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■ HopkinsLung.com
New Hope for Idiopathic Pulmonary Fibrosis
Centers around the country are studying innovative treatment approaches
Idiopathic pulmonary fibrosis (IPF)
is a disease of mysteries. It has no
known cause, no cure, and reports
of it are on the rise, although re-
searchers aren’t quite sure why.
Today 200,000 Americans—most
over age 50—suffer from IPF, and
it will claim the lives of nearly two
thirds of them within five years of
diagnosis. Unfortunately, current
treatments cannot be counted on
to stop the progressive lung scar-
ring (fibrosis) that is the hallmark of
IPF—and only one treatment, lung
transplantation, has been shown to
improve survival.
Fortunately, the National Heart,
Lung, and Blood Institute (NHLBI)
is spearheading a massive effort to
find an effective treatment for this
devastating disease. Several new
therapies are being studied around
the country, many of them at 12
medical centers that are part of the
NHLBI’s Idiopathic Pulmonary
Fibrosis Network (IPFnet). Under
the guidance of the NHLBI, these
centers are conducting clinical tri-
als designed to identify better ther-
apies for IPF, in both its early and
advanced stages.
What Is IPF?
For years, researchers suspected
that inflammation triggered the
lung scarring that occurs in people
with IPF. But more recent research
suggests that IPF’s chronic cycle
of injury leads to an exaggerated or
uncontrolled healing response that,
over time, produces fibrous scar
tissue. This scarring, in turn, caus-
es the walls of the tiny air sacs
(alveoli), and the tissue between
them to thicken, making them less
able to function and provide the
body with the oxygen it needs.
The main symptom of pulmon-
ary fibrosis is shortness of breath,
which may first appear during ex-
ercise. As the disease gets worse,
breathlessness can occur even
when walking on level ground. Dry
cough is also a common symptom.
Often, a person with IPF will as-
sume their shortness of breath is
simply a sign of aging or weight
gain and, therefore, won’t seek
medical help until the problem
becomes severe and the lungs are
seriously scarred. Symptoms of
IPF may also be mistaken for other
lung diseases, such as asthma,
further delaying diagnosis and
treatment. As the disease pro-
gresses, however, other serious,
possibly life-threatening condi-
tions, including pulmonary arterial
hypertension (high blood pressure
in the arteries of the lungs) and
heart failure, may develop.
Limited Treatment Options
The goal of current treatments for
IPF is to prevent more lung scar-
ring. What today’s treatments can’t
do, however, is reverse scarring
that has already occurred.
Steroids. The most common
treatment is the corticosteroid
prednisone, which is used to re-
duce inflammation. It is often com-
bined with azathioprine (Imuran) or
cyclophosphamide (Cytoxan),
drugs that suppress the body's
immune response. But because
researchers now know that inflam-
mation is not at the root of IPF, it’s
not surprising that this treatment
option is effective in only a small
number of people. Nonetheless, in
the absence of good alternatives,
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doctors still may prescribe the
combination therapy for three to six
months to see if it has any effect.
Lung transplantation. This pro-
cedure is an option for some peo-
ple with advanced IPF who are
younger than age 65 and have no
other major health problems. How-
ever, lung rejection is a common
problem, often leading to signifi-
cant illness or death—only about
half of IPF patients who have a
lung transplant are alive after five
years. Those who do survive must,
for the rest of their lives, take drugs
that suppress the immune system
in order to prevent rejection and
undergo frequent bronchoscopic
testing to look for infectious and
inflammatory complications. Still,
lung transplantation offers the best
chances for survival.
Supportive Care
The goals of supportive care are to
relieve symptoms, keep patients as
active as possible, and improve
quality of life.
Oxygen therapy. Supplemental
oxygen therapy has been shown to
improve quality of life and the abili-
ty to exercise in people with chron-
ic obstructive pulmonary disease
(COPD) and other lung diseases
and is often given to people with
IPF who have low blood oxygen
levels. But few studies have been
conducted to evaluate its effective-
ness in IPF.
