Benefits of ibuprofen shown to outweigh risks of gastrointestinal bleeding in children with cystic fibrosis

Treatment with ibuprofen is associated with a significantly slower rate of decline in lung function in children and adolescents with cystic fibrosis, according to a new study.

Researchers found that patients with cystic fibrosis (CF) who took high doses of ibuprofen had a 29 percent reduction in loss of lung function compared to those who did not use the anti-inflammatory drug twice daily over a period of two to seven years.

“It is fairly evident that the lung damage that occurs in cystic fibrosis is due to inflammation, and that this lung damage is what shortens the lives of these patients,” said lead researcher Michael W. Konstan, M.D., Director of the Cystic Fibrosis Center at Rainbow Babies and Children's Hospital, and a professor of pediatrics at Case Western Reserve University School of Medicine in Cleveland. “Since ibuprofen is an anti-inflammatory drug, we presume that it works by decreasing inflammation in the lung, thereby slowing damage.”

The study, which concluded that the benefits of ibuprofen therapy outweigh the small risk of gastrointestinal bleeding, appears in the first issue for December 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Cystic fibrosis is a genetic disorder that causes mucus to be thick and sticky. The mucus clogs the lungs, which causes breathing problems and makes it easy for bacteria to grow. The persistence of bacterial infections leads to chronic inflammation, causing lung damage, which eventually proves fatal.

Dr. Konstan led a clinical trial 12 years ago that found ibuprofen reduced the loss of lung function in CF patients, but questions have remained about the safety of regular high-dose ibuprofen use, which in some cases can lead to gastrointestinal bleeding. This study showed that gastrointestinal bleeding was rare, with an annual incidence of 0.37 percent in those taking ibuprofen, compared with 0.14 percent in those not taking the drug.

“There is still some concern about the safety of ibuprofen,” Dr. Konstan noted. “Although we found only a small increase in gastrointestinal bleeding due to ibuprofen, we continue to search for even safer approaches to anti-inflammatory treatment for CF. In the meantime, we think that CF patients, especially children and adolescents with early lung disease, should be treated with ibuprofen.”

While the earlier trial was conducted under tightly controlled conditions to ensure that patients strictly adhered to their medication regimens, the new study looked at “real-world” use of ibuprofen. “In a clinical trial, things are done very carefully, and we don't know if the findings hold true in clinical practice,” explained Dr. Konstan. The new study—which used data from 1996 to 2002 on patients from ages 6 to 17 who were part of the Cystic Fibrosis Foundation Patient Registry—“confirms that ibuprofen therapy works in the real world.”

The new study included data on 1,365 patients who took ibuprofen and 8,960 who did not, who were of similar age and disease severity. Each dose of ibuprofen ranged from 20 to 30 milligrams per kilogram of the patient's weight. Some patients took up to 1,600 milligrams of ibuprofen per dose. (Generally, over-the-counter preparations of ibuprofen advise a maximum daily dose of 1,200 mg for adults and children over the age of 12.)

While the research does not address whether CF patients who take ibuprofen live longer, Dr. Konstan said it is likely the case. “The lung function of these patients declines over time, and rate of decline is associated with survival,” he said. “Although we don't have evidence to prove it, we would like to think that this slowing of lung function decline due to ibuprofen therapy translates into increased years of survival for patients with CF.”