Rhode Islanders with lung diseases can now get the latest in care right at home.
When she fainted, Jennifer M. was in the Ft. Lauderdale airport, traveling home to Queens, NY, from Costa Rica, where she had gone to mark the one-year anniversary of the death of her mother, who was buried there. She remembers telling an immigration officer that she was nervous about missing her connecting flight. Then—nothing. When she came to, in an ambulance, she felt so much better that she thought she was high.
“This is heaven,” Jennifer told the paramedic. “What drug are you giving me?”
It was oxygen.
The year before, in March 2015, the otherwise healthy 40-year-old mother of three noticed that she was increasingly short of breath. Eventually she couldn’t walk a fraction of a city block or climb more than three steps in the subway without having to stop and rest. Suspecting heart disease, she consulted a cardiologist, who instead diagnosed her with pulmonary arterial hypertension, a rare, progressive disease in which the tiny arteries in the lung narrow and thicken, raising the blood pressure in the lungs and causing strain on the heart. By 2017, Jennifer says, simply walking her son to school was “torture.”
Jennifer is not alone. According to the American Lung Association, women between 30 and 60 years of age are more likely to suffer from PAH, which also disproportionately affects Black and Hispanic women.
“With PAH you inhale as much you can, but it’s like your lungs are not taking in oxygen at all,” Jennifer says. “You feel like you have a plastic bag over your head. You wish you could just breathe through your skin.” When she decided to move the family to Rhode Island, where her partner had relocated for work, her cardiologist gave her the name of a doctor he knew there.
“You’re going to be seen by the best of the best,” he told her.
He was referring to Corey E. Ventetuolo RES’07, MD, MS, an associate professor of medicine at The Warren Alpert Medical School and a pulmonary and critical care physician specializing in PAH. Ventetuolo took Jennifer on as a patient and has been treating her ever since. When Jennifer’s condition continued to worsen, Ventetuolo was able to enroll her in a clinical trial of the drug sotatercept-csrk, a first-in-class molecule that directly targets the disease’s major biologic pathway. The drug is administered by injection every three weeks. Jennifer started feeling better after the third dose.
“I’m getting the best medical care in Rhode Island,” Jennifer says. “Dr. Ventetuolo; Mary Whittenhall, her nurse practitioner; my cardiologist, my neurologist— I trust them. They communicate with each other about my treatment plan. They’re all on the same page.”
That “on-the-same-page” approach is one of the defining characteristics of the recently opened Center for Advanced Lung Care, which Ventetuolo oversees and where Jennifer now receives her care. The center’s mission is to provide comprehensive, state-of-the-art care to patients with advanced lung and heart-lung diseases. Located in Providence, the CALC has brought many of the Medical School’s internationally recognized pulmonary programs and practitioners under one roof, and offers destination care for pulmonary hypertension, acute and chronic pulmonary embolism, interstitial lung disease, pregnancy-related breathing disorders, and advanced airways disorders such as severe asthma and chronic obstructive pulmonary disease, or COPD. It also features an Advanced Lung Nodule Program, for early detection of lung cancer.
With a footprint of 3,500 square feet and plans to expand, the center also houses a wide range of testing capabilities, including echocardiography, pulmonary function testing, exercise testing, and laboratory and radiology. Crucially, this means that CALC patients, for whom traveling from one location to the next is burdensome, can undergo evaluation and see their provider at the same time, in the same place.
But that’s not all. Unlike the country’s other top lung care centers, Ventetuolo says, the CALC was designed to care for the “whole patient” by providing integrated wraparound services: dedicated pharmacists, to supply the specialty medications used to treat complex lung diseases; psychologists, to provide patients with support as they cope with the anxiety, depression, and other mental health challenges that can accompany these conditions; nurses and advanced practice providers such as nurse practitioners and physician’s assistants, to help patients manage the day-to-day details of their health; and, importantly, navigators, to advocate for patients and help guide them on what is often a complicated health care journey.
