 µg·day −1 fluticasone propionate or equivalent. In this post hoc evaluation, we included patients who were on baseline medium-dose ICS. Outcomes assessed were rate of clinically significant exacerbations (CSEs) at week 52, time to first CSE, St George's Respiratory Questionnaire (SGRQ) score, pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ), asthma control questionnaire-5 (ACQ-5) score and rate of clinical remission. Results At week 52, in the medium-dose ICS subgroup, mepolizumab (n=115) versus placebo (n=104) significantly reduced the rate of CSEs (0.53 versus 1.30 events·yr −1 ; rate ratio 0.41 (95% CI 0.25–0.66); p<0.001), with a lower probability of CSE (Kaplan–Meier estimate, 27.0% versus 49.3%; HR 0.47 (95% CI 0.30–0.73); p<0.001), greater improvements, as measured by difference in least-square mean, in SGRQ score (−5.58, 95% CI −10.73 to −0.44), FEV 1 (119.06 mL, 95% CI 6.66–231.45) and ACQ-5 score (−0.25, 95% CI −0.46 to −0.04), and a higher proportion of patients achieving three- or four-component clinical remission (31.3–57.4% versus 13.5–36.5%). The rate of clinical remission was higher in patients on medium-dose ICS than those on high-dose ICS. Conclusions Mepolizumab provided greater clinical benefit across multiple outcomes including clinical remission versus placebo in Chinese SA-EP patients on medium-dose ICS. Earlier treatment could increase the chance of clinical remission.

BACKGROUND:MG-K10 is a long-acting, humanised monoclonal antibody against interleukin-4 receptor alpha (IL-4Rα), which inhibits IL-4 and IL-13-mediated signalling to reduce type 2 inflammation in asthma. OBJECTIVE:This Phase Ib/II study aimed to evaluate the preliminary efficacy, safety and pharmacodynamic characteristics of MG-K10 in Chinese patients with asthma. METHODS:This study included an initial phase Ib to evaluate safety and tolerability, followed by a phase II study in which eligible patients with moderate-to-severe asthma were randomised 1:1:1 to receive MG-K10 300 mg every 2 weeks (Q2W), MG-K10 300 mg every 4 weeks (Q4W), or a matched placebo (2 mL) Q2W subcutaneously for 24 weeks. The primary endpoint was the absolute change from baseline in the prebronchodilator forced expiratory volume in 1 s (FEV1) at week 12. Secondary efficacy endpoints, including asthma control, the rate of severe exacerbations and safety, were assessed. This trial is registered with ClinicalTrials.gov (NCT05382910). RESULTS:A total of 64, 60 and 63 patients were randomised to the MG-K10 Q2W, MG-K10 Q4W and placebo groups respectively. At week 12, the least squares mean improvements in prebronchodilator FEV1 were significantly greater in both MG-K10 groups than in the placebo group [Q2W vs. placebo: 0.35 L (95% CI, 0.208-0.490), Q4W vs. placebo: 0.30 L (95% CI, 0.156 to 0.441), both p < 0.0001]. Greater FEV1 improvements were observed in patients with baseline blood eosinophils ≥ 0.3 × 109/L. The incidence of adverse events was similar across groups [MG-K10 300 mg, Q2W (79.7%), MG-K10 300 mg Q4W (85.0%) and placebo groups (79.4%)]. MG-K10 was safe and well-tolerated, and consistent with the known safety signals. CONCLUSIONS:MG-K10 was superior to placebo in improving lung function, enhancing asthma control and reducing severe exacerbations in patients with asthma. The once-every-4-week regimen offers extended dosing intervals that may enhance medication adherence.

The trends in allergic comorbidities secondary to the environmental variations in China remain unclear. We aimed to determine the variation of allergic comorbidities and polysensitization among asthma and/or rhinitis patients in the past decade. We assessed two nationally representative cross-sectional datasets from 2008 to 2009 and 2018 to 2019, which enrolled 2322 and 2353 patients, respectively. Over the present 10-year study period, the prevalence of allergic symptoms and allergen sensitivity among patients with multiple sensitivities in the 2018-2019 cohort was significantly higher than that in the 2008-2009 cohort, especially for mites, pollen, and animal allergens. The comorbidity rates of asthma, allergic rhinitis, conjunctivitis, and eczema were significantly increased in the 2018-2019 cohort. Also in that cohort, IgE polysensitization was significantly associated with the coexistence of asthma and rhinitis, and the number of IgE-reactive allergens was significantly associated with the number of multimorbidities. Use of an air-conditioner and carpet in the home, and keeping pet were linked to the risk of polysensitization. Our findings suggest an increase in the comorbidity rate and multimorbid polysensitized phenotype of allergic diseases in China. Asthma occurred in both cohorts more frequently with coexisting allergies than as a single entity.

