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Scientists Discover Potential New Treatment For Pulmonary Hypertension
Researchers at Indiana University and Notre Dame have discovered a potential new treatment for pulmonary hypertension, focusing on reversing vascular remodeling through an epigenetic pathway involving the protein SPHK2, as reported in Circulation Research. This innovative approach could transform the treatment of this serious lung condition.
Researchers at the Indiana University School of Medicine, at the school's South Bend regional campus, and their colleagues at the University of Notre Dame, have discovered a novel therapeutic target for treating pulmonary hypertension. This form of high blood pressure specifically impacts the blood vessels in the lungs. The team's research and findings have been recently published in the journal Circulation Research.
Pulmonary hypertension is a complex and often fatal condition that makes the heart work harder than normal to pump blood into the lungs. While the exact causes of pulmonary hypertension are unknown, one of its hallmarks is the thickening of the pulmonary blood vessels caused by an overgrowth of cells, also known as vascular remodeling.
New Therapeutic DiscoveriesMargaret A. Schwarz, MD, a professor of pediatrics at IU School of Medicine and senior author on the study, said there are few treatments for pulmonary hypertension, and they typically treat the symptoms of vascular remodeling rather than the remodeling itself.
Schwarz said what's exciting about her team's findings is the discovery of an epigenetic pathway mediated via the protein SPHK2 that can reduce and potentially reverse vascular remodeling in pulmonary hypertension.
Dushani Ranasinghe, PhD, left, and Margaret Schwarz, MD, at Ranasinghe's graduation ceremony from the University of Notre Dame. Credit: Courtesy of Margaret Schwarz
"This is one of the very first mechanisms of pulmonary hypertension identified that can be reversible," she said. "Normally, pulmonary hypertension patients are given medications to reduce the vascular pressure in the lungs or to help the heart squeeze better to pump blood, which are both symptoms of vascular remodeling. Our study looks at targeting the epigenetic reversal of this mechanism. Ultimately, the treatment would be to stop the vascular remodeling process entirely."
The concept is similar to cancer treatment, Schwarz said.
"In cancer, we stop tumor growth instead of just treating symptoms," she said. "Vascular remodeling is a different mechanism, but the idea is that the treatment would target the mechanism instead of the symptoms."
Key Findings and Future DirectionsOther key findings from the study include:
Schwarz and the study's first author, Dushani Ranasinghe, Ph.D., who was a member of Schwarz's lab while she was a graduate student at Notre Dame, were also interviewed about their findings for an episode of the "Discover CircRes" podcast, which is produced by Circulation Research.
Schwarz said the next steps for her research include further exploration of the SPHK2 protein as a therapeutic target for pulmonary hypertension, in collaboration with Brian Blagg, director of the Warren Center for Drug Discovery and Development at Notre Dame.
Reference: "Altered Smooth Muscle Cell Histone Acetylome by the SPHK2/S1P Axis Promotes Pulmonary Hypertension" by A. Dushani C.U. Ranasinghe, Maggie Holohan, Kalyn M. Borger, Deborah L. Donahue, Rafael D. Kuc, Martin Gerig, Andrew Kim, Victoria A. Ploplis, Francis J. Castellino and Margaret A. Schwarz, 12 September 2023, Circulation Research.DOI: 10.1161/CIRCRESAHA.123.322740
Other IU authors on the study include Maggie Holohan and Martin Gerig.
This study was made possible in part by funding from the National Institutes of Health, the Lilly Endowment, the O'Brien Family Endowment for Excellence, the National Science Foundation and the Buckner Family Scholarship.
Delayed PAH Diagnosis Increased Economic Burden, Study Says
Increased pulmonary arterial hypertension (PAH) awareness and earlier screening in routine clinical practice could provide an opportunity for earlier treatment, resulting in reduced economic burden for payers, employers, and society at large.
Delayed pulmonary arterial hypertension (PAH) diagnoses increased the economic burden on payers, employers, and society at large, according to a study published in PharmacoEconomics - Open.
The researchers explained that PAH remains a progressive and potentially fatal disease despite advances in treatment. A major contributor to the severity of this disease is delayed diagnosis as the researchers noted that, on average, time between initial symptom presentation and PAH diagnosis can range from 2.5 to 3.9 years.
Delayed diagnoses remain a challenge due to the lack of a straightforward test used to diagnose PAH early on; the researchers explained that current guidelines recommend the highly invasive right heart catheterization (RHC) since the non-invasive transthoracic echocardiography is less accurate. Consequently, patients may only be diagnosed and treated when their PAH is more severe, the delayed diagnoses potentially leading to poorer treatment responses, faster disease progression, and worse clinical outcomes.
