March

March 2024 2024 | www.nhlbi.nih.govWWW.NHLBI.NIH.GOV

ADVANCING

Heart, Lung, Blood, and Sleep Research 
“

Director’s Message

Advancing Heart, Lung, Blood, 

and Sleep Research

NHLBI Director Gary H. Gibbons, M.D.

Last year, the National Heart, Lung, and Blood Institute (NHLBI) celebrated 75 years of 

funding biomedical research to prevent and treat heart, lung, blood, and sleep (HLBS) 

disorders, which continue to be the leading causes of death and disability in the United 

States. On October 17, 2023, the NHLBI Constituency Group, co-chaired by the 

American Heart Association and the American Thoracic Society, hosted a reception on 

Capitol Hill joined by representatives from health advocacy nonprofits, associations, and 

foundations, along with lawmakers who support NHLBI research. It was a night filled with 

inspiration and gratitude, capped by a performance by Caesar Sant, a violin prodigy who 

was born with sickle cell anemia and received a life-saving bone marrow transplant at the 

NIH Clinical Center.

Mr. Sant’s performance was significant. As it turns out, 1948 was a banner year for 

NHLBI’s birth. It was the year when sickle cell disease was first defined as a molecular 

disorder — the result of a single genetic mutation that causes life-threatening conditions. 

Seventy-five years later, 2023 was also momentous: At the end of the year, thanks to 

NIH-funded CRISPR technology, the biomedical community was able to announce a 

cure for sickle cell disease. Not just a better treatment. A cure.

NHLBI will continue to fund research into single-gene variant diseases and disorders. But 

our research portfolio is rich and complex, full of common diseases and disorders that 

are multifactorial, are chronic, and often worsen over time unless carefully managed. The 

beginning of the Framingham Heart Study (FHS) in 1948 was also a landmark event in the 

history of NHLBI. The FHS began as a bold effort to use broad, community-based health 

measures to identify common factors that contribute to cardiovascular disease. Since 

then, the FHS has evolved into a multigenerational study that analyzes family patterns 

of cardiovascular and other diseases, gathers genetic information from generations that 

followed the original study participants, and has expanded to include diverse populations 

and their unique patterns of risk factors.

Cardiovascular disease. High blood pressure. Lung diseases, such as asthma and 

pulmonary fibrosis. Sleep disorders. The incidence and outcomes of these common 

chronic diseases offer an eye-opening look into the stark discrepancies among people 

living in the United States who do much better at either avoiding them or living longer 

with better medical treatment and those who have significantly more disability and shorter 

life spans. For example, the enduring burden of heart failure is expected to increase 

significantly among Americans, yet it does not fall evenly across communities in the 

United States.

The persistence of these health inequities is as complex as the diseases’ causes. 

Genetic disposition and health behaviors can combine to increase risks for everything 

from asthma to hypertension to heart failure and lung disease, reflecting a complicated 

dance between genes, socioeconomic status, and environmental exposure, among other 

factors. Resilience depends on who and where you are. For example, a simple 

Thanks to NIHfunded CRISPR 

technology, 

the biomedical 

community was 

able to announce a 

cure for sickle cell 

disease. Not just a 

better treatment. 

A cure.

Director’s Message: Advancing Heart, Lung, Blood, and Sleep Research / 1
“ lack of walkability in some neighborhoods creates barriers to behaviors that could 

increase resilience to disease and decrease vulnerability. An individual’s lived experience 

and health exist within that confluence of the individual, the community, and their 

socioeconomic structure.

Where you live matters, and your ZIP code may matter more than your genetic code. 

For example, the inequities in COVID-19 incidence and outcomes during the pandemic 

have laid bare other kinds of health vulnerabilities in all kinds of communities across the 

United States. As a consequence, NHLBI developed the Risk Underlying Rural Areas 

Longitudinal (RURAL) Cohort Study to address the high burden of chronic heart and lung 

disease in 10 rural counties in the heartland states of Alabama, Kentucky, Louisiana, and 

Mississippi by using community-engaged partners and high-tech mobile research units 

to collect data including medical histories, familial, lifestyle, and behavioral factors. These 

and other data from cohort studies will be fed into the analytic platform of NHLBI’s TransOmics for Precision Medicine (TOPMed) program to support discovery of genomic and 

other complex risk factors that influence health disparities wherever they are found.

It would be foolish to ignore the promise that biomedical research offers to create ways 

to preempt disease by using carefully targeted community-level interventions to help the 

most vulnerable before disease even has a chance to start. Fortunately, NHLBI has a long 

history of funding research that excels at approaching people where they are.

For example, the Maternal Health Community Implementation Project (MH-CIP) is a 

community-driven initiative that uses evidence-based interventions, such as regular blood 

pressure readings, to help reduce cardiac risk factors before and during pregnancy. 

Another initiative, Early Intervention to Promote Cardiovascular Health of Mothers and 

Children (ENRICH), is a partnership with other federal agencies and certified local home 

visiting programs to promote cardiovascular health in mothers and children up to 5 years 

old. ENRICH researchers work directly with communities that have a high burden of 

cardiovascular disease, including those of lower socioeconomic status and access to 

care and tribal nations.

These kinds of community-based efforts are now accelerated because of lessons 

learned from the COVID-19 pandemic. In 2020, the Community Engagement Alliance 

(CEAL) initiative was developed to reach out to communities across the country that 

bore disproportionate burdens of infection with the virus that causes COVID-19 by using 

meaningful engagement strategies to raise awareness about the risks of the disease and 

the value of mitigation strategies, including vaccination. CEAL created participatory space 

for all — patients, advocates, community leaders, scientific partners, and others — to 

leverage the power of community involvement to improve public health.

