Intratracheal recombinant human deoxyribonuclease in acute life-threatening asthma refractory to conventional treatment

Abstract

Recombinant human deoxyribonuclease (rhDNase) is a mucolytic agent used to relieve peripheral airway obstruction in patients with cystic fibrosis. We report dramatic sustained improvement following the intratracheal administration of rhDNase to a 3-yr-old boy with acute life-threatening asthma in whom 48 h of aggressive therapy had failed.

Recombinant human deoxyribonuclease for the treatment of acute asthma in children

“…Intervention with rhDNase, administered endotracheally or by means of a bronchoscope, was safe and improved ventilator settings12 13 and arterial blood gas values13 and resolved atelectasis10 12 in children receiving intensive care. Nebulisation of rhDNase in three children brought to the emergency department improved lung function parameters, the effectiveness of coughing and resolved atelectasis 11…”

“…To date, only case reports have suggested a benefit from rhDNase in children with status asthmaticus unresponsive to conventional treatment,10 – 13 and in children with acute severe asthma treated at the emergency department 11. Intervention with rhDNase, administered endotracheally or by means of a bronchoscope, was safe and improved ventilator settings12 13 and arterial blood gas values13 and resolved atelectasis10 12 in children receiving intensive care.…”

“…Such mucus can be liquefied by recombinant human deoxyribonuclease (rhDNase; dornase alfa) which cleaves extracellular DNA 7 8. The efficacy of rhDNase has been well documented in patients with cystic fibrosis,9 and several publications suggest that it is also effective in children with severe acute asthma with10 – 12 or without atelectasis 11 13…”

Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review

“…Treatment seems as more efficacious, as more bacteria or neutrophil are present in tracheal aspirate fluid [98]. In four children, dornase-a [99][100][101][102] also allowed a quick resolution of refractory status asthmaticus, in which other conventional therapies or bronchoscopic lavage failed to resolve airway obstruction.…”

The pulmonary physician in critical care * 12: Acute severe asthma in the intensive care unit

“…82 Recently, recombinant DNase, a mucolytic prescribed for sputum liquefaction in cystic fibrosis, has been used to treat mucus impaction in asthma but there are no clinical trials. 83 Inhalational anaesthetic agents Halothane, isoflurane, and sevoflurane are potent bronchodilators in asthmatic patients receiving mechanical ventilation who have failed to respond to conventional β adrenergic 84 Experimental evidence indicates a direct effect on bronchial smooth muscle mediated via calcium dependent channels as well as by modulating vagal, histamine, allergen, and hypoxia induced bronchoconstrictor mechanisms. 85 86 Furthermore, these agents reduce pulmonary vascular tone resulting in lower pulmonary artery pressures in acute asthma.…”