ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
Search Tips:
- Use the keyword search to search by keyword or author's name.
- Filter your search results by selecting the checkboxes that apply.
- Click on "Clear" to clear the form and start a new search. .
Search results will display below the form.
PT010 Treatment Ameliorates Chronic Obstructive Pulmonary Disease and Subsequent Development of Pulmonary Hypertension
Session Title
TP85 - TP085 A HARD DAY'S NIGHT - NOVEL MOLECULAR MECHANISMS AND TREATMENT OPTIONS IN PAH AND BEYOND: FROM PULMONARY VASCULATURE TO RV
Abstract
A3668 - PT010 Treatment Ameliorates Chronic Obstructive Pulmonary Disease and Subsequent Development of Pulmonary Hypertension
Author Block: R. Suraya1, T. Nagano1, G. R. T. Ryanto2, W. I. Effendi1, D. Hazama1, M. Yamamoto1, K. Kobayashi1, N. Emoto2, Y. Nishimura1; 1Respiratory Medicine, Kobe University, Kobe, Japan, 2Laboratory of Clinical Pharmaceutical Science, Kobe Pharmaceutical University, Kobe, Japan.
Introduction COPD has been a global health problem, causing high mortality and morbidity rate. One of the main contributors of COPD mortality is the presence of pulmonary hypertension (PH), where almost 20% of COPD patients develop COPD-PH that is caused by chronic hypoxia-driven pulmonary vascular remodeling. Unfortunately, no specific treatment has been found for this condition. Recently, three COPD drug classes, namely ICS, LAMA, and LABA were reported to have beneficial effects on the molecular process in the pulmonary vasculature cells related to vascular remodeling. Recently, a budesonide/formoterol/glycopyrronium inhalation therapy, termed PT010, clinically showed beneficial effects in improving the lung functions of COPD patients; however, its use in preventing COPD-PH has not been elucidated. Methods We induced emphysema as a COPD model in 8 weeks old female BALB/c mice via intratracheal elastase injection. We divided the experiments into three different termination time points to analyze the phases of COPD development: inflammatory (1 day post-elastase), emphysema (3 weeks post-elastase) and PH phase (4 weeks post-elastase). Treatments of PT010 and control groups consisting of vehicle, single drug class (budesonide/BUD, glycopyrronium/GLY or formoterol/FOR), and dual drug combinations (BUD+FOR and GLY+FOR) were started either just before elastase (for inflammation phase) or on day 7 (for emphysema phase) or day 14 (for PH phases). Appropriate phenotypic analysis, including bronchoalveolar lavage fluid (BALF), histological, hemodynamic, mRNA and protein expression level analysis, were performed in accordance to each phase. Results Elastase treatment induced acute inflammatory reaction evidenced by increased overall BALF cell count and protein level, in addition to an increase in neutrophil percentage and upregulation of tissue mRNA inflammatory markers. PT010 treatment was the most successful to abolish said pro-inflammatory phenotype comparable to control groups. In the emphysema phase, PT010 histologically ameliorated emphysematous lung structure induced by elastase treatment. Lastly, PT010 treatment prevented substantial increase in right ventricular systolic pressure and right ventricular hypertrophy observed in 4 weeks post-elastase mice, in addition to preventing echocardiographic decrease in pulmonary artery acceleration time. Conclusion We showed for the first time that PT010 administration is not only beneficial for treating COPD and COPD-PH condition. Further studies are warranted to establish PT010 as a COPD-PH treatment option.
Author Block: R. Suraya1, T. Nagano1, G. R. T. Ryanto2, W. I. Effendi1, D. Hazama1, M. Yamamoto1, K. Kobayashi1, N. Emoto2, Y. Nishimura1; 1Respiratory Medicine, Kobe University, Kobe, Japan, 2Laboratory of Clinical Pharmaceutical Science, Kobe Pharmaceutical University, Kobe, Japan.
Introduction COPD has been a global health problem, causing high mortality and morbidity rate. One of the main contributors of COPD mortality is the presence of pulmonary hypertension (PH), where almost 20% of COPD patients develop COPD-PH that is caused by chronic hypoxia-driven pulmonary vascular remodeling. Unfortunately, no specific treatment has been found for this condition. Recently, three COPD drug classes, namely ICS, LAMA, and LABA were reported to have beneficial effects on the molecular process in the pulmonary vasculature cells related to vascular remodeling. Recently, a budesonide/formoterol/glycopyrronium inhalation therapy, termed PT010, clinically showed beneficial effects in improving the lung functions of COPD patients; however, its use in preventing COPD-PH has not been elucidated. Methods We induced emphysema as a COPD model in 8 weeks old female BALB/c mice via intratracheal elastase injection. We divided the experiments into three different termination time points to analyze the phases of COPD development: inflammatory (1 day post-elastase), emphysema (3 weeks post-elastase) and PH phase (4 weeks post-elastase). Treatments of PT010 and control groups consisting of vehicle, single drug class (budesonide/BUD, glycopyrronium/GLY or formoterol/FOR), and dual drug combinations (BUD+FOR and GLY+FOR) were started either just before elastase (for inflammation phase) or on day 7 (for emphysema phase) or day 14 (for PH phases). Appropriate phenotypic analysis, including bronchoalveolar lavage fluid (BALF), histological, hemodynamic, mRNA and protein expression level analysis, were performed in accordance to each phase. Results Elastase treatment induced acute inflammatory reaction evidenced by increased overall BALF cell count and protein level, in addition to an increase in neutrophil percentage and upregulation of tissue mRNA inflammatory markers. PT010 treatment was the most successful to abolish said pro-inflammatory phenotype comparable to control groups. In the emphysema phase, PT010 histologically ameliorated emphysematous lung structure induced by elastase treatment. Lastly, PT010 treatment prevented substantial increase in right ventricular systolic pressure and right ventricular hypertrophy observed in 4 weeks post-elastase mice, in addition to preventing echocardiographic decrease in pulmonary artery acceleration time. Conclusion We showed for the first time that PT010 administration is not only beneficial for treating COPD and COPD-PH condition. Further studies are warranted to establish PT010 as a COPD-PH treatment option.
