Pulmonary pharmacology & therapeutics最新文献

{"title":"Medication use in people with cystic fibrosis before and after modulator therapy","authors":"Louise Lord ,&nbsp;Mark Hew ,&nbsp;Miriam TY. Leung ,&nbsp;Jedidiah I. Morton ,&nbsp;Jenni Ilomaki","doi":"10.1016/j.pupt.2023.102264","DOIUrl":"https://doi.org/10.1016/j.pupt.2023.102264","url":null,"abstract":"<div><h3>Background</h3><p>Long-term changes in medication dispensings post cystic fibrosis transmembrane conductance regulator<span> (CFTR) modulator initiation have not been described. Our study aimed to investigate changes in medication use following the initiation of modulator therapy in people with cystic fibrosis (PwCF) in Australia.</span></p></div><div><h3>Methods</h3><p>Using a 10% sample of the Australian Pharmaceutical Benefits Scheme (PBS) data between 2013 and 2022, linear regression was used to analyse dispensings in PwCF who initiated any modulator (cases) and matched PwCF controls not dispensed a modulator. The difference in mean number of total monthly dispensings pre- and post-modulator initiation was analysed, with separate analyses by medication class.</p></div><div><h3>Results</h3><p>A total of 247 cases were matched 1:1 to controls (case and control median age 21 years (IQR: 13–32), 55.1% male). Immediately after modulator initiation, the mean number of dispensings was 0.9 higher in the modulator group, but then decreased to the level of controls after approximately 5 years. After 7.5 years, cases had decreased opioids compared to the pre-modulator period (β-coefficient: −0.00131, 95% CI: −0.00164, −0.00097) whilst controls did not (β: −0.00014, 95% CI: −0.00042, 0.00014). Over the same time period controls had an increase in psychotropics<span> (β: 0.00389, 95% CI:0.00295, 0.00484) whilst cases remained stable (β: −0.00014, 95% CI: −0.0006, 0.00031). Women's health medications increased in cases (β:0.00026, 95% CI:0.0001, 0.00042) but decreased in controls (β: 0.00044, 95% CI: 0.00063, −0.00025).</span></p></div><div><h3>Conclusions</h3><p>Modulator initiation in PwCF was associated with decreased dispensings of opioids and psychotropics, and increased dispensings of women's health medications, suggesting improved patient outcomes across multiple clinical domains.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102264"},"PeriodicalIF":3.2,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91956640","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 SIRT3 activator ganoderic acid D regulates airway mucin MUC5AC expression via the NRF2/GPX4 pathway","authors":"Jiancheng Wang ,&nbsp;Jiayao Li ,&nbsp;Yingying He ,&nbsp;Xiaochun Huang ,&nbsp;Jianguo Feng ,&nbsp;Li Liu ,&nbsp;Yulin Liu ,&nbsp;Xian Jiang ,&nbsp;Jing Jia","doi":"10.1016/j.pupt.2023.102262","DOIUrl":"10.1016/j.pupt.2023.102262","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span>The expression of MUC5AC, a highly prevalent </span>airway mucin, is regulated by stimulatory factors such as </span>oxidative stress<span><span>. Ganoderic acid D (GAD) activates mitochondrial deacetylase SIRT3. SIRT3 regulates mitochondrial function through deacetylation of </span>mitochondrial proteins, thereby playing a significant role in alleviating oxidative stress-related diseases. Therefore, this study aimed to investigate the mechanisms and rationale underlying the regulation of MUC5AC expression by GAD.</span></p></div><div><h3>Methods</h3><p><span>Human airway epithelial cells (NCI–H292) were exposed to pyocyanin (PCN) to establish an </span><em>in vitro</em><span> cell model of airway mucus hypersecretion. The expression of SIRT3, MUC5AC, and NRF2 pathway proteins in cells was assessed. Cellular mitochondrial morphology and oxidative stress markers were analyzed. C57BL/6 mice were induced with </span><span><em>Pseudomonas aeruginosa</em></span> (PA) to establish an <em>in vivo</em><span> mouse model of airway mucus hypersecretion. The expression of SIRT3 and MUC5AC in the airways was examined. In addition, the differential expression of target genes in the airway epithelial tissues of patients with chronic obstructive pulmonary disease (COPD) was analyzed using publicly available databases.</span></p></div><div><h3>Results</h3><p>The results revealed a significant upregulation of MUC5AC expression and a significant downregulation of SIRT3 expression in relation to airway mucus hypersecretion. GAD inhibited the overexpression of MUC5AC in PCN-induced NCI-H292 cells and PA-induced mouse airways by upregulating SIRT3. GAD activated the NRF2/GPX4 pathway and inhibited PCN-induced oxidative stress and mitochondrial morphological changes in NCI-H292 cells. However, ML385 inhibited the regulatory effects of GAD on MUC5AC expression.