Pulmonary pharmacology & therapeutics最新文献

{"title":"Development of an inhaled anti-TSLP therapy for asthma","authors":"Paul M. O'Byrne ,&nbsp;Reynold A. Panettieri Jr. ,&nbsp;Christian Taube ,&nbsp;Caterina Brindicci ,&nbsp;Margaret Fleming ,&nbsp;Pablo Altman","doi":"10.1016/j.pupt.2022.102184","DOIUrl":"10.1016/j.pupt.2022.102184","url":null,"abstract":"<div><p><span>Thymic stromal lymphopoietin<span><span><span> (TSLP), an epithelial cell-derived cytokine, acts as a key mediator in airway inflammation and modulates the function of multiple cell types, including dendritic cells and group 2 innate </span>lymphoid cells<span>. TSLP plays a role in asthma pathogenesis as an upstream cytokine, and data suggest that TSLP blockade with the anti-TSLP monoclonal antibody, </span></span>tezepelumab, could be efficacious in a broad asthma population. Currently approved asthma biologic therapies target allergic or </span></span>eosinophilic<span> disease and require phenotyping; therefore, an unmet need exists for a therapy that can address Type 2 (T2)-high and T2-low inflammation in asthma. All currently approved biologic treatments are delivered intravenously or subcutaneously; an inhaled therapy route that allows direct targeting of the lung with reduced systemic impact may offer advantages.</span></p><p><span>Currently in development, ecleralimab (CSJ117) represents the first inhaled anti-TSLP antibody fragment that binds soluble TSLP and prevents TSLP receptor activation, thereby inhibiting further inflammatory signalling cascades. This anti-TSLP antibody fragment is being developed for patients with severe uncontrolled asthma despite standard of care inhaled therapy. A Phase IIa proof of concept study, using allergen bronchoprovocation as a model for asthma exacerbations, found that ecleralimab was well-tolerated and reduced allergen-induced </span>bronchoconstriction in adult patients with mild asthma. These results suggest ecleralimab may be a promising, new therapeutic class for asthma treatment.</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":"9181570","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 house dust mite subcutaneous immunotherapy in polysensitized children with allergic asthma","authors":"Panpan Zhang ,&nbsp;Yuanyuan Jia ,&nbsp;Zenghui Jing,&nbsp;Jinli Huang,&nbsp;Huajie Wu,&nbsp;Xin Sun","doi":"10.1016/j.pupt.2022.102187","DOIUrl":"10.1016/j.pupt.2022.102187","url":null,"abstract":"<div><h3>Introduction</h3><p><span>The aim of this study was to compare the efficacy and safety of 3 years of HDM<span> subcutaneous immunotherapy (HDM-SCIT) in </span></span>allergic asthma (AA) children with mono- and polysensitized.</p></div><div><h3>Methods</h3><p>This was a retrospective observational study, 51 AA children (aged 4–14 years) who had completed 3 years of standardized HDM-SCIT were enrolled in. Based on skin prick tests (SPT) and allergen-specific IgE antibody<span><span><span> (sIgE) test results, children were classified into two groups: the monosensitized group (n = 31) and the polysensitized group (n = 20). Total asthma symptoms score (TASS), total medication score (TMS), visual analog scale (VAS) scores, fractional exhaled </span>nitric oxide (FeNO), lung function parameters, and adverse reactions were evaluated before </span>treatment and at 6 months, 1, 2, 3 years of HDM-SCIT.</span></p></div><div><h3>Results</h3><p>In terms of effectiveness, compared to baseline, TASS, TMS, VAS, FeNO and lung function parameters were significantly improved in both groups after 3 years of HDM-SCIT (all <em>P</em> &lt; 0.05). The comparison between the two groups showed that efficacy indicators were no statistically significant difference at follow-up time points (all <em>P</em> &gt; 0.05) except PEF%pred at 6 months (<em>P</em> = 0.048). In terms of security, the number of adverse reactions in both groups also no statistical difference between the two groups (all <em>P</em> &gt; 0.05).