07 January 2022

This week in PVD

Could GLP-1 RAs improve COVID-19-induced pulmonary arterial hypertension?

Recent studies show that glucagon-like peptide-1 receptor agonists have anti-inflammatory effects in human and rodent pathological models, making them a potential therapeutic strategy for treating pulmonary arterial hypertension after COVID-19 infection.

Glucagon-like peptide-1 (GLP-1) is a hormone well-known for regulating blood sugar, and GLP-1 receptor agonists (GLP-1RAs) have been used in treatment for type 2 diabetes. But recent research shows that GLP-1RAs have anti-inflammatory effects in human and rodent models that might make them a novel therapeutic strategy for treating pulmonary arterial hypertension (PAH) after COVID-19 infection.

In many cases, patients with COVID-19 experience a cytokine storm — a systemic inflammatory syndrome caused by elevated levels of circulating cytokines. It is a leading cause of inflammatory lung damage, pneumonia, and death in COVID-19 patients. A recent article published in Medical Hypotheses noted that even in patients who recover from COVID-19, some studies show evidence of lung damage present after inflammatory biomarkers return to normal.

An autopsy of lung tissue from a COVID-19 patient revealed a thickened pulmonary vascular wall, which is a key characteristic of PAH. Therefore, author Jong Han Lee, of the Department of Marine Bio and Medical Science at Hanseo University in South Korea, presented the hypothesis that GLP-1RAs have the potential to play a role in combating COVID-19 in patients with characteristics of PAH.

Pulnovo medical announced results from PADN-CFDA pivotal trial for the treatment of pulmonary arterial hypertension (PAH) meet the efficacy primary endpoint

SHANGHAI, Jan. 1, 2022 /PRNewswire/ -- Pulnovo Medical Limited, a globally recognized device pioneer in treatment for cardiopulmonary disease, today announced the positive results from the Pulmonary Artery Denervation (PADN)-CFDA pivotal study, being the first global completed pulmonary hypertension treatment device RCT study. PADN is an innovative radiofrequency ablation technique in treating PH, was recognized as a CFDA innovative medical device in 2018, and designated as a "breakthrough device" by the US FDA in 2021. The data from the PADN-CFDA pivotal study meet the primary efficacy and safety endpoint.

About PH

Pulmonary Hypertension is defined as an increase in mean pulmonary arterial pressure (PAPm) ≥25 mmHg at rest as assessed by right heart catheterization (RHC), caused by different etiologies, which eventually lead to the right heart increased load, right heart failure and sudden death. The term PAH describes a group of PH patients characterized hemodynamically by the presence of pre-capillary PH, defined by a pulmonary artery wedge pressure (PAWP) ≤15 mmHg and a PVR.

As a pathological phenomenon, pulmonary hypertension includes a variety of diseases, such as left heart disease, lung disease, chronic pulmonary thrombosis and others. Many has considered PH as the "cancer" of cardiovascular disease, due to its low chance of survival rate. Without proper treatment, the average life span of patients is estimated to be 2.8 years.Previously, the existing treatments for patients with pulmonary hypertension mainly relied on targeted drugs and lung transplantation.

Fluticasone-based ICS, LABA therapy changes airway microbiome in COPD

Fluticasone-based inhaled corticosteroid treatment substantially changed airway microbiome diversity in patients with COPD, according to new data published in the American Journal of Respiratory and Critical Care Medicine.

“Inhaled corticosteroids, especially potent ones like fluticasone, can change the microbial communities (which are called microbiome) of airways of COPD patients, rendering them more susceptible for pneumonia,” Don D. Sin, MD, director and De Lazzari Family Chair at the Centre for Heart Lung Innovation, Canada Research Chair in COPD and professor of medicine in the division of respiratory medicine in the department of medicine at St. Paul’s Hospital, Vancouver, British Columbia, told Healio. “We were puzzled as to why the use of inhaled corticosteroids increased the risk of pneumonia in COPD patients. We hypothesized that these therapeutics would adversely change the airway microbiome of COPD patients.”

The study enrolled 63 clinically stable patients with COPD. Use of inhaled corticosteroid (ICS) was discontinued and substituted with formoterol (Teva) 12 µg twice daily. Patients were randomly assigned to receive budesonide/formoterol 400/12 µg (n = 20; mean age, 66.3 years; 85% men), fluticasone/salmeterol 250/50 µg (n = 22; mean age, 66 years; 77.3% men) or formoterol only 12 µg (n = 21; mean age, 62.5 years; 85.7% men), all twice daily for 12 weeks.

