Pulmonary pharmacology & therapeutics最新文献

{"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}

{"title":"Pulmonary drug delivery for acute respiratory distress syndrome","authors":"Qinqin Fei ,&nbsp;Ian Bentley ,&nbsp;Samir N. Ghadiali ,&nbsp;Joshua A. Englert","doi":"10.1016/j.pupt.2023.102196","DOIUrl":"10.1016/j.pupt.2023.102196","url":null,"abstract":"<div><p>The acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes respiratory failure. Despite numerous clinical trials, there are no molecularly targeted pharmacologic therapies to prevent or treat ARDS. Drug delivery during ARDS is challenging due to the heterogenous nature of lung injury and occlusion of lung units by edema fluid and inflammation. Pulmonary drug delivery during ARDS offers several potential advantages including limiting the off-target and off-organ effects and directly targeting the damaged and inflamed lung regions. In this review we summarize recent ARDS clinical trials using both systemic and pulmonary drug delivery. We then discuss the advantages of pulmonary drug delivery and potential challenges to its implementation. Finally, we discuss the use of nanoparticle drug delivery and surfactant-based drug carriers as potential strategies for delivering therapeutics to the injured lung in ARDS.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9209620","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":"An open label trial of nemiralisib, an inhaled PI3 kinase delta inhibitor for the treatment of Activated PI3 kinase Delta Syndrome","authors":"Malcolm Begg ,&nbsp;Augustin Amour ,&nbsp;Emily Jarvis ,&nbsp;Teresa Tang ,&nbsp;Sara Santos Franco ,&nbsp;Andrew Want ,&nbsp;Misba Beerahee ,&nbsp;Disala Fernando ,&nbsp;Yakshitha Karkera ,&nbsp;Clare Sander ,&nbsp;Thomas Southworth ,&nbsp;Dave Singh ,&nbsp;Jonathan Clark ,&nbsp;Sergey Nejentsev ,&nbsp;Klaus Okkenhaug ,&nbsp;Alison Condliffe ,&nbsp;Anita Chandra ,&nbsp;Anthony Cahn ,&nbsp;Edward Banham Hall","doi":"10.1016/j.pupt.2023.102201","DOIUrl":"10.1016/j.pupt.2023.102201","url":null,"abstract":"<div><p>Activated PI3Kδ Syndrome (APDS) is a rare inherited inborn error of immunity caused by mutations that constitutively activate the p110 delta isoform of phosphoinositide 3-kinase (PI3Kδ), resulting in recurring pulmonary infections. Currently no licensed therapies are available. Here we report the results of an open-label trial in which five subjects were treated for 12 weeks with nemiralisib, an inhaled inhibitor of PI3Kδ, to determine safety, systemic exposure, together with lung and systemic biomarker profiles (Clinicaltrial.gov: NCT02593539).</p><p>Induced sputum was captured to measure changes in phospholipids and inflammatory mediators, and blood samples were collected to assess pharmacokinetics of nemiralisib, and systemic biomarkers.</p><p>Nemiralisib was shown to have an acceptable safety and tolerability profile, with cough being the most common adverse event, and no severe adverse events reported during the study. No meaningful changes in phosphatidylinositol (3,4,5)-trisphosphate (PIP3; the enzyme product of PI3Kδ) or downstream inflammatory markers in induced sputum, were observed following nemiralisib treatment. Similarly, there were no meaningful changes in blood inflammatory markers, or lymphocytes subsets. Systemic levels of nemiralisib were higher in subjects in this study compared to previous observations.</p><p>While nemiralisib had an acceptable safety profile, there was no convincing evidence of target engagement in the lung following inhaled dosing and no downstream effects observed in either the lung or blood compartments. We speculate that this could be explained by nemiralisib not being retained in the lung for sufficient duration, suggested by the increased systemic exposure, perhaps due to pre-existing structural lung damage.</p><p>In this study investigating a small number of subjects with APDS, nemiralisib appeared to be safe and well-tolerated. However, data from this study do not support the hypothesis that inhaled treatment with nemiralisib would benefit patients with APDS.