Pulmonary pharmacology & therapeutics最新文献

{"title":"Safety and efficacy of transitioning from selexipag to oral treprostinil in pulmonary arterial hypertension: Findings from the ADAPT registry.","authors":"D. Lachant, R. Minkin, J. Swisher, Mohammed Mogri, R. Zolty, Stephanie S. Hwang, S. Seaman, M. Broderick, S. Sahay","doi":"10.2139/ssrn.4361306","DOIUrl":"https://doi.org/10.2139/ssrn.4361306","url":null,"abstract":"PURPOSE\u0000Oral treprostinil and selexipag are drugs targeting the prostacyclin pathway and are approved for treatment of pulmonary arterial hypertension (PAH). In the setting of unsatisfactory clinical response or side effects while on selexipag, there is little data on clinical benefit, safety, or strategies on transitioning to oral treprostinil. Using prospective data from the ADAPT registry, we aimed to evaluate clinical outcomes, safety, and transition strategies in ten patients with PAH transitioning from selexipag to oral treprostinil.\u0000\u0000\u0000METHODS\u0000ADAPT was a prospective, real-world, multicenter, United States-based registry of patients with PAH newly started on oral treprostinil, with a cohort of patients (n = 10) transitioning from selexipag to oral treprostinil. PAH variables of interest were collected from standard-of-care clinic visits. Clinical improvement was defined by modified REPLACE criterion, and risk was assessed by REVEAL Lite 2 from baseline to last follow-up. Real world transition strategies were recorded. Healthcare utilization or worsening PAH was evaluated within 30 days of transitions.\u0000\u0000\u0000RESULTS\u0000Seven patients transitioned due to worsening PAH or lack of efficacy on selexipag, and three patients transitioned due to tolerability issues. Based on the modified REPLACE criterion, five patients demonstrated clinical improvement after transition from selexipag to oral treprostinil. Using REVEAL Lite 2 to assess risk, three patients improved and five patients maintained risk category from baseline to last follow-up. All transitions occurred in an outpatient setting either as abrupt stop/start or cross-titration, without parenteral treprostinil bridging.\u0000\u0000\u0000CONCLUSION\u0000Transition from selexipag to oral treprostinil was safe, performed without parenteral prostacyclin bridging, and resulted in clinical and categorical risk improvements in some patients.","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48971892","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":"Amygdalin epimers exert discrepant anti-pulmonary fibrosis activity via inhibiting TGF-β1/Smad2/3 pathway.","authors":"Haoyan Jiao, Shuyu Li, Qing-fa Tang","doi":"10.2139/ssrn.4357033","DOIUrl":"https://doi.org/10.2139/ssrn.4357033","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) represents a chronic and progressive tissue repair response that leads to irreversible scarring and lung remodelling. The decoction of bitter almond usually contains amygdalin epimers in traditional clinical application for lung disease. To reveal the differences of cytotoxicity and antifibrotic effect between amygdalin epimers, and potential mechanism is also explored. The cytotoxicity of amygdalin epimers were evaluated with MRC-5 cells in vitro. Their antifibrotic activities were evaluated in bleomycin-induced C57BL/6 mice and TGF-β1-induced MRC-5 cells. Here we demonstrated that L-amygdalin is more toxic of the amygdalin epimers in MRC-5 cells, and D-amygdalin is more effective in anti-pulmonary fibrosis among the amygdalin epimers in bleomycin-induced C57BL/6 mice. Herein, it was observed that D-amygdalin had a stronger inhibitory effect on inflammation than L-amygdalin, and had similar results in inhibiting the mRNA and protein expression levels of fibrosis-related biomarkers. The mechanism of anti-pulmonary fibrosis showed that amygdalin epimers suppressing expression of phosphorylation of Smads2/3, which implying deactivation of the TGF-β1induced