Because of the initiative’s success, CEAL funding has been sustained to strategically 

leverage the initiative as a platform to gather data and test interventions using uniform 

measures and analytic processes. Additional initiatives, including those from other NIH 

Institutes, have been incorporated into CEAL to strategically use the initiative’s model to 

tackle major public health issues. The Implementing a Maternal health and PRegnancy 

Outcomes Vision for Everyone (IMPROVE) initiative and the Climate Change and Health 

(CCH) Initiative use the CEAL platform as a powerful research resource for NHLBI and 

other NIH Institutes to work effectively within communities.

2 / Director’s Message: Advancing Heart, Lung, Blood, and Sleep Research

Where you live 

matters, and 

your ZIP code 

may matter 

more than your 

genetic code.
“

NHLBI’s Innovative Magnetic Resonance 

Imaging (MRI) Technology Program 

NHLBI’s innovative magnetic resonance imaging (MRI) technology program now makes it possible to maintain 

good image quality when testing for certain lung diseases while eliminating radiation exposure. To achieve this, 

NHLBI researchers developed new techniques to capture and process images with low-field MRI scanners. 

Researchers then applied novel, advanced reconstruction methods using contemporary computational power 

integrated into the clinical environment with the Gadgetron, an open-source tool for medical image reconstruction. 

The program emphasizes translation of new methods to clinical applications by collaborating with cardiologists, 

pulmonologists, radiologists, and critical care physicians.

However, we can’t stop there. We have to look further. Now is the time to both 

sharpen and widen our focus and dive into the future embracing new technologies 

to tackle the most complicated and persistent public health challenges.

Artificial intelligence and machine learning technologies have been the focus of much 

discussion this past year. People fear that these new tools will make humans and our 

innate humanity not just irrelevant but unwanted. But as a scientist and a biomedical 

researcher, I believe that if we have the will, we have the power to harness these 

technologies for good as we have always done throughout history. Fire. Wheels. 

Telescopes. Microscopes. Computers that were once as big as a house but are now 

fitted onto microchips manufactured so inexpensively that anyone can buy one online.

We have to take that leap into these new technologies strategically and with deep 

thought about their opportunities and challenges. NHLBI has consistently funded 

data gathering and analysis initiatives. TOPMed. The Disparities Elimination through 

Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk 

(DECIPHeR) Alliance. BioData Catalyst. The ability to analyze the functions of a single 

cell in its native environment has created the Human Lung Cell Atlas, an open-source 

resource of molecular and cellular maps of the organ.

With this kind of careful and strategic funding, we can accelerate our understanding 

of the activities and interactions of any cellular or molecular mechanism in the human 

body that contributes to HLBS diseases and disorders. We must fund initiatives that 

encourage slicing, dicing, and crunching data at levels both big and small to connect 

the dots between health and disease. Using this information, we will be able to assemble 

predictive models for any individual over the course of their lifetime. We will discover 

new targets for interventions that can unbend those unjust curves in outcomes that 

have been, up to now, resistant to budging.

People often say that if you have your health, you have everything. It’s time to start 

thinking about and planning for what “having everything” might begin to look like 

for everyone.

Director’s Message: Advancing Heart, Lung, Blood, and Sleep Research / 3

We have to 

take that leap 

into these new 

technologies 

strategically and 

with deep thought 

about their 

opportunities and 

challenges. 
4 / Highlights in Heart Health

“

Highlights in

Heart Health

Maternal Health

• Maternal morbidity and mortality have risen to crisis

levels, an unacceptable indicator of health in the United 

States. According to the Centers for Disease Control 

and Prevention, more than 1,200 women died of 

causes related to pregnancy in the United States in 

2021, the most recent year for which complete data 

are available. These numbers have steadily increased 

in the past few years, with 754 and 861 deaths in 2019 

and 2020, respectively. Adverse pregnancy outcomes, 

including death, for Black women continue to be 

significantly higher than rates for other racial and ethnic 

groups. American Indian, Alaska Native, Native Hawaiian, 

and other Pacific Islander populations also experience 

increased risk.

• The Early Intervention to Promote Cardiovascular

Health of Mothers and Children (ENRICH) initiative 

is a partnership with the Health Resources and Services 

Administration, the Administration for Children and 

Families, and certified local home visiting programs. The 

initiative promotes cardiovascular health in mothers and 

children up to 5 years old. ENRICH researchers work 

directly with communities that have a high burden of 

cardiovascular disease; these include communities of 

lower socioeconomic status, tribal nations, and people 

who live and work in low-resource areas. The initiative 

includes seven clinical centers around the country that 

investigate ways to lower the incidence of cardiovascular 

risk factors, including examining social determinants of 

health, obesity, hypertension, diabetes, and those at risk 

of developing preeclampsia or gestational diabetes.

• NHLBI supports research that examines how to prevent or

manage cardiovascular risk factors and disease in women 

across their lifespan. The nuMoM2b Heart Health 

Study, co-funded by the Eunice Kennedy Shriver National 

Institute of Child Health and Human Development, is 

studying the effects of pregnancy complications on future 

cardiovascular health, including social factors that correlate 

with the future heart health of new parents, especially in 

communities of color.

Improving Access and Outcomes 

in Rural Populations

• According to the U.S. Census Bureau, approximately

60 million people, or 1 in 5 Americans, live in rural areas. 

It is well-established that there is no higher burden of 

disease and disparities than in rural America. A recent 

study conducted by the HHS Healthy People initiative 

found that healthcare quality and access was the top 

priority for health in rural America. NHLBI strongly 

supports finding ways to bring care to where people 

are, which includes funding research to address health 

disparities experienced by rural populations.

• Lead exposure is known to harm the health of children

by damaging the brain and nervous system and slowing 

growth and development. It has also been associated 

with increased risks for heart disease in adults. Exposure 

to elevated levels of lead and other metals has been 

disproportionately higher among American Indian 

communities. Through the Strong Heart Family Study, 

NIH-supported researchers found that adults who had 

the greatest reductions in blood lead levels saw their 

systolic blood pressure fall by about 7 mm Hg, an 

amount comparable to the effects of blood pressure–

lowering medication. Public health policies and efforts 

implemented in recent decades have led to reduced lead 

exposure through paint, gasoline, water, plumbing, and 

canned items.