</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":"9208235","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":"Up-regulation of PPAR-γ involved in the therapeutic effect of icariin on cigarette smoke-induced inflammation","authors":"Qiuping Li ,&nbsp;Hongying Zhang ,&nbsp;Xinpeng Yan ,&nbsp;Zhengxiao Zhao ,&nbsp;Jian Qiu ,&nbsp;Lingli Hu ,&nbsp;Shan Jiang ,&nbsp;Qing kong ,&nbsp;Jing Sun ,&nbsp;Lulu Li","doi":"10.1016/j.pupt.2023.102197","DOIUrl":"10.1016/j.pupt.2023.102197","url":null,"abstract":"<div><p><span><span>Icariin (ICA) might be a potential anti-inflammatory medication in a variety of </span>diseases including COPD, and previous studies showed that ICA could attenuate cigarette smoke (CS)-induced inflammation by inhibiting nuclear factor (NF)-κB. Peroxisome proliferator-activated receptor (PPAR) γ, a </span>nuclear hormone receptor<span><span>, has been reported to play a critical role in the inflammatory process in COPD. Whether PPAR-γ is involved in the anti-inflammatory effect of icariin on COPD has scarcely been explored. This study aimed at investigating the role of ICA in PPAR-γ expression in the CS-induced model, and then elucidating the therapeutic effects of ICA on COPD based on the PPARγ–NF–κB signaling pathway. The Beas-2B cells and H292 cells were induced with cigarette smoke extract (CSE) for 8 h after </span>treatment<span> with ICA for 16 h. The PPARγ expression and NF-κB pathway-related indicators were detected by western blotting<span>, cellular immunofluorescence<span><span>, and Real-time PCR. The PPARγ knock down or T0070907-treated Beas-2B cells were constructed to further investigate the relationship between the inhibition of NF-κB by ICA and PPARγ. A COPD model was established by CS exposure for 6 months, and ICA (40 mg/kg) was administrated by gastric perfusion. Then, the pulmonary function, lung histology, inflammatory cytokine levels, and </span>protein expressions<span> were detected. We found ICA up-regulated PPARγ protein expression in both Beas-2B cells and H292 cells, and it improved CSE-induced PPARγ down regulation and NF-κB activation. Furthermore, the inhibition of NF-κB pathway by ICA was partially dependent on PPARγ in the PPARγ knock down or T0070907-treated Beas-2B cells, suggesting that ICA attenuated CSE-induced inflammatory responses were associated with modulating the PPARγ–NF–κB pathway. Moreover, ICA showed similar effects on PPARγ and NF-κB expressions in the COPD model, and it effectively ameliorated the pulmonary function and lung inflammatory infiltration in the COPD rat model. Conclusively, the therapeutic effect of ICA on COPD was indirectly achieved by reducing airway inflammation, which was partially associated with modulating the PPARγ–NF–κB signaling pathway.</span></span></span></span></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":"9255348","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":"A retro-inverso modified peptide alleviated ovalbumin-induced asthma model by affecting glycerophospholipid and purine metabolism of immune cells","authors":"Shumei Ma ,&nbsp;Kuan Yang ,&nbsp;Zhihong Li ,&nbsp;Liang Li ,&nbsp;Yue Feng ,&nbsp;Xiaowei Wang ,&nbsp;Jiahui Wang ,&nbsp;Zhengdan Zhu ,&nbsp;Zhiyong Wang ,&nbsp;Juan Wang ,&nbsp;Yizhun Zhu ,&nbsp;Li Liu","doi":"10.1016/j.pupt.2022.102185","DOIUrl":"10.1016/j.pupt.2022.102185","url":null,"abstract":"<div><p>Allergic asthma is a heterogeneous disease involving a variety of inflammatory cells. Immune imbalance or changes in the immune microenvironment are the essential causes that promote inflammation in allergic asthma. Tetraspanin CD81 can be used as a platform for receptor clustering and signal transmission owing to its special transmembrane structure and is known to participate in the physiological processes of cell proliferation, differentiation, adhesion, and migration. Previous studies have shown that CD81-targeting peptidomimetics exhibit anti-allergic lung inflammation. However, due to the low metabolic stability of peptide drugs, their druggability is limited. Here, we aimed to generate a metabolically stable anti-CD81 peptide, evaluate its anti-inflammatory action and establish its mechanism of action. Based on previous reports, we applied retro-inverse peptide modification to obtain a new compound, PD00 (NH2-D-Gly-D-Ser-D-Thr-D-Tyr-D-Thr-D-Gln-D-Gly-COOH), with high metabolic stability. Enhanced ultraperformance liquid chromatography–tandem mass spectrometry was used to investigate the in vitro and in vivo metabolic stabilities of PD00. The affinities of PD00 and CD81 were studied using molecular docking and surface plasmon resonance techniques. An ovalbumin (OVA)-induced asthma model was used to evaluate the effects of PD00 in vivo. Mice were treated with different concentrations of PD00 (175 and 350 μg/kg) for 10 days. Airway hyperresponsiveness (AHR) to acetyl-β-methacholine (Mch), inflammatory cell counts in the bronchoalveolar lavage fluid, and serum OVA-specific IgE levels were detected in the mice at the end of the experiment. Lung tissues were collected for haematoxylin and eosin staining, untargeted metabolomic analysis, and single-cell transcriptome sequencing. PD00 has a high affinity for CD81; therefore, administration of PD00 markedly ameliorated AHR and airway inflammation in mice after OVA sensitisation and exposure. Serum OVA-specific IgE levels decreased considerably. In addition, PD00 treatment increased glycerophospholipid and purine metabolism in immune cells. Collectively, PD00 may regulate the glycerophospholipid and purine metabolism pathways to ameliorate the pathophysiological features of asthma. These findings suggest that PD00 is a potential compound for the treatment of asthma.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10574219","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":"β-sitosterol targets glucocorticoid receptor to reduce airway inflammation and remodeling in allergic asthma","authors":"Jianfeng Xu ,&nbsp;Lei Yang ,&nbsp;Tiantian Lin","doi":"10.1016/j.pupt.2022.102183","DOIUrl":"10.1016/j.pupt.2022.102183","url":null,"abstract":"<div><h3>Introduction</h3><p>In most asthma patients, symptoms are controlled by treatment<span> with glucocorticoid<span>, but long-term or high-dose use can produce adverse effects. Therefore, it is crucial to find new therapeutic strategies. β-sitosterol could suppress type Ⅱ inflammation in ovalbumin (OVA)-induced mice, but its mechanisms have remained unclear.</span></span></p></div><div><h3>Methods</h3><p><span><span><span>A binding activity of β-sitosterol with </span>glucocorticoid receptor<span> (GR) was analyzed by molecular docking. Human bronchial epithelial cells (BEAS-2B) and human bronchial </span></span>smooth muscle cells<span> (HBSMC) were treated with different concentrations (0, 1, 5, 10, 20, and 50 μg/mL) of β-sitosterol for suitable concentration selection. In transforming growth factor (TGF)-β1 treated BEAS-2B and HBSMC, cells were treated with 20 μg/mL β-sitosterol or dexamethasone (Dex) to analyze its possible mechanism. In OVA-induced mice, 2.5 mg/kg β-sitosterol or Dex administration was performed to analyze the therapeutic mechanism of β-sitosterol. A </span></span>GR antagonist<span><span> RU486 was used to confirm the mechanism of β-sitosterol in the </span>treatment of asthma.</span></p></div><div><h3>Results</h3><p><span>A good binding of β-sitosterol to GR (score = −8.2 kcal/mol) was found, and the GR expression was upregulated with β-sitosterol dose increase in BEAS-2B and HBSMC. Interleukin (IL)-25 and IL-33 secretion was significantly decreased by β-sitosterol in the TGF-β1-induced BEAS-2B, and the levels of collagen 1A and α-smooth muscle actin (SMA) were reduced in the TGF-β1-induced HBSMC. In the OVA-challenged mice, β-sitosterol treatment improved airway inflammation and remodeling through suppressing type Ⅱ immune response and collagen deposition. The therapeutic effects of β-sitosterol were similar to Dex treatment </span><em>in vitro</em> and <em>in vivo.</em> RU486 treatment clearly hampered the therapeutic effects of β-sitosterol in the TGF-β1-induced cells and OVA-induced mice.</p></div><div><h3>Conclusion</h3><p><span>This study identified that β-sitosterol binds GR to perform its functions in asthma treatment. β-sitosterol represent a potential therapeutic drug for </span>allergic asthma.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194438","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":"Impact of beta blockers on resting respiratory rate in older adults: A cross-sectional study","authors":"Atsushi Takayama ,&nbsp;Takashi Yoshioka ,&nbsp;Takahiko Nagamine","doi":"10.1016/j.pupt.2022.102186","DOIUrl":"10.1016/j.pupt.2022.102186","url":null,"abstract":"<div><p>[Purpose] Beta blockers, commonly prescribed for older adults, affect heart rates and blood pressure and may reduce respiratory rates, which are used to evaluate patient status and predict outcomes. However, limited clinical evidence is available on the impact of beta blockers on respiratory rates. This study aimed to investigate the impact of beta blockers on respiratory rates in older adults.