Although diabetic complications are well-established in multiple organs, their impact on the respiratory system remains unclear. Clinical evidence indicates accelerated chronic obstructive pulmonary disease (COPD) progression in individuals with diabetes, yet the underlying mechanisms are poorly defined. Using single-cell RNA sequencing of airway epithelium, we identified distinct transcriptional alterations in COPD patients with or without diabetes, particularly in host–defense pathways related to viral infection, which is a key driver of COPD exacerbations. Functionally, hyperglycemia enhanced influenza virus susceptibility in both COPD-derived epithelial cells and COPD mice with diabetes, indicating compromised airway defense. We further demonstrated that hyperglycemia promotes advanced glycation end products (AGEs) accumulation in airway epithelium, with AGEs levels correlating with infection severity. Pharmacological inhibition of AGEs formation with aminoguanidine significantly reduced viral load both in vitro and in vivo. Mechanistically, AGEs activate p38/ERK/IKK proinflammatory signaling via RAGE and MD2 receptors, leading to epithelial injury and heightened viral susceptibility. Our findings reveal a hyperglycemia-AGEs-RAGE/MD2 axis that increases viral susceptibility in COPD, highlighting AGEs targeting as a promising therapeutic strategy for COPD patients with diabetes. Diabetes worsens COPD by promoting airway epithelial accumulation of advanced glycation end products (AGEs), which increase viral susceptibility via RAGE/MD2-dependent pro-inflammatory signaling. Diabetes worsens COPD by promoting airway epithelial accumulation of advanced glycation end products (AGEs), which increase viral susceptibility via RAGE/MD2‑dependent pro‑inflammatory signaling.

Objective To visualize and quantify regional pulmonary aerosol deposition and early airway clearance using aerosolized [ 18 F]NaF PET/CT in bronchiectasis. Methods In this prospective study, 77 adults with CT-confirmed bronchiectasis underwent aerosolized [ 18 F]NaF PET/CT. Regional deposition in bronchiectatic versus healthy lung was assessed on the 0-min scan using target-to-blood ratio (TBR) and total deposited activity. Deposition robustness was evaluated across different nebulizer types. A subgroup underwent dynamic imaging (0–30 min) followed by serial static scans up to 120 min, with kinetic analysis using a dual-pathway clearance model. Results The 0-min PET/CT demonstrated visually apparent photopenic defects in bronchiectatic regions. Quantitatively, bronchiectatic lung showed significantly lower deposition than healthy lung (TBR: 1.30 [0.63–1.58] vs. 2.30 [1.60–2.65]; p < 0.05) and markedly reduced total activity (43.18 [5.7–47.08] vs. 1413.33 [581.95–2155.68]; p < 0.0001). These findings were consistent across all nebulizer systems. Dynamic imaging showed early clearance was dominated by mucociliary transport (kmc > kabs), with minimal systemic absorption. Serial imaging (0–120 min) showed no increase in bronchiectatic activity, while healthy lung activity declined gradually, indicating 0 min as the optimal time point for deposition assessment. Bronchodilator administration did not alter clearance kinetics in bronchiectatic regions. Conclusion Aerosolized [ 18 F]NaF PET/CT enables quantitative assessment of regional aerosol deposition and airway clearance in bronchiectasis, revealing persistent deposition deficits in diseased airways and mucociliary-dominant early clearance with minimal systemic absorption.

