Pulmonary pharmacology & therapeutics最新文献

{"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}

{"title":"Anlotinib prove to be a potential therapy for the treatment of pulmonary fibrosis complicated with lung adenocarcinoma","authors":"Shanshan Chen ,&nbsp;Dandi Gao ,&nbsp;Ronghao Sun ,&nbsp;Jiali Bao ,&nbsp;Chunya Lu ,&nbsp;Zihui Zhang ,&nbsp;Ting Xiao ,&nbsp;Xiaoting Gu ,&nbsp;Honggang Zhou","doi":"10.1016/j.pupt.2023.102202","DOIUrl":"10.1016/j.pupt.2023.102202","url":null,"abstract":"<div><p><span>Pulmonary fibrosis is a chronic </span>interstitial fibrosis<span><span><span> lung disease with high mortality, which is often complicated with lung cancer. The incidence of IPF complicated with lung cancer is getting higher and higher. At present, there is no consensus on the management and </span>treatment<span><span><span> of pulmonary fibrosis patients with lung cancer. There is an urgent need to develop preclinical drug evaluation methods for IPF with lung cancer and potential therapeutic </span>drugs<span><span><span> for IPF with lung cancer. The pathogenic mechanism of IPF is similar to that of lung cancer, and the multi-effect drugs with anticancer and anti-fibrosis will have potential value in the treatment of IPF complicated with lung cancer. In this study, we established an animal model of IPF complicated with lung cancer in situ to evaluate the therapeutic effect of the </span>antiangiogenic drug </span>anlotinib. The </span></span>pharmacodynamic<span> results in vivo showed that anlotinib could significantly improve the lung function of IPF-LC mice, reduce the content of collagen in lung tissue, increase the survival rate of mice, and inhibit the growth of lung tumor in mice. The results of Western blot and immunohistochemical analysis of lung tissue showed that anlotinib significantly inhibited the expression of fibrosis marker protein α-SMA, Collagen I and </span></span></span>Fibronectin<span><span> and tumor proliferation marker protein PCNA in mouse lung tissue, and down-regulated the content of serum tumor marker CEA. Through transcriptome<span> analysis, we found that anlotinib regulates MAPK signal pathway, PARP signal pathway and coagulation cascade signal pathway in lung cancer and pulmonary fibrosis, which all play an important role in lung cancer and pulmonary fibrosis. In addition, there is crosstalk between the signal pathway participated by the target of anlotinib and MAPK, JAK/STAT and </span></span>mTOR signal pathway. In summary, anlotinib will be a candidate for IPF-LC treatment.</span></span></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":"9627162","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":"Weight loss in nintedanib-treated patients with idiopathic pulmonary fibrosis","authors":"Hiromi Tomioka,&nbsp;Masaaki Iwabayashi,&nbsp;Makoto Yokota,&nbsp;Rika Hashimoto,&nbsp;Hisanori Amimoto","doi":"10.1016/j.pupt.2023.102213","DOIUrl":"10.1016/j.pupt.2023.102213","url":null,"abstract":"<div><p><span><span><span>Nintedanib is approved for the </span>treatment of </span>idiopathic pulmonary fibrosis<span><span><span><span> (IPF). Weight loss is recognized as an adverse event during nintedanib treatment, and is a common complication exploitable as a prognostic indicator of IPF. Here, we report a single-center, retrospective cohort study to assess </span>body weight changes during nintedanib therapy </span>in patients with IPF. Sixty-one patients treated with nintedanib for &gt;6 months were included (45 males, mean age ± standard deviation 73.1 ± 7.4 years). Baseline body weight and </span>body mass index were 60.1 ± 12.0 kg and 23.2 ± 3.5 kg/m</span></span>²<span>, respectively. Mean weight loss during the first 6 months of nintedanib treatment was significant (−3.2 ± 3.4 kg, p &lt; 0.0001) with Common Terminology Criteria for Adverse Events (CTCAE) grades 0,1,2 or 3 of 30, 17, 13 and 1, respectively. Pulmonary function test<span> records 6 months before nintedanib administration were available in a subset of patients (n = 40). Significant differences in weight change over the 6 months before-vs-after nintedanib administration were also observed in these patients [mean differences −2.5 ± 3.4 kg, 95% confidence interval (CI) −3.6, −1.4, p &lt; 0.0001]. Multivariate analysis showed that only baseline body weight was significantly associated with weight loss of CTCAE grade ≧2 (odds ratio 0.921, 95% CI 0.854, 0.994). Median follow-up from starting nintedanib was 34.8 months. There was a significant difference in overall survival between patients with CTCAE grade ≧2-vs-grade&lt;2 (median survival of 25.5 months and 55.2 months, p = 0.014). In the model adjusting for age, sex and lung function, weight loss CTCAE grade ≧2 was an independent predictor for all-cause mortality (hazard ratio 2.448, 95% CI 1.080–5.551). In conclusion, weight loss is an important issue for the management of patients with IPF treated with nintedanib.</span></span></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":"9689948","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":"Effect of roflumilast on airway remodeling in asthmatic mice exposed to or not exposed to cigarette smoke: Comparison with the effect of dexamethasone","authors":"Yukihisa Takeda ,&nbsp;Maki Takahashi ,&nbsp;Jun-ichi Fuchikami ,&nbsp;Hiroyuki Nakamura ,&nbsp;Kazutetsu Aoshiba","doi":"10.1016/j.pupt.2023.102198","DOIUrl":"10.1016/j.pupt.2023.102198","url":null,"abstract":"<div><p><span><span>Cigarette smoking constitutes a risk factor for severe asthma, which is frequently linked to remodeling of the airways. Appropriate drug </span>treatment<span><span> for smokers with asthma is uncertain because many smokers with asthma are less sensitive to glucocorticoid<span> treatment than non-smokers with asthma. The purpose of this study was to compare the anti-airway remodeling effects of dexamethasone (Dex) and </span></span>roflumilast<span><span> (Rof), a selective phosphodiesterases-4 inhibitor, in smoking and non-smoking mice with asthma. BALB/c mice were sensitized with ovalbumin<span> (OVA) and then challenged with OVA for two weeks, either with or without concurrent exposure to cigarette smoke (CS). Dex (1 mg/kg body weight), Rof (5 mg/kg body weight), or vehicle alone was given orally to the mice once daily. To assess the histopathological effects of airway remodeling<span>, lung tissue sections were obtained. Repeated OVA challenges resulted in fibrosis, </span></span></span>goblet cell hyperplasia, and thickening of the airway but not the </span></span></span>smooth muscle<span> layer. The presence of CS did not have an impact on the degree of airway remodeling brought on by repeated OVA challenges. In mice repeatedly exposed to OVA either with or without CS, Dex treatment reduced the remodeling alterations. In these mice group, the Rof Treatment had a less significant impact than the Dex treatment. Dex was still more effective than Rof at reducing airway remodeling in asthmatic smoking mice. According to the current study's findings, Dex effectively prevented airway remodeling in a two-week asthma model in mice exposed to CS or not. In contrast, we found that Rof had little to no inhibitory effect of Rof on the airway in our mouse model of asthma, whether or not it had been exposed to CS. We were unable to find solid proof to support CS-induced steroid resistance to treat airway remodeling.</span></p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9255352","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}