Therapeutic Advances in Respiratory Disease最新文献

{"title":"The effectiveness of non-invasive positive pressure ventilation combined with rehabilitation training in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.","authors":"Shuqin Li, Xun Yang, Ying Wu, Jing Zhu, Mei Feng, Xiaoling Wu","doi":"10.1177/17534666261424364","DOIUrl":"10.1177/17534666261424364","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary rehabilitation (PR) is a cornerstone of chronic obstructive pulmonary disease (COPD) management, but exercise intolerance often limits its effectiveness. Non-invasive positive pressure ventilation (NPPV) during PR may enhance training tolerance and outcomes, yet the overall evidence remains uncertain.</p><p><strong>Objectives: </strong>To evaluate the effects of adding NPPV to PR on exercise capacity, dyspnea, and respiratory muscle strength in patients with COPD.</p><p><strong>Design: </strong>Systematic review and meta-analysis of randomized controlled trials (RCTs).</p><p><strong>Data sources and methods: </strong>We searched PubMed, Web of Science, Embase, the Cochrane Library, and CINAHL from inception to December 2024 for RCTs evaluating NPPV combined with PR in patients with COPD. Two reviewers independently assessed risk of bias using the Cochrane Risk of Bias Assessment Tool for Randomized Trials (RoB 2), extracted data, and performed analyses using RevMan 5.3.</p><p><strong>Results: </strong>A total of 17 RCTs (489 participants; predominantly GOLD stage III-IV) were included. NPPV + PR significantly improved 6-minute walk distance (MD = 29.1 m, 95% CI: 3.6-54.6), incremental shuttle walk test distance (MD = 21.8 m, 95% CI: 5.0-38.7), peak oxygen uptake (SMD = 0.53, 95% CI: 0.23-0.83), maximal inspiratory pressure (Pimax; MD = 5.8 cmH₂O, 95% CI: 1.0-10.7), and maximal expiratory pressure (Pemax; MD = 14.9 cmH₂O, 95% CI:4.1-25.7). Significant reductions were observed in blood lactate levels (MD = -0.49 mmol/L, 95% CI:-0.79 to -0.19), BORG dyspnea score (MD = -1.1, 95% CI: -1.7 to -0.6), and mMRC scale (MD = -0.3, 95% CI: -0.5 to -0.1). No significant effect was found on quality of life.</p><p><strong>Conclusion: </strong>Adding NPPV to exercise-based PR provides clinically meaningful improvements in exercise capacity, dyspnea, and respiratory muscle strength in patients with COPD who have significant exercise limitation. NPPV may be a valuable adjunct to optimize PR outcomes in this population.</p><p><strong>Trial registration: </strong>This review was prospectively registered in PROSPERO (CRD42023486598).</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666261424364"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12923938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers for selecting biologic therapies in asthma.","authors":"Sergio E Chiarella, Isabella Novoa-Caicedo, Thanai Pongdee, Chung-Il Wi, Young J Juhn","doi":"10.1177/17534666261430646","DOIUrl":"10.1177/17534666261430646","url":null,"abstract":"<p><p>Asthma is a heterogeneous chronic respiratory disease driven by diverse inflammatory pathways that vary across patients. The recognition of distinct molecular endotypes has led to the development of targeted biologic therapies that have transformed the management of moderate-to-severe asthma. However, selecting the most appropriate biologic therapy for each patient remains challenging. Health providers often rely on trial-and-error approaches that may delay disease control, increase costs, and expose patients to unnecessary side effects. Biomarkers are key to precision asthma care, as they provide objective measures of underlying disease mechanisms. Established biomarkers such as blood eosinophil count, fractional exhaled nitric oxide, and serum total immunoglobulin E are important for identifying type 2-high asthma. Sputum biomarkers offer direct insight into airway inflammation, but their use is limited by technical complexity and availability across centers. Emerging biomarkers, including proteomic, transcriptomic, metabolomic, and genomic biomarkers, show promise in further refining biologic therapy selection. In addition, digital biomarkers derived from electronic health records, wearable devices, and artificial intelligence-based algorithms offer new opportunities to capture real-world changes in disease and treatment response. Non-medical drivers of health, particularly socioeconomic factors, are increasingly recognized as modifiers of biologic effectiveness and may also be helpful in selecting biologic therapies. This review summarizes the existing evidence on established and emerging biomarkers used to guide biologic therapy selection in asthma. Integrating multiple biomarkers will be essential to improve biological selection, monitor response, and ultimately achieve the goal of remission in asthma.