</p><p><span>[Methods] This cross-sectional study included patients aged ≥60 years who underwent an annual checkup. Patients were excluded if they had a diagnosis of severe heart failure, chronic obstructive pulmonary disease, </span>interstitial pneumonitis<span>, severe anemia, or neurodegenerative disease. Doubly robust estimation with inverse probability weighting was applied to estimate the mean differences between beta blocker users and non-users. The dose-response relationship between the administered beta blockers and respiratory rates was examined using multivariable regression models.</span></p><p>[Results] Of 637 participants, 108 had received beta blockers regularly. The adjusted mean differences (95% confidence interval, CI) in respiratory rates, pulse rates, systolic blood pressure<span>, and diastolic blood pressure<span> between beta blocker users and non-users were 0.35 (−0.68 to 1.37), −3.56 (−6.34 to −0.78), −5.53 (−8.53 to −2.52), and −4.70 (−8.27 to −1.14), respectively. The adjusted mean differences (95% CI) in respiratory rates per 1 mg of a carvedilol equivalent dose in all beta blocker users, liposoluble beta blocker users, and carvedilol users were −0.10 (−0.18 to −0.02), −0.35 (−0.59 to −0.11), and −0.29 (−0.54 to −0.06), respectively.</span></span></p><p>[Conclusions] Beta blockers may dose-dependently reduce the respiratory rates of older adults. However, in clinical settings, the impact of beta-blocker use or non-use on the respiratory rate may not occur at a clinically important level. Clinicians should note the potentially suppressive impact of beta blockers on respiratory rates according to the situation.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9124972","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":"Efficacy and safety of non-prostanoid prostacyclin receptor agonist for pulmonary hypertension: A meta-analysis","authors":"Pengwei Wang ,&nbsp;Hongyan Feng ,&nbsp;Yongli Guo ,&nbsp;Nan Wu ,&nbsp;Honglei Yin ,&nbsp;Yongxiang Zhang ,&nbsp;Sujuan Pei ,&nbsp;Jianlian Gao ,&nbsp;Yizhong Lu ,&nbsp;Yang Hu ,&nbsp;Yongheng Zhang ,&nbsp;Zhijian Deng","doi":"10.1016/j.pupt.2022.102182","DOIUrl":"10.1016/j.pupt.2022.102182","url":null,"abstract":"<div><h3>Background</h3><p>Oral non-prostanoid prostacyclin receptor<span><span> agonists therapies have been recommended for </span>pulmonary arterial hypertension in many countries.</span></p></div><div><h3>Objective</h3><p>We aimed to evaluate the specific impact of non-prostanoid prostacyclin receptor agonists on pulmonary hypertension and to explore the influence of study characteristics on results.</p></div><div><h3>Methods</h3><p>PubMed, Embase, and <span>ClinicalTrials.gov</span><svg><path></path></svg><span> were systematically searched from inception to July 12, 2022. Randomized controlled trials comparing non-prostanoid prostacyclin receptor agonists administration with placebo for treating pulmonary hypertension were included. Two researchers independently selected eligible studies, assessed the bias risk and extracted related data. RevMan5.1 was used for performing the statistical analysis and the assessment of bias risk of the enrolled studies. PROSPERO registered number CRD42022304172.</span></p></div><div><h3>Results</h3><p><span>Seven trials involving 1727 patients were included. Pooled analyses indicated non-prostanoid prostacyclin receptor agonists significantly reduced clinical worsening events (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54 to 0.74), increased 6-min walk distance (mean difference [MD], 10 m; 95% CI, 3–17 m), decreased pulmonary vascular resistance (MD, −121 dyn s/cm</span>⁵; 95% CI, −172 to −69 dyn s/cm⁵) and increased cardiac index (MD, 0.38 L/min/m²; 95% CI, 0.26–0.50 L/min/m²<span><span>) compared with the control. No significant differences in all-cause mortality (RR, 0.86; 95% CI, 0.26 to 2.78), NYHA/WHO functional class (RR, 1.16; 95% CI, 0.61 to 2.18), mean pulmonary artery pressure (MD, −0.88 mmHg; 95% CI, −2.20 to 0.44 mmHg), </span>right atrial pressure (MD, 0.66 mmHg; 95% CI, −0.59 to 1.90 mmHg) and total adverse events (RR, 1.05; 95% CI, 0.99 to 1.10) were found between non-prostanoid prostacyclin receptor agonists group and control group.</span></p></div><div><h3>Conclusion</h3><p>Non-prostanoid prostacyclin receptor agonists treatment exerted benefits on clinical worsening, pulmonary vascular resistance, and cardiac index in pulmonary hypertension patients, without increasing the incidence of total adverse events.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10626166","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}