“These patients have complex conditions that require a higher level of care,” says Professor of Medicine Ghada Bourjeily, MD, a pulmonologist who runs the CALC’s Pregnancy-Related Breathing Disorders Program (see sidebar, p. 23). “Having the right people in the right place assisting patients means we don’t have to refer them across town” for different components of their treatment, “so patients are not overwhelmed by their chronic conditions, and they feel well taken care of.”
Providing this high level of transformative care is important to Ventetuolo, a native of Cranston. “One of the things I’m passionate about is giving back to my community and making sure Rhode Islanders get world-class care,” she says, adding that she hopes the CALC will become a national referral center.
Under One Roof
That’s great news for patients in the Ocean State—as well as in neighboring Connecticut, Massachusetts, and beyond—who have chronic thromboembolic pulmonary hypertension, or CTEPH. A pulmonary embolism occurs when a blood clot forms, often in a deep vein in the leg, travels to the lung, and blocks an artery there; with CTEPH, such clotting becomes chronic, creating scar-like tissue in the pulmonary arteries. The result is reduced blood flow to and increased blood pressure in the lungs. Unlike acute pulmonary embolism, which can be addressed with anticoagulants, or blood thinners, these clots cannot be effectively treated with such medication alone.
But while CTEPH can lead to heart failure and death, it can also be treated. This is done primarily through a highly complex surgical procedure known as pulmonary thromboendarterectomy, or PTE, which involves connecting the patient to a cardiopulmonary bypass machine, radically cooling the body to stop circulation, and then surgically removing all the clots through an incision in the chest. Pioneered in the 1970s at the University of California, San Diego, the technique has been refined elsewhere over decades. Today, PTE is still available at only a few sites in the country—and the CALC is now one of them.
“When I first started here, we had to send patients diagnosed with CTEPH elsewhere,” says Assistant Professor of Medicine Chris Mullin, MD, MHS, a pulmonary and critical care specialist and director of the CTEPH Program. That meant losing significant control over his patients’ care, he says—not to mention the fact that some patients simply refused to travel. Now they won’t have to.
Not all patients are candidates for PTE, however. For those who aren’t, the CALC offers another, more recently developed and less invasive procedure, balloon pulmonary angioplasty. During BPA, a thin catheter is threaded through veins to get to the right heart and pulmonary arteries; a small balloon at the end of the catheter is then inflated, widening blocked passages and improving blood flow. The procedure is repeated several times over many weeks.
But before any of that can happen, a patient must know they have the condition, and CTEPH is underdiagnosed and underrecognized by clinicians, Mullin says. He is eager for pulmonologists and cardiologists in the community to refer patients who are short of breath or not symptomatically recovered after a pulmonary embolism to the CALC. There, he can administer the not-insignificant series of tests and procedures necessary to diagnose the condition, and then determine a treatment plan. He, Ventetuolo, and other physicians regularly review cases together. “That’s the strength of this program,” Mullin says. “We can access the expertise of all these different subspecialists to come up with the best treatment plan.”
Cool Tools
Assistant Professor of Medicine Douglas Martin RES’06 F’10, MD, an interventional pulmonologist, sees the CALC as a potential “magnet”—not just for patients, but also for physicians who, like him, want to provide the latest in diagnostic procedures. Martin is excited by the recent acquisition of cutting-edge tools that improve the ways physicians can evaluate spots or shadows on the lungs that have shown up on a chest x-ray or CT scan.
One of these, an endobronchial ultrasound system (EBUS), can be threaded down the trachea and into the lungs to explore and biopsy airway-adjacent masses. (A conventional radiologist, on the other hand, inserts a needle through the chest wall and into the lung, which has the potential to cause bleeding and lung collapse.) In addition, the EBUS can be used to obtain a biopsy of the lymph nodes as well as the masses. Another technology, called navigational bronchoscopy with cone beam CT, uses a catheter synchronized to the patient’s CT scan data to provide a three-dimensional image that helps guide a needle with precision into a pulmonary nodule; the cone beam CT provides a single-slice CT confirmation, allowing a high degree of precision when performing a biopsy. Martin and Assistant Professor of Medicine Andrew Foderaro RES’14 F’17, MD, director of bronchoscopy for Rhode Island and The Miriam hospitals, perform three to four such procedures every Monday morning as part of the CALC’s Advanced Lung Nodule Program. When a mass is deemed malignant, the patient is referred to the Lifespan Cancer Institute.