</p></div><div><h3>Conclusion</h3><p>The SIRT3 activator GAD downregulated MUC5AC expression, potentially through activation of the NRF2/GPX4 pathway. Accordingly, GAD may be a potential treatment approach for airway mucus hypersecretions.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"83 ","pages":"Article 102262"},"PeriodicalIF":3.2,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50162573","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":"Safety and efficacy of transitioning from selexipag to oral treprostinil in pulmonary arterial hypertension: Findings from the ADAPT registry","authors":"D. Lachant ,&nbsp;R. Minkin ,&nbsp;J. Swisher ,&nbsp;M. Mogri ,&nbsp;R. Zolty ,&nbsp;S. Hwang ,&nbsp;S. Seaman ,&nbsp;M. Broderick ,&nbsp;S. Sahay","doi":"10.1016/j.pupt.2023.102232","DOIUrl":"10.1016/j.pupt.2023.102232","url":null,"abstract":"<div><h3>Purpose</h3><p>Oral 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 tolerability issues 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.</p></div><div><h3>Methods</h3><p>ADAPT 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.</p></div><div><h3>Results</h3><p>Seven 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.</p></div><div><h3>Conclusion</h3><p>Transition from selexipag to oral treprostinil was safe, performed without parenteral prostacyclin bridging, and resulted in clinical and categorical risk improvements in some patients.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"82 ","pages":"Article 102232"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231170","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":"Real world outcomes of CFTR modulator therapy in Australian adults and children","authors":"Stephanie Kuek ,&nbsp;Angela McCullagh ,&nbsp;Eldho Paul ,&nbsp;David Armstrong","doi":"10.1016/j.pupt.2023.102247","DOIUrl":"10.1016/j.pupt.2023.102247","url":null,"abstract":"<div><h3>Background</h3><p>Recent advances in CFTR modulator therapy have the potential to change the face of cystic fibrosis (CF). This retrospective observational study describes real world experience of the four available CFTR modulators in adults and children with CF in a single centre in Melbourne, Australia.</p></div><div><h3>Method</h3><p>Data were collected for all patients treated with CFTR modulators at MonashCF between May 2012 and September 2020. Primary outcomes included lung function, admission days and BMI/BMI centile over time. Adverse events and reasons for changing or ceasing medications were also analysed.</p></div><div><h3>Results</h3><p><span>55% (74/133) adult and 46% (55/119) paediatric patients were treated with CFTR modulators. FEV1<span> increased in adults treated with ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) by 4.73% and 10.07% respectively, and </span></span>BMI also improved in these groups. Nutrition improved in adults and children treated with lumacaftor/ivacaftor (LUM/IVA). There was no significant improvement in FEV1 or admission days with LUM/IVA or tezacaftor/ivacaftor (TEZ/IVA). 36% (31/85) ceased LUM/IVA, due to adverse effects in 81% (25/31). Of these, 92% (23/25) changed to TEZ/IVA, 78% (18/23) without significant adverse effects.</p></div><div><h3>Conclusions</h3><p>Our findings for LUM/IVA and TEZ/IVA are less encouraging than those seen in clinical trials, with no significant improvement in lung function or admission days and a higher rate of adverse effects with LUM/IVA compared with phase 3 clinical trials. TEZ/IVA was generally well tolerated by those who experienced side effects with LUM/IVA. The small number of patients treated with ELX/TEZ/IVA had improvements in all parameters. These findings support ongoing use of IVA for individuals with gating mutations, and transition to ELX/TEZ/IVA once available for patients with at least one Phe508del mutation.