Nina Ireland: Transforming Lung Health

reprinted from Issue 15, Fall 2012 of Frontiers of Medicine (PDF)

“In all the time I talked to her, she never mentioned her bequest plans. This gift is profound. It gives us the opportunity to catalyze transformational changes in how we treat lung disease.”

– Jeffrey Golden, MD, Nina Ireland Distinguished Professor in Pulmonary Medicine

From left: Drs. Dean Sheppard, Steve Hays, Paul Wolters and Jeffrey Golden. Not pictured are Drs. John Balmes and Hal Collard.

Nina Ireland

Nina Ireland suffered from emphysema for decades. But with excellent selfcare and the help of her longtime doctor, UCSF pulmonologist Jeffrey Golden, MD, she lived an active life, tending her beautiful gardens and walking the San Francisco hills with her beloved German shepherds. After a brief illness, Ireland, 67, died in October 2010.

A few weeks later, UCSF learned some astonishing news: Nina Ireland had left almost her entire $48 million estate to the UCSF Division of Pulmonary Medicine, to be directed by Golden. Her bequest, the largest ever given to UCSF and likely the largest gift to pulmonary medicine, created the Nina Ireland Lung Disease Program. Today, the endowment's income is starting to have a real impact on UCSF's efforts to build and sustain the world's leading program for clinical care, training and research in lung disease.

"Dr. Golden was a true hero to her," says Philip Spalding, Ireland's attorney and trustee. "She thought the world of him, and believed his work was so important. She had no children, and did not have other charities that were as important to her. It meant a lot to her to be able to do this."

Ireland was already a generous supporter of UCSF, previously funding the Nina Ireland Distinguished Professorship in Pulmonary Medicine – a position Golden currently holds – the Nina Ireland Distinguished Professorship in Child Psychiatry, and the Nina Ireland Laboratory of Developmental Neurobiology. Yet her bequest surprised everyone.

Simple Lifestyle, Exceptional Generosity

In 1916, Ireland's great-grandfather purchased the Birmingham Slag Company. Her father was eventually elected president of the company, which later became the Vulcan Materials Company. Today, it is the country's largest producer of construction materials such as crushed stone, sand and gravel.

Ireland was born in Birmingham, Alabama, one of five girls. She graduated from Chatham Hall, a boarding school in Virginia, and attended Rollins College in Florida. She moved to San Francisco, lived for a while in the Mission District, and was married briefly. She worked as a bank teller, and then held a government job.

She lived modestly, shying away from the limelight. "She wasn't a society person by any means," says Spalding. However, she enthusiastically renovated her Pacific Heights home, and often worked alongside her gardener to cultivate her exquisite yard. Ireland enjoyed art, collecting everything from ancient Chinese vases to delicate glass paperweights with floral designs, and she herself painted, mostly watercolors.

"She was extremely intelligent and well-read, and loved to talk," says Spalding. "She also liked having a strong hand in the management of her finances, and would study the market. She was very much her own person. It was a great honor to be her attorney, because she was interesting, generous and wanted to do good things.

“Dr. Golden was a true hero to her. She thought the world of him, and believed his work was so important.”
– Philip Spalding, Attorney and Trustee to Nina Ireland

Jeffrey Golden, MD (above), with patient Michele DesMarais

"Dr. Golden helped her a lot," says Spalding. "I think his work was important for her living as long as she did, because she had pretty severe emphysema. She knew this would be an extraordinary gift, and thought that Dr. Golden would do right by it." Because Ireland's instructions for the gift were broad – just two sentences in her will – Golden worked closely with internal and external advisory boards to develop a wise stewardship plan. Together, they chose to support the research programs of budding fellows and junior faculty, establish a biorepository and clinical database and focus on four thematic areas of particular interest to Ireland: interstitial lung disease (ILD), lung transplantation, pulmonary rehabilitation, and global lung health and the underserved.