</p></div><div><h3>Conclusion</h3><p>This study confirmed that no significant difference was observed in the clinical efficacy and safety of HDM-SCIT between mono-and polysensitized children with 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":"9139393","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":"Patients with moderate to severe COVID-19 outcomes on remdesivir according to baseline 4C mortality score","authors":"Jacob Sellers ,&nbsp;Jongwha Chang ,&nbsp;Jessica Jones ,&nbsp;Trager D. Hintze","doi":"10.1016/j.pupt.2022.102188","DOIUrl":"10.1016/j.pupt.2022.102188","url":null,"abstract":"<div><h3>Background</h3><p>Remdesivir was the first antiviral to show clinical benefit in patients with moderate-to-severe COVID-19. Previous trials demonstrated a faster time to recovery in hospitalized patients treated with remdesivir vs placebo. Current guidelines recommend treatment with remdesivir based on hospitalization status, oxygen requirements, and time from symptom onset. However, other factors may be evaluated to determine disease severity and risk for progression. The 4C mortality score is a validated, eight variable score that may be used to categorize patients by mortality risk at the time of hospital admission for COVID pneumonia. The objective of this study was to determine if the 4C mortality score may be used to predict which patients with moderate to severe COVID-19 would benefit the most from remdesivir at the time of hospital admission.</p></div><div><h3>Methods</h3><p>This was a single-center retrospective cohort study comparing time to recovery among hospitalized patients with moderate-to-severe COVID-19 who were treated with remdesivir compared to those who were treated with standard of care (SOC). The primary outcome was time to recovery, defined as discharge from the hospital or no longer requiring supplemental oxygen, stratified by the 4C mortality score risk group. Secondary outcomes included in-hospital mortality, hospital length of stay, and time to recovery in patients who were started on remdesivir within 7 days from symptom onset vs after 7 days from symptom onset. A survival analysis was used to analyze time to recovery outcomes.</p></div><div><h3>Results</h3><p>Data was collected and analyzed for a total of 300 patients, of which 200 received remdesivir and 100 received SOC. Patients in the remdesivir group had a longer time to recovery compared to patients in the SOC group (6 days vs 4 days). This finding was driven by patients who were categorized to the intermediate risk and high risk mortality groups. Additionally, patients who received remdesivir had a longer length of hospital stay compared to those who received SOC (12 days vs 9 days). Remdesivir was not associated with an increased rate of adverse events.</p></div><div><h3>Conclusions</h3><p>This study of patients admitted with moderate-to-severe COVID-19 found that patients who were treated with remdesivir had a longer time to recovery and a longer length of stay compared to those who received SOC. These findings add to the body of evidence questioning the benefit of remdesivir therapy among patients hospitalized with COVID-19.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9196148","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":"Oncogenic lncRNA MALAT-1 recruits E2F1 to upregulate RAD51 expression and thus promotes cell autophagy and tumor growth in non-small cell lung cancer.","authors":"Rui Xin, Boqi Hu, Danhua Qu, Dawei Chen","doi":"10.1016/j.pupt.2023.102199","DOIUrl":"10.1016/j.pupt.2023.102199","url":null,"abstract":"<p><strong>Introduction: </strong>LncRNA MALAT-1 expression is involved in regulating activities of non-small-cell lung cancer (NSCLC) cells. This study aimed to investigate the effects of lncRNA MALAT-1 on chemosensitivity of NSCLC cells by regulating autophagy.</p><p><strong>Methods: </strong>We first validated the expression of lncRNA MALAT-1 in NSCLC cell lines. NSCLC cell lines with high lncRNA MALAT-1 expression were exposed to doxorubicin (DOX) to assess chemosensitivity. Further LncMAP database retrieval and ChIP, RIP and luciferase activity assays were conducted to explore interplay between lncRNA MALAT-1, RAD51, and E2F1. Immunofluorescence staining was performed to evaluate formation of autophagosomes in NSCLC cells. Ectopic expression and knockdown methods were used for in vitro mechanism experiments and in vivo substantiation.</p><p><strong>Results: </strong>LncRNA MALAT-1 was overexpressed in NSCLC cells, and could promote NSCLC cell autophagy and inhibit its chemosensitivity. In vitro cell mechanism verification experiments showed that lncRNA MALAT-1 could recruit transcription factor E2F1 to bind to the promoter of RAD51, so as to promote the transcriptional expression of RAD51. In addition, cell function experiments in vitro showed that ectopically expressed lncRNA MALAT-1 promoted NSCLC cell autophagy and inhibited its chemosensitivity, while RAD51 knockdown negated its effect. Finally, in vivo animal experiments confirmed that lncRNA MALAT-1 silencing could impede the tumor growth.</p><p><strong>Conclusions: </strong>Taken together, this study revealed that silencing lncRNA MALAT-1 enhanced chemosensitivity of NSCLC cells by promoting autophagy, highlighting a feasible approach to prevent chemoresistance in NSCLC treatment.