For the first time, researchers have demonstrated a
close correlation between the decline in a
key component of the lung's antioxidant defense system and
the progression of chronic obstructive
pulmonary disease in humans. COPD is a degenerative
condition that decreases the flow of air through
the lungs as the lung's air sacs are damaged.
A study of lung tissue samples from COPD patients by
scientists at the Johns
Hopkins Bloomberg School of Public Health found that
expression of the regulating gene NRF2 was
significantly decreased in smokers with advanced COPD
compared to smokers without COPD. The
study is published in the Sept. 15 edition of the American
Journal of Respiratory and Critical Care
Medicine.
The study team was led by Shyam Biswal, an associate
professor in the Bloomberg School's
Department of Environmental Health Sciences and in the
Division of Pulmonary and Critical Care
Medicine at the Johns Hopkins School of Medicine.
According to Biswal, NRF2 works as a "master
gene" to turn on numerous antioxidant and
pollutant-detoxifying genes to protect the lungs from
environmental pollutants, such as cigarette smoke. Biswal
previously identified that disruption of
NRF2 expression in mice caused early onset and severe
emphysema, which is a major component of
COPD in humans. However, the status of this critical
pathway in humans with COPD was unclear.
"This work clearly demonstrates that decline in our
antioxidant system is involved in progression
of COPD, which could also be the case for other
environmental diseases," Biswal said. "There is no
treatment of COPD, but NRF2 could be a novel target for the
development of new drug therapies."
Rubin Tuder, a co-author of the study now on the
faculty of the University of Colorado, added,
"As we learn how the protective actions of NRF2 are
decreased in the course of a lifetime of
exposure to cigarette smoke, it opens new venues for the
development of novel drugs fitted for
individual patients in specific stages of the disease."
The research was supported by the National Institutes
of Health through an investigator-
initiated grant, as well as by the Specialized Center for
Clinically Oriented Research at the Johns
Hopkins School of Medicine. Lung specimens were provided by
the Lung Tissue Research Consortium,
which is supported by the National Heart, Lung and Blood
Institute.
"COPD affects more than 16 million Americans and is
the fourth highest cause of death in the
United States," said Robert Wise, professor at the School
of Medicine and director of the Johns
Hopkins SCCOR initiative. "It is the only disease among the
top 10 causes of death with a rising
mortality rate in the United States. It is predicted to be
the third largest cause of death by 2020
and has already reached worldwide epidemic proportions."
Additional authors of the study are Deepti Malhotra,
Rajesh Thimmulappa, Ana Navas-Acien,
Andrew Sandford, Mark Elliott, Anju Singh, Linan Chen,
Xiaoxi Zhuang, James Hogg and Peter Pare.