2007-2008 Lung Disease Research
at the
American Lung Association®
in Washington

The American Lung Association® in Washington's Research program fosters both laboratory and patient-centered research designed to find cures and to prevent and relieve the suffering associated with lung disease. Our annual portfolio of awards and grants is unique in its breadth and approach to achieving our mission.

The American Lung Association® in Washington has supported research since 1915 and believes that research is the key that will unlock the door to a better tomorrow for all people with lung disease. We depend on our scientists not only to pursue basic and clinical research but also to illuminate our public health education and outreach efforts.

Many scientists are conducting research in the Lung Association's main areas of focus: asthma; tobacco-related diseases such as lung cancer and emphysema; and environmental health. The Lung Association also funds research in other areas, such as lung diseases that strike infants and children, the mechanisms of breathing, tuberculosis and AIDS, and deadly lung infections.

The following researchers received American Lung Association® in Washington funding in 2007-2008:

William Altemeier, MD

Two year Research Grant*
University of Washington, Seattle, WA
Biomedical Research Grant • Support of this grant comes from the Mary Fuller Russell Research Fund

Studying Protein’s Role In Acute Lung Injury

Fas-Induced Inflammation: Mechanisms And Role In Acute Lung Injury. Acute lung injury remains a cause of illness and death in the intensive care unit. Despite extensive research efforts, the mechanisms involved in the development of acute lung injury are still not completely understood. Research studies on humans and animal models have identified activation of a protein named Fas as a potentially important mechanism in the development of lung injury and inflammation. The researchers will study the mechanism by which Fas causes inflammation and evaluate the role of inflammation in Fas-induced lung injury. The results of this research will provide new insight into how Fas activation contributes to the development of acute lung injury. This will in turn guide future efforts to develop novel therapies effective in preventing acute lung injury.

David Au, MD

University of Washington, Seattle, WA
Career Investigator Award • Co-Funded by the American Lung Association and the American Lung Association of in Alaska, Idaho, and Washington

Importance Of Getting COPD Patients To Adhere To Therapy

Effect Of Medication Adherence On Outcomes And Costs Among Patients With Chronic Obstructive Pulmonary Disease. Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. Drug therapy has become the mainstay of treatment for COPD, but there is little evidence about the effects of adhering to pharmaceutical therapy on the risk of death or COPD flare-ups. There is also no data about the effects of adhering to drug therapies on utilization of resources or cost of care. The researchers, by studying veterans receiving care in the Pacific Northwest, will address this gap by examining the effects of adhering to drug therapy on important patientrelated outcomes including COPD flare-ups, death, and costs to the health care payer. The researchers hope to inform payers of medical care, health care systems, individual providers, and patients about the importance of adhering to medical therapy and identify those patients who may benefit from interventions that improve adherence to medical therapies.

Teal Hallstrand, MD

Three year Career Investigator**
University of Washington, Seattle, WA
Career Investigator Award • Co-funded by the American Lung Association and the American Lung Association in Alaska, Idaho, and Washington

Does Injury To Surface Airway Cells Lead To Exercise-Induced Bronchoconstriction?

Epithelial Basis Of Exercise-Induced Bronchoconstriction. Exercise-induced bronchoconstriction (EIB) is a disorder that causes wheezing and shortness of breath following a short period of exercise. This disorder commonly occurs in people with asthma, as well as athletes and people with nasal allergies who do not have other symptoms of asthma. The researchers hope to determine if injury to the cells that line the surface of the airways causes susceptibility to EIB. They will take small samples of the airway lining cells from asthmatics who have EIB, and compare them with samples from asthmatics who do not have EIB, as well as nonasthmatic individuals. The study will lead to a better understanding of the cause of EIB, which may lead to new therapies to treat this common disorder.