• In 2023, a study funded by NHLBI demonstrated

that parental history of obesity and smoking 

were associated with a higher risk of future 

cardiovascular disease in offspring. However, some 

other parental modifiable risk factors (e.g., parental history 

of hypertension, diabetes, high cholesterol) were not 

associated with offspring’s cardiovascular disease risk. 

Maternal morbidity and mortality 

have risen to crisis levels, an 

unacceptable indicator of health 

in the United States. 
Highlights in Heart Health / 5

These findings suggest that the presence of parental 

obesity should prompt a focus on disease prevention 

in offspring of parents with cardiovascular disease and/

or obesity. Future research should develop and test 

interventions before conception and during pregnancy to 

treat parental obesity and smoking to prevent obesity and 

cardiovascular disease risk in the offspring.

• A recent study by NHLBI-supported researchers used

cardiovascular disease modeling to estimate the longterm impact of adopting home blood pressure 

monitoring versus usual care on myocardial 

infarction, stroke, and healthcare costs. Compared 

with usual care, adopting home blood pressure monitoring 

was estimated to reduce myocardial infarction cases by 

4.9 percent and stroke cases by 3.8 percent, as well 

as saving an average of $7,794 in healthcare costs per 

person over 20 years. Women, non-Hispanic Black people, 

and rural residents had more averted cardiovascular events 

and greater cost savings related to home blood pressure 

monitoring when compared with men, non-Hispanic 

White people, and urban residents. The study provides 

compelling evidence for healthcare systems and payers to 

support the broader implementation of this intervention.

Advancing Heart Disease Research

• In 2023, NIH supported studies related to postural

orthostatic tachycardia syndrome (POTS), including a 

large grant to the University of Texas Southwestern 

Medical Center to further elucidate the disease. This 

study aims to improve scientists’ understanding of 

POTS by comprehensively examining a large group of 

patients. It will be the first study to define the full picture 

of different POTS subtypes and the relationship between 

these subtypes, allowing clinicians to better evaluate and 

individualize treatment for POTS and guide future research. 

It is expected that the efforts will further stimulate interest 

in POTS research across a wider range of NIH Institutes, 

and NHLBI plans to seek participation from other these 

other Institutes.

• Hypertrophic cardiomyopathy (HCM) is a chronic disease

and a well-recognized cause of sudden cardiac death 

in previously undiagnosed young individuals. There has 

been a long-standing, intense debate about whether 

vigorous intensity exercise is associated with an increase 

in risk of ventricular arrhythmias in individuals with HCM. 

The prospective, multinational, Lifestyle and Exercise 

in Hypertrophic Cardiomyopathy (LIVE-HCM) study

was designed to provide data to inform patient–clinician 

decisions around exercise. Results of this cohort study 

suggest that among individuals with HCM, vigorous 

exercise did not lead to a higher rate of death or lifethreatening arrhythmias than among those exercising 

moderately or those who were sedentary. Given that 

individuals with HCM exercise less than the general 

population and report a higher prevalence of obesity, 

heightened anxiety, and reduced emotional well-being, 

these data may inform discussions between the patient 

and their expert clinician around exercise participation.

• As part of its broader commitment to research on heart

and vascular diseases, NHLBI leads and supports research 

and programs on heart valve diseases in the United States 

and around the world. In December 2022, Congress 

authorized $100 million over five years to NIH to support 

more research into the causes of and risk factors for 

valvular heart disease via the Cardiovascular Advances 

in Research and Opportunities Legacy (CAROL Act). 

Through this funding, NHLBI is supporting expanded 

valvular heart disease research, including on risk factors 

for sudden cardiac arrest or sudden cardiac death from 

valvular heart disease, most commonly associated with 

mitral valve prolapse (MVP) and use of advanced imaging 

techniques. Research activities include basic science 

research aimed at addressing current knowledge gaps in 

valvular heart disease, development of artificial intelligence 

or machine learning techniques for comprehensive risk 

assessment and improved phenotypic characterization 

of individuals with MVP, and studies to establish ideal 

intervals for imaging and electrophysiological monitoring.

• Dilated cardiomyopathy is a type of heart disease in which

the chambers of the heart thin and stretch, becoming 

enlarged. Current treatments aim to reduce symptoms 

and prevent further heart damage through medications 

or surgically implanted devices. Myocardial remodeling 

devices use a tether wrapped around a ventricle to reduce 

the chamber size and wall stress, but these surgeries have 

several significant limitations. NHLBI-funded researchers 

recently developed a new approach to reduce the 

circumference of the heart’s left ventricle to overcome 

previous surgical limitations and increase survival rates, 
“

an approach known as MIRTH (myocardial intramural 

remodeling by transvenous tether). The new method 

allows researchers to steer a guidewire through the coronary 

vein and uses EDEN (electrocardiographic radial depth 

navigation) electrocardiograms to direct the user to any 

location within the ventricular walls, increasing procedural 

accuracy and speed and allowing the user to integrate 

the tether within the heart’s walls. MIRTH was performed 

on swine, resulting in positive measures of left ventricle 

performance, including increased contractility, efficiency, 

and reduced oxygen demand in cardiomyopathic animals. 

The technique may also have uses in the treatment of certain 

forms of acute myocardial infarction.

• NHLBI-funded scientists now utilize innovative new

stem cell–based technologies to grow highly complex 

3D balls of heart cells functioning much like a full-size 

heart — but in a dish. Termed organoids, these mini-organs 

develop from human stem cells and allow scientists to study 

the heart in ways they never have before. Isolating organoids 

from other organ systems will help researchers understand 

how organs such as the heart develop and function in both 

healthy and diseased states. Without other biological factors, 

such as blood, hormones, or signals from other organs, 

researchers can focus on elements like the genetic pathways 

that guide organ development or structural changes that 

happen during disease. This technology is a key step along 

the path to precision medicine.