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666261430646"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12979892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, hemodynamic, and safety outcomes of sotatercept in pulmonary arterial hypertension: a meta-analysis of randomized trials with time-to-event data.","authors":"Mohamed R Murad, Ameer Awashra, Mohamed S Elgendy, Ahmed Wahdan Kasem, Abdalhakim Shubietah, Fadi Safi","doi":"10.1177/17534666261459209","DOIUrl":"10.1177/17534666261459209","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH) remains progressive despite contemporary background therapy. Sotatercept is a novel activin signaling inhibitor that targets pulmonary vascular remodeling and may improve clinical and hemodynamic outcomes.</p><p><strong>Objectives: </strong>To evaluate the efficacy, hemodynamic effects, and safety of sotatercept in patients with PAH.</p><p><strong>Design: </strong>Systematic review and meta-analysis of randomized controlled trials (RCTs).</p><p><strong>Data sources and methods: </strong>Five electronic databases were searched through October 2, 2025, for eligible RCTs. Time-to-event outcomes were analyzed using pooled individual patient data with hazard ratios (HRs), while secondary outcomes were assessed using random-effects risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CI). Trial-sequential analysis (TSA) evaluated the conclusiveness of results.</p><p><strong>Results: </strong>In four RCTs (<i>n</i> = 889), sotatercept reduced clinical worsening or death by 77% (HR 0.23, 95% CI 0.16-0.32, <i>p</i> < 0.001) and prolonged event-free survival by ~40 weeks. World Health Organization (WHO) functional class improved in 40.3% vs 24.3% (RR 1.71, 95% CI 1.32-2.21), and 6-minute walk distance increased by MD 30.27 m (95% CI 13.45-47.08), while pulmonary vascular resistance (PVR) declined significantly (MD -247 dyn·s·cm-⁵, 95% CI -301.7; -192.2). Serious adverse events were slightly less frequent with sotatercept (26.2% vs 31.7%, RR 0.83); however, total bleeding (37.9% vs 18.7%, RR 2.00), epistaxis (26.7% vs 5.4%, RR 4.89), and telangiectasia (19.8% vs 6.4%, RR 3.24) were more common. TSA revealed conclusiveness in clinical worsening, WHO functional class, and PVR, as well as increases in bleeding events and epistaxis.</p><p><strong>Conclusion: </strong>Sotatercept significantly improves clinical outcomes and extends event-free survival in PAH, with an acceptable safety profile; however, caution is warranted regarding bleeding events. These results support its role as an add-on therapy in PAH management.</p><p><strong>Trial registration: </strong>PROSPERO ID: CRD420251166414.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666261459209"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in orphan drug development for alpha-1 antitrypsin deficiency: a 2025 update from the FDA and EMA.","authors":"Philipp Höger, Markus Ries, Arturo Olivares Rivera, Hilal Ersöz, Katharina Buschulte, Sebastian Fähndrich, Konstantina Kontogianni, Felix Herth, Franziska C Trudzinski","doi":"10.1177/17534666251411227","DOIUrl":"10.1177/17534666251411227","url":null,"abstract":"<p><strong>Background: </strong>Research into safe and effective treatments for alpha-1 antitrypsin deficiency (AATD) has been ongoing for more than four decades. There is still a high medical need for better treatment options: Safe, effective, and convenient therapies that target both the lungs and other AATD organ manifestations are eagerly awaited by patients.</p><p><strong>Objectives: </strong>The purpose of this study is to provide a quantitative clinical-regulatory insight into the current status of the Food and Drug Administration (FDA) and European Medicines Agency (EMA) orphan drug approvals and designations for compounds intended to treat AATD.