Postacute sequelae of COVID-19 (PASC), a multisystem disorder with prevalent respiratory manifestations, affecting millions of individuals worldwide, yet the organ-/system-specific PASC pathogenesis and targeted interventions remain largely undefined. In this longitudinal cohort study of individuals followed up at 4 (n = 57) and 7 months (n = 54) after the Omicron BA.5 outbreak in China, we comprehensively analyzed physician-administered PASC symptom assessments, clinical respiratory evaluations (pulmonary function and chest computed tomography), immunological response profiles, and inflammatory markers. Our findings demonstrated that patients with respiratory system-specific PASC (R-PASC) endure long-term pulmonary function impairment (restrictive ventilation and diffusion dysfunction), sustained severe residual lung lesions (predominant fibrosis), and chronic systemic inflammatory responses. Patients with R-PASC exhibited enhanced SARS-CoV-2-specific T-cell responses, whereas in the control group, moderate-magnitude and polyfunctional virus-specific T-cell response correlated with improved lung function and alleviated inflammation. Sustained neutralizing antibody titers were also observed in patients with R-PASC, whereas humoral responses showed minimal association with disease pathophysiology. Moreover, prolonged activation of complement classical and alternative pathway in patients with R-PASC is associated with worsening respiratory parameters, whereas mannose-binding lectin within the lectin pathway exhibits protective correlations with pulmonary tissue function preservation. Overall, our study delineates the extensively perturbed immune-inflammation-organ dysfunction in patients with R-PASC, thereby providing valuable insights into the pathogenesis of this condition and highlighting potential targets for therapeutic intervention.

BACKGROUND:The chronic obstructive pulmonary disease (COPD) guidelines recommend selecting initial treatment based on the severity of respiratory symptoms or exacerbation history. However, some patients still experience clinically important deterioration (CID) despite this strategy. Therefore, we aimed to identify the risk factors to guide initial treatment, focusing on mild-to-moderate COPD patients whose annualized CID cannot be controlled by a single-bronchodilator. METHODS:Patients in the tiotropium group from a randomized controlled trial were included. Over 2 years, annualized CID was defined as forced expiratory volume in one second (FEV1) decline at least 100 ml, COPD assessment test (CAT) increasing at least 2 points, or having experienced at least two moderate or one severe acute exacerbations of COPD (AECOPD) in this study. Random coefficients model within a bayesian framework was adapted to estimate the change in FEV1 and CAT scores. The logistic regression analysis was adapted to detect the risk factors. The risk of annualized CID was evaluated using the incidence risk ratio (IRR) for patients with risk factors. RESULTS:Of 312 patients with mild-to-moderate COPD receiving tiotropium, 29.2% still experienced annualized CID. The proportions of patients who developed annualized CID regarding FEV1, CAT, and AECOPD was 20.5, 8.0, and 6.1%, respectively. Post-bronchodilator FEV1:FVC ≤ 60% (OR = 1.73, 95%CI: 1.06-2.84) and smoking pack-years ≥50 (OR = 1.95, 95%CI: 1.11-3.41) were associated with higher risk of experiencing annualized CID. The IRR of annualized CID was increased with more risk factors at baseline. CONCLUSION:Patients with more prominent airflow limitation and higher smoking pack-years warrant intensified initial treatment to control their annualized CID.

Background Lung cancer incidence and mortality continue to rise in China, highlighting the need for a deeper understanding of its epidemiology and optimal screening targets. Methods A total of 10,560 participants with 5–30 mm pulmonary nodules incidentally detected via low-dose computed tomography (LDCT)/CT were enrolled from 23 hospitals (October 2018–May 2021) and followed for 2–3 years for evaluation of circulating tumor DNA (ctDNA) biomarkers to distinguish malignant and benign nodules. Demographic, clinical, and imaging data were collected and analyzed. Lung cancer risk factors were assessed using stepwise single and multiple-factor binary logistic regression. This study reports only the baseline epidemiological characteristics of the population and the associated risk factors of lung cancer. Results A higher proportion of females (56.56%) were present across all age groups, with a median age of 53 years (45–62), younger than males (55 years [46–63], P < 0.001). While 97.1% of females and 37.8% of males were non-smokers, and 68.65% of participants had no occupational exposure, 71.10% had a history of second-hand smoke exposure. Most nodules were solitary (81.24%), sub-centimeter (78.22%), and non-solid (62.49%). Malignancy was identified in 17.33% of nodules, with 97.32% classified as early-stage lung adenocarcinoma (AJCC stage 0–I: 90.35%). The malignant rate increased with age and nodule size and was also associated with multiple nodules, ground-glass nodules (GGNs), upper lobe location, and female sex. Proportion of patients with malignant nodules was similar between non-high-risk (21.04%) and high-risk (17.92%) groups based on current Chinese screening guidelines, while proportions of benign nodules were notably high for solid nodules (37.21%) and small nodules (20.15%). Conclusion Our large-scale investigation provides updated data to guide future precise clinical management of pulmonary nodules, with a particular focus on younger females and reducing overtreatment.