Dietary Interventions to Reduce 

Cardiovascular Disease

• High-density lipoprotein (HDL) cholesterol, often called

“good cholesterol,” removes extra cholesterol from the 

arteries by binding early-forming plaque and transporting 

it to the liver, which flushes it out of the body. Researchers 

recently developed a quick and simple diagnostic 

test that measures HDL function and have shown in 

clinical studies that their test can predict cardiovascular 

disease risk better than general levels of HDL cholesterol, 

which is currently used to assess such risk. The test is still 

years away from potential use in a medical setting, but it 

holds promise for physicians looking to gather additional 

information that could help inform their treatment decisions.

• Two NHLBI-supported diets, Dietary Approaches to

Stop Hypertension (DASH) and Therapeutic Lifestyle 

Changes (TLC), have collectively earned five top spots 

in the U.S. News & World Report’s 2023 “Best Diets” 

rankings. To receive top rankings, a diet must be nutritious, 

safe, easy to follow, effective for weight loss, and protective 

against diabetes and heart disease. DASH, which supports 

overall heart health and helps lower blood pressure and 

cholesterol, ranked first in the “Best Heart-Healthy Diets,” 

“Best Diets for Diabetes,” and “Best Diets for Bone and 

Joint Health” categories. TLC, which focuses on lowering 

cholesterol, ranked first in the “Easiest Diets to Follow” and 

“Best Family-Friendly Diets” categories.

• A recent study explored the impact of dietary sodium

intake on blood pressure after one week on a lowsodium (500 mg) diet compared with a high-sodium diet 

in middle-aged and elderly adults. The study found that, 

regardless of a person’s starting blood pressure, a majority 

of individuals experienced an average 8 mm Hg reduction 

in systolic blood pressure after one week on a low-sodium 

diet, regardless of their hypertension status and use of 

antihypertensive medication.

Isolating organoids from other 

organ systems will help researchers 

understand how organs such as the 

heart develop and function in both 

healthy and diseased states.

Dr. David Goff 

@NHLBI_HEARTDir

NHLBI’s Division of Cardiovascular Sciences (DCVS) supports research to advance understanding of 

and interventions for promoting heart and vascular health across the lifespan. It also supports research 

aimed at preventing and treating pediatric and adult cardiovascular diseases, including heart attack, heart 

failure, stroke, and congenital heart disease. DCVS is led by David Goff, M.D., Ph.D.
“

Highlights in

Lung Health

Increasing Odds of 

Successful Diagnostic and 

Therapeutic Procedures

• Chronic obstructive pulmonary disease (COPD) remains

underdiagnosed in primary care settings, particularly among 

African American patients and current or former smokers. 

Underdiagnosed patients experience impaired health and 

a greater risk of acute respiratory events and mortality. The 

diagnostic test for COPD is spirometry. However, disease 

symptoms of COPD (e.g., airway inflammation, airflow 

obstruction, emphysema, shortness of breath, exercise 

intolerance) are more complex and informative. Systematic 

failure to diagnose the disease may hamper understanding 

of disease manifestations and progression in populations 

more at risk of deprivation, as well as perpetuating health 

disparities. NHLBI-funded researchers have been working 

on new tools to mitigate missed COPD diagnoses. A 

recent NHLBI-funded study found that participants with 

tobacco exposure and preserved spirometry (TEPS) 

and symptoms (symptomatic TEPS) had a similar 

rate of decline in lung function and similar incidence 

of COPD defined by spirometry as those with TEPS 

without symptoms (asymptomatic TEPS), but participants 

with symptomatic TEPS experienced significantly more 

respiratory exacerbations over 2 to 10 years of follow-up.

• Some critically ill patients, such as those with ventilatorassisted pneumonia, are routinely prescribed empiric 

antibiotics with activity against anaerobic gut bacteria. Yet in 

other disease states and animal models, gut anaerobes are 

protective against pneumonia, organ failure, and mortality. 

Researchers studied the effects of anti-anaerobic 

antibiotics on the risk of adverse clinical outcomes 

among critically ill patients receiving mechanical 

ventilation, finding that the drugs are associated with 

increased mortality. The increased mortality, from both 

observational clinical data and animal modeling, is not 

completely explained by infections alone, and the protective 

effects of gut anaerobes are likely multifaceted. However, 

these results suggest that the widespread use of antianaerobic antibiotics in hospitalized patients should be 

reconsidered.

• Given their need for intense immunosuppressive regimens,

lung transplant patients are at a significantly increased 

risk of infection and organ rejection soon after transplant. 

Highlights in Lung Health / 7

Post-transplant monitoring typically involves routine 

bronchoscopies along with biopsies, especially during the 

first year post-transplant. In an effort to implement a lessinvasive detection and monitoring approach during the 

COVID-19 pandemic, NIH researchers tested levels of 

cell-free DNA (cfDNA) in the blood of lung transplant 

recipients. Transplant recipients have cfDNA from both 

their own cells and the donated cells. Previous research has 

shown that the relative amounts of donor-derived cfDNA 

(dd-cfDNA) compared with recipient-derived cfDNA has 

the potential to be a useful biomarker of organ rejection, 

but this has not been tested as a method of routine clinical 

monitoring. NHLBI researchers periodically collected blood 

from patients within three years of their transplant and found 

that increased levels of dd-cfDNA indicated either rejection 

or infection of the donated tissue, suggesting that this 

method is a convenient and reliable way to monitor health. 

Additional testing is needed to establish clinical guidelines; 

the process may ultimately be used to monitor the health of 

other transplanted organs.

