Jeffrey Golden, MD (above), with patient Michele DesMarais.
Photo: Noah Berger

by Elizabeth Chur

From increasing the number of donor lungs to testing stoves that may reduce smoke exposure among Guatemalan women, a recent $48 million bequest is helping UCSF build one of the world’s leading programs in lung disease research.

The bequest, the largest ever given to UCSF, was made by Nina Ireland, who died in 2010 at the age of 67. She had emphysema for decades, but lived an active life, partly because of the care she received from her longtime doctor, Jeffrey Golden, MD, professor of medicine and surgery and the Nina Ireland Distinguished Professor in Pulmonary Medicine.

Ireland’s will named Golden as the director of what has become the Nina Ireland Lung Disease Program. This program currently supports the research of budding fellows and junior faculty; is establishing a biorepository and clinical database; and focuses on four thematic areas of particular interest to Ireland: interstitial lung disease (ILD), lung transplantation, pulmonary rehabilitation, and global lung health and the underserved.

“This gift is profound,” said Golden. “It gives us the opportunity to catalyze transformational changes in how we treat lung disease.”

“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,” said Dean Sheppard, MD, professor of medicine and 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 lung fellowship programs, providing extensive research and clinical training to aspiring pulmonologists. So far, the Ireland program has helped twelve fellows enrich their educational experiences, and it has supported six junior faculty members who are establishing their own independent laboratories.

The Ireland gift also created an opportunity fund, which provides seed money for innovative research in lung disease and is now open to all UCSF faculty at the associate professor level and below. In the first round, 40 projects were submitted, and an expert panel of basic, translational and clinical scientists chose six for funding.

Other initiatives funded by the Nina Ireland Lung Disease Program include:

ILD and Lung Transplant

UCSF is a leader in treating patients with ILD, a set of conditions that involve scarring of the lungs. ILD is the leading indication for lung transplantation. Funds are supporting Mark Looney, MD, associate professor of medicine, in developing a mouse model to study what happens to transplanted lungs during rejection. Jonathan Singer, MD, assistant clinical professor of medicine, is investigating factors impacting quality of life before and after lung transplant.

Michael Matthay, MD, professor of medicine and anesthesiology, and Jasleen Kukreja, MD, MPH, associate professor of clinical surgery and surgical director of the UCSF Lung Transplant Program, are implementing a new technology called ex vivo lung perfusion, which could help rehabilitate up to half of the 70 percent of donor lungs that are currently discarded because they do not meet transplantation criteria.

After lungs are removed from a donor, they are connected to a device that functions similarly to a heart-lung machine, supplying the organ with oxygen, removing carbon dioxide, and allowing physicians to administer antibiotics, steroids and other medications to treat pneumonia and reduce inflammation.

“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,” said Steven Hays, MD, associate professor of clinical medicine and medical director of the lung transplantation program. “We are also planning to use this technology to look at possible ways to heal lung injury using stem cells. This funding is allowing projects to take place that otherwise would have a hard time getting started.”

Pulmonary Rehabilitation

UCSF is developing a program of exercise training, education and palliative care for patients with lung disease. Similar programs have been shown to help patients with chronic obstructive pulmonary disease (COPD) to better control symptoms, avoid unnecessarily hospitalizations and improve quality of life. “Often, when someone has shortness of breath, they tend to do less, get more deconditioned, and become more short of breath,” said Michelle Milic, MD, associate clinical professor of medicine, who will lead the new pulmonary rehabilitation program. “Yet many of these things can be addressed and improved.”

She will work with DorAnne Donesky, PhD, NP, assistant adjunct professor of physiological nursing, to develop a robust research arm of the program to study 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.

Global Lung Health and The Underserved

“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,” said John Balmes, MD, professor of medicine, who holds a joint appointment at the UC Berkeley School of Public Health. He received Ireland pilot funds to test whether several different commercially available stoves can reduce exposure. He and his colleagues will distribute these stoves to Guatemalan volunteers with COPD, and 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.

Fund from the Ireland program are also supporting other international efforts, including treating tuberculosis and HIV-associated pneumonia in Uganda. Closer to home, funds are helping UCSF researchers to 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,” said Balmes. “They are also more likely to live in an environment with mold and poor ventilation. We are 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.”

Biorepository and Clinical Database

The Ireland program provides core support for the processing and storage of blood and tissue specimens, as well as the development of a web-based clinical database focusing on lung transplant, ILD, granulomatous disease (a specific type of ILD), and scleroderma, a rare autoimmune disorder that can affect the lungs, skin and joints.

These research tools helped to spark a new partnership with Stanford, called the Northern California Scleroderma Research Consortium, which involves pulmonologists, dermatologists and rheumatologists. Although individual patient records will be shielded to protect anonymity, researchers from either institution will be able to access patient data and biosamples to conduct research. Because the database is web-based, it will be easy to invite other institutions to participate, spurring national and international collaborations. This model of data sharing could also be adapted to other areas of pulmonary research.

“The power is in numbers,” said Paul Wolters, MD, associate professor of medicine, who oversees the biorepository and database. “This is an ongoing, longitudinal, multi-institutional, 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.”