Lung disease experts at Johns Hopkins are calling for
physicians to show much greater caution
in prescribing inhaled corticosteroid drugs for people with
chronic obstructive pulmonary disease
after finding evidence that the widely used
anti-inflammatory medications increase the risk of
pneumonia by a full third.
More than 11 million Americans, the vast majority of
them former or current smokers, are living
with so-called COPD, which is marked by the potentially
fatal lung-diminishing conditions of
emphysema and chronic bronchitis. The inhalers in question
greatly relieve such symptoms as
shortness of breath, wheezing, phlegm and physical
exhaustion from light exercise.
The call for caution is based on the Johns Hopkins
team's review and analysis of adverse events
recorded in 11 clinical studies that in total involved more
than 14,000 men and women with COPD. The
review, believed to be the largest and most comprehensive
performed in the last decade among COPD
sufferers, compared adverse events among those who took
inhaled corticosteroids and others who did
not.
In their report, which appears in the Journal of
the American Medical Association online Nov.
26, researchers found that the increased risk mostly
occurred in people taking the highest possible
doses, such as 500 micrograms of fluticasone twice daily
for a relatively short time (less than two
years); whose lung function was 40 percent or lower than
expected; and who combined their steroid
therapy with bronchodilators, used to keep the airways
open.
Researchers say it remains unclear why the treatment
increases risk of lung infection, but they
suspect that the drugs suppress the immune system.
Despite the increased pneumonia risk, the team found
no clear evidence that the drug therapy
pushes up rates for other steroid-related problems, such as
bone fractures, nor was there an increase
in deaths.
Senior study investigator and critical care specialist
Eddy Fan says the results of the analysis
should not alarm patients or cause them to stop taking
their medications but should spur physicians to
screen and monitor patients to find the lowest possible
steroid dose that works, especially in the
elderly, people with immune system problems and people who
have had multiple bouts of pneumonia and
for whom repeat bacterial infection might be a
life-threatening complication.
"Inhaled corticosteroids are not of equal benefit to
all, and what we are seeing is that the
treatment may be more harmful and pose a greater risk of
harm to some," said Fan, an instructor at
the Johns Hopkins University School of Medicine.
Pulmonologist M. Brad Drummond, who led the study,
said, "Physicians really need to strongly
evaluate a patient's individual characteristics before
prescribing these steroid medications, and
patients, in turn, should weigh the risks and benefits of
taking the drugs, despite their proven record
in providing symptomatic relief. Catching this bacterial
infection can seriously disrupt quality of life,"
he said, "making it harder for COPD patients to breathe and
possibly leading to hospitalization."
Drummond says that the new findings should serve as a
reminder to people with the severe lung
disease to take steps that reduce the chance of getting
pneumonia, which doubles their risk of dying
when compared to people with healthy lungs. He also advises
COPD sufferers, in addition to weighing
the benefits and harms of steroids, to get a pneumonia
vaccination every five years and a flu
vaccination annually because these shots reduce the chance
of getting a lung infection. Drummond, a
postdoctoral clinical research fellow at Johns Hopkins,
also advises lung disease sufferers to take
additional precautions, including washing hands more
frequently and vigilantly monitoring for the first
signs of sickness.
In their analysis, researchers culled their 11 key
studies from more than 3,100 conducted in
more than 40 countries. All the studies tracked men and
women with COPD for complications from
treatment, including some for pneumonia, bone cracking and
death. The 11 studies were randomized
controlled trials completed between 1999 and 2007 that
involved participants who had seriously
diminished lung function, at less than 70 percent of
expected. In addition, all subjects were initially
diagnosed with COPD at age 40 and older, typically the age
group most affected by COPD. About half
were prescribed the handheld, disposable corticosteroid
inhalers, while the rest were not. And all
were monitored for between six months and three years, with
some participants taking steroid
therapy alone or in combination with bronchodilators, which
contain different drugs. Studies that
included people with asthma, a related lung disease that
complicates treatment of COPD, were
excluded from the analysis.
The merged analysis from seven studies that kept track
of infections from pneumonia revealed
a 34 percent higher rate among those who underwent steroid
therapy (777 infections in 5,405 people),
compared to those who did not (561 infections in 5,371)
during the same time frame. In five studies
that recorded death rates and three that counted bone
fractures, no significant differences emerged
between the groups.
In breaking down the overall rise in risk, the
researchers found that in people taking the
highest possible dose of each inhaled corticosteroid, there
was a 46 percent increase in risk for
pneumonia. Infection risk nearly doubled in those who had
less than 40 percent normal lung function,
as opposed to those whose lungs were stronger.
Drummond says that the absence of an overall
difference in death rates between users and
nonusers of corticosteroids was likely due to the
short-term follow-up of three years or less across
all the studies.
Fan says that further research is needed to identify
precisely which groups benefit in the long
term, and which ones do not, from inhaled corticosteroids,
and to see if there is a link between higher
risk and death.
COPD kills more than 120,000 Americans every year and
is expected to become the nation's
third-leading cause of death in the United States by 2020,
ahead of stroke and behind heart disease
and cancers.
Funding for this study was provided by The Johns
Hopkins Hospital's General Clinical Research
Center.
In addition to Fan and Drummond, researchers involved
in this study, conducted solely at Johns
Hopkins, were Elliott Dasenbrook; Marshall Pitz, now at the
University of Manitoba, in Winnipeg,
Canada; and David Murphy.