Susanna Harju, PhD

Two year Research Training Fellowship ***

University of Washington, Seattle, WA
Senior Research Training Fellowship • Funded by the American Lung Association in Alaska, Idaho, and Washington

Understanding How the Lung Protects Itself Against Noxious Agents

Role Of Matrilysin-Mediated E-Cadherin Shedding In Wound Healing. The epithelium is a layer of cells that protects the lungs against toxins, pollutants, and infectious agents, and initiates the body’s inflammatory responses if the lungs are injured. Epithelial cells are tightly joined and establish a nearly impassable barrier to bacteria. Upon injury, these cells begin a series of responses to heal wounded tissue. It is likely that the lung’s epithelial cells are constantly being subjected to minor injuries. The ability of these tissues to rapidly and efficiently repair these wounds is essential to restoring the barrier function of the epithelium, and preventing the establishment of infection. The epithelium is chronically disrupted in a variety of lung conditions, such as COPD, cystic fibrosis, asthma, and cancer. The researchers will study two proteins, matrilysin (MMP-7) and E-cadherin, which are involved in wound repair in the lungs. Their study will contribute to a better understanding of the fundamental repair mechanisms of lung epithelium.

Danny Hsia, MD

University of Washington, Seattle, WA
Junior Research Training Fellowship • Funded by the American Lung Association in Alaska, Idaho, and Washington

Predicting Which Children With RSV Will Develop Asthma

Exhaled Nitric Oxide Output In Infants With Pulmonary Hyperinflation Following Respiratory Syncytial Virus Bronchiolitis. Most lower respiratory tract illnesses with wheezing that occur in the first three years of life are associated with infection with respiratory syncytial virus (RSV). Many studies have shown an association between RSV, subsequent wheezing, and the development of asthma. Between 20-40% of young children who have RSV suffer from recurrent wheezing episodes that resolve on their own as the child gets older. A major challenge for doctors is predicting which infants are at increased risk for developing asthma after RSV and which will resolve on their own. The researchers will use two measurements to see how each alone and in combination predicts recurrent wheezing as the child grows. One measurement, called the thoracic index, measures persistent airway narrowing, while the nitric oxide index measures ongoing airway inflammation. If these measurements prove useful, they will allow doctors to identify which children who have had RSV might benefit from asthma therapy very early in life and avoid complications of asthma in very young children.

Sergei Rybalkin, MD

University of Washington, Seattle, WA
Biomedical Research Grant • Co-Funded by the American Lung Association and the American Lung Association in Alaska, Idaho, and Washington

"Viagra" For The Lungs: Understanding How It Works May Improve Effectiveness

Characterization Of cGMP Phosphodiesterase (PDE5) Isoforms Expressed In Lung. Phosphodiesterase 5 (PDE5) is an enzyme (protein) produced in the lungs and other parts of the body that breaks down a substance called cyclic GMP. Cyclic GMP causes the blood vessels to widen. Sildenafil, well known as the drug Viagra, inhibits PDE5, leading to accumulation of cyclic GMP and widening of the blood vessels. Recently the U.S. Food and Drug Administration approved sildenafil under the brand name Revatio to treat pulmonary arterial hypertension (PAH), a life-threatening disease. The researchers will study the mechanisms of sildenafil’s action on the lung. The research could lead to improved effectiveness and new applications for PDE5 inhibitors in the treatment of lung disorders.

Teresa Wagner, MD

Two year Research Training Fellowship***
University of Washington, Seattle, WA
Senior Research Training Fellowship • Funded by the American Lung Association in Alaska, Idaho, and Washington

Seeking Better Understanding Of Lung Development May Help Premature Newborns

Mechanisms Of Alveolar Septation. Little is known about how normal alveoli, or the lung’s air sacs, develop. Alveoli are formed primarily after birth up until 18 months of age. This can be disrupted by premature birth, infection, mechanical ventilation, or too much or too little oxygen, resulting in a lung disease called bronchopulmonary dysplasia, which involves impaired formation of the alveoli. The researchers hope to gain a better understanding of how alveoli develop in the lung after birth, a process called alveolar septation. A better understanding of the molecular processes involved in alveolar development can lead to preventive and/or therapeutic measures in caring for premature newborns.