</p><p><strong>Design: </strong>A cross-sectional approach was applied, involving a one-time comprehensive search of relevant databases.</p><p><strong>Methods: </strong>The primary endpoint of this study was to determine the number and nature of FDA and EMA-approved orphan drugs. The secondary endpoint was the registration of compounds with orphan drug designation status. All database searches were performed since the inception of the FDA database in 1983 and the EMA database in 2000, as well as for all compounds listed in the FDA and EMA drug label databases up to 20 January 2025. The search terms 'antitrypsin' and 'proteinase' were used.</p><p><strong>Results: </strong>In 1987, the FDA approved the first human alpha1-proteinase inhibitor, representing the only approved active substance (5%) out of 20 with orphan drug designation in the FDA for the treatment of AATD. Conversely, the EMA has granted orphan drug designation to nine active substances, though none of these have yet been approved. However, there are several new active substances that have been granted orphan drug designation: oral neutrophil elastase inhibitor (FDA 2021, EMA 2025), IgG4 Fc-bound recombinant human AAT (FDA 2022), HSV vector therapy (FDA 2023), and A1AT modulator/protein folding stabiliser (FDA 2023, EMA 2024). Furthermore, the development of RNA interference therapeutics has progressed in the United States and Europe.</p><p><strong>Conclusion: </strong>The development of new therapies may offer expanded treatment options for patients with AATD in the future. In addition to pulmonary manifestations, extrapulmonary manifestations could also be treated in the future.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666251411227"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic utility of erythrocyte sedimentation rate and anti-Scl-70 positivity for interstitial lung disease in diffuse systemic sclerosis.","authors":"Kadir Burak Akgün, Gezmiş Kimyon, Sahinur Aycan Alkan, Mete Pekdiker, İnan Korkmaz, İbrahim Barışcan Soydan, Ömer Atar","doi":"10.1177/17534666261481715","DOIUrl":"10.1177/17534666261481715","url":null,"abstract":"<p><p>BackgroundInterstitial lung disease (ILD) is a major cause of mortality in patients with diffuse cutaneous systemic sclerosis (dcSSc). Although high-resolution computed tomography (HRCT) is recommended for diagnosis, it is costly, time-consuming, and prone to subjective interpretation.ObjectivesThis study aimed to investigate the utility of hematological biomarkers, specifically routine blood parameters and their derived indices in discriminating dcSSc-ILD to support clinical decision-making.DesignRetrospective, cross-sectional study.MethodsPatients monitored with dcSSc who underwent HRCT evaluation were analyzed. The cohort was divided into two groups based on the presence of ILD to evaluate routine blood parameters and derived indices. Significant parameters from univariate analysis were further evaluated using two separate multivariable logistic regression models adjusted for age, gender, erythrocyte sedimentation rate (ESR), anti-Scl-70, immunosuppressive use, newly diagnosed status and monocyte-to-lymphocyte ratio (MLR).ResultsOut of 117 patients (mean age: 49.03 ± 13.48 years, 90.6% female), dcSSc-ILD was detected in 53% (n=62). Within the cohort, 42.7% (n=50) were receiving immunosuppressive therapy, and 35.0% (n=41) were newly diagnosed with dcSSc. Patients with dcSSc-ILD demonstrated significantly higher ESR (p=0.002), ESR-to-C-reactive protein ratio (ECR) (p=0.042), and ESR-to-lymphocyte ratio (SLR) (p=0.003) levels compared to those without ILD. Anti-Scl-70 positivity was observed in 39.3% of the cohort and was significantly more prevalent in the ILD group (50.0% vs. 27.3%, p=0.012). ROC curve analysis revealed an optimal ESR cut-off value of >23.5 mm/hour for identifying ILD, yielding a high specificity of 90.9% and a sensitivity of 43.5% (AUC: 0.667, 95% CI: 0.569-0.766, p=0.002). In multivariable regression analyses, the diagnostic value of ESR and anti-Scl-70 remained significant and independent after adjusting for age, gender, MLR and immunosuppressive therapy (Model 1), as well as new diagnosis status (Model 2). Each 1 mm/hour increase in ESR was associated with an approximately 7% increase in the probability of dcSSc-ILD.ConclusionESR and Anti-Scl-70 positivity serve as modest but highly specific independent indicators of lung involvement in dcSSc. While Anti-Scl-70 provides significant etiological stratification, ESR's high specificity makes it a valuable, cost-effective preliminary triage tool for identifying patients at higher risk for ILD.