scholarly journals Riociguat for treatment of pulmonary hypertension in COPD: a translational study

2019 ◽  
Vol 53 (6) ◽  
pp. 1802445 ◽  
Author(s):  
Alexandra Pichl ◽  
Natascha Sommer ◽  
Mariola Bednorz ◽  
Michael Seimetz ◽  
Stefan Hadzic ◽  
...  

Chronic obstructive pulmonary disease (COPD), which comprises the phenotypes of chronic bronchitis and emphysema, is often associated with pulmonary hypertension (PH). However, currently, no approved therapy exists for PH-COPD. Signalling of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) axis plays an important role in PH and COPD.We investigated the treatment effect of riociguat, which promotes the NO–cGMP pathway, in the mouse model of smoke-induced PH and emphysema in a curative approach, and retrospectively analysed the effect of riociguat treatment on PH in single patients with PH-COPD.In mice with established PH and emphysema (after 8 months of cigarette smoke exposure), riociguat treatment for another 3 months fully reversed PH. Moreover, histological hallmarks of emphysema were decreased. Microarray analysis revealed involvement of different signalling pathways, e.g. related to matrix metalloproteinases (MMPs). MMP activity was decreased in vivo by riociguat. In PH-COPD patients treated with riociguat (n=7), the pulmonary vascular resistance, airway resistance and circulating MMP levels decreased, while oxygenation at rest was not significantly changed.Riociguat may be beneficial for treatment of PH-COPD. Further long-term prospective studies are necessary to investigate the tolerability, efficacy on functional parameters and effect specifically on pulmonary emphysema in COPD patients.

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Jie Yang ◽  
Chuanmei Liu ◽  
Lingling Li ◽  
Xiongwen Tu ◽  
Zhiwei Lu

Purpose. This study aims at investigating the predictive value of red blood cell distribution width (RDW) in pulmonary hypertension (PH) secondary to chronic obstructive pulmonary disease (COPD). Methods. 213 eligible in-hospital COPD patients were reviewed between May 2016 and May 2018, including 39 cases with PH and 174 without PH. Clinical data including demographic characteristics, comorbidities, and results of ultrasound scans, imaging examinations, and laboratory tests were recorded. Results. Increased RDW level was observed in COPD patients with PH compared with COPD patients without PH, with 15.10 ± 1.72% versus 13.70 ± 1.03%, respectively (p<0.001). RDW shared positive relationships with brain natriuretic peptide (BNP) (p=0.001, r = 0.513), pulmonary artery (PA) systolic pressure (p=0.014, r = 0.390), and PA-to-ascending aorta (A) ratio (PA : A) (p=0.001, r = 0.502). Multivariate analysis indicated that RDW, BNP, and PA : A > 1 were the independent risk factors of PH secondary to COPD (p<0.05). The AUC of the RDW in patients with PH was 0.749 ± 0.054 (p<0.001). The optimal cutoff value of RDW for predicting PH was 14.65, with a sensitivity and a specificity value of 69.2% and 82.8%, respectively. Conclusion. RDW is significantly increased in COPD patients with PH and thus may be a useful biomarker for PH secondary to COPD.


Author(s):  
Somayeh Ghadimi ◽  
Atefeh Fakharian ◽  
Mohsen Abedi ◽  
Reyhaneh Zahiri ◽  
Mahsan Norouz Afjeh ◽  
...  

Background: Chronic Obstructive Pulmonary Disease (COPD) leads to limited activity and reduced quality of life. Treatment of this disease is a long-term process that requires the cooperation of patients in monitoring and treatment. Methods: In the present study which was conducted from April 2019 to March 2021 in Masih Daneshvari Hospital, Tehran, Iran, 75 patients were randomly divided into telerehabilitation and control groups. Patients in the control group received pulmonary rehabilitation including respiratory, isometric, and aerobic exercises for 8 weeks, three times per week. In the second group, patients were given a lung rehabilitation booklet and asked to repeat the exercises three times a week for four weeks according to a specific schedule. In addition, patients installed Behzee care application on the mobile phone that recorded various indicators such as heart rate, SpO2, dyspnea, fatigue, and daily activities. This application reminded the patient of the program every day and at a specific time. Finally, the patients’ conditions were compared in the two groups after 8 weeks using CAT and mMRC questionnaires and 6-Minute Walk (6MW) exercise indices as well as spirometry tests. Results: In all four indicators (6MW, CAT,  and mMRC questionnaires as well as spirometry), patients showed improvement after rehabilitation (p<0.001). This improvement was significantly higher in the telemedicine group compared to the other group (p<0.01). Conclusion: The use of telerehabilitation in COPD patients is effective in improving spirometry indices, quality of life, as well as activity and sports indices.