Exploring Biological 

Differences in Disease

• Puberty is a period marked by hormonal, metabolic, and

immune changes. It also marks a shift in sex differences 

in susceptibility to asthma. Males have higher asthma 

prevalence in childhood, but starting from young adulthood, 

females are more affected. A recent NHLBI-funded study 

examined pubertal development and leukocyte gene 

expression in a cohort of 163 children with asthma; 

participants were between 10 and 17 years old when the 

study began and were followed annually for up to three 

Puberty is a period marked 

by hormonal, metabolic, and 

immune changes. It also marks 

a shift in sex differences in 

susceptibility to asthma.
“

years. The investigators used quantitative measures 

of asthma symptoms (e.g. chest tightness, coughing, 

wheezing) and severity to investigate whether changes 

in gene expression in immune cells during puberty were 

also associated with changes in disease status. In males, 

gene expression changes associated with puberty and 

age were inversely correlated with those associated with 

asthma symptoms and positively correlated with those 

associated with pulmonary function. Conversely, the 

opposite correlations were observed with gene expression 

changes linked to puberty and age in females. The study 

is the first to document these differences and also offers 

the first genome-wide characterization of patterns of 

gene expression changes in peri-pubertal males and 

females, adding to the knowledge base of epigenetic 

reprogramming of immune cells during puberty.

• Although studies have improved our understanding of

idiopathic pulmonary fibrosis (IPF) disease development, 

effective therapeutics for IPF are still limited, and the 

molecular mechanisms of the development of fibrotic 

lesion remain poorly understood. Recently, a study 

in animal models showed that the circadian rhythm–

regulating protein REV-ERBα, which is known for its roles 

in lung injury and repair, also plays critical roles in the 

injury-induced fibrogenesis. Interestingly, mouse lungs 

injured at night displayed exacerbated lung fibrogenesis. 

All these suggested a critical role for circadian rhythms 

in the development of IPF, and night shift workers could 

face a higher chance of fibrotic disease development. 

Therapeutics targeting REV-ERBα receptors might be 

one potential strategy to overcome the risk of fibrosis 

development.

8 / Highlights in Lung Health

Using Innovative Technology to Understand Lung Function

The human lungs face a slew of daily threats from 

airborne pathogens and pollutants and are also the 

site of many fatal diseases. Although procedures like 

magnetic resonance imaging (MRI) and computed 

tomography (CT) scans can shed critical light on what 

is going wrong when a patient has lung disease or 

illness, these techniques fail to provide the real-time 

information key to fully understanding the intricate 

workings of the lung at the cellular level. A new 

technological advancement called the crystal ribcage 

allows researchers to witness the moment-to-moment 

dynamics of respiration and circulation, the body’s 

response to airborne pathogens, and what happens 

when tumor and immune cells move into the lungs. 

The system uses a ventilator and perfusion pump 

to keep the lung functioning outside the body while 

maintaining its natural shape. The crystal ribcage that 

encloses it then makes optical imaging of the organ 

possible, and researchers can capture everything from 

the entire lung to a single lung cell.

A new technological 

advancement called the crystal 

ribcage allows researchers 

to witness the momentto-moment dynamics of 

respiration and circulation, the 

body’s response to airborne 

pathogens, and what happens 

when tumor and immune cells 

move into the lungs. 
“ Understanding the Causes and 

Consequences of E-Cigarette Uses

• The use of electronic cigarettes (e-cigarettes, or vapes) has

increased among adolescents and young adults in recent 

years. Use of these products produces aerosols that contain

volatile chemicals, including flavorings and oxidant metals 

with known lung toxicity.

• It is important to understand why these young people

start using e-cigarettes. Researchers recently analyzed 

data from more than 12,000 participants in the 2019 

National Youth Risk Behavioral Survey, examining the 

association between stressors (e.g., bullying, sexual assault, 

depressive symptoms, weapon threats) and e-cigarette use 

in the month before the survey. There were significant links 

between participants with higher psychosocial stress scores 

and e-cigarette use. E-cigarette use was also positively 

associated with higher psychosocial stressor burden scores; 

the strength of the association is comparable to that of 

psychosocial stressors with combustible cigarette use.

• In a recent NHLBI-funded study, researchers evaluated

the associations of e-cigarette use with self-reported 

respiratory symptoms in a group of more than 2,000 

U.S. teens during a series of annual surveys across a fouryear span. The participants were part of the University of 

Southern California Children’s Health Study between 2014 

and 2018. The odds of wheezing among the participants 

were 81 percent higher among those who had used 

e-cigarettes in the past 30 days than among those who had

never vaped. Similarly, the odds of bronchitis-like symptoms 

were twice as high in users, while those of shortness of 

breath were 78 percent higher after adjustments for age, sex, 

race, and other factors. The findings remained statistically 

significant even after further adjustment for concurrent use 

of cigarettes and cannabis and secondhand exposure to 

e-cigarettes, cigarettes, and/or cannabis.

Improving Quality of Life for Those 

Who Use Supplemental Oxygens

• More than 1.5 million Americans use supplemental oxygen

for a range of medical conditions. When asked, users 

consistently express a desire for a lighter, more portable 

oxygen supply that lasts longer and has flow rates that 

supply the appropriate amounts of oxygen for their needs. 

Through the Air You Wear Challenge competition, NHLBI 

aimed to broadly stimulate the research and development 

of processes and technologies designed to improve the 

accessibility, efficacy, and usability of supplemental oxygen. 

The competition had two phases: one that focused on 

the concepts and feasibility of solutions and a second 

30-week phase during which teams developed working

prototypes of their solutions. During the second phase, 

NHLBI helped finalists engage with subject matter experts 

from NIH, NHLBI’s Catalyze Program, the National Science 

Foundation, the U.S. Food and Drug Administration (FDA), 

and the Centers for Medicare & Medicaid Services. In 

February 2023, NHLBI named three winning teams and 

one honorable mention. Since then, two teams successfully 

completed the competitive National Institute of Biomedical 

Imaging and Bioengineering Spring 2023 Concept to 

Clinic: Commercializing Innovation (C3i) Education 

Program, and all three winners have submitted small 

business applications to help conduct preclinical and/or 

clinical feasibility studies.

