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Lung Scarring Diseases Linked to Genes and Smoking


New research shows that idiopathic interstitial pneumonia (IIP), a group of potentially fatal disorders that affects the lungs, may be caused by an interaction between a specific genetic background and cigarette smoking. In a study of 111 families that had at least two relatives with IIP, people who smoked cigarettes were three times more likely than non-smokers to develop the disease. The research was supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Environmental Health Sciences (NIEHS), both institutes within the National Institutes of Health.

IIPs are often accompanied by scarring and inflammation of the lung known as pulmonary fibrosis. Pulmonary fibrosis makes the delivery of oxygen to the body’s tissues difficult and is often fatal. About one-half of patients die within the first five years of being diagnosed with idiopathic pulmonary fibrosis. The study appearing in the November 1 issue of the American Journal of Respiratory and Critical Care provides new insight into what might cause IIP and new directions for preventing these diseases.

"This study illustrates the important role that a specific environmental exposure, in this case cigarette smoking, can play in the development of this type of lung disease among people who have a specific gene,” said David A. Schwartz, M.D., NIEHS Director and a lead researcher on the study. “It once again underscores why people should not smoke.”

“Pulmonary fibrosis currently affects approximately 100,000 people in the United States, with an estimated 30,000 people being diagnosed each year,” added Elizabeth G. Nabel, MD, NHLBI Director. “This study enhances our understanding of one form of pulmonary fibrosis, which could help lead us to strategies for genetic testing, prevention, and treatment of this devastating and complex disease.”

Researchers from three sites enrolled and evaluated 111 families with a diagnosis of IIP in at least two affected relatives. The sample included 309 people affected with an IIP and 360 unaffected relatives. Each participant completed a detailed health and environmental exposure questionnaire, a chest x-ray, and a lung diffusion test, which determines how well oxygen passes from the air sacs of the lungs into the blood.

The researchers evaluated the data in many different ways. They used a family-based case control study to determine if there was a relationship between cigarette smoking and familial interstitial pneumonia (FIP). They also used two methods to determine if there was in fact a genetic component to FIP. FIP is the term used when 2 or more cases of IIP occur in the immediate family.

The researchers found that there is a genetic basis for this disease. In addition to the fact that 111 families had 2 or more relatives with this disease, the researchers also found similar age-at-diagnosis and significant risk among siblings. Older people, males, and those who smoked also showed a greater risk of developing FIP. After controlling for age and gender, having ever smoked cigarettes increased the likelihood of developing this disease 3.6 times.

“We now know that a certain genotype places someone at risk for this disease,” said Mark Steele, M.D., Associate Professor, Duke University Medical Center, the lead author on the paper. “Independent of genes, cigarette smoking also contributes to the development of this disease. The next step is to identify the specific gene or genes that cause the disease.”

Steele also noted that because this is the first study to include different types of IIP within the same families, it may be plausible that although a common gene may predispose one to develop FIP, some other factor, such as the environment, may result in a unique type of IIP.

In addition to Duke University Medical Center, Vanderbilt University School of Medicine and National Jewish Medical and Research Center participated in the study. The University of Colorado Health Sciences Center served as coordinating center.

NIH-supported research on the causes and treatments of pulmonary fibrosis is ongoing. For example, NHLBI established an Idiopathic Pulmonary Fibrosis Clinical Trials Network in May 2005 to conduct randomized, multi-drug therapeutic trials to stabilize pulmonary fibrosis in newly diagnosed patients.

NHLBI and NIEHS are part of the National Institutes of Health (NIH), the Federal Government’s primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services. NIEHS information on the effects of the environment on human health is available at NHLBI information on lung diseases is available at

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

NHLBI Communications Office | EurekAlert!
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