2021 ◽  
Vol 11 ◽  
Author(s):  
Chung-Yu Chen ◽  
Wen-Ting Wu ◽  
Ya-Ling Wang ◽  
Kuang-Ming Liao

Background: Patients with chronic obstructive pulmonary disease (COPD) are at risk for pulmonary hypertension (PH). The aim of our study was to investigate the benefit of statins for PH in patients with COPD.Methods: The study enrolled 23 million individuals from Taiwan’s population database from January 1, 2002, to December 31, 2017. COPD patients who met the inclusion criteria were enrolled, and patients with lung cancer, less than one year of observation, specific drug therapy for PH and lung transplantation were excluded.Results: A total of 643,131 COPD patients were included in the study, and only 12,308 patients developed PH during follow-up. Based on the inclusion and exclusion criteria, 8,577 PH patients were included in the cohort of patients with PH related to COPD for analysis. According to the definition of statin exposure, the final study population had 1,487 statin users and 7,090 statin non-users. The statin user group had a lower mortality related to PH than the non-user group (3.87 vs. 5.55 per 100 person-years, p &lt; 0.001). The mortality rate for PH in the multivariate analysis (aHR = 0.78, 95% CI = 0.62–0.98, p = 0.046) was significantly lower for statin users than for non-users.Conclusion: Statins seem to benefit patients with PH and COPD.


2019 ◽  
Vol 6 (4) ◽  
pp. 222-230
Author(s):  
Mariusz Tomaniak ◽  
Ply Chichareon ◽  
Kuniaki Takahashi ◽  
Norihiro Kogame ◽  
Rodrigo Modolo ◽  
...  

Abstract Aims To evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing percutaneous coronary interventions (PCIs) in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as adverse event (AE) that may lead to treatment non-adherence. Methods and results This is a non-prespecified, post hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. Impact of COPD and dyspnoea AE (as a time-dependent covariate) on clinical outcomes was evaluated up to 2 years. The primary endpoint was a 2-year all-cause mortality or non-fatal, centrally adjudicated, new Q-wave myocardial infarction. The presence of COPD (n = 832) was the strongest clinical predictor of 2-year all-cause mortality after PCI [hazard ratio (HR) 2.84; 95% confidence interval (CI) 2.21–3.66; P adjusted = 0.001] in this cohort (n = 15 991). No differential treatment effects on 2-year clinical outcomes were found in patients with and without COPD (primary endpoint: HR 0.88; 95% CI 0.58–1.35; P = 0.562; P int = 0.952). Overall, at 2 years dyspnoea was reported as an AE in 2101 patients, more frequently among COPD patients, irrespective of treatment allocation (27.2% in experimental arm vs. 14.5% in reference arm, P = 0.001). Its occurrence was not associated with a higher rate of the primary endpoint (P adjusted = 0.640) in the experimental vs. the reference arm. Conclusion In this exploratory analysis, COPD negatively impacted long-term prognosis after PCI. Despite higher incidence of dyspnoea in the experimental arm, in particular among COPD patients, the safety of the experimental treatment strategy appeared not to be affected. Clinical trial registration unique identifier NCT01813435.


2018 ◽  
Vol 4 (2) ◽  
pp. 00012-2018 ◽  
Author(s):  
Marieke L. Duiverman

Long-term noninvasive ventilation (NIV) to treat chronic hypercapnic respiratory failure is still controversial in severe chronic obstructive pulmonary disease (COPD) patients. However, with the introduction of high-intensity NIV, important benefits from this therapy have also been shown in COPD. In this review, the focus will be on the arguments for long-term NIV at home in patients with COPD. The rise of (high-intensity) NIV in COPD and the randomised controlled trials showing positive effects with this mode of ventilation will be discussed. Finally, the challenges that might be encountered (both in clinical practice and in research) in further optimising this therapy, monitoring and following patients, and selecting the patients who might benefit most will be reviewed.


