Pulmonary Hypertension Program | Research & Innovation

There is tremendous focus on understanding the underlying causes of pulmonary disease — findings that will improve not just treatment but possibly find a cure. The Pulmonary Hypertension Program at Boston Children’s is dedicated to learning more about PH so we can better treat and hopefully someday prevent the disease. To that end, we’re involved in dozens of research projects and clinical and therapeutic trials — work that is already making a difference.

Clinical studies of pulmonary hypertension

• TBX4 mutations and deletions are associated with abnormal distal lung development, persistent pulmonary hypertension of a newborn, and pediatric pulmonary hypertension, as well as multiple congenital anomalies and developmental disabilities. Those are the findings of Boston Children’s Mary Mullen, MD; Pankaj Agrawal, MD; and several pediatric clinicians from around the world, who researched the spectrum of clinical manifestations associated with TBX4 genetic variants in newborns and children with PH. Their findings are helping us better understand how pulmonary vascular disease manifests, and they will be key in further research that aims to discover cures.
• To collect more robust and high-quality data about the range of diseases, their natural histories, and optimal care for children with PH, Dr. Mullen and Boston Children’s Lynn Sleeper, ScD, along with other researchers, characterized the distribution and clinical features associated with pediatric PH, as defined by World Symposia on Pulmonary Hypertension classifications. They determined nearly half of patients enrolled in a PH registry had pulmonary hypertension because of lung disease. Their findings reflect growing recognition of PH in diverse developmental lung diseases and how improving the phenotyping of a child’s DNA sequence, based on these disease-specific characterizations, could improve PH care and research.
• The post-lung transplant recovery of patients with PH and right ventricular (RV) dysfunction has not been well-detailed, prompting persistent questions about their stay in the hospital during a transplant procedure, as well as their cardiac function after transplantation. Dr. Mullen, Boston Children’s Gary Visner, DO; Francis Fynn-Thompson, MD; and other researchers found that all transplant PH patients who also had RV dysfunction were shown to have improved right ventricular function following transplantation — justifying the consideration of a lung transplant for pediatric patients with end-stage PH and RV dysfunction.

Ongoing pulmonary hypertension research

• We’re looking at how variants of the gene SOX17 might contribute to pulmonary arterial hypertension (PAH), a severe form of PH that leads to severe congenital heart disease (CHD).
• Along with the Boston Children’s Division of Gastroenterology, Hepatology and Nutrition, we are studying PH patients with liver issues to determine the cause-effect relationship between the conditions.
• In a clinical trial funded by the National Institutes of Health, we are studying the efficacy of single versus combination oral therapies for PH patients.
• Along with the Boston Children’s Pulmonary Genetics Program, we are researching genetic connections between Noonan syndrome, a genetic disorder that prevents growth in many areas of the body, and PH.
• We’re working with the Boston Children’s Neonatal Intensive Care Unit to learn how to improve the treatment and follow-up of infants who have matured past the premature birth stage and have bronchopulmonary dysplasia and pulmonary hypertension.
• Studying the genetics of PAH, we’re finding that elevated right ventricular pressure may be found in children who show symptoms of or have a family history of a genetic blood disorder known as hereditary hemorrhagic telangiectasia (HHT) — particularly those with an identified ALK1 genetic mutation.
• We are participating in a multi-center study on the mental health of patients with pulmonary hypertension, as we aim to understand how clinicians can better help children and their families accept and manage the emotional stresses of the condition.

New techniques

• We’re developing new techniques to expand the use echocardiographs and MRIs to capture images of the right ventricle, so that we can more effectively diagnose and treat PH.