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666261481715"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sputum antimicrobial susceptibility patterns and clinical outcomes among adult Aboriginal Australians with bronchiectasis.","authors":"Timothy Howarth, Angelou Castro, Debora Kirojan, Alison O'Connor, Stuart Campbell, Subash S Heraganahally","doi":"10.1177/17534666261480883","DOIUrl":"10.1177/17534666261480883","url":null,"abstract":"<p><p>BackgroundPrevalence of bronchiectasis among the adult Aboriginal Australians is high, estimated to be up to 19.4/1000 people, with associated higher morbidity and mortality. However, despite evidence to suggest that adult Aboriginal Australians have higher bronchiectasis disease burden, the knowledge surrounding sputum antimicrobial susceptibility data is sparce.ObjectivesTo assess the sputum antimicrobial susceptibility patterns among adult Aboriginal patients with bronchiectasis in the Northern Territory of Australia.DesignRetrospective study.MethodPatients aged 18 years and over with sputum antimicrobial susceptibility results available between 2011-2020 during a respiratory related hospital admission (restricted to ICD J presentations) were included. The sputum samples were processed and antibacterial susceptibility reported as per recommended selective susceptibility testing guidelines.ResultsA total of 183 patients had positive sputum cultures. Of these, 167 had antimicrobial susceptibility tested. Antimicrobial resistance to at least one antibiotic was noted for <i>Haemophilus spp.</i> 12 (7%), <i>Pseudomonas spp.</i> 26 (15.4%), <i>Streptococcus pneumoniae</i> 18 (23.1%), <i>Staphylococcus spp.</i> 17 (47.2%) and <i>Klebsiella spp.</i> 8 (88.9%). The greatest frequency of antimicrobial resistance was recorded against Ampicillin for <i>Haemophilus spp</i>. (5.8%), Ceftazidime for <i>Pseudomonas spp.</i> (7.7%), Erythromycin for <i>Streptococcus pneumoniae</i> (20.5%), Flucloxacillin and Amoxycillin/Clavulanate for <i>Staphylococcus spp.</i> (27.8%) and Ampicillin for <i>Klebsiella spp.</i> (88.9%). Multi-antimicrobial resistance was recorded in 31 unique patients. In univariate logistic regression models advancing age was associated with increased odds for antimicrobial resistance for <i>Haemophilus spp.</i> and patients with multi-antimicrobial resistance recorded a higher hospitalisation rate (median 14 vs. 8), more hours in intensive care (median 225.5 vs. 131) and left upper lobe bronchiectasis (41.9 vs 20.4%). Although, statistically not significant, the overall mortality was higher among patients demonstrating multi-antimicrobial resistance, including younger age at death.ConclusionThe results of this study may be of utility in advocating antimicrobial stewardship among adult Aboriginal/Indigenous patients with bronchiectasis.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666261480883"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a clinical prediction model for cough variant asthma.","authors":"Haodong Bai, Baiyi Yi, Tongyangzi Zhang, Yiqing Zhu, Wanzhen Li, Shengyuan Wang, Xianghuai Xu, Li Yu","doi":"10.1177/17534666261450064","DOIUrl":"10.1177/17534666261450064","url":null,"abstract":"<p><strong>Background: </strong>Cough variant asthma (CVA) is a common cause of chronic cough but remains underdiagnosed due to limited access to bronchial provocation test.</p><p><strong>Objective: </strong>To develop a clinical prediction model for CVA based on more accessible indicators.</p><p><strong>Design: </strong>A single-center retrospective cohort study.