Advanced Research into Lung and Heart-Lung Diseases, Critical Illness, and Sleep Disorders

Pulmonary Arterial Hypertension (PAH)

Pulmonary arterial hypertension (PAH), a serious disease of the arteries in the lungs, impacts mostly women. Our group has conducted some of the first studies to understand the impact of biological sex and gender on pulmonary hypertension and right heart function, leading to clinical trials in this area.

We have found connections between sex hormones and the risk and severity of PAH, which has led us to testing treatments that adjust hormone levels in PAH patients. We are also studying how body composition and muscle and fat stored in the body may impact sex and gender differences in pulmonary hypertension as well as disease severity and outcomes. This research is funded by the National Institutes of Health.

We study how pulmonary hypertension affects patients' quality of life, especially their intimate and sexual experiences, and how this might differ by gender.

The Retina as a Window in Pulmonary Hypertension

We found that people with pulmonary arterial hypertension (PAH) have abnormalities in the blood vessels in their eyes, and the extent of these abnormalities is linked to the severity of their PAH.

We are studying whether retinal images may be a useful screening test and way to monitor patients with or at risk for pulmonary vascular disease. This work is supported by the American Heart Association.

PH and the Liver

We believe the liver plays a role in the development of pulmonary arterial hypertension (PAH), even in patients without liver disease initially. In animal studies, we observed signs of inflammation in the livers of rats with pulmonary hypertension. In the future, we'll continue to investigate how PAH affects other parts of the body, such as the liver and the eyes, using imaging and other techniques to study their characteristics and changes over time. This work is supported by the American Thoracic Society.

The Role of Stem Cells

Research suggests that stem cells from the bone marrow are drawn to the lungs in people with pulmonary hypertension. Initially, it was believed that this was a healing response, but now we're finding that these cells contribute to inflammation around the blood vessels in the lungs, leading to changes that worsen the disease.

We've also discovered that people with pulmonary hypertension have higher levels of a protein called RUNX1. RUNX1 is a key player in causing stem cells towards becoming inflammatory cells. Mutations in another gene, SOX17, which regulates RUNX1, have been linked to an increased risk of pulmonary hypertension.

Previous experiments in our lab have shown that blocking RUNX1 can reverse pulmonary hypertension in animals. This suggests that targeting RUNX1 could be a new approach to treating people with pulmonary hypertension. This research is supported by the National Institutes of Health.

Developing Individualized Therapies

By collecting cells from the pulmonary arteries of pulmonary hypertension patients, we can understand how the disease progresses in each patient.

Until now, researchers have not had direct access to study the pulmonary circulation in living patients, which has been a major obstacle in research on lung blood vessel diseases. With this new method, we can tailor treatments to individual patients based on their unique biology. This work is supported by the National Institute of Health.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a VTE lung disease caused by old blood clots, called pulmonary emboli (PE), that build up and form scar-like tissue that can narrow or block the arteries. This condition is usually a result of a previous acute PE, when a blood clot travels from the leg to the lungs and gets lodged there. These blockages create extra pressure, known as hypertension, or high blood pressure, in the lungs.

While not everyone who has a PE develops CTEPH, some people experience ongoing symptoms like difficulty exercising, poor quality of life, and limited daily activities due to long-lasting blood clots in the lungs.

Research suggests that females might be more likely to develop this type of pulmonary hypertension, but more research is needed to better understand this. We will gather all relevant clinical information and collect additional tissue or blood samples during procedures and surgeries through our Center for Advanced Lung Care Biobank to improve our understanding of this disease.

We are currently gathering biological samples and clinical data from all willing patients and healthy volunteers for the Center for Advanced Lung Care's Biobank.

Our goal is to use these samples in both new and ongoing research to better understand complex heart and lung conditions. By studying these samples, we hope to discover new mechanisms and treatments to find ways of improving quality of life for patients affected by these conditions.

To find out if you are eligible to participate, please ask your CALC provider or contact any one of our research team members.

Extracorporeal membrane oxygenation (ECMO) has become a crucial treatment for patients with severe illnesses that don't respond to other therapies. It's been used in over 200,000 cases so far and has been increasingly used for a variety of conditions. During the H1N1 and COVID-19 pandemics, ECMO played a vital role in saving lives.

Many patients who survive intensive care, including those treated with ECMO, experience a range of long-term cognitive and psychiatric problems known as post-intensive care syndrome (PICS). There is little research on how common PICS is among ECMO survivors or what causes the neurocognitive problems after ECMO treatment. ECMO itself can also lead to significant neurological problems, both during and after treatment.