Background:Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic subtype in non-small cell lung cancer (NSCLC) among Asians. EGFR tyrosine kinase inhibitors (TKIs) have become the mainstay of therapy, significantly improving survival outcomes. However, prognostic factors influencing survival in real-world settings among patients treated with EGFR-TKIs remain underexplored. This study aims to identify prognostic factors in EGFR-TKI-treated patients using data from a nationwide registry. Methods:Patient data were sourced from the "Meina Xinsheng" registry, with survival metrics provided by the China Center for Disease Control. We analyzed the impact of sex, age, disease stage, histology, gene mutation type, and Karnofsky Performance Status (KPS) score on duration of treatment (DoT), overall survival (OS), and the incidence of long-term survival (>5 years), using both univariate and multivariate analyses. A reference cohort of EGFR wild-type patients receiving EGFR-TKI therapy was also included. Results:Among 231,699 patients registered for EGFR-TKI treatment across 3,445 hospitals nationally, 221,788 cases of advanced NSCLC were analyzed. Within the subset of 83,791 patients eligible for survival analysis spanning 2012 to 2018, the median OS was 3.2 years [95% confidence interval (CI): 3.18-3.3], and the median lung cancer-specific survival (LCSS) was 4.1 years (95% CI: 4.02-4.1). At least 7.7% of patients achieved a survival milestone of more than 5 years. Factors associated with improved OS and higher long-term survival rates included female sex, stage IIIb disease, adenocarcinoma histology, EGFR exon 19 deletion, superior KPS scores, prolonged DoT, receiving EGFR-TKI as first-line treatment, and achieving a complete response (CR). Younger patients (<40 years) exhibited better OS, albeit with a shorter DoT. Notably, patients maintaining disease control for 22 months had significantly higher long-term survival (12.8%) compared with those who did not (2.7%). Conclusions:In this large real-world cohort of advanced NSCLC patients treated with EGFR-TKI, female sex, stage IIIb (vs. stage IV) disease, adenocarcinoma histology, EGFR exon 19 deletion, and the use of EGFR-TKI as first-line therapy were independently associated with longer DoT and/or OS. These factors may help identify patients more likely to derive durable benefit from EGFR-TKIs and support risk stratification and treatment optimization in EGFR-mutant NSCLC.

Eosinophilic granulomatosis with polyangiitis (EGPA) and severe eosinophilic asthma (SEA) share a Type 2 (T2) inflammatory signature but exhibit distinct pathophysiology. We hypothesized that EGPA involves additional inflammatory mechanisms, beyond T2 immunity, that drive its systemic manifestations and treatment resistance. Using single-cell RNA sequencing, we identify interferon (IFN-I)-driven inflammation in EGPA, in contrast to TNF predominant pathway activation in SEA. IL1B+MX1+ neutrophils in EGPA express IFN-stimulated genes and promote tertiary lymphoid structure formation with autoantibody production. In addition, other IFN-activated granulocytes, including APOC1+ eosinophils, SCN7A+ mast cells, and basophils, further contribute to immune dysregulation in EGPA, unlike TNF activated granulocytes in SEA. Longitudinal single-cell analysis of EGPA reveals an IGF1+ macrophage population linked to EGPA relapse. In animal models of both conditions, IGF1 blockade attenuates T2 inflammation, mucin production, and goblet cell hyperplasia, highlighting IGF1 as a possible therapeutic target in T2 inflammation disease. There are similarities in airway inflammatory endotype between eosinophilic granulomatosis with polyangiitis (EGPA) and type 2 eosinophilic asthma. Here, the authors perform single-cell transcriptomics to compare EGPA with severe eosinophilic asthma and find differences in the innate immune cell populations and use mouse models to characterise the function and phenotype of these cells.