Investing in the Next Generation

Already, the funds have made an impact. "We are enthusiastic about the ways the Nina Ireland gift is supporting people," says Dean Sheppard, MD, chief of the Division of Pulmonary, Critical Care, Allergy and Sleep Medicine at UCSF Medical Center. The division has one of the world's leading fellowship programs, and provides extensive research and clinical training to young doctors who want to become pulmonologists. So far, the funds have helped 12 fellows enrich their educational experiences, as well as six junior faculty members who are establishing their own independent laboratories.

"We will have the biggest impact on lung disease around the world by investing in people early in their careers, making sure that they are primed to accomplish the most they possibly can," says Sheppard.

The funds have also been instrumental in recruiting two new faculty members – Steven Hays, MD, medical director of the lung transplantation program, and Anthony Shum, MD, who conducts research on the causes of interstitial lung disease, with a third recruitment in process. In addition, they are helping support Jasleen Kukreja, MD, MPH, surgical director of the lung transplantation program.

The Ireland gift's reach has extended to all UCSF campuses, providing funding for the John Murray Distinguished Professorship, which supports the chief of the Division of Pulmonary and Critical Care Medicine at San Francisco General Hospital (SFGH), and providing ongoing support to the San Francisco Veterans Affairs Medical Center's Division of Pulmonary and Critical Care Medicine. It also created an Opportunity Fund open to all UCSF faculty, which will provide seed money for innovative research projects in lung disease. In the first round, faculty submitted 40 applications, and an expert panel of basic, translational and clinical scientists chose six projects for funding.

The Ireland funds have also brought leading scientists, researchers and clinicians together to brainstorm about the development of a transformative research initiative. While the discussions are still in the early stages, one big idea is "lung regeneration" – discovering ways to help damaged lungs repair themselves.

Building Research Tools

The Nina Ireland Lung Disease Program is also supporting the development of a more robust biorepository and clinical database, which will provide a wealth of information to researchers. Paul Wolters, MD, who is overseeing this initiative, began collecting blood and tissue samples of lung fibrosis patients 12 years ago. Other UCSF colleagues have made similar efforts over the years, and the ILD Program developed a clinical database with detailed information about patients who donated tissue. But without dedicated funding, it was difficult to collect information and specimens in a comprehensive way. The Ireland funds provide core support for the processing and storage of specimens and for the development of a web-based clinical database focusing on lung transplant, ILD, granulomatous disease (a specific type of ILD), and scleroderma, an auto-immune disorder that can affect the lungs, skin and joints.

The enhanced biorepository and database helped to spark a new partnership with Stanford – called the Northern California Scleroderma Research Consortium – involving pulmonologists, dermatologists and rheumatologists. Although individual patient records will be shielded to protect anonymity, researchers from either institution will be able to use these patient data and biosamples to conduct research.

"The power is in numbers," says Wolters. The UCSF-Stanford collaboration will give researchers access to information about more patients with this rare disease. And because the database is web-based, it will be easy to invite other institutions to participate, supporting national and even international collaborations. The web interface also allows patients to answer symptom questionnaires online, further increasing the information available to researchers and reducing the data entry burden on staff. This model of data sharing could also be adapted to other areas of pulmonary research.

"We're excited," says Wolters. "This is an ongoing, longitudinal, multiinstitutional, and hopefully one day multinational effort, with a very sophisticated level of detail related to patients with scleroderma. The Nina Ireland funds are helping things we have talked about for years actually happen."

ILD and Lung Transplant

For many years, UCSF has been a leader in treating patients with ILD, a set of conditions involving fibrosis or scarring of the lungs. Many of these conditions are progressive and fatal. "I view the Ireland funds as a source of support for the ILD Program's goals in the areas of patient care, education and research," says Harold R. Collard, MD, the program's director. "We've grown a lot in the last five years, and we want to continue that growth. It's always a challenge to have the people and the time to do what you want to do, so this financial support can help us focus on our goals."