</p>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10612723","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 house dust mite subcutaneous immunotherapy in polysensitized children with allergic asthma.","authors":"Panpan Zhang, Yuanyuan Jia, Z. Jing, Jinli Huang, Huajie Wu, Xin Sun","doi":"10.2139/ssrn.4249980","DOIUrl":"https://doi.org/10.2139/ssrn.4249980","url":null,"abstract":"INTRODUCTION\u0000The aim of this study was to compare the efficacy and safety of 3 years of HDM subcutaneous immunotherapy (HDM-SCIT) in allergic asthma (AA) children with mono- and polysensitized.\u0000\u0000\u0000METHODS\u0000This was a retrospective observational study, 51 AA children (aged 4-14 years) who had completed 3 years of standardized HDM-SCIT were enrolled in. Based on skin prick tests (SPT) and allergen-specific IgE antibody (sIgE) test results, children were classified into two groups: the monosensitized group (n = 31) and the polysensitized group (n = 20). Total asthma symptoms score (TASS), total medication score (TMS), visual analog scale (VAS) scores, fractional exhaled nitric oxide (FeNO), lung function parameters, and adverse reactions were evaluated before treatment and at 6 months, 1, 2, 3 years of HDM-SCIT.\u0000\u0000\u0000RESULTS\u0000In terms of effectiveness, compared to baseline, TASS, TMS, VAS, FeNO and lung function parameters were significantly improved in both groups after 3 years of HDM-SCIT (all P < 0.05). The comparison between the two groups showed that efficacy indicators were no statistically significant difference at follow-up time points (all P > 0.05) except PEF%pred at 6 months (P = 0.048). In terms of security, the number of adverse reactions in both groups also no statistical difference between the two groups (all P > 0.05).\u0000\u0000\u0000CONCLUSION\u0000This study confirmed that no significant difference was observed in the clinical efficacy and safety of HDM-SCIT between mono-and polysensitized children with allergic asthma.","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44977180","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":"Considerations into pharmacogenomics of COVID-19 pharmacotherapy: Hope, hype and reality","authors":"Anmar AL-Taie ,&nbsp;Ayşe Şeyma Büyük ,&nbsp;Semra Sardas","doi":"10.1016/j.pupt.2022.102172","DOIUrl":"10.1016/j.pupt.2022.102172","url":null,"abstract":"<div><p>COVID-19 medicines, such as molnupiravir are beginning to emerge for public health and clinical practice. On the other hand, drugs display marked variability in their efficacy and safety. Hence, COVID-19 medicines, as with all drugs, will be subject to the age-old maxim “one size prescription does not fit all”. In this context, pharmacogenomics is the study of genome-by-drug interactions and offers insights on mechanisms of patient-to-patient and between-population variations in drug efficacy and safety. Pharmacogenomics information is crucial to tailoring the patients' prescriptions to achieve COVID-19 preventive and therapeutic interventions that take into account the host biology, patients’ genome, and variable environmental exposures that collectively influence drug efficacy and safety. This expert review critically evaluates and summarizes the pharmacogenomics and personalized medicine aspects of the emerging COVID-19 drugs, and other selected drug interventions deployed to date. Here, we aim to sort out the hope, hype, and reality and suggest that there are veritable prospects to advance COVID-19 medicines for public health benefits, provided that pharmacogenomics is considered and implemented adequately. Pharmacogenomics is an integral part of rational and evidence-based medical practice. Scientists, health care professionals, pharmacists, pharmacovigilance practitioners, and importantly, patients stand to benefit by expanding the current pandemic response toolbox by the science of pharmacogenomics, and its applications in COVID-19 medicines and clinical trials.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10397627","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":"SRSF1 promotes ASMC proliferation in asthma by competitively binding CCND2 with miRNA-135a","authors":"Ya-li Guo ,&nbsp;Zhuo-chang Chen ,&nbsp;Nan Li ,&nbsp;Cui-jie Tian ,&nbsp;Dong-jun Cheng ,&nbsp;Xue-yi Tang ,&nbsp;Luo-xian Zhang ,&nbsp;Xiao-yu Zhang","doi":"10.1016/j.pupt.2022.102173","DOIUrl":"10.1016/j.pupt.2022.102173","url":null,"abstract":"<div><h3>Background</h3><p><span>Asthma is an inflammatory syndrome characterized by airway hyperresponsiveness<span>, bronchial inflammation, and airway remodeling. Abnormal proliferation of </span></span>airway smooth muscle cells<span> (ASMCs) is the main pathological feature of asthma. This study investigated the function and mechanism of serine arginine-rich splicing factor 1 (SRSF1) in ASMC proliferation in asthma.