Dr. James Kiley 

@NHLBI_LUNGDir

NHLBI’s Division of Lung Diseases (DLD) supports research on the causes, diagnosis, prevention, and 

treatment of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic 

fibrosis, acute lung injury, pulmonary complications of HIV/AIDS, pediatric lung diseases, and pulmonary 

fibrosis and other rare lung disorders. DLD is led by James Kiley, Ph.D.

There were significant links 

between participants with higher 

psychosocial stress scores and 

e-cigarette use.
Highlights in

Blood Health

Investing in a Multi-Pronged 

Approach to Address 

Sickle Cell Disease

• NHLBI was pleased to learn that on December 8, 2023,

the FDA approved two gene therapies for the treatment of 

sickle cell disease in patients ages 12 years and older. NIH 

has long invested in basic genetics and genomics research, 

clinical trials, and translational medicine and social science 

studies to advance our understanding of this widespread 

illness and help develop effective therapies. However, 

these advances need to go hand in hand with scalable 

innovations that will ensure equitable access to life-altering 

care. To this end, NHLBI continues to engage in additional 

research endeavors that will minimize or eliminate potential 

risks that might be associated with such therapies.

• The Cure Sickle Cell Initiative (CureSC), an NHLBIled collaborative research effort, aims to transform the 

lives of many people affected by sickle cell disease 

by creating a collaborative, patient-focused research 

environment. CureSCi has identified and supports 

promising genetic therapies, which are currently being 

evaluated in multicenter clinical trials. Two therapies have 

been submitted to the FDA for review and approval by 

the investigational new drug sponsors; preliminary results 

from these clinical trials are expected within three to five 

years. CureSCi has focused on curative strategies that use 

genetic therapies to modify hematopoietic stem cells to 

prevent genetic mutations from making sickle-shaped red 

blood cells. This could make curative therapies available 

to a wider range of people with sickle cell disease. One 

CureSC clinical trial opened for enrollment in 2022, and 

enrollment in the second is expected to begin in the first 

half of 2024.

• In 2023, more than 20,000 people were diagnosed with

acute myeloid leukemia (AML), a group of rare blood 

cancers associated with a five-year relative survival rate 

of 31.7 percent. One method of treatment for patients 

who are in remission is a stem cell transplant from a 

donor. Unfortunately, the disease recurs in approximately 

30 percent of patients after allogeneic hematopoietic 

cell transplant and is the most common cause of posttransplant death. NHLBI researchers aimed to create 

a metric to determine whether a patient receiving an 

allogeneic stem cell transplant was at increased risk for 

subsequent relapse and death. Research suggests that 

measuring the small number of cancer cells that remain 

post-treatment, or measurable residual disease (MRD), 

may provide information regarding risk for subsequent 

relapse and mortality. However, there is no standard 

method for AML MRD testing. Researchers used targeted 

deep DNA sequencing to look for disease-associated 

variants using the blood of AML patients. Among patients 

with AML in first remission before stem cell transplant, 

the presence of two genetic variants (FLT3-ITD or NPM1) 

above a certain level was associated with increased rates 

of relapse and worse survival compared with patients 

without variants detected. This strategy may also be 

applied to diagnose and understand the etiology of other 

chronic diseases, such as sickle cell disease.

Finding New Treatments for 

Blood Clotting Disorders

• Hereditary hemorrhagic telangiectasia (HHT), also known

as Osler-Weber-Rendu disease, is a rare genetic disorder 

that affects 1 in 5,000 people worldwide. Historically, 

there have been no effective medical therapies for HHT. 

People of all ages, sexes, genders, races, and ethnicities 

are affected and experience the problems associated 

with the disorder, some of which are life-threatening. 

The Pomalidomide for the Treatment of Bleeding 

in HHT (PATH-HHT) trial explored the use of an oral 

medication called pomalidomide, approved by the FDA 

for use in some cancers, for treating HHT symptoms at 

11 research centers across the United States. NHLBIfunded researchers began to enroll adult patients with 

moderate to severe epistaxis in 2019; with the active 

support of the patient organization Cure HHT, researchers 

achieved a sufficient number of participating patients to 

conclude, earlier than expected, that pomalidomide is 

efficacious for treating HHT. The early conclusion of the 

trial for investigational drug efficacy is strong evidence that 

pomalidomide will become the first effective treatment 

option for patients with this rare disorder.

• Venous and arterial thrombotic disorders — such

as pulmonary embolism, venous thromboembolism, 

myocardial infarction, and stroke — are major causes 

of global morbidity and mortality. Certain diseases and 

10 / Highlights in Blood Health
conditions, including stroke, paralysis, chronic heart 

disease, high blood pressure, surgical procedure, or 

recent cancer treatment, can also raise a person’s 

chances of thrombosis, commonly called a blood clot. 

Women who take hormone therapy pills or birth control 

pills, are pregnant, or are within the first six weeks after 

giving birth are also at higher risk for clotting disorders. 

People who smoke and older adults (age 60 and older) are 

also at increased risk. Improved therapeutic strategies that 

diminish bleeding risk due to anticoagulants and platelet 

antagonists would have a huge clinical impact. In a recent 

animal study funded by NHLBI, researchers designed 

a new compound called macromolecular polyanion 

inhibitor (MPI-8). The compound prevented blood clots 

in mice, did not increase bleeding, and was tolerated well 

even at high doses. This finding may lead to significant 

changes in how doctors care for patients at risk for 

thrombosis without raising the risk of bleeding.

