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 www.niehs.nih.gov.
NHLBI information on lung diseases is available at
www.nhlbi.nih.gov.
Reference: Steele MP et al. The clinical and pathologic
features of familial interstitial pneumonia (FIP).
American Journal of Respiratory and Critical Care
Medicine.
|