Studies of Inhaled Iloprost in Children
With Pulmonary Hypertension Yield Mixed Results
The prostaglandin iloprost, delivered via inhalation (Ventavis),
appears to be safe and well tolerated in children with
pulmonary arterial hypertension (PAH), but evidence presented
here this week raises a possible adverse effect on lung
function in this population.
Inhaled iloprost is approved for use in adults with
PAH, but data is lacking on its use in children. New
data on inhaled iloprost's safety and efficacy in this
population were presented this week at CHEST 2006, the
72nd annual meeting of the American College of Chest
Physicians.
Duncan D. Ivy, MD, chief and Selby's chair of pediatric
cardiology, director of the Pediatric Pulmonary Hypertension
Program and an associate professor of pediatrics at
The Children's Hospital in Denver, Colorado, presented
data on the acute and chronic effects of inhaled iloprost
in 11 children with PAH. In 4 children, the PAH was
of idiopathic origin, and in 7 children, the result
of a congenital heart defect.
In the study by Dr. Ivy and colleagues, children ranging
in age from 6.9 to 16.5 years received inhaled iloprost,
2.5 µcg/dose or 5.0 µg/dose, 5 to 9 times
daily, for 3 to 11 months (median, 7.8 months). Subjects
continued with intravenous prostacyclin therapy (bosantan
or sildenafil) throughout the study period.
Dr. Ivy's team compared pretreatment response of inhaled
iloprost with nitric oxide, 20 ppm, on cardiac catheterization.
Pulmonary arterial response was essentially the same,
with a 9 mm Hg drop in pressure.
Three children had a decline in airflow of 20% or greater
after inhaled iloprost therapy. Treatment was discontinued
in 2 children as a result of this evidence of airway
reactivity.
Seven patients were available for follow-up at 6 months.
World Health Organization (WHO) functional class had
improved in 4 and remained stable in 3 children.
Six-minute mean walk distance improved by 10% or more
in 2 patients, improved slightly in 2 patients, and
decreased more than 10% in 1 patient.
Dr. Ivy described adverse effects as "minimal."
Four patients receiving intravenous prostanoids were
able to be safely switched to inhaled iloprost therapy.
Two patients who switched initially had to be switched
back to intravenous therapy. Three patients with an
acute decrease of more than 20% in mean pulmonary artery
pressure with inhaled iloprost had "a favorable
long-term response," Dr. Ivy reported.
Dr. Ivy's study was funded by CoTherix Inc, the maker
of Ventavis.
Airway reactivity was also investigated by Kelly J.
Smith, MD, senior pediatric pulmonary fellow at Texas
Children's Hospital in Houston, and colleagues. They
evaluated 13 children diagnosed with PAH before and
after inhaled iloprost treatment using spirometry testing.
Age range of the children was 6.9 to 16.5 years. Patients
continued to receive their usual oral pulmonary vasodilation
medications during the study period. Inhaled iloprost
was delivered according to American Thoracic Society
guidelines.
Five of the 13 children had a decrease in forced expiratory
force during the middle half of forced expiratory volume
(FEF25%-75%) ranging from 17% to 53%. Four children
experienced a decrease in forced expiratory volume in
1 second (FEV1) ranging from 7% to 18%.
Iloprost inhalation therapy was discontinued in 2 children.
Albuterol therapy returned expiratory flow back to baseline
levels.
Dr. Smith speculated that this restriction in the lower
airways may explain previous reports of chest pain with
inhaled iloprost in adults.
"On average, there was a drop of 4.2% in the FEV1
and a drop of 10% in the FEF25%-75%. That is statistically
significant," Dr. Smith told Medscape. "But
the clinical significance over the long term is still
unknown.
"This is a good medication that has a definite
role," Dr. Smith said. "We can't recommend
against it at this point. We now need randomized trials"
of inhaled iloprost in children.
Dr. Smith's study was independently funded.
Mark J. Rosen, MD, FCCP, president of the American
College of Chest Physicians, emphasized that "the
pros and cons of any treatment always need to be considered.
[PAH] is a very serious disease and iloprost has good
efficacy in treating it." Dr. Rosen is a professor
of medicine at Albert Einstein College of Medicine in
Hyde Park, New York, and Long Island Jewish Hospital.
The risk of lower airway obstruction "may be a
small price to pay" considering the risks of undertreatment
of PAH. "But treatment risks always have to be
considered," Dr. Rosen warned.
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