"Although she never wanted a lung transplant, Nina was just fascinated by it," says Golden. UCSF has performed more than 340 lung transplants since the program was established in 1991, and currently performs between 40 and 50 transplants annually. Despite caring for some of the most complex patients, the UCSF program's outcomes are excellent: half of patients who receive lung transplants live for at least seven years, compared to a national average of only five and a half years. However, for reasons that are not well understood, nationally, survival rates are lower for lung transplant than patients who receive other transplanted organs, such as heart, kidney and liver, and have improved only marginally in the last 20 years. "We are hoping to use the resources from the Nina Ireland Lung Disease Program to better understand the issues related to improved survival after lung transplantation," says Hays. For example, funds are supporting Mark Looney, MD, in developing a mouse model of lung transplant to study what happens to transplanted lungs during rejection. In another project, Jonathan Singer, MD, is investigating factors that may impact a patient's quality of life before and after lung transplant.

Michael Matthay, MD, and Kukreja have received support to implement a new technology called ex vivo lung perfusion, which could increase availability of donor lungs. Currently, about 70 percent of donor lungs are discarded because they do not meet transplantation criteria, but up to half of these discarded organs might become suitable if conditions such as infection and inflammation could be treated prior to transplant.

After lungs are removed from a donor, ex vivo lung perfusion ventilates them, supplies them with oxygen and removes carbon dioxide. This allows more time to evaluate the organs to determine their suitability for transplant. Eventually, this technology may allow the team to administer antibiotics, steroids and other medications to these "lungs in a box" to treat pneumonia and reduce inflammation. Similar technology has been successfully used in Europe and Canada. "We hope to take lungs that would otherwise be denied for transplantation, improve the viability of the organ, and potentially even administer treatments that may make the transplant more successful," says Hays. "We are also planning to use this technology to look at possible ways to heal lung injury using stem cells."

"The ability to lead a program that can do innovative projects is very appealing," says Hays. "This funding is allowing projects to take place that otherwise we would have a hard time getting started. We are building a comprehensive spectrum of research, which will improve outcomes in all areas. Through all of these efforts, we want to be a transformative program in lung transplantation."

Pulmonary Rehabilitation

The Nina Ireland Lung Disease Program will also help patients maximize their quality of life – something that Ireland herself did by self-managing many aspects of her disease. "She knew how to measure her lung function at home, and set up nebulizers to help her inhale medicines," says Golden. "She was into every kind of exercise, and would take her German shepherd, Star, up the hills and around the city."

"We don't have cures for many lung diseases, and a lot of our patients suffer quietly," says Michelle Milic, MD. "Often, when someone has shortness of breath, they tend to do less, get more deconditioned, and become more short of breath. It's a vicious spiral, where even the simplest of tasks can be overwhelming. Patients can get very depressed and anxious, often withdrawing from their social circles. Yet many of these things can be addressed and improved."

To accomplish this, Milic is developing an interdisciplinary pulmonary rehabilitation program, which will include education, exercise and symptom management. Particularly with chronic obstructive pulmonary disease (COPD), such programs have been shown to help patients better control their symptoms, avoid unnecessary hospitalizations and improve their quality of life.

A typical program has group exercise sessions twice a week for six to eight weeks. Patients' blood pressure, heart rate and oxygen levels are monitored, and staff develops an exercise regimen for each patient, which includes cardiovascular activity and strength training. Patients also learn about topics such as nutrition, how to use their inhalers, and stress reduction.

"Pulmonary rehabilitation can empower patients to understand more about their disease, become more involved in their own health, and know what to expect as their lung disease advances," says Milic. "The program helps them with their physical level of function, and also helps with the psychosocial and sometimes spiritual aspects of their care. If a patient's goal at the beginning of rehab is to dance at his or her granddaughter's wedding, and you make that happen, that's a really lifechanging moment."

She will work with DorAnne Donesky, RN, PhD, NP, to study the long-term effects of pulmonary rehabilitation. The program will also help trainees gain experience in providing more extensive symptom management and advance care planning for patients with lung disease.

