Pulmonary pharmacology & therapeutics最新文献

{"title":"Artificial intelligence in the development of Rentosertib: A novel TNIK inhibitor for idiopathic pulmonary fibrosis – A letter to editor","authors":"Devipriya R. Namboothiri , Aswathy Sivanandan , Gladyston Netto , Midhun Mathew","doi":"10.1016/j.pupt.2025.102405","DOIUrl":"10.1016/j.pupt.2025.102405","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"92 ","pages":"Article 102405"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847739","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":"Echocardiographic effects of dupilumab in patients with severe type 2 asthma","authors":"Corrado Pelaia ,&nbsp;Giuseppe Armentaro ,&nbsp;Chiara Lupia ,&nbsp;Antonio Giacalone ,&nbsp;Gianluca Ippolito ,&nbsp;Daniela Pastore ,&nbsp;Sofia Miceli ,&nbsp;Carlo Alberto Pastura ,&nbsp;Giandomenico Severini ,&nbsp;Carlo Fuoco ,&nbsp;Alberto Panza ,&nbsp;Filippo Capilupi ,&nbsp;Maria Rosangela Scarcelli ,&nbsp;Giovanna Lucia Piazzetta ,&nbsp;Emanuela Chiarella ,&nbsp;Alessandro Vatrella ,&nbsp;Girolamo Pelaia ,&nbsp;Angela Sciacqua","doi":"10.1016/j.pupt.2026.102409","DOIUrl":"10.1016/j.pupt.2026.102409","url":null,"abstract":"<div><h3>Background</h3><div>Severe asthma is characterized by impaired lung function and elevated cardiovascular risk. Type 2 inflammation, primarily mediated by IL-4 and IL-13, contributes to both airway and cardiac remodeling. Dupilumab, an IL-4Rα antagonist, has shown efficacy in improving respiratory outcomes; however, its impact on cardiac function remains insufficiently studied.</div></div><div><h3>Objective</h3><div>To assess the 12-month effects of dupilumab on echocardiographic parameters and evaluate its potential association with clinical remission in patients with severe type 2 asthma.</div></div><div><h3>Methods</h3><div>This single-centre observational study enrolled 24 patients with severe type 2 asthma receiving dupilumab. Echocardiographic assessments and lung function tests were conducted at baseline and after 12 months. Clinical remission was defined by meeting all of the following: zero exacerbations, zero OCS use, ACT score ≥20, and pre-bronchodilator FEV₁ ≥ 80 % predicted.</div></div><div><h3>Results</h3><div>Twelve-month dupilumab therapy led to significant improvements in both cardiac and respiratory parameters. LV-GLS improved from −17.00 % to −19.00 % and RV-GLS from −17.33 % to −19.11 % (both p &lt; 0.0001). TAPSE and TAPSE/S-PAP ratio also increased significantly (p &lt; 0.0001). Lung function showed notable gains in FEV₁ and FEF25-75, alongside reductions in residual volume and airway resistance. Clinical remission was achieved by 45.83 % of patients. Baseline LV-GLS emerged as a strong predictor of remission (AUC = 0.832), unlike RV-GLS (AUC = 0.545).</div></div><div><h3>Conclusions</h3><div>Dupilumab markedly improved cardiac and pulmonary function and may promote clinical remission. Baseline LV-GLS may serve as a predictive marker, supporting cardiovascular assessment in asthma management.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"92 ","pages":"Article 102409"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019533","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":"Posaconazole attenuates arsenic trioxide toxicity and enhances safety and efficacy while reducing invasion and metastasis in non-small-cell lung cancer","authors":"Shima Karami,&nbsp;Azra Rabbani-Chadegani,&nbsp;Jamshid Davoodi","doi":"10.1016/j.pupt.2026.102412","DOIUrl":"10.1016/j.pupt.2026.102412","url":null,"abstract":"<div><div>The clinical use of the anti-cancer drug arsenic trioxide (ATO) has been limited due to its side effects and the development of cancer cell resistance, highlighting the need for combination therapy. In this study, we optimized and characterized the combination of antifungal drug posaconazole (PCZ) and ATO in A549 lung cancer cells using single-drug monotherapy and sequential/pretreatment combination assays. In the pretreatment approach, the cells were incubated with PCZ for 6 h, followed by incubation with ATO for 48 h. MTT assay indicated that the sequential (pretreatment) combination of ATO and PCZ produced an IC50 value of 25 μmol/L, whereas PCZ and ATO alone exhibited IC50 values of 100 μmol/L and 75 μmol/L, respectively. qRT-PCR analysis showed that treatment at the IC50 concentration of ATO upregulated HMGA2 and Bcl-2 gene expression, while the combination of ATO with PCZ significantly countered these effects. Additionally, overexpression of HMGA2, VEGF, and MMP-9 indicated a high potential for invasion and metastasis, particularly at 75 μmol/L ATO, as demonstrated by wound healing and transwell invasion assays. In contrast, the pretreatment combination showed high efficacy in inducing cytotoxicity in lung cancer cells with minimal risk of invasion and metastasis. The results indicated that this enhanced cytotoxicity occurs through apoptosis induction and modulation of the Hedgehog signaling pathway via targeting SMO and Gli1. Furthermore, flow cytometry and colony formation assays revealed that PCZ attenuates and reduces the apoptotic/necrotic effects of ATO. In conclusion, PCZ synergistically and effectively reduces the adverse cytotoxic effects of ATO in lung cancer cells, providing a promising new therapeutic strategy for lung cancer treatment.