Improving the Lives of 

Those With HIV

• As people living with HIV age, they are at higher risk of

various chronic medical conditions, including hypertension 

and other forms of cardiovascular disease. NHLBI’s Heart, 

Lung, and Blood Co-morbiditieS Implementation 

Models in People Living with HIV (HLB-SIMPLe)

program is a collection of research studies co-funded by 

the NIH Fogarty International Center. Researchers from 

African and American universities are working together with 

governments, community partners, and health facilities 

to test strategies for delivering effective hypertension 

detection, prevention, and treatment initiatives to affected 

individuals. There are currently studies in Botswana, 

Mozambique, Nigeria, South Africa, Uganda, and 

Zambia. These distinctive implementation clinical trials are 

designed to test and estimate costs for strategies to foster 

sustainable and scalable uptake of effective interventions 

in routine clinical, public health, and community settings. 

These implementation studies will help ensure that all 

people living with HIV can access the care they need 

to maintain their health and well-being — beyond just 

medications to suppress HIV. Moreover, the ongoing 

methodological training opportunities supported by this 

program will increase the late-stage translation research 

workforce available to move discoveries into practice.

Improving the Availability and 

Safety of the Nation’s Blood Supply

• NHLBI started the Recipient Epidemiology and Donor

Evaluation Study (REDS) program in 1989 to protect 

the nation’s blood supply from threats, improve the 

benefits of transfusions, and reduce the risks of 

transfusions. After 30 years, now in its fourth phase, 

REDS aims to evaluate and improve the safety and 

availability of the nation’s blood supply, as well as 

the safety and effectiveness of transfusion therapies 

across the lifespan, with a new focus on understudied 

populations, including newborns, children, and pregnant 

women. This phase involves a seven-year multicenter 

program in the United States and Brazil and is charged 

with conducting epidemiologic and laboratory studies in 

blood donors and transfusion recipients.

• NHLBI funds the BLOODSAFE program, the goal of which

is to enhance the availability and delivery of safe blood for 

transfusion into patients from low- or lower-middle-income 

countries in sub-Saharan Africa. BLOODSAFE supports 

projects that develop and test effective and sustainable 

strategies to increase the number of safe blood donors. 

It also aims to improve the quality and safety of blood 

supplies and enhance blood delivery to patients in need, 

especially in remote settings.

Dr. Julie Panepinto

@NHLBI_BLOODDir

NHLBI’s Division of Blood Diseases and Resources (DBDR) leads research on the causes, prevention, 

and treatment of congenital and acquired blood diseases. The program also helps ensure the safety of the 

world’s blood supply and supports stem cell biology and new gene- and cell-based therapies to repair and 

regenerate human tissues. DBDR is led by Julie Panepinto, M.D., M.S.P.H.
“

Highlights in 

Sleep Health

Studying Sleep Health 

Across the Lifespan

• In a recent NHLBI-funded study, researchers gathered

data from wearable devices, similar to Fitbits or 

Apple Watches, from more than 1,000 women 

during pregnancy. Feeding the data into a new artificial 

intelligence algorithm, the researchers were able to 

detect even minute changes in sleep and physical activity 

during pregnancy. The algorithm also used the data to 

build a “clock” that was able to predict how far along a 

pregnancy was. In typical pregnancies, as the women 

advanced toward later-stage pregnancy, they became less 

physically active and their sleep more disrupted. However, 

some women’s sleep and activity patterns changed on 

a faster timeline relative to how far along they were in 

their pregnancies, with those women sleeping less and 

becoming more sedentary earlier in their pregnancies. 

The study found that these individuals were more likely to 

have a preterm birth. The results suggest that continuous 

monitoring of sleep and activity throughout pregnancy may 

enable doctors to better support patients who could be at 

higher risk of preterm birth.

• Researchers recently found that surgical removal of the

tonsils and adenoids in children with snoring and mild 

breathing problems during sleep appears to improve 

their sleep, quality of life, and blood pressure a 

year after surgery. The study is believed to be the 

first large randomized trial to address the effects of 

adenotonsillectomy on children with mild sleep-disordered 

breathing (SDB). During the trial, half the participants 

received an adenotonsillectomy, and the other half 

received supportive care without surgery, including 

standardized education on healthy sleep and lifestyle and 

referral for untreated allergies or asthma. Researchers 

then evaluated neurodevelopmental, behavioral, health, 

and sleep-related outcomes in both groups, using 

measurements of attention and executive function, which 

includes a set of cognitive skills that help children manage 

everyday activities. Sleep outcomes were measured by 

polysomnography, a standard sleep test that measures 

breathing, heart rate, eye movement, and other factors. 

Secondary results showed several beneficial changes in 

the surgery group: less daytime sleepiness, reduced SDB, 

less snoring, fewer behavioral problems, better quality of 

life, and lower blood pressure. The children treated with 

surgery were also less likely to show disease progression 

into full-blown sleep apnea.

• According to a recent study, chronic insufficient sleep

can increase insulin resistance in otherwise healthy 

women, with more marked effects in postmenopausal 

women. Previous studies have shown that sleep restriction 

can elevate risk for conditions such as cardiovascular 

disease, hypertension, and disordered glucose 

metabolism, which can lead to insulin resistance and 

type 2 diabetes. However, many of those studies were 

done only in men or focused on short-term, severe sleep 

restriction. The current study enrolled only women and 

sought to determine whether a prolonged, mild restriction 

of sleep — a reduction of just 1.5 hours each night — 

increased women’s blood glucose and insulin levels. The 

findings highlight the importance of adequate sleep in 

minimizing the risk for type 2 diabetes, which can develop 

when the body fails to effectively use a key hormone, 

insulin, to maintain healthy blood sugar levels.

12 / Highlights in Sleep Health

Continuous monitoring of 

sleep and activity throughout 

pregnancy may enable doctors 

to better support patients 

who could be at higher risk of 

preterm birth.
“

Developing New Diagnostic Tools

Obstructive sleep apnea (OSA) is one of the most 

prevalent chronic sleep disorders, estimated to affect up 

to 30 million people in the United States. It is associated 

with an increased risk for cardiovascular disease and 

mortality. The primary diagnostic tool for OSA is the 

apnea-hypopnea index (AHI), which measures the 

average number of times per hour breathing either 

partially or fully stops during sleep; however, the AHI has 

limitations. NHLBI-funded researchers have developed 

a more accurate tool for diagnosing OSA, using 

a metric called ventilatory burden (VB), that effectively 

captures breath-by-breath reductions in airflow and 

isolates the purely ventilatory burden of the disorder. 