Smads2/3 signal pathway. This study evaluates the amygdalin epimers cytotoxicity and antifibrotic effect, and its mechanisms were related to the TGF-β1/Smads2/3 signal pathway. It provides a reference for clinical safety and effectiveness of amygdalin epimers.","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45923832","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":"Transcriptional factor MAZ promotes cisplatin-induced DNA damage repair in lung adenocarcinoma by regulating NEIL3","authors":"Tao Wang,&nbsp;Xu Zhu,&nbsp;Kai Wang,&nbsp;Jianglun Li,&nbsp;Xiao Hu,&nbsp;Peng Lin,&nbsp;Jian Zhang","doi":"10.1016/j.pupt.2023.102217","DOIUrl":"10.1016/j.pupt.2023.102217","url":null,"abstract":"<div><h3>Background</h3><p><span>Cisplatin remains a common chemotherapy </span>drug<span><span><span> for lung adenocarcinoma (LUAD) in clinical </span>treatment. Long-term use of cisplatin </span>in patients<span> may lead to acquired drug resistance, resulting in poor prognoses of patients. NEIL3 was a glycosylase-encoding gene highly expressed in LUAD. NEIL3 can repair telomerase DNA damage in the S phase. Nevertheless, there are few reports on whether NEIL3 is involved in cisplatin resistance and its related mechanisms in LUAD.</span></span></p></div><div><h3>Methods</h3><p><span><span>The expression of NEIL3 in LUAD patients was analyzed by bioinformatics. The regulator upstream of NEIL3 was predicted via hTFtarget. The possibly involved pathways of NEIL3 were obtained by performing Gene Set Enrichment Analysis. qRT-PCR and </span>western blot were applied to test the expression level of genes and protein LUAD cells. Dual</span><strong>-</strong><span>luciferase<span> assay and chromatin immunoprecipitation (ChIP) assay were conducted to validate the binding relationship between MAZ and NEIL3. Cell function assays were performed to test the DNA damage, cell viability, cell migration and invasion, and cell cycle of LUAD cells in the treatment group.</span></span></p></div><div><h3>Results</h3><p><span>NEIL3 and its upstream regulatory factor MAZ were highly expressed in LUAD tissue, and NEIL3 was enriched in cell cycle and mismatch repair pathways. Dual-luciferase assay and ChIP assay proved that MAZ could target NEIL3. Cell experiments identified that MAZ/NEIL3 axis could repress DNA damage to advance cisplatin resistance of </span>cancer cells, and foster cell migration and invasion in LUAD.</p></div><div><h3>Conclusion</h3><p>MAZ-activated NEIL3 could propel the cisplatin resistance in LUAD by repressing DNA damage.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9628173","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":"Combination of pioglitazone, a PPARγ agonist, and synthetic surfactant B-YL prevents hyperoxia-induced lung injury in adult mice lung explants","authors":"Chie Kurihara ,&nbsp;Reiko Sakurai ,&nbsp;Tsai-Der Chuang ,&nbsp;Alan J. Waring ,&nbsp;Frans J. Walther ,&nbsp;Virender K. Rehan","doi":"10.1016/j.pupt.2023.102209","DOIUrl":"10.1016/j.pupt.2023.102209","url":null,"abstract":"<div><h3>Introduction</h3><p>Hyperoxia-induced lung injury is characterized by acute alveolar injury, disrupted epithelial-mesenchymal signaling, oxidative stress<span>, and surfactant dysfunction, yet currently, there is no effective treatment<span>. Although a combination of aerosolized pioglitazone<span> (PGZ) and a synthetic lung surfactant (B-YL peptide, a surfactant protein B mimic) prevents hyperoxia-induced neonatal rat lung injury, whether it is also effective in preventing hyperoxia-induced adult lung injury is unknown.</span></span></span></p></div><div><h3>Method</h3><p>Using adult mice lung explants, we characterize the effects of 24 and 72-h (h) exposure to hyperoxia<span><span> on 1) perturbations in Wingless/Int (Wnt) and Transforming Growth Factor (TGF)-β signaling pathways, which are critical mediators of lung injury, 2) aberrations of lung </span>homeostasis and injury repair pathways, and 3) whether these hyperoxia-induced aberrations can be blocked by concomitant treatment with PGZ and B-YL combination.