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"92 ","pages":"Article 102412"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228330","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":"Targeting ELK-1 transcription factor and mechanosensitive MDM4 receptor using an HCN channel blocker alleviates lung fibrosis","authors":"Sahar A Helmy,&nbsp;Nesma A. Abd Elrazik","doi":"10.1016/j.pupt.2026.102408","DOIUrl":"10.1016/j.pupt.2026.102408","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis is a progressive interstitial lung disease associated with poor prognosis and high mortality rate. It is a chronic irreversible lung disorder, mainly characterized by matrix stiffening. This study aims to investigate the therapeutic potential of targeting ELK-1 transcription factor and mechanosensitive MDM4 receptor using Ivabradine (IVA), an HCN channel blocker, in bleomycin (BLM)-induced pulmonary fibrosis (PF) rat model. Total, differential cell counts and LDH activity were assessed in bronchoalveolar lavage fluid. Pulmonary levels of MDA, GSH, IL-1β, α-SMA, COL1A1, ELK-1, MDM4, p-53, caspase-3, cleaved caspase-3, and CX3CL-1 were measured. Our study demonstrated that IVA induced a marked decrease in MDA and increase in GSH levels. Also, rats treated with IVA revealed a significant reduction in inflammation scores, LDH, IL-1β, α-SMA and COL1A1 levels. IVA-treated group showed a marked downregulation of MDM4 and ELK-1 along with significant upregulation of p-53, caspase-3, cleaved caspase-3, and CX3CL-1 levels when compared to BLM-induced PF group. In conclusion, these findings highlight the therapeutic potential of IVA in the treatment of pulmonary fibrosis. The antifibrotic effects of IVA in the bleomycin-induced rat model may be attributed to restoring redox balance, alleviation of aberrant inflammatory response, sensitizing lung myofibroblasts to apoptosis and promoting their clearance by macrophages.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"92 ","pages":"Article 102408"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019593","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":"Effectiveness of Mepolizumab and Dupilumab in patients with asthma-COPD overlap (ACO) compared to severe uncontrolled asthma (SUA): A retrospective observational cohort study","authors":"Belén Muñoz-Sánchez,&nbsp;Antonio León-Lloreda,&nbsp;David Carlos Echavarría,&nbsp;María Polonio-González,&nbsp;Juan Francisco Medina-Gallardo,&nbsp;Marta Ferrer-Galván,&nbsp;Auxiliadora Romero-Falcón,&nbsp;Javier Díez-Sierra,&nbsp;Francisco Javier Álvarez-Gutiérrez","doi":"10.1016/j.pupt.2025.102407","DOIUrl":"10.1016/j.pupt.2025.102407","url":null,"abstract":"<div><h3>Background</h3><div>The coexistence of asthma and chronic obstructive pulmonary disease (COPD), known as asthma-COPD overlap (ACO), presents unique diagnostic and therapeutic challenges. Although biological therapies such as Mepolizumab and Dupilumab have transformed the management of severe eosinophilic asthma, their role in ACO remains poorly defined due to the exclusion of this phenotype from most clinical trials.</div></div><div><h3>Methods</h3><div>This retrospective observational study aimed to evaluate the real-world effectiveness of Mepolizumab and Dupilumab in patients with ACO compared to those with severe uncontrolled asthma (SUA). We included 212 patients treated in a specialized asthma unit between 2017 and 2024, all with at least 12 months of follow-up. Treatment response was assessed using clinical tools (EXACTO scale and SEPAR-REMAS criteria).</div></div><div><h3>Results</h3><div>Among Mepolizumab-treated patients (ACO n = 10; SUA n = 132), those with ACO had significantly lower baseline FEV₁ and lower rates of good/complete response (14.2 % vs. 60 %, p &lt; 0.03) and clinical remission (0 % vs. 20.9 %). In the Dupilumab group (ACO n = 10; SUA n = 60), ACO patients showed lower baseline ACT scores and FEV₁, with reduced response rates (25 % vs. 55 %) and no clinical remission, although differences were not statistically significant. Despite limited power due to small ACO sample sizes, the magnitude of these differences suggests a clinically relevant reduction in biologic effectiveness in ACO.