Pulmonary rehabilitation. Peo-
ple with IPF may benefit from pul-
monary rehabilitation. This is a pro-
gram of education and exercise
classes that teach you about your
lungs, how to exercise and do
activities with less shortness of

breath, and how to live better with
your lung condition. A recent small
study showed that it improved
exercise capacity and quality of life
in people with IPF.
What’s on the Horizon?
Several new treatments being
studied may actually reverse the
scarring in the lungs of people with
IPF, holding out hope for a cure.
However, researchers are cautious
about their prospects. Many were
enthusiastic about promising
results from interferon gamma
(Actimmune), a man-made version
of a substance the body normally
produces to help fight infections.
Small early trials suggested that it
might suppress the scarring pro-
cess in the lungs. But larger trials
showed no benefit from the treat-
ment in terms of survival or disease
progression. Thus, the quest for an
effective treatment continues.
Here’s a roundup of potential
new therapies under investigation:
N-acetylcysteine (NAC). This
antioxidant is used to thin mucus
in patients with other lung condi-
tions. One recent study showed
that adding NAC to prednisone
and Imuran helped prevent further
damage to the lungs of people with
IPF, but it did not examine whether
this treatment regimen is better
than no treatment at all. To answer
that question, researchers are con-
ducting the Prednisone, Azathio-
prine, and NAC in people with IPF
(PANTHER-IPF) study, in which
about 400 people will be randomly
assigned to receive NAC, a combi-
nation of all three drugs, or place-
bo for 60 weeks. Results are ex-
pected by 2012.
Pirfenidone. This drug, which is
not available in the United States,
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If You Have Pulmonary Fibrosis
Ask your pulmonologist if he or she knows of a clinical trial that
you might be a candidate for. Also visit www.ipfnet.org and
www.clinicaltrials.gov for more information on clinical trials for
new IPF treatments. For a condition that has so few treatment
options, a clinical trial could offer a chance to try an experimental
treatment before it becomes available to the general public.
may help stabilize or improve lung pressure in the lungs, is used to
function in people with IPF. One treat pulmonary hypertension.
Japanese study found that treat- Results from one recent study
ment with pirfenidone slowed the showed that eight of 14 people
loss of vital capacity (the total with IPF and pulmonary hyperten-
amount of air that can be exhaled sion who took sildenafil for three
after a deep inhalation) and pre- months were able to walk a greater
vented acute flare-ups of IPF dur- distance in six minutes than they
ing the nine months of follow-up. could before treatment. Results
Results from a larger study evalu- from larger, randomized, placebo-
ating this drug’s safety and effec- controlled trials should be pub-
tiveness are expected this year. lished within one to two years.
Etanercept (Enbrel). Used to Thalidomide. This drug, which
slow the progress of rheumatoid was widely used in Europe in the
arthritis (RA), Enbrel also helps alle- late 1950s to combat insomnia and
viate joint swelling, pain, tiredness, to treat pregnant women with
and morning stiffness in people morning sickness, was removed
with RA. It is believed to work by from the market around the world
blocking an immune system pro- when it was found to cause birth
tein known as tumor necrosis fac- defects (it was never approved for
tor- (TNF-) alpha, which plays a these uses in the United States).
role in the development of fibrosis. Since that time, thalidomide has
Results from a recent study of been approved by the U.S. Food
Enbrel for the treatment of IPF are and Drug Administration (FDA) for
expected in the near future. the treatment of a type of cancer
Bosentan (Tracleer). This drug known as multiple myeloma and
is currently approved to treat pul- for a skin condition called erythe-
monary arterial hypertension. ma nodosum leprosum.
Results from one recent trial sug- Because thalidomide has anti-
gest that it may delay the progres- inflammatory properties that seem
sion of IPF. Researchers are also to suppress the increased activa-
studying whether it can suppress tion of sensory fibers within the
the scarring process in the lungs. respiratory tract of people with IPF,
More results from a number of researchers at Johns Hopkins are
studies investigating Tracleer are investigating its use in IPF patients
expected by the end of this year. with chronic cough. The study
Sildenafil (Viagra, Revatio). should be completed by the end of
Sildenafil, which lowers blood this year. ■
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