</span></p></div><div><h3>Results</h3><p>Our study reveals that hyperoxia exposure to adult mouse lung explants causes activation of Wnt (upregulation of key Wnt signaling intermediates β-catenin and LEF-1) and TGF-β (upregulation of key TGF-β signaling intermediates TGF-β type I receptor (ALK5) and SMAD 3) signaling pathways accompanied by an upregulation of myogenic proteins (calponin and fibronectin) and inflammatory cytokines (IL-6, IL-1β, and TNFα), and alterations in key endothelial (VEGF-A and its receptor FLT-1, and PECAM-1) markers. All of these changes were largely mitigated by the PGZ + B-YL combination.</p></div><div><h3>Conclusion</h3><p>The effectiveness of the PGZ + B-YL combination in blocking hyperoxia-induced adult mice lung injury ex-vivo is promising to be an effective therapeutic approach for adult lung injury in vivo.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10205668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9635436","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":"Chronic inhaled antibiotic therapy in people with cystic fibrosis with Pseudomonas aeruginosa infection in Germany","authors":"S. Naehrig ,&nbsp;B. Schulte-Hubbert ,&nbsp;S. Hafkemeyer ,&nbsp;J. Hammermann ,&nbsp;M. Dumke ,&nbsp;S. Sieber ,&nbsp;Registry working group of the German CF Registry ,&nbsp;L. Naehrlich","doi":"10.1016/j.pupt.2023.102214","DOIUrl":"10.1016/j.pupt.2023.102214","url":null,"abstract":"<div><h3>Background</h3><p>Several clinical guidelines recommend chronic inhaled therapy for pwCF (people with cystic fibrosis) and chronic <span><em>Pseudomonas</em><em> aeruginosa</em></span> infection of the lungs.</p></div><div><h3>Methods</h3><p>To demonstrate what kind of therapy regimens are used in Germany, we retrospectively analysed chronic inhaled antibiotic therapy within the cohort of the German CF Registry in 2020. For comparison we also analysed the use of inhaled antibiotics in pwCF with intermittent Pseudomonas or without Pseudomonas infection.</p></div><div><h3>Results</h3><p>A total of 1960 pwCF had chronic <span><em>P. aeruginosa</em></span><span> infection and were retrospectively evaluated. Almost 90% (n = 1751) received at least one inhaled antibiotic. The most commonly used inhaled antibiotic was colistin<span><span><span> solution for inhalation (55.2%), followed by aztreonam solution for inhalation (32.6%) and </span>tobramycin solution for Inhalation (30%). Almost 56% of adults and 44% of children alternated two antibiotics for inhalation. In children, alternating colistin + tobramycin was the most often used regimen. In adults, only 23% used colistin + tobramycin; there was a wide range of </span>treatment regimens among adults using two inhaled antibiotics alternately. 2456 pwCF had no Pseudomonas infection, but almost 24% had a chronic inhaled antibiotic therapy, while 56% of 361 pwCF and intermittent chronic Pseudomonas infection had a chronic inhaled antibiotic therapy.</span></span></p></div><div><h3>Conclusion</h3><p>In all three groups the most commonly used inhaled antibiotic was colistin solution for inhalation. Almost 56% of adults and 44% of children with chronic Pseudomonas infection alternated two antibiotics for inhalation. It will be interesting to see how the introduction of the highly effective modulator elexacaftor/tezacaftor/ivacaftor will change the use of inhaled antibiotics.