</p><p><strong>Methods: </strong>A retrospective cohort of patients with chronic cough from January 2024 to December 2024 was included. The patients were randomly divided into a training set and an internal validation set at a ratio of 7:3. Univariable and multivariable logistic regression analyses were used to identify independent predictors of CVA. A nomogram prediction model was constructed based on these factors. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).</p><p><strong>Results: </strong>A total of 323 patients with chronic cough were included, with 226 assigned to the training set (45 with CVA, 181 with non-CVA) and 97 to the internal validation set (23 with CVA, 74 with non-CVA). Multivariable logistic regression analysis identified increased eosinophils in induced sputum, elevated peripheral blood eosinophil count (PBEC), raised FeNO₅₀, and reduced maximal mid-expiratory flow (MMEF) as independent predictors of CVA (all <i>p</i> < 0.05). The nomogram model developed based on these indicators demonstrated strong discriminative ability, with area under the ROC curve (AUC) of 0.93 in the training set and 0.92 in the internal validation set. Calibration curves indicated favorable predictive performance of the model. DCA confirmed net clinical benefit.</p><p><strong>Conclusion: </strong>The CVA clinical prediction model based on induced sputum cytology, PBEC, FeNO₅₀ and MMEF shows excellent discrimination, accuracy, calibration, and clinical applicability.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666261450064"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood eosinophils in COPD: are biologics for everyone?","authors":"Marco Vanetti, Dina Visca, Francesco Ardesi, Antonia M Taglioretti, Martina Zappa, Patrizia Pignatti, Antonio Spanevello","doi":"10.1177/17534666261471839","DOIUrl":"https://doi.org/10.1177/17534666261471839","url":null,"abstract":"<p><strong>Background: </strong>Type 2 (T2) biologics represent a promising treatment option for chronic obstructive pulmonary disease (COPD) patients with eosinophilic inflammation.</p><p><strong>Objectives: </strong>To evaluate the prevalence of stable COPD patients who may be eligible for T2 biologics.</p><p><strong>Design: </strong>Real-world, retrospective, monocentric study in COPD patients undergoing inpatient pulmonary rehabilitation.</p><p><strong>Methods: </strong>Clinical, functional, and inflammatory data were collected. Patients were considered eligible for T2 biologic therapy whether they were receiving optimized inhaled therapy and had a history of ⩾2 moderate and/or ⩾1 severe exacerbations in the previous year, together with a blood eosinophil count ⩾300 cells/μL.</p><p><strong>Results: </strong>Among 441 patients, 21.5% had blood eosinophil counts ⩾300 cells/μL and 6.8% fulfilled the combined eligibility criteria. A high burden of respiratory and cardiometabolic comorbidities and increased cardiovascular risk was observed in the overall population.</p><p><strong>Conclusion: </strong>Only a subgroup of patients seems eligible for biologics, treatment escalation should be based on optimized standard care management and patient phenotyping.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666261471839"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic nutritional index predicts nintedanib outcomes in idiopathic pulmonary fibrosis.","authors":"Eri Hayakawa, Motoyasu Kato, Haruhiko Hirano, Chisato Tadokoro, Makiko Kohmaru, Takashi Akimoto, Soichiro Soma, Yuta Arai, Shun Nakazawa, Hiroaki Motomura, Takuto Sueyasu, Haruki Hirakawa, Yusuke Ochi, Issei Sumiyoshi, Junko Watanabe, Yukiko Namba, Shinsaku Togo, Shinichi Sasaki, Kazuhisa Takahashi","doi":"10.1177/17534666261478394","DOIUrl":"10.1177/17534666261478394","url":null,"abstract":"<p><p>BackgroundMalnutrition is common in patients with idiopathic pulmonary fibrosis (IPF), and potentially affects the tolerability of antifibrotic therapy and survival. The prognostic nutritional index (PNI) is a validated prognostic marker in various diseases; however, its role in antifibrotic therapy remains unclear.ObjectivesTo investigate associations between the PNI and adverse effects associated with nintedanib, treatment discontinuation, and survival in patients with IPF.DesignMulticenter retrospective study.MethodsData from 167 Japanese patients with IPF who received nintedanib therapy were retrospectively analyzed. Information on clinical characteristics, laboratory