2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Lidia Frejo ◽  
Daniel A. Grande

Abstract Congenital tracheomalacia and tracheal stenosis are commonly seen in premature infants. In adulthood, are typically related with chronic obstructive pulmonary disease, and can occur secondarily from tracheostomy, prolong intubation, trauma, infection and tumors. Both conditions are life-threatening when not managed properly. There are still some surgical limitations for certain pathologies, however tissue engineering is a promising approach to treat massive airway dysfunctions. 3D-bioprinting have contributed to current preclinical and clinical efforts in airway reconstruction. Several strategies have been used to overcome the difficulty of airway reconstruction such as scaffold materials, construct designs, cellular types, biologic components, hydrogels and animal models used in tracheal reconstruction. Nevertheless, additional long-term in vivo studies need to be performed to assess the efficacy and safety of tissue-engineered tracheal grafts in terms of mechanical properties, behavior and, the possibility of further stenosis development.


2017 ◽  
Vol 14 (2) ◽  
pp. 9-12
Author(s):  
Anish Hirachan ◽  
Arun Maskey ◽  
Ram Kishore Shah ◽  
Bishal KC ◽  
Miqdhaadh Shareef ◽  
...  

Background and Aims: Chronic obstructive pulmonary disease (COPD) is highly prevalent in the Nepalese population. It is associated with significant extrapulmonary effects among which cardiovascular complications are most common. Echocardiography evaluation mainly focused on effects on the right heart function is a salient tool to evaluate the presence of degree of pulmonary hypertension and also identify those group of patients who need more early aggressive therapy for the underling lung disease . We aimed to prospectively study the patients with diagnosed COPD with echocardiogram for evaluating the right heart.Methods: An observational, cross sectional study was done on 50 patients with COPD who were admitted at Bir Hospital and underwent echocardiographic evaluation from Dec 2015 –Dec 2016. All echocardiogaphic parameters focused on right heart and its function were assessed .Results: Out of total 50 COPD patients studied, majority of them were female (32 patients. 64%). The mean age group of the studied patients was 60.9 ±11.4 years. Pulmonary hypertension defined as sPAP>30 mmHg was evident in all of the patients ; with 30 patients (60% ), 14 (28 %) and 6(12 %) patients having severe, moderate and mild pulmonary hypertension respectively. RV dysfunction was evident with reduced average TAPSE values (1.59± 0.38 cm) and elevated RIMP values (0.58±0.16).Conclusion: Majority of COPD patients had evidence of pulmonary hypertension. Echocardiogram can be a helpful tool to assess early changes on the right heart size and function in patients with COPD and also monitor these patients for rapid progression of the illness.Nepalese Heart Journal 2017; Vol 14(2), 9-12


2008 ◽  
Vol 76 (8) ◽  
pp. 3481-3490 ◽  
Author(s):  
Paul J. Christensen ◽  
Angela M. Preston ◽  
Tony Ling ◽  
Ming Du ◽  
W. Bradley Fields ◽  
...  

ABSTRACT Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow obstruction and lung destruction with airspace enlargement. In addition to cigarette smoking, respiratory pathogens play a role in pathogenesis, but specific organisms are not always identified. Recent reports demonstrate associations between the detection of Pneumocystis jirovecii DNA in lung specimens or respiratory secretions and the presence of emphysema in COPD patients. Additionally, human immunodeficiency virus-infected individuals who smoke cigarettes develop early emphysema, but a role for P. jirovecii in pathogenesis remains speculative. We developed a new experimental model using immunocompetent mice to test the interaction of cigarette smoke exposure and environmentally acquired Pneumocystis murina infection in vivo. We hypothesized that cigarette smoke and P. murina would interact to cause increases in total lung capacity, airspace enlargement, and pulmonary inflammation. We found that exposure to cigarette smoke significantly increases the lung organism burden of P. murina. Pulmonary infection with P. murina, combined with cigarette smoke exposure, results in changes in pulmonary function and airspace enlargement characteristic of pulmonary emphysema. P. murina and cigarette smoke exposure interact to cause increased lung inflammatory cell accumulation. These findings establish a novel animal model system to explore the role of Pneumocystis species in the pathogenesis of COPD.


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