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"82 ","pages":"Article 102247"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231712","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 statin treatment and exposure on the risk of chronic allograft dysfunction in Chinese lung transplant recipients","authors":"Dan Zhang ,&nbsp;Xiaoxing Wang ,&nbsp;Wenwen Du ,&nbsp;Wei Qin ,&nbsp;Wenqian Chen ,&nbsp;Xianbo Zuo ,&nbsp;Pengmei Li","doi":"10.1016/j.pupt.2023.102243","DOIUrl":"10.1016/j.pupt.2023.102243","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span>Chronic lung allograft dysfunction (CLAD) was a common complication following </span>lung transplantation that contributed to long-term morbidity and mortality. </span>Statin<span> therapy had been suggested to attenuate recipient inflammation and immune response, potentially reducing the risk and severity of CLAD. This study aimed to evaluate the impact of statin use and in vivo exposure on the incidence of CLAD in lung transplant recipients (LTRs), as well as their effects on immune cells and inflammatory factors.</span></p></div><div><h3>Methods</h3><p>A retrospective cohort study<span> was conducted on patients who underwent lung transplantation between January 2017 and December 2020. The incidence of CLAD, as per the 2019 ISHLT criteria, was assessed as the clinical outcome. The plasma concentrations of statin were measured using a validated UPLC-MS/MS method, while inflammation marker levels were determined using ELISA kits.</span></p></div><div><h3>Results</h3><p>The statin group exhibited a significantly lower rate of CLAD (P = 0.002). Patients receiving statin therapy showed lower CD4⁺<span> T-cell counts, total T-lymphocyte counts, and IL-6 levels (P = 0.017, P = 0.048, and P = 0.038, respectively). Among the CLAD groups, the atorvastatin level (2.51 ± 1.31 ng/ml) was significantly lower than that in the non-CLAD group (OR = 1.438, 95%CI (1.007–2.053), P = 0.046).</span></p></div><div><h3>Conclusion</h3><p>Statin therapy significantly reduced the incidence of CLAD, as well as immune cell counts and inflammatory cytokine levels in LTRs. Although the statin exposure was significantly lower in CLAD patients, it was not associated with the incidence of CLAD.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"82 ","pages":"Article 102243"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231175","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":"Safety and usefulness of nebulized liposomal amphotericin B: Systematic scoping review","authors":"Hideharu Hagiya ,&nbsp;Yoshito Nishimura ,&nbsp;Fumio Otsuka","doi":"10.1016/j.pupt.2023.102233","DOIUrl":"10.1016/j.pupt.2023.102233","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Invasive fungal infections<span><span> potentially result in fatal outcomes in immunocompromised hosts. Compared to </span>intravenous administration, a nebulization therapy can achieve a high concentration of </span></span>drug<span> delivered in the respiratory tract, without a systematic absorption. We herein summarized the study findings on the safety and clinical utility of nebulized liposomal amphotericin B therapy.</span></p></div><div><h3>Methods</h3><p>According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with relevant keywords, including “inhaled liposomal amphotericin B″, “nebulized liposomal amphotericin B″, or “aerosolized liposomal amphotericin B″, from the inception of these databases to August 31, 2022.</p></div><div><h3>Results</h3><p>Of the 172 articles found, 27 articles, including 13 case reports, 11 observational studies, and 3 clinical trials<span><span>, were selected. Generally, findings showed that nebulized liposomal amphotericin B treatment<span><span> appeared to be safe and without severe adverse effects. We found an accumulated evidence for the safety, tolerability, and effectiveness of nebulized liposomal amphotericin B prophylaxis among </span>lung transplantation recipients; however, a randomized controlled study has yet to be reported. Data on hemato-oncological patients are relatively scarce; however, a randomized controlled study suggested the prophylactic effect of nebulized liposomal amphotericin B on </span></span>invasive pulmonary aspergillosis. Observational and randomized controlled studies to evaluate therapeutic efficacy of the nebulized liposomal amphotericin B therapy have not been performed.</span></p></div><div><h3>Conclusion</h3><p><span>In conclusion, we found increasing evidence for the effectiveness of the inhalation therapy among patients after lung transplantation and with hemato-oncological </span>diseases.