Martin also is part of the center’s Interstitial Lung Disease Program. ILD refers to a group of disorders that can cause scarring in the lungs, making it hard to breathe. The CALC is well suited to ILD patients, he says, many of whom require complex, long-term care. He and Caitlin Butler, MD, an assistant professor of medicine and an ILD specialist, evaluate patients at the center— taking a thorough history (as some ILD can be caused by environmental exposure, inhalation, or autoimmune disease), doing extensive blood work, sometimes even taking a lung biopsy—and then develop a multidimensional treatment plan. Such a plan can include medication, psychosocial support, oxygen therapy, and longitudinal monitoring, including for toxicity of the treatments themselves, Martin says.
Steady Growth
The Medical School’s strength in understanding, diagnosing, and caring for diseases of the lung isn’t new. Professor of Medicine James Klinger F’91, MD, has been researching and treating pulmonary hypertension here since the late 1980s, before there were many treatment options. Most of his patients—most of them women—died.
But 1991 saw the formation of what became the Pulmonary Hypertension Association, an advocacy, awareness, and education group with a mission to increase understanding of the rare disease. That year, Klinger and his mentor, pulmonologist and former Professor of Medicine Nicholas Hill, MD, established the Pulmonary Hypertension Center at Rhode Island Hospital. They began appealing to area physicians to send them their patients with PH for treatment, and enrolled them in clinical trials. At the same time, more and more medications were being shown to be effective in managing the disease. In 2011, Klinger recruited Ventetuolo, who was finishing a research fellowship and on faculty at Columbia University, and hired nurse practitioner Mary Whittenhall. Two years later, the PHC received certification by the Pulmonary Hypertension Association as a center of excellence—the sixth in the country and the first in New England to do so. In 2017, the PHC moved to a larger facility in East Providence, making it possible to take on more patients. When the CALC opened in August, it welcomed the PHC’s busy outpatient practice of 400 to 500 patients, and Klinger hopes to expand the practice further.
“When you develop a center like this, you have to staff it not just with experts, but with experts who have access to a large number of patients. Because the more patients you treat,” he says, “the better the care.”
What’s more, the PH practitioners are all involved in robust bench-to-bedside research, so they can give patients access to the most novel medications being studied in clinical trials. For example, in March, to great fanfare, the FDA approved WINREVAIR, the brand name of the injectable drug in Jennifer’s trial, for adults with PAH; because she was in the trial, she had access to this drug before it was approved and will continue to, during a time when access is still limited. The PH physicians are currently onboarding five new clinical trials in partnership with industry to test novel compounds in patients with PH and ILD. One such trial, which got underway last year, is testing a new, injectable medication that has never been used in PH.
“When I started treating pulmonary hypertension, there were no medications,” Klinger says. “All of the meds patients are on now—we participated in the clinical trials that led to their approval.”
Still, most PH patients have to be on three to four medications, all of which carry high costs and significant side effects, according to Ventetuolo, and finding the right combination requires some trial and error. To bypass that, she and colleagues at Brown and the University of Maryland are pioneering a novel approach: following catheterization of the patient’s right heart (part of the standard diagnostic workup), they culture the diseased blood vessel cells that have adhered to the balloon to obtain their genetic signature. They hope to be able to use an innovative network medicine pipeline to inform treatment selection at the bedside. “The dream is point-of-care testing, where we could precisely tell a patient which drugs, both approved and investigational,” will be most effective for them, Ventetuolo says.
Like Klinger, Ventetuolo remembers a time when many patients died of PAH, and acknowledges that much progress has been made. “A patient would walk in hopeless or bewildered about why they’re out of breath, unable to do their basic daily living activities,” she says. Now, “I’ve seen people return to work. I’ve seen people travel. I’ve seen people get their lives back.”
Recalling a recent visit by a patient he hadn’t seen in several years, Klinger notes something else that’s changed: “The patient told me that when she was first diagnosed, she was told to go to Boston. Now, she said, that same organization told her to come to us.”
Klinger, who directs the CALC’s Pulmonary Hypertension Program, notes that consolidating testing, treatment, and trials, not to mention implementing a new patient portal that facilitates patient-provider communication, is convenient. But, he says, the center offers much more than that: “It’s access to physicians who have a long experience, not just by themselves but as a team. Now we can all work together and hone our practice.”
- In the early 2000s, shortly after pulmonologist and obstetric medicine specialist Ghada Bourjeily began working at Women & Infants Hospital, she noticed that some of her pregnant patients with obstructive sleep apnea were also developing preeclampsia, a form of high blood pressure that occurs after 20 weeks of pregnancy. She wondered if sleep-disordered breathing (a.k.a. snoring), maternal health, and pregnancy outcomes might somehow be connected.
As it turns out, they are. In 2010, Bourjeily authored what would become one of many papers that have since shown that sleep-disordered breathing during pregnancy is associated with a slew of negative outcomes. These include preeclampsia and gestational diabetes; severe complications, such as cardiomyopathy, congestive heart failure, and pulmonary edema; and an increased risk of hysterectomy and admission to the ICU for the mother and pre-term birth and congenital abnormalities for the child. In fact, not only do preeclampsia and gestational diabetes have a harmful impact on the mother, fetus, and newborn, but the diseases also adversely affect women’s and children’s metabolic and cardiovascular health over the long term. (Recent research has shown that Hispanic/Latina women who had high-blood-pressure-related complications during pregnancy are, 10 or 15 years later, more likely to have changes in heart structure and function—which in turn can be predictors of heart failure and death.)
“We know that drops in oxygen level and adrenaline spikes several times a night impact organs like the heart, kidney, or brain in the non-pregnant population. Things that are dependent on those organs’ function are also likely affected,” Bourjeily says. “So when a woman’s breathing is disturbed during sleep—which is very common in pregnancy—it may impact her whole biological system. That includes the placenta, which sends nutrients and delivers oxygen to the fetus.”
Bourjeily’s current research involves harnessing AI to identify abnormalities in breathing patterns. She is also working with international experts to develop guidelines for obstructive sleep apnea and pregnancy, and on labor, delivery, anesthesia, and pain medication in the context of women with sleep-disordered breathing.
Like Corey Ventetuolo, Bourjeily is very interested in how sex and gender impact lung disease, and hopes that more fellows and faculty will develop an interest in the women’s-health angle too. She also hopes to bring sleep services to the center: “If a patient is here and they have pulmonary hypertension and we suspect they might have sleep-disordered breathing as well, it would be great if we could do the testing and treat them all in one place.”
Doing Right By Rhode Island
In addition to growing research funding and providing high-end care, Ventetuolo hopes that the CALC will help address unmet patient needs in Rhode Island caused by the state’s shortage of pulmonary docs. This can happen not only by attracting pulmonologists to the center, but also by creating a pipeline of future specialists through fellowship training. Starting next year, she says, the CALC will offer cardiology and pulmonology fellows an additional year of training in advanced lung disease. In this way, she hopes, the new center can help reduce the number of people in the region who are still awaiting care.
Klinger is optimistic: “When trainees see the high level of care in a specialty center like this, it really drives their enthusiasm.”
Martin, who originally wanted to become an interventional cardiologist, agrees. “There’s a saying in pulmonary/ critical care medicine fellowship training: ‘People come for the critical care, but stay for the pulmonary,’” he says. “One of the things that attracted me to pulmonary/critical care—and I think this is probably true of other people—is the diversity. In the ICU, we take care of all sorts of stuff, because pulmonary medicine touches a lot of different fields.” Plus, it’s an exciting time to be in this field, he adds. “If you look at cystic fibrosis, asthma, lung cancer, there’s an explosion in new treatments.”
Yet while much progress has been made, living with lung disease remains challenging. Pulmonary arterial hypertension has taught Jennifer something she wishes everyone understood: “Just to breathe is a luxury.”