The researchers leveraged data from four different NIHfunded cohorts to derive the normative range of VB from 

analysis of more than 34 million breaths. The team then 

assessed the relationship between the degree of upperairway obstruction and VB and, using a unique algorithm, 

the relationship between VB and mortality risks, including 

cardiovascular disease and hypertension. Their method 

effectively assessed the severity of OSA and predicted 

mortality associated with cardiovascular diseases, 

potentially making it a more successful diagnostic tool 

than the AHI. The team now plans to use an artificial 

intelligence algorithm along with the VB measure 

to identify patients who will benefit from continuous 

positive airway pressure treatment.

Dr. Marishka Brown

The National Center for Sleep Disorders Research (NCSDR) supports research on the causes, diagnosis, 

prevention, and treatment of sleep disorders. NCSDR is led by Dr. Marishka Brown, Ph.D.

OSA is one of the most 

prevalent chronic sleep 

disorders, estimated to affect 

up to 30 million people in the 

United States. It is associated 

with an increased risk for 

cardiovascular disease and 

mortality.
“

Highlights in

Translation Research 

and Implementation 

Science

Working with Communities to 

Create Meaningful Change

• In July 2020, NHLBI and the National Institute on Minority

Health and Health Disparities (NIMHD) started the 

Community Engagement Alliance (CEAL) to establish 

a research approach that ensured the participation of 

racial and ethnic minority communities in COVID-19 

vaccine research trials that were underway. Moving 

forward, CEAL’s successes provide a foundation for 

broadening its mission to address the host of health 

disparities that plague the very same communities. 

CEAL teams are located in 21 regions across the 

country, leverage existing relationships and partnerships, 

and recently expanded activities to address state and 

local concerns, including social determinants that 

challenge health within specific communities.

• NHLBI is leveraging this community engagement

research platform to support scientific initiatives that 

address other major public health issues, including 

maternal health and the impact of climate on health in 

areas across the country. NHLBI is utilizing the lessons 

learned through CEAL to enhance research within 

American Indian, Alaska Native, Asian, Native Hawaiian, 

and Pacific Islander communities and is partnering with 

other NIH programs to address other research priorities, 

like the National Human Genome Research Institute’s 

interest in improving understanding of and participation 

in genomic research. Through meaningful community 

engagement, CEAL has the potential to transform 

discovery into health impact and reduce disparities.

• The Maternal Health Community Implementation

Project (MH-CIP) is a community-driven initiative that 

uses evidence-based interventions, such as regular blood 

pressure readings, to help reduce cardiac risk factors 

before and during pregnancy. Through this program, 

NHLBI supports four community coalitions, consisting 

of research organizations and community partners, to 

engage communities and pilot-test the implementation of 

proven interventions in vulnerable populations. In addition 

to involving community coalitions, MH-CIP includes patient 

advocacy groups and subject matter experts in both 

governance and guidance roles.

• Because of CEAL’s success, the program’s funding

has also been sustained in order to leverage it as a 

comprehensive research platform to address health 

disparities. Additional scientific initiatives have already been 

incorporated, and other NIH Institutes are also leveraging 

CEAL to address other major issues of public health. In 

addition to MH-CIP, examples include the Implementing a 

Maternal Health and Pregnancy Outcomes Vision for 

Everyone (IMPROVE) initiative and the Climate Change 

and Health Initiative. CEAL has become a powerful, 

strategic research resource that enables NHLBI and other 

NIH Institutes to work alongside and within communities to 

meet their missions.

NHLBI is leveraging this community engagement research platform 

to support scientific initiatives that address other major public 

health issues, including maternal health and the impact of climate 

on health in areas across the country. 

14 / Director’s Message: Advancing Heart, Lung, Blood, and Sleep Research
“

Leveraging Data Science 

to Advance Health 

Disparities Research

• Heart and lung disease are the leading causes of illness

and death in the United States, and the disease burden

is unequal across groups defined by race, ethnicity, sex,

gender, and socioeconomic status. Numerous programs

have been proven to reduce heart or lung disease, but

too often they are not put into practice in the communities

where they are most needed. In September 2020,

the Disparities Elimination through Coordinated

Interventions to Prevent and Control Heart and

Lung Disease Risk (DECIPHeR) Alliance was created,

consisting of seven implementation research centers

throughout the country.

• This seven-year (2020–2027) cooperative agreement has

two phases. The first phase (2020–2023) was exploratory,

including community engagement activities such as

establishing community advisory boards and working

Heart and lung disease are the 

leading causes of illness and 

death in the United States, and 

the disease burden is unequal 

across groups defined by race, 

ethnicity, sex, gender, and 

socioeconomic status.

with high-burden communities to articulate locally relevant 

implementation strategies. The second phase, which 

began in 2023, builds on connections made and lessons 

learned in the first phase to test implementation strategies 

for optimally and sustainably delivering evidence-based 

multilevel interventions in clinical practice and community 

settings to reduce or eliminate cardiovascular and 

pulmonary health disparities.

Dr. George Mensah 

@NHLBI_TRANSLATE

NHLBI’s Center for Translation Research and Implementation Science (CTRIS) supports research 

addressing both domestic and global health disparities and inequities and provides training and career 

development opportunities in these areas. CTRIS is led by George Mensah, M.D., FACC.
This document honors the legacy of 

Dr. Claude Lenfant, NHLBI’s Director 

from 1982 to 2003. His years of 

dedication to research on heart, lung, 

blood, and sleep health paved the way 

for today’s advances. 

1928-2023
March 2024 | www.nhlbi.nih.gov

Twitter: twitter.com/nih_nhlbi | Facebook: facebook.com/nhlbi