</span></p></div><div><h3>Methods</h3><p><span>SRSF1 expressions in the bronchi of ovalbumin-induced asthmatic mice and IgE-treated mouse ASMCs (mASMCs) were evaluated using quantitative real-time PCR and Western blot. The localization and expression of SRSF1 in the bronchi of asthmatic mice were assessed by </span>immunohistochemistry<span>. Functionally, gain- and loss-of-function assays, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were conducted. Mechanistically, RNA degradation<span> assay, RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter gene assays were carried out.</span></span></p></div><div><h3>Results</h3><p>SRSF1 was highly expressed in the bronchi of ovalbumin-induced asthma mice and IgE-treated mASMCs and was mainly located in the nucleus. Experiments on the function of SRSF1 showed that the silencing of SRSF1 induced the cell cycle of mASMC arrest and restrained mASMC proliferation. Investigations into the mechanism of SRSF1 revealed that SRSF1 and miR-135a are competitively bound to the 3′UTR region of Cyclin D2 (CCND2). SRSF1 overexpression repressed the degradation of CCND2 mRNA, and miR-135a negatively regulated CCND2 expression. Furthermore, SRSF1 knockdown inhibited ASMC proliferation in asthma mouse models by regulating the levels of miR-135a and CCND2.</p></div><div><h3>Conclusion</h3><p>SRSF1 knockdown repressed ASMC proliferation in asthma by regulating miR-135a/CCND2 levels.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10710731","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":"Allopurinol treatment reduced vascular remodeling and improved vascular functions in monocrotaline-induced pulmonary hypertensive rats","authors":"Telli Gokcen ,&nbsp;Kazkayasi Inci ,&nbsp;Ergonul E. Inci ,&nbsp;Onder Sevgen ,&nbsp;Uma Serdar","doi":"10.1016/j.pupt.2022.102166","DOIUrl":"10.1016/j.pupt.2022.102166","url":null,"abstract":"<div><p><span><span>Increased oxidative stress<span> and high uric acid<span> are implicated in the pathogenesis of pulmonary hypertension (PH). This provides opportunity to benefit from </span></span></span>drugs<span><span><span> like allopurinol<span> which suppresses both contributing factors. Therefore, we aimed to investigate the effects of allopurinol in preventing as well as reversing the pathological changes occurring in monocrotaline (MCT)-induced rat model of PH. Male rats were assigned into three groups based on the follow-up time: 7, 21 and 35 days. Time-matched controls of each group received single injections of MCT (60 mg/kg) intraperitoneally. Test groups consisted of rats who were treated with MCT on day 0 plus oral allopurinol (60 mg/kg) daily for 7 or 21 days. 35-day group received allopurinol for two weeks starting on the 22nd day following MCT injection. At the end of all-time points, rats were killed and basal pulmonary perfusion pressure, Fulton index, pulmonary arterial wall thickness and pulmonary arterial relaxations along with oxidative stress markers (MDA, </span></span>SOD<span>, XO), NO and uric acid levels were measured in all groups. MCT-injected rats had evidence of raised oxidative stress (high </span></span>MDA<span> and XO, low SOD levels) which was reversed by allopurinol co-treatment in all-time groups. Marked elevation of uric acid seen in 21- and 35 day-groups was also reversed by allopurinol. Reduced NO levels of 21 and 35 days were unchanged in allopurinol treated groups. Apart from an increase in </span></span></span>arterial wall thickening<span> which was maintained in all-time groups, no alterations in other cardiovascular parameters were observed in 7-day group. However, basal lung perfusion pressure and Fulton index significantly increased, while arterial relaxations decreased in 21- and 35-day groups. Co-treatment with allopurinol for 21 days improved these functional alterations, whereas late allopurinol treatment failed to affect them. Our results indicate that early treatment of MCT-induced PH with allopurinol ameliorated the impaired functional characteristics via suppressing the increased oxidative stress and uric acid, while treatment started after progression of the disease had no significant effect.