The researchers noted that there is limited data on how delayed PAH diagnoses burden the health care system. Because of this, they conducted a study to characterize the health care resource utilization (HRU) and health care cost burden associated with delayed PAH diagnoses in the United States.
The economic burden of PAH diagnosis delays can be attributed to increased hospitalization costs.Image Credit: Pixelbliss - stock.Adobe.Com
The researchers created their study population by using data obtained from Optum's deidentified Clinformatics Data Mart (CDM) Database between October 2015 and September 2021. They explained that CDM consists of data from administrative health claims for members of large commercial and Medicare Advantage health plans nationwide.
The researchers assigned eligible patients to mutually exclusive cohorts based on the time between the first PAH-related symptom and the first PAH diagnosis (≤ 12 months' delay, > 12 to ≤ 24 months' delay, or > 24 months' delay). They assessed all-cause HRU and health care costs per patient per month (PPPM) during the first year following diagnosis and compared across cohorts using regression analysis adjusted for baseline covariates.
The study population consisted of 538 patients. Patients had a mean age at PAH symptom onset of 65.6 years, and 60.6% were female. Additionally, 327 (60.8%) had a diagnosis delay of 12 or fewer months, 126 (23.4%) had a diagnosis delay between 12 and 24 months, and 85 (15.8%) had a diagnosis delay greater than 24 months. The researchers noted that the mean (median) diagnosis delay was 4.0 (2.9) months in the 12 months or less delay cohort, 17.4 (17.7) months in the between 12 and 24 months delay cohort, and 33.5 (31.7) months in the greater than 24 months delay cohort; the overall mean (median) diagnosis delay was 11.8 (8.3) months.
Longer delays and increased hospitalizations resulted in higher all-cause health care costs. Compared to the total all-cause health care costs of patients with a diagnosis delay of 12 months or fewer, the costs PPPM were $3986 (95% CI, $1439-$6436) higher in patients with a diagnosis delay between 12 and 24 months and $5366 (95% CI, $2107-$8524) higher in patients with a diagnosis delay greater than 24 months; the researchers explained that these increased costs are due to hospitalization costs.
Compared to patients with diagnosis delays of 12 months or fewer, those with delays between 12 and 24 months had increased hospitalizations (incidence rate ratio [IRR], 1.40; 95% CI, 1.11-1.71) and outpatient visits (IRR, 1.17; 95% CI, 1.06-1.30). Patients with delays greater than 24 months also had increased hospitalizations (IRR, 1.71; 95% CI, 1.29-2.12) and outpatient visits (IRR, 1.26; 95% CI, 1.08-1.41) in comparison to patients with diagnosis delays of 12 months or fewer. Overall, both cohorts had more ICU stays and 30-day readmissions.
The researchers acknowledged their study's limitations, one being that their study population was predominantly from the Southern United States and enrolled in commercial or Medicare Advantage plans. Consequently, they explained that their findings may not be generalizable to those throughout the rest of the country. Despite the limitations, the researchers used their findings to make future suggestions on how to mitigate delayed PAH diagnoses.
"These findings highlight the need for increased awareness and earlier screening in routine clinical practice, as this could provide an opportunity for earlier treatment which might lead to better clinical outcomes among patients with PAH and reduced economic burden for payers, employers, and society at large," the authors concluded.
Reference
DuBrock HM, Germack HD, Gauthier-Loiselle M, et al. Economic burden of delayed diagnosis in patients with pulmonary arterial hypertension (PAH). Pharmacoecon Open. Doi:10.1007/s41669-023-00453-8
Only Device For Janssen Pulmonary Hypertension Drug Discontinued
Janssen is recommending physicians withhold prescribing its pulmonary arterial hypertension drug because Philips Respironics is discontinuing the only approved delivery system for the drug.
Philips Respironics' now-discontinued I-neb AAD System, an inhalation drug delivery device, was the only FDA-approved product for Janssen's brand-name drug Ventavis (iloprost inhalation ampules).
The American Society of Health-System Pharmacists reported the issue Nov. 28, which comes with implications for patient care.
"Providers will need to work to switch patients to an alternative pulmonary hypertension treatment," the ASHP said. "New prior authorizations for alternative treatments will likely be required. Ensure a plan is in place to prevent patients from running out of iloprost inhalation solution without another option."
A Janssen spokesperson told Becker's solutions of Ventavis are available, but without an approved drug delivery method, healthcare providers are encouraged to "explore alternative treatment options for patients utilizing Ventavis and to refrain from initiating new patients on this medication."
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