The primary outcome was the comparison of airway microbiome changes during 12 weeks between the ICS/long-acting beta agonist (LABA) and LABA only groups.

Low forced expiratory volume in chronic thromboembolic pulmonary hypertension

Lower forced expiratory volume is significantly correlated with obstruction seen on computed tomography angiogram (CTA) in patients with chronic thromboembolic pulmonary hypertension CTEPH). This was among the findings of a recent study published in the journal BMC Pulmonary Medicine.

In the current study, investigators hypothesized that etiological factors might be related to (1) the finding that individuals with CTEPH have lower forced expiratory volume in 1 second (FEV1) than healthy controls; and (2) the frequent clinical observation that individuals with CTEPH often show obstructive ventilatory impairment for unknown reasons.

Researchers therefore retrospectively analyzed CTEPH patients who had undergone a pulmonary function test and respiratory impedance test to evaluate their exertional dyspnea during admission for right heart catheterization between January 2000 and December 2019. Patients with a smoking history were excluded, in order to rule out the effect of smoking on obstructive impairment.

Exacerbation history, dyspnea severity predicts future COPD events

History of exacerbations, as well as severity of dyspnea, may predict future exacerbations in patients with COPD, according to results of an observational study published in Respiratory Medicine.

Researchers conducted an observational study that included 96,462 adults from the Copenhagen General Population Study; of those, 13,380 adults had COPD. The researchers evaluated the risk for moderate and severe exacerbations from 2003 to 2013 based on COPD exacerbation history, dyspnea score, and the presence or absence of maintenance treatment with inhaled long-acting bronchodilators and/or inhaled corticosteroids.

During follow-up, those with COPD had 1,543 moderate exacerbations and 348 severe exacerbations.

In both treatment-naive individuals and those on maintenance treatment, history of exacerbations and dyspnea, though to a smaller degree, were associated with increased risk for future exacerbations. A moderate exacerbation in the following year occurred in 32% of treatment-naive individuals with a dyspnea score of at least 2 and a single moderate exacerbation in the previous year compared with 3% of individuals with a similar dyspnea severity but no previous exacerbations (HR = 6.26; 95% CI, 3.7-10.58).

Tenax plans phase 3 trial of TNX-201 for later this year

Tenax Therapeutics has completed a pharmacological assessment of TNX-201, the company’s new oral formulation of imatinib for pulmonary arterial hypertension (PAH), in healthy volunteers.

The assessment included comparisons against Gleevec, another oral formulation of imatinib sold by Novartis that is approved to treat certain blood cancers, but was not developed for PAH due to safety issues. Tenax now is modifying the formulation of TNX-201 to help ensure optimal efficacy and tolerance in an upcoming Phase 3 clinical trial, which is expected to launch in the second half of this year.

“TNX-201 represents a potential major advancement in the treatment of patients suffering from PAH — a disease for which there are currently no disease-modifying treatment options. We believe the short time required to optimize the TNX-201 formulation will increase our probability of success in Phase 3 and we look forward to providing additional updates on this program in the months ahead,” Christopher Giordano, Tenax’s president and CEO, said in a press release.

Tenax also announced updates related to the development of levosimendan, an investigational treatment for pulmonary hypertension and heart failure with preserved ejection fraction, called PH-HFpEF. That is a type of pulmonary hypertension in which the heart beats normally, but is too stiff to properly fill up with blood during the diastolic (filling) phase of heartbeats.

Pulmonary hypertension tied to increased cancer risk

People with pulmonary hypertension are at increased risk of developing cancer, especially lung and skin cancers, a new study indicates.

The study, “Pulmonary hypertension is associated with an increased incidence of cancer diagnoses,” was published in the journal Pulmonary Circulation.

Pulmonary hypertension (PH) refers to high blood pressure in the lung’s blood vessels, which puts strain on the lungs and the heart. People with PH are known to be at increased risk of certain other health conditions (comorbidities), including some respiratory and cardiovascular diseases as well as diabetes and depression. Whether PH is associated with cancer has not been clear.

Here, a team of scientists in Germany used a medical database to identify clinical and demographic data for 11,109 people with PH, and an equal number without. In both groups, the mean age was about 70 years, and slightly more than half of the patients were female.

Notably, there were no differences between the two groups in terms of comorbidities. There also was no difference in the prevalence of risk factors for PH and cancer such as obesity, diabetes, heart failure, atrial fibrillation (an irregular and often very rapid heart rate) and lipid (fat) metabolism.

Within 10 years of being diagnosed with PH, 23.2% of patients were diagnosed with cancer. By comparison, over a matched 10 years, 18.5% of those without PH were diagnosed with cancer.

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