</div></div><div><h3>Conclusion</h3><div>These findings emphasize the urgent need for dedicated studies in ACO, a population with a high disease burden and limited treatment guidance. Individualized therapeutic approaches should be prioritized until robust clinical trial data becomes available.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"92 ","pages":"Article 102407"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948774","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":"Setting expectations with oral selexipag: an expert consensus-based approach on best practices to initiate, dose, titrate, and manage side effects (SEs) in patients with pulmonary arterial hypertension (PAH)","authors":"Sheryl E. Wu ,&nbsp;Jeremy A. Mazurek ,&nbsp;Jennalyn D. Mayeux ,&nbsp;Naomi G. Habib ,&nbsp;Gurinderpal S. Doad ,&nbsp;Christina K. Benninger ,&nbsp;Michelle C. Cho ,&nbsp;Paul M. Strachan ,&nbsp;Richard M. Perry ,&nbsp;Daisy Bridge ,&nbsp;Medi A. Stone ,&nbsp;Charlotte W. Oswald ,&nbsp;Luis Val-Maranes ,&nbsp;J. Wesley McConnell","doi":"10.1016/j.pupt.2025.102406","DOIUrl":"10.1016/j.pupt.2025.102406","url":null,"abstract":"<div><h3>Background</h3><div>Oral selexipag, a prostacyclin receptor agonist, has been shown to delay pulmonary arterial hypertension (PAH) progression and reduce the risk of hospitalization for PAH. To ensure optimal patient outcomes with selexipag, careful treatment titration and expected side effect (SE) management are required. This study aimed to obtain expert consensus on the appropriate management of patients with PAH treated with selexipag.</div></div><div><h3>Methods</h3><div>United States (US) healthcare professionals (N = 17, 11 physicians; 5 nurse practitioners; 1 registered nurse) participated in this modified-Delphi panel comprising two online surveys and a consensus meeting. Consensus was defined as ≥80% panelists agreeing using a 9-point Likert scale.</div></div><div><h3>Results</h3><div>Panelists prescribed selexipag according to FDA label recommendations to patients with PAH. Panelists acknowledged considerations prompting adjustment in titration speed, agreeing that individual maximum dose is based on SE tolerability.</div><div>It was agreed that the duration of SEs is variable and patient-specific, however, SEs often become manageable over time. Panelists identified methods for managing SEs, agreeing this should be proactive. Panelists highlighted the importance of communicating with patients to set expectations, to enhance engagement and adherence.</div><div>Panelists agreed that treatment initiation, titration, and SE management should be individualized to suit each patient, with decision-making primarily based on patient characteristics and treatment preference.</div></div><div><h3>Discussion</h3><div>This panel provided expert opinions on the clinical use of and best practices for treatment titration and management of expected SEs for oral selexipag. Insights are valuable for developing standardized clinical guidelines and best practices, as well as ensuring personalized treatment to improve patient care.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"92 ","pages":"Article 102406"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948812","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":"The importance of biomarkers in the treatable-trait approach to chronic airway diseases","authors":"Mario Cazzola ,&nbsp;Mauro Maniscalco ,&nbsp;Maria Gabriella Matera ,&nbsp;Paola Rogliani","doi":"10.1016/j.pupt.2026.102410","DOIUrl":"10.1016/j.pupt.2026.102410","url":null,"abstract":"<div><div>Chronic airway diseases (CAD), including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and cystic fibrosis, are increasingly recognized as heterogeneous and overlapping syndromes that share treatable biological and clinical characteristics. The Treatable Traits (TT) approach is a precision medicine framework that transcends diagnostic labels. It identifies and targets modifiable pulmonary, extrapulmonary, and behavioral characteristics in each patient. Biomarkers are central to this paradigm, translating latent endotypes into measurable traits that inform diagnosis, treatment selection, and longitudinal monitoring.