Research has discovered that certain proteins associated with brain diseases, (Alzheimer's dementia), are produced by the lungs in response to severe pneumonia. In our research, we've seen that levels of these proteins are higher in patients on ECMO, especially those who don't survive or who have bleeding in the brain.

Based on our early findings, we plan to create a clinic for patients who have been on ECMO and survived, where we will assess their neurocognitive function and collect data on their health both in the hospital and after they are discharged. We'll also collect blood samples to measure the levels of these proteins, which could help us understand and prevent neurological complications after ECMO treatment.

Conditions like asthma and sleep-disordered breathing are among the most frequently seen medical conditions during pregnancy. Pregnancy also raises the risk of developing a blood clot in the lungs, known as pulmonary embolism.

Respiratory problems during pregnancy, possibly due to episodes of low oxygen levels or increased stress on the body, have been linked to various negative outcomes for both the mother and the baby.

Studies have consistently found connections between respiratory disorders and pregnancy outcomes. For example, pregnant individuals with sleep apnea, a condition where breathing repeatedly stops and starts during sleep, have a higher risk for gestational diabetes and preeclampsia. Similarly, conditions such as asthma, are also linked to pregnancy outcomes. Hence, appropriate management of these conditions during pregnancy is key to optimizing mother’s health and baby’s health. 

Our team studies respiratory conditions during sleep in pregnancy. None of the work we have performed would have been possible without the help and the dedication of the pregnant women who have agreed and volunteered to participate in our research program. 

Sleep Apnea

Sleep apnea is a condition where breathing stops or is inadequate multiple times per night during sleep. These events are usually associated with a reduction in oxygen levels and interrupt the brain’s ability to sleep more deeply. Sleep apnea is a disorder in the spectrum of sleep disordered breathing, characterized by abnormal breathing during sleep. In the general population, sleep apnea is associated with increased risks of various conditions such as cardiovascular disease, stroke, diabetes, as well as trouble with concentration, and mental health disorders. Treatment of sleep apnea improves quality of life and blood pressure. 

The team’s research on sleep apnea has funded by the National Institutes of Health, the Chest Foundation, the American Academy of Sleep Medicine Foundation, and other sponsors.

Sleep Apnea and Pregnancy Outcomes

We have demonstrated that sleep apnea is associated with pregnancy specific conditions such as preeclampsia and gestational diabetes, as well as a severe maternal morbidity. Women with sleep apnea were more likely to need admission to the intensive care unit. In addition, in women with preeclampsia, we demonstrated that those who also had sleep apnea were more likely to have cardiovascular outcomes and utilized healthcare services more extensively in the form of longer hospital stays, higher risk for having a Cesarean delivery and more. Hence, we believe that improving sleep in pregnancy is an opportunity to improving the health of the pregnancy.

Sleep Apnea and Fetal Outcomes

We have demonstrated that exposure to abnormal breathing during sleep is linked to abnormal growth of the fetus, an increase in the risk for preterm birth, as well as a slight increase in the risk of a baby being born with a birth defect. Our work has also been reproduced by others and we are currently examining the effects of various forms of abnormal breathing during sleep may impact the health of babies. 

Pregnancy and the Risk of Sleep Apnea

Our team has examined the risk of developing sleep apnea in pregnancy and demonstrated that in women who have a higher than normal body mass index who snored in early pregnancy but did not have sleep apnea then, 40 percent would go on to develop sleep apnea in later pregnancy. We are examining specific factors that impact that risk in pregnancy.

Diagnosis of Sleep Disordered Breathing

Our team has demonstrated that there are specific features to sleep disordered breathing in pregnancy, when compared to women who are not pregnant. Further, we demonstrated that the criteria we are currently using to define the disorder may not be optimal and may miss significant abnormalities. In collaboration with a team of computer scientists, we are testing the incorporation of sophisticated artificial intelligence and deep learning techniques in the identification of sleep disordered breathing in this population.

Treatment of Sleep Apnea in Young Women

Through collaboration with clinical psychologists, we are examining factors that may act as barriers to treatment and others that may act as facilitators to treatment in young women diagnosed with sleep apnea, pregnant and non-pregnant. This research has assisted us in the identification of areas of focus that could help us improve how well pregnant women may utilize their treatment for sleep (CPAP). 

Sleep, Stress, and Nutrition in Pregnancy

This new project aims to examine how stress and diet interact with sleep in pregnancy in women from different racial backgrounds. We are examining sleep and different measures of stress, and looking at the quality of pregnant individuals’ diet. This area of research will help us identify ways to create interventions that will improve various aspects of the health of pregnant individuals.