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Title: CHEST: Instilled DNase Dissolves Mucus Plugs in Cystic Fibrosis
URL: http://www.pslgroup.com/dg/20D4DA.htm
Doctor's Guide
November 9, 2001


By Dan Keller
Special to DG News

PHILADELPHIA, PA -- November 9, 2001 -- Instillation of recombinant human DNase I (rhDNase, Dornase alfa) through a bronchoscope can remove mucus plugs causing atelectases in the lungs of patients with cystic fibrosis (CF).

Patrick Daigneault, MD and colleagues at the Sainte-Justine Hospital in Montreal, Quebec, Canada, applied the treatment to two patients, ages four and 12 years, who had persistent lobar atelectases that did not respond to intensive physiotherapy and intravenous antibiotics.

The team were able to determined the location of the mucus plugs using bronchoscopy, then administered the medication directly on the plug through the bronchoscope, Dr. Daigneault explained at the 2001 annual meeting of the American College of Chest Physicians, in Philadelphia, Pennsylvania.

In each case, flexible bronchoscopy showed thick, purulent mucus obstructing a lobar bronchus. After attempts at suctioning failed, Dr. Daigneault placed 2.5 mg of rhDNase in 2.5 mL of brochoalveolar lavage fluid at the site of obstruction through the bronchoscope.

On subsequent x-rays, there was no evidence of atalectasis, he said. "They probably coughed up their own mucus plugs." Improvement on x-ray was apparent at 24 hours.

Besides a moderate fever that quickly and spontaneously resolved after the procedure, no other complications occurred, including bronchospasm, hemoptysis, or chest pain.

Both patients also showed clinical improvement, and at three months follow up, radiological and clinical improvements were maintained. Pulmonary function tests, although not very abnormal to begin with, did show some improvement at three months, Dr. Daigneault noted.

He concluded that in these two patients, locally instilled DNase was an effective adjunct therapy to relieve persistent atelectases. While the treatment appeared completely safe in these two patients, he is attempting to accumulate results on several more CF patients to truly demonstrate the safety and efficacy of delivering rhDNase by this route.

CF is characterized by thick mucus, the viscosity of which is largely the result of DNA from decaying neutrophils in the area of inflammation and obstruction. Dr. Daigneault said the technique may be applicable in other conditions, but it would have to be tried in those specific situations. However, he warned that not all mucus is the same. In asthma, for example, it contains more eosinophils compared to the preponderance of neutrophils in CF.

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