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"82 ","pages":"Article 102233"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10227220","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":"Serum exosomal m6A demethylase FTO promotes gefitinib resistance in non-small cell lung cancer by up-regulating FLRT3, PTGIS and SIRPα expression","authors":"Qi Wang ,&nbsp;Lin Zhang ,&nbsp;Zhenzhong Su ,&nbsp;Wei Li ,&nbsp;Yuxi Jia ,&nbsp;Jie Zhang","doi":"10.1016/j.pupt.2023.102227","DOIUrl":"10.1016/j.pupt.2023.102227","url":null,"abstract":"<div><p><span>This study investigates the molecular mechanism of FTO m6A demethylase in non-small cell lung cancer (NSCLC) and gefitinib<span> resistance using GEO and TCGA databases. Differentially expressed genes (DEGs) were screened from RNA-seq data sets of serum exosomes of gefitinib-resistant NSCLC patients in the GEO database and the NSCLC data set in the GEPIA2 database. From this analysis, FTO m6A demethylase was found to be significantly upregulated in the serum exosomes of gefitinib-resistant NSCLC patients. To identify downstream genes affected by FTO m6A demethylase, weighted correlation network analysis and differential expression analysis were performed, resulting in the identification of three key downstream genes (FLRT3, PTGIS, and SIRPA). Using these genes, the authors constructed a prognostic risk assessment model. Patients with high-risk scores exhibited a significantly worse prognosis. The model could predict the prognosis of NSCLC with high accuracy measured by AUC values of 0.588, 0.608, and 0.603 at 1, 3, and 5 years respectively. Furthermore, m6A sites were found in </span></span>FLRT3, PTGIS, and SIRPA genes, and FTO was significantly positively correlated with the expression of these downstream genes. Overall, FTO m6A demethylase promotes gefitinib resistance in NSCLC patients by upregulating downstream FLRT3, PTGIS, and SIRPA expression, with these three downstream genes serving as strong prognostic indicators.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"82 ","pages":"Article 102227"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10282148","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":"Assessing the relationship between cardiovascular and small airway disease and acute events in COPD: The ARCADIA study protocol","authors":"Paola Rogliani ,&nbsp;Dejan Radovanovic ,&nbsp;Josuel Ora ,&nbsp;Nadia Starc ,&nbsp;Stefano Verri ,&nbsp;Elena Pistocchini ,&nbsp;Luigino Calzetta","doi":"10.1016/j.pupt.2023.102231","DOIUrl":"10.1016/j.pupt.2023.102231","url":null,"abstract":"<div><p>The initial alterations of chronic obstructive pulmonary disease<span><span> (COPD) involve the small airways. Small airway disease<span><span> (SAD) is related to lung hyperinflation and air trapping. Several </span>lung function tests<span><span> may detect the presence of SAD, namely forced mid-expiratory flows, residual volume<span> (RV), RV/total lung capacity (TLC) ratio, functional residual capacity, </span></span>airway resistances obtained with body-plethysmography and </span></span></span>oscillometry<span><span>, and the single-breath nitrogen washout test. Additionally, high-resolution computed tomography can detect SAD. In addition to SAD, COPD is related to cardiovascular disease (CVD) such as heart failure, </span>peripheral vascular disease<span>, and ischemic heart disease. No studies have assessed the relationship between CVD, COPD, and SAD. Therefore, the main objective of the Assessing the Relationship between Cardiovascular and small Airway Disease and Acute events in COPD (ARCADIA) study is to assess the risk of CVD in COPD patients according to SAD in a real-life setting. The correlation between CVD, mortality, and acute exacerbation of COPD (AECOPD) is also evaluated.</span></span></span></p><p>ARCADIA is a 52-week prospective, multicentre, pilot, observational, cohort study conducted in ≥22 pulmonary centres in Italy and that enrols ≥500 COPD patients, regardless of disease severity (protocol registration: ISRCTN49392136). SAD is evaluated at baseline, after that CVD, mortality, and AECOPD are recorded at 6 and 12 months. Bayesian inference is used to quantify the risk and correlation of the investigated outcomes in COPD patients according to SAD.</p><p>The ARCADIA study provides relevant findings in the daily clinical management of COPD patients.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"82 ","pages":"Article 102231"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10227222","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":"Effects of elexacaftor-tezacaftor-ivacaftor on daily treatment burden and airflow obstruction in adults with cystic fibrosis","authors":"Angelica Tiotiu ,&nbsp;Iulia Ioan ,&nbsp;Yves Billon","doi":"10.1016/j.pupt.2023.102248","DOIUrl":"10.1016/j.pupt.2023.102248","url":null,"abstract":"<div><h3>Background</h3><p>The drug combination elexacaftor-tezacaftor-ivacaftor (ETI) proved highly effective in the improvement of the respiratory symptoms, the percentage of predicted forced expiratory volume<span> in 1 s (FEV1), and to reduce rates of pulmonary exacerbations in people with cystic fibrosis (CF) with at least one F508del mutation.