Lung experts from Johns Hopkins and elsewhere are
calling on physicians to suspend the routine
use of potent heartburn medications in asthmatics solely to
temper recurrent attacks of wheezing,
coughing and breathlessness.
Calling the long-standing practice "ineffective" and
"unnecessarily expensive," the experts say
there is no benefit from using so-called proton pump
inhibitors in the absence of the stomach upset.
The condition plagues 5 million asthma sufferers in the
United States, of whom half have what is
known as "silent" reflux and lack the characteristic
symptom of heartburn from the backup of acid
into the esophagus.
Overall, as much as $10 million is spent each year in
the United States treating
gastroesophageal reflux disease in asthmatics struggling to
control their lung symptoms.
The scientists base their call on their latest
research, believed to be the most extensive
monitoring ever done of how well the drugs, first made
available in the 1990s, tame respiratory flare-
ups in asthmatics for whom steroid therapy and other drugs
have already failed.
Senior study investigator Robert A. Wise, a
pulmonologist at Johns Hopkins, said the results
dispel some common assumptions about the disease, offering
the first solid evidence against silent
acid reflux as having any significant role in poor asthma
control.
Reporting in the New England Journal of
Medicine online April 9, researchers at 20 medical
centers in the United States collected detailed health
reports on 412 men and women who still have
asthma symptoms despite drug therapy. Half took daily doses
of the most commonly used proton pump
inhibitor — 80 milligrams of esomeprazole (Nexium)
— while the rest received a placebo.
After six months, the average number of self-reported
episodes of breathlessness — those that
required use of inhalers and that stirred nighttime
awakenings or led to visits to the hospital
emergency room — were the same for both groups (at
2.5 and 2.3 per person per year, respectively),
disproving any drug benefit. Moreover, researchers saw no
improvements in overall health or other
quality-of-life measures, such as how much time study
participants spent going out with friends or how
well they performed their work or kept pace with their
college course work.
"The bottom line here is that proton pump inhibitors
do not improve control of asthma on their
own," said Wise, a professor at the Johns Hopkins
University School of Medicine.
Four out of 10 asthma sufferers, he noted, are
struggling to control their asthma whether or
not they have symptoms of gastroesophageal reflux disease,
or GERD.
Patients can easily confuse their heartburn symptoms
with their asthma symptoms, a problem
that Wise said only adds to the difficulty in deciding
which treatment to use.
Yet surveys show that as many as 65 percent of these
people take proton pump inhibitors
anyway, because doctors have presumed that it may improve
their asthma.
But until now, no study had closely monitored
asthmatics shown to have the silent form of GERD
by taking precise measures of esophageal pH acidity levels,
in which only patients free of any
heartburn were treated.
"Our recommendation to physicians is that these drugs
should only be considered for
asthmatics who have symptoms of gastroesophageal reflux at
least twice a week," Wise said.
In the study, each asthmatic participant kept a daily
diary of lung health. Researchers
supported these records with two tests of lung function
plus a test to see if airways constricted or
not in response to chemical irritants. These results were
combined with two surveys that measured
illness-related behavior changes, such as not going out to
parties or cutting back on physical exercise
due to fear of an asthma attack.
Results showed that none of these factors changed
markedly between the esomeprazole-
treated group and the placebo group. Three participants
taking esomeprazole had asthma attacks
serious enough to warrant a stay in the hospital, and four
in the placebo group had attacks that
required hospitalization — numbers that researchers
say are statistically the same.
Besides asthma attacks, study participants were
surveyed for actual backup of stomach acid. In
the test, probes were slid through the nose, down the
throat and into the esophagus to measure
acidity levels. Some 40 percent of participants were found
to have gastroesophageal reflux, recorded
as prolonged periods of severe acidity in the esophagus, as
measured by a pH acidity level of less than
4 lasting more than two hours throughout the day.
But even among this group of asthma sufferers, the
study showed that proton pump inhibiting
drugs offered no improvements in how fast people could blow
air out of their lungs. Drug therapy also
did not help open the airways in patients tested with
bronchodilator medications.
According to study co-investigator Janet Holbrook, a
"significant outlay" of money goes toward
treating asthma and related gastric reflux. Proton pump
inhibitors cost on average between $150 and
$180 per month for the half-dozen most common brands, and
probe tests used to gauge the severity
of the heartburn can cost as much as $1,200.
"It's only when you conduct placebo-controlled
clinical trials that you have a fair test of what
works best and what does not in controlling asthma," said
Holbrook, an associate professor at the
Johns Hopkins Bloomberg School of Public Health. "These
drugs are safe and work well for controlling
heartburn and healing acid irritation in the esophagus, but
they simply do not pass the efficacy test
for millions of people with this lung disease."
Wise said that the study results provide important
evidence for the National Asthma Education
and Prevention Program — an expert group coordinated
by the National Heart, Lung and Blood Institute
and the National Institutes of Health — to consider
when it next updates its evidence-based treatment
guidelines.
He said that the research team has already begun
testing proton pump inhibitors in children
with asthma. Children, he notes, have a shorter esophagus
than adults, making it easier for stomach
fluids to back up and into the throat and get sucked into
the lungs. This, he says, could explain why
children may benefit from these drugs while adults do
not.
Funding support for the study was provided by the
National Heart, Lung and Blood Institute and
the American Lung Association. Johns Hopkins is the
coordinating center among 20 Asthma Clinical
Research Centers, which are funded by the American Lung
Association as part of a dedicated effort
to conduct clinical trials in the disease impacting
lives.
The esomeprazole drug used in the study was provided
by its manufacturer, AstraZeneca. Wise
is a paid consultant to AstraZeneca. The terms of these
arrangements are being managed by The
Johns Hopkins University in accordance with its
conflict-of-interest policies.