</div><div>This review synthesizes contemporary evidence on the role of biomarkers in implementing the TT model across CAD. Peripheral and airway biomarkers, including blood eosinophil count (BEC), fractional exhaled nitric oxide (FeNO), and sputum cell profiles, enable the identification of type 2 inflammatory traits and the prediction of corticosteroid or biologic responsiveness. Imaging and quantitative computed tomography metrics extend trait definition to structural and functional domains. Meanwhile, multi-omic and microbiome signatures reveal the molecular endotypes that underpin disease heterogeneity. Canonical examples include BEC predicting the benefit of inhaled corticosteroids in COPD and FeNO indicating steroid responsiveness in asthma. Additionally, emerging data suggest that rapid trait identification during acute exacerbations may facilitate targeted biologic therapy, extending precision care into acute management contexts.</div><div>Integrating biomarker-guided assessment with individualized therapy redefines the management of CAD by offering a pathway toward biologically precise, dynamically adaptive care. Continued research should focus on standardizing biomarker thresholds, validating composite panels, and translating omic and imaging discoveries into routine clinical tools to optimize outcomes across the chronic airway disease spectrum.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"92 ","pages":"Article 102410"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114012","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":"Advances in novel therapeutics for idiopathic pulmonary fibrosis","authors":"Menghao Li ,&nbsp;Bokun Chen ,&nbsp;Xinhui Zhang,&nbsp;Tingting Zhuo,&nbsp;Xiuju Liu","doi":"10.1016/j.pupt.2025.102396","DOIUrl":"10.1016/j.pupt.2025.102396","url":null,"abstract":"<div><div>IPF is a chronic, progressive interstitial lung disease characterized by irreversible lung scarring, leading to exertional dyspnea and a gradual decline in pulmonary function. Its pathogenesis involves multiple mechanisms, including chronic inflammation, aberrant cytokine signaling, and alveolar epithelial injury. Currently, IPF remains incurable, and treatment primarily aims to slow disease progression and improve survival. This paper systematically reviews recent clinical trials of novel IPF drug therapies that have demonstrated promising efficacy, aiming to inform future drug development.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"91 ","pages":"Article 102396"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337490","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":"Drug-drug interactions in vanzacaftor–tezacaftor–deutivacaftor versus elexacaftor–tezacaftor-ivacaftor","authors":"Esen Deniz Akman Ar,&nbsp;Nadir Yalcin","doi":"10.1016/j.pupt.2025.102395","DOIUrl":"10.1016/j.pupt.2025.102395","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"91 ","pages":"Article 102395"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329926","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":"Targeting the immunometabolism interface: A novel strategy for IPF therapy","authors":"Ganggang Li ,&nbsp;Yuzhi Huo ,&nbsp;Xiaochuan Pan ,&nbsp;Nan Jia ,&nbsp;Xuanyu Wu ,&nbsp;Xinhui Wu ,&nbsp;Fei Wang ,&nbsp;Quanyu Du","doi":"10.1016/j.pupt.2025.102394","DOIUrl":"10.1016/j.pupt.2025.102394","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by aberrant tissue remodeling and excessive deposition of extracellular matrix components. Emerging evidence underscores the critical role of the immunometabolism in the pathogenesis of IPF, highlighting how dysregulated metabolic pathways modulate immune responses and contribute to fibrotic progression. Key molecular regulators such as <em>PPARG</em> (<em>peroxisome proliferator activated receptor gamma</em>) and <em>SPP1</em> (<em>secreted phosphoprotein 1</em>), along with signaling pathways including mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and <em>hypoxia-inducible factor 1-alpha (HIF-1α)</em>, orchestrate immune cell polarization, fibroblast activation, and extracellular matrix production. These insights reveal promising therapeutic targets at the intersection of metabolism and immunity. This review synthesizes current findings on immunometabolism interactions in IPF, emphasizing the potential of metabolic reprogramming and immune modulation as novel treatment strategies. Despite substantial advances, significant challenges persist in elucidating the precise mechanisms underlying these interactions and translating preclinical insights into effective clinical interventions. Future research should prioritize the identification of actionable metabolic biomarkers, refinement of molecular targets, and development of personalized therapeutic approaches. Addressing these gaps may pave the way for innovative therapies capable of halting or even reversing fibrosis, ultimately improving outcomes for patients with IPF.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"91 ","pages":"Article 102394"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048269","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}