title: The use of rhDNAse in severely ill, non-intubated adult asthmatics refractory to bronchodilators: a pilot study.
abstract: BACKGROUND
  Mucous plugging is associated with fatal asthma and may have a causative role for non-fatal cases of severe acute asthma. However, mucolytic agents have not been found effective in reversing the obstruction of acute asthma. We test the hypothesis that rhDNAse, an agent that reduces viscoelasticity of sputum in patients with cystic fibrosis, has a therapeutic role in acute asthma.
  
  
  METHODS
  