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9639823","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":"Inhibition of poly (ADP-ribose) Polymerase-1 (PARP-1) improves endothelial function in pulmonary hypertension","authors":"Mohammad Shafiq ,&nbsp;Zahid Rasool Lone ,&nbsp;Adam Olaitan Abdulkareem ,&nbsp;Gurpreet Kaur ,&nbsp;Sai Navya ,&nbsp;Himalaya Singh ,&nbsp;Kumaravelu Jagavelu ,&nbsp;Kashif Hanif","doi":"10.1016/j.pupt.2023.102200","DOIUrl":"10.1016/j.pupt.2023.102200","url":null,"abstract":"<div><p><span><span><span>Endothelial dysfunction is critical in the </span>pulmonary vasculature<span> during pulmonary hypertension (PH). Moreover, in PH, increased inflammation and oxidative/nitrosative stress cause DNA damage, activating poly (ADP-ribose) polymerase-1 (PARP-1). Meloche et al. (2014) and our previous research have shown that inhibiting PARP-1 is protective in PH and associated RV hypertrophy. However, the role of PARP-1 in pulmonary arterial endothelial dysfunction has not been explored completely. Therefore, the current study aims to investigate the involvement of PARP-1 in endothelial dysfunction associated with PH. </span></span>Hypoxia<span><span><span> (1% O2) was used to induce a PH-like phenotype in human pulmonary artery endothelial cells<span> (HPAECs), and PARP-1 inhibition was achieved via siRNA (60 nM). For the in vivo study, male </span></span>Sprague Dawley rats<span><span> were administered monocrotaline (MCT; 60 mg/kg, SC, once) to induce PH, and 1, 5-isoquinolinediol (ISO; 3 mg/kg) was administered daily intraperitoneally to inhibit PARP-1. PARP-1 inhibition decreased proliferation and inflammation, as well as improved mitochondrial dysfunction in hypoxic HPAECs. Furthermore, PARP-1 inhibition also promoted </span>apoptosis<span><span> by increasing DNA damage in hypoxic HPAECs. In addition, inhibition of PARP-1 reduced cell migration, VEGF expression, and tubule formation in hypoxic HPAECs. In in vivo studies, PARP-1 inhibition by ISO significantly decreased the RVP and </span>RVH as well as improved </span></span></span>endothelial function by increasing the pulmonary </span></span>vascular reactivity and expression of p-eNOS in MCT-treated rats.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9627143","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":"Remote preconditioning combined with nebulized budesonide alleviate lipopolysaccharide induced acute lung injury via regulating HO-1 and NF-κB in rats","authors":"Liang Zhao ,&nbsp;Zhuo Chen ,&nbsp;Jing Cheng ,&nbsp;Baojun Chen ,&nbsp;Yong Liu","doi":"10.1016/j.pupt.2023.102215","DOIUrl":"10.1016/j.pupt.2023.102215","url":null,"abstract":"<div><h3>Background</h3><p>Acute lung injury (ALI) may result in severe systemic inflammation and is life-threatening. Remote inflammatory preconditioning (RIPC) has been confirmed to have an endogenous protective effect against ALI. Budesonide (BS) is a potent corticosteroid typically administered through nebulization that reduces inflammation in the lungs. We speculate that the combined use of RIPC and nebulized BS has a stronger protective effect on ALI.</p></div><div><h3>Methods</h3><p>48 Sprague-Dawley male rats were used for the experiments. Animals were divided evenly and randomly into three groups, control (NS injection), LPS (LPS injection), and RIPC (LPS injection with RIPC). Each group was then divided into two subgroups with inhalation of nebulized normal saline (NS) or BS. Prior to injection of LPS, RIPC was performed by tying and untying the right hind limb for three cycles of 5 min each. Following LPS injection, animals in each subgroup were placed in a same cage for nebulized inhalation. Animals were sacrificed 6 h after LPS injection. Histological evaluation of ALI and lung wet-to-dry weight ratio were measured. Serum lactate acid, inflammatory cytokines, oxidative stress indicators were detected. The expression of HO-1, NF-κB p65 and p-p65 was measured by western blotting.</p></div><div><h3>Results</h3><p>RIPC combined with nebulized BS significantly attenuated the LPS-induced ALI in rats. Reduction of MDA, increasing of SOD activity were found significantly improved by the joint strategy. TNF- and IL-1β rise brought on by LPS was reduced, but IL-10 production dramatically enhanced when compared to the LPS group. The expression of HO-1 was significantly increased by RIPC combined with nebulized BS while the expression of NF-κB p65 and p-p65 was decreased when compared with the LPS group.