</span></p><p>The objectives of the study were to evaluate the impact of ETI on the daily treatment burden due to patient decision and the evolution of lung function parameters at 6 months of treatment in real life.</p></div><div><h3>Methods</h3><p>A single-center observational study was realized including adult patients starting ETI therapy from March 10, 2020 to April 5, 2022. Clinical characteristics were collected at initiation (T0) and at 6 months (T6) of treatment. Outcome measures included names and number of chronic daily medications, respectively lung function parameters: FEV1, forced vital capacity<span><span> (FVC), FEV1/FVC ratio, peak expiratory flow (PEF), </span>forced expiratory flow at 25–75% of FVC (FEF25-75), β‐angle and FEF50/PEF ratio.</span></p></div><div><h3>Results</h3><p>Sixty-five patients were included with a mean age of 29.4 ± 8.5 years old, 48% of them F508del homozygous previously treated by lumacaftor-ivacaftor. At T6, the median number of daily medications decreased from 13 [2-24] to 9 [1-19] (p &lt; 0.001). All the studied functional respiratory parameters were improved: FEV1 +18%, FVC +14%, FEF25-75% + 18% (all p &lt; 0.001), as well the airflow obstruction: FEV1/FVC +6%, FEF50/PEF by 0.1 ± 0.1 and β‐angle by 10° ± 13° (all p ≤ 0.007).</p></div><div><h3>Conclusion</h3><p>ETI therapy can reduce the daily treatment burden in real-life at 6 months of treatment, increase a large number of lung function parameters and improve airflow obstruction.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"82 ","pages":"Article 102248"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231709","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":"Preventive effect of LCZ696 on hypoxic pulmonary hypertension in rats via regulating the PI3K/AKT signaling pathway","authors":"Jie Wang ,&nbsp;Yan-Rong Ma ,&nbsp;Ya-e Chang ,&nbsp;De-Long Duo ,&nbsp;Kun-Kun Duan ,&nbsp;Ni Zhao ,&nbsp;Wen-Li Cui ,&nbsp;Zhi-Lan Huan ,&nbsp;Ya-Feng Wang","doi":"10.1016/j.pupt.2023.102229","DOIUrl":"10.1016/j.pupt.2023.102229","url":null,"abstract":"<div><p><span>Hypoxic pulmonary hypertension (HPH) is a devastating disease worldwide; however, effective therapeutic </span>drugs<span><span><span><span> are lacking. This study investigated the effects and underlying mechanisms of LCZ696 </span>treatment on hypoxia-induced pulmonary hypertension. Male Sprague-Dawley (SD) rats were kept in a </span>hypobaric chamber with an oxygen concentration of 5% for 4 weeks. Rats were treated with either LCZ696 (18 mg/kg, 36 mg/kg, and 72 mg/kg) or </span>sildenafil<span>. The mean pulmonary artery pressure<span><span><span><span> (mPAP), right ventricle hypertrophy index (RVHI), and lung system index were measured. Hematoxylin-eosin (HE) staining, Masson staining, and </span>immunofluorescence<span> staining were used for histological analysis. Enzyme linked immunosorbent assay (ELISA) kits were used to determine the concentrations of inflammatory and hypoxia-related factors. </span></span>Western blotting<span><span><span> was used to examine the expression of apoptotic and PI3K/AKT signaling pathway proteins in rat lung tissue. Hypoxia increased mPAP, RVHI, and lung system index and induced pulmonary </span>vascular remodeling, pulmonary arteriomyosis, and pulmonary </span>artery fibrosis. LCZ696 treatment reduced the increase in mPAP, RVHI, and the lung system index and ameliorated the induced pathological changes. Hypoxia upregulated expression of NF-kB, TNF-α, IL-6, HIF-1α, and Vascular endothelial growth factor (VEGF), decreased the ratio of Bax/Bcl-2, and activated the PI3K/AKT signaling pathway in lung tissue, and these effects were partially reversed by treatment with LCZ696. These results demonstrated that LCZ696 can ameliorate hypoxia-induced HPH by suppressing </span></span>apoptosis, inhibiting the inflammatory response, and inhibiting the PI3K/AKT signaling pathway. It provides a reference for clinical rational drug use and lays a foundation for the study of HPH therapeutic drugs.</span></span></span></p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"82 ","pages":"Article 102229"},"PeriodicalIF":3.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230631","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}