</span></p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10358617","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":"Treatment of respiratory viral infections through inhalation therapeutics: Challenges and opportunities","authors":"Nidhi Nainwal","doi":"10.1016/j.pupt.2022.102170","DOIUrl":"10.1016/j.pupt.2022.102170","url":null,"abstract":"<div><p>Respiratory viral infections are the leading cause of death worldwide. The current pandemic of coronavirus infection (COVID-19) challenged human beings for the treatment and prevention of this respiratory viral infection since its outbreak in 2019. Despite advancements in the medical field, scientists were helpless to give timely treatment and protection against this viral infection. Several drugs, whether antiviral or not, were given to the patients to reduce mortality and morbidity rate. Vaccines from various pharmaceutical manufacturers are now available to give immunization against covid-19. Still, coronavirus is continuously affecting people in the form of variants after mutation. Each new variant increases the infection risk and forces scientists to develop some innovative and effective treatments for this infection. The virus uses the host's cell machinery to grow and multiply in numbers. Therefore, scientists are facing challenges to develop antivirals that stop the virus without damaging the host cells too. The production of suitable antivirals or vaccines for the new virus would take several months, allowing the strain to cause severe damage to life. Inhalable formulation facilitates the delivery of medicinal products directly to the respiratory system without causing unwanted side effects associated with systemic absorption. Scientists are focusing on developing an inhaled version of the existing antivirals for the treatment of respiratory infections. This review focused on the inhalable formulations of antiviral agents in various respiratory viral infections including the ongoing covid-19 pandemic and important findings of the clinical studies. We also reviewed repurposed drugs that have been given through inhalation in covid-19 infection.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10388907","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":"Effect of daily dosing with tiotropium against methacholine induced bronchoconstriction in asthmatics","authors":"Beth E. Davis,&nbsp;Donald W. Cockcroft","doi":"10.1016/j.pupt.2022.102174","DOIUrl":"10.1016/j.pupt.2022.102174","url":null,"abstract":"<div><h3>Introduction</h3><p>Loss of bronchoprotection against direct and indirect acting stimuli following regular use of inhaled beta₂<span><span><span><span>-agonists occurs with both short and long-acting formulations. Comparatively little is known about the development of tolerance following regular use of inhaled muscarinic receptor antagonists. Two investigations with the short-acting muscarinic receptor antagonist </span>ipratropium bromide have reported no tolerance after regular use against inhaled </span>methacholine<span>. To our knowledge, there are no data regarding loss of bronchoprotection following regular use of long-acting muscarinic receptor antagonist. We therefore looked at the effect of daily dosing with tiotropium on </span></span>methacholine induced bronchoconstriction in a population of mild asthmatics.</span></p></div><div><h3>Methods</h3><p>We performed a randomized, double-blind, placebo-controlled cross-over study comparing tiotropium Respimat® 5 μg to placebo in adult asthmatics. Each treatment arm began with baseline methacholine challenge followed immediately by treatment administration. One hour later a post treatment methacholine challenge was performed. Participants dosed daily (two puffs) at home for the next six days and returned to the lab on Day 8 for a final dose of treatment 1 h prior to methacholine challenge.</p></div><div><h3>Results</h3><p><span>The average doubling dose increase in methacholine PD</span>₂₀ following a single dose of tiotropium was 3.9 doubling doses whereas that following placebo was 0.93 (p = 0.003). After regular use, methacholine PD₂₀ was further increased to 6.4 doubling doses following tiotropium whereas that following placebo decreased by 0.57 doubling doses (p &lt; 0.001).</p></div><div><h3>Conclusion</h3><p><span>LAMA are indicated for use as add-on monotherapy or in triple therapy combination for poorly controlled asthma. It may be reassuring to know therefore, that regular use does not result in loss of bronchoprotection like that which occurs with beta</span>₂<span>-agonist bronchodilators.</span></p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10710762","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}