</p></div><div><h3>Conclusion</h3><p>RIPC combined with nebulized budesonide is protective for ALI induced by LPS in rats.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9627674","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":"Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea","authors":"Hyuna Noh ,&nbsp;Suhyeon Yoon ,&nbsp;Sung-Hee Kim ,&nbsp;Jiseon Kim ,&nbsp;Jung Seon Seo ,&nbsp;Jeong Jin Kim ,&nbsp;In Ho Park ,&nbsp;Jooyeon Oh ,&nbsp;Joon-Yong Bae ,&nbsp;Gee Eun Lee ,&nbsp;Sun-Je Woo ,&nbsp;Sun-Min Seo ,&nbsp;Na-Won Kim ,&nbsp;Youn Woo Lee ,&nbsp;Hui Jeong Jang ,&nbsp;Seung-Min Hong ,&nbsp;Se-Hee An ,&nbsp;Kwang-Soo Lyoo ,&nbsp;Minjoo Yeom ,&nbsp;Hanbyeul Lee ,&nbsp;Je Kyung Seong","doi":"10.1016/j.pupt.2023.102189","DOIUrl":"10.1016/j.pupt.2023.102189","url":null,"abstract":"<div><p>Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9636184","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":"Activating transcription factor 6 in the endothelial context","authors":"Nektarios Barabutis","doi":"10.1016/j.pupt.2023.102216","DOIUrl":"10.1016/j.pupt.2023.102216","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10043875","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":"Inhaled nebulised unfractionated heparin (UFH) for the treatment of hospitalised patients with COVID-19: A randomised controlled pilot study","authors":"Gilberto DeNucci ,&nbsp;Tom Wilkinson ,&nbsp;Carlos Sverdloff ,&nbsp;Tainah Babadopulos ,&nbsp;Ashley Woodcock ,&nbsp;Jan Shute ,&nbsp;Pedro Renato Guazelli ,&nbsp;Luis Frederico Gerbase ,&nbsp;Paulo A.S. Mourão ,&nbsp;Dave Singh ,&nbsp;Frank M.P. van Haren ,&nbsp;Clive Page","doi":"10.1016/j.pupt.2023.102212","DOIUrl":"10.1016/j.pupt.2023.102212","url":null,"abstract":"<div><p>There is a strong scientific rationale to use nebulised unfractionated heparin (UFH) in treating patients with COVID-19. This pilot study investigated whether nebulised UFH was safe and had any impact on mortality, length of hospitalisation and clinical progression, in the treatment of hospitalised patients with COVID-19. This parallel group, open label, randomised trial included adult patients with confirmed SARS-CoV-2 infection admitted to two hospitals in Brazil. One hundred patients were planned to be randomised to either “standard of care” (SOC) or SOC plus nebulized UFH. The trial was stopped after randomisation of 75 patients due to falling COVID-19 hospitalisation rates. Significance tests were 1-sided test (10% significance level). The key analysis populations were intention to treat (ITT) and modified ITT (mITT) which excluded (from both arms) subjects admitted to ITU or who died within 24 h of randomisation.</p><p>In the ITT population (n = 75), mortality was numerically lower for nebulised UFH (6 out of 38 patients; 15.8%) versus SOC (10 out of 37 patients; 27.0%), but not statistically significant; odds ratio (OR) 0.51, p = 0.24. However, in the mITT population, nebulised UFH reduced mortality (OR 0.2, p = 0.035).</p><p>Length of hospital stay was similar between groups, but at day 29, there was a greater improvement in ordinal score following treatment with UFH in the ITT and mITT populations (p = 0.076 and p = 0.012 respectively), while mechanical ventilation rates were lower with UFH in the mITT population (OR 0.31; p = 0.08). Nebulised UFH did not cause any significant adverse events. In conclusion, nebulised UFH added to SOC in hospitalised patients with COVID-19 was well tolerated and showed clinical benefit, particularly in patients who received at least 6 doses of heparin.</p><p>This trial was funded by The J.R. Moulton Charity Trust and registered under REBEC RBR-8r9hy8f (UTN code: U1111-1263-3136).</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9635461","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}