data, and adverse events was collected, and the PNI was calculated. The optimal PNI cut-off value was determined using receiver operating characteristic (ROC) curves. Risk factors for treatment discontinuation and survival were identified using Cox proportional hazards models.ResultsThe median treatment duration and survival time were 18 and 55 months, respectively. The PNI was significantly higher in patients who experienced nintedanib-associated adverse effects than in those who did not. ROC curve analysis identified an optimal PNI cut-off value of 47.3. Patients with a high PNI had significantly longer treatment durations and survival than those with a low PNI. Multivariate analyses identified the PNI as the only factor independently associated with both time to nintedanib discontinuation and survival.ConclusionThe PNI predicted treatment feasibility and survival in patients with IPF. These findings highlight the clinical utility of the PNI as a dual biomarker of nutritional status and demonstrate its potential to guide individualized treatment strategies based on nutritional status.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666261478394"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics identifies a four-gene diagnostic signature linking immune dysfunction and airway remodeling in COPD.","authors":"Wenbo Du, Yukun Wang, Xiang Li, Ruirui Wang, Shuping Tong","doi":"10.1177/17534666261478820","DOIUrl":"10.1177/17534666261478820","url":null,"abstract":"<p><p>BackgroundEarly diagnosis of chronic obstructive pulmonary disease (COPD) remains challenging due to the limited sensitivity of spirometry and imaging in early-stage disease and the lack of reliable blood-based biomarkers. COPD is increasingly recognized as a heterogeneous disorder driven by coordinated immune dysregulation and airway structural remodeling; however, clinically applicable molecular signatures that capture these processes are still lacking.ObjectivesTo identify and validate a blood-based diagnostic signature for COPD and to explore the underlying immune and structural remodeling mechanisms.DesignA multi-stage integrative study combining retrospective bioinformatics analysis with prospective experimental validation.MethodsPublic lung transcriptomic datasets were used to identify COPD-associated candidate genes through differential expression, co-expression network, and machine-learning analyses. Candidate genes were validated by RT-qPCR in peripheral blood samples from stable COPD patients and healthy controls. Exploratory immune, single-cell, virtual perturbation, and molecular simulation analyses were performed to assess potential biological relevance.ResultsFour lung-derived candidate genes, AC079767.4, CEP55, EMR3, and ATP6V0D2, were identified. In peripheral blood validation, CEP55 and ATP6V0D2 showed the strongest diagnostic performance, whereas AC079767.4 showed limited blood-based discriminatory ability. Functional and immune analyses suggested that these genes may be associated with intracellular pH regulation, vesicular acidification, cytokinesis, immune imbalance, and inflammatory pathways. Single-cell analysis indicated that CEP55 was mainly enriched in epithelial, endothelial, and smooth muscle cells, whereas ATP6V0D2 was enriched in macrophages and monocytes. Virtual perturbation and molecular simulation analyses provided hypothesis-generating evidence for possible involvement in antigen presentation, T-helper-cell-related pathways, and ligand-target interactions.ConclusionThis study identified four lung-derived COPD-associated candidate genes through integrative transcriptomic, network, and machine-learning analyses. Among them, CEP55 and ATP6V0D2 showed the strongest peripheral-blood diagnostic performance and biological plausibility, supporting their prioritization as candidate circulating biomarkers for further validation. Exploratory docking and MD simulations suggested possible ligand-target interactions involving CEP55 and ATP6V0D2, but these computational findings require experimental pharmacological validation before any therapeutic relevance can be inferred.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"20 ","pages":"17534666261478820"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}