"I hope the program will eventually provide a holistic, world-class level of care for patients, along with a robust research arm, and that we'll be able to match the impact of some of the great basic science discoveries that UCSF has made in pulmonary medicine," says Milic.

Global Lung Health and the Underserved

Ireland wanted UCSF discoveries to reach patients who needed them, both locally and globally. "Although she was raised in wealth and had wealth at the end of her life, she saw people who did not have the resources that she had," says Golden. "She felt very strongly that they should get more, and also wanted discoveries from a place like UCSF to be transmitted worldwide."

COPD – a condition whose symptoms include cough, fatigue and shortness of breath – is a major problem both in San Francisco and worldwide, and the fourth leading cause of death globally, according to the World Health Organization. "Probably the biggest cause of COPD in women in the developing world is exposure to biomass smoke from cooking with wood and other solid fuels," says John Balmes, MD, a pulmonologist at SFGH who has a joint appointment at the UC Berkeley School of Public Health.

Recently, Secretary of State Hillary Rodham Clinton brought media attention to the health impacts of biomass smoke exposure. Yet more research is needed to identify scientifically proven ways to prevent or reduce biomass smoke exposure in these resource-poor communities. Balmes received Ireland pilot funds to test whether several different stoves that are affordable can reduce exposure. "There are all these stoves out there, but whether they work or not is another story," says Balmes.

In collaboration with UC Berkeley professor Kirk Smith, MPH, PhD, and partners at the University del Valle de Guatemala, Balmes will distribute stoves to Guatemalan volunteers with COPD. Although the new stoves still produce some smoke, a built-in fan helps them burn wood more cleanly. The study will measure lung function and biomarkers in sputum and blood, both in women who receive the new stoves, as well as controls, who continue to cook on open fires.

To be successful, the stoves must reduce smoke exposure while also gaining acceptance from the women. "The women have always cooked on wood fires and don't necessarily recognize that wood smoke is bad for them," says Balmes. "Their lives are hard enough to start with, and you don't want to add to their workload."

He hopes that preliminary data gathered by his team will help the project garner federal grants for a larger study. "The funding climate is such that you have to have pilot data to be successful in getting NIH funding, and the Nina Ireland funds give us a chance to get that data," he says.

The Ireland funds are also supporting other international efforts, including the work of Laurence Huang, MD, Adithya Cattamanchi, MD, and J. Lucian Davis, MD, MAS, in treating tuberculosis and HIV-associated pneumonias in Uganda. Closer to home, funds are helping UCSF researchers better understand asthma risk factors among farmworker families near Modesto, and COPD in the San Francisco population.

"Often, people of low socioeconomic status have the dirty jobs, where they get exposed to vapors, gases, dust and fumes," says Balmes. "They are also more likely to live in an environment with mold and poor ventilation. We see this all the time at San Francisco General. We are trying to honor the memory of Nina Ireland by doing research into the root causes of global respiratory diseases as well as respiratory health disparities here in San Francisco, so we can address them with appropriate interventions."

Vision for the Future

"The Nina Ireland gift will support us in making enormous progress towards the bold goals we have set for ourselves," says Golden. "We are proud that the Nina Ireland gift is already making a difference for those in need in the Bay Area and globally."

The Ireland gift is a living legacy, generating about $2 million annually in investment income to support a broad range of patient care, research and educational activities. While endowment income is already committed to thematic initiatives described above, this gift is expected to encourage grateful patients or others inspired by the work of division faculty to designate support for all areas of pulmonary medicine. "Lung disease reaches beyond the four thematic areas supported by this program, and we will be in a much better position to accomplish any dream that people have to impact lung disease, because of the base that is built from the Nina Ireland program," says Sheppard.

"By raising additional operational funds, we will have the flexibility to pursue emerging opportunities," says Golden. "This, combined with Nina Ireland's extraordinary generosity, will allow us to take a nimble and entrepreneurial approach to leading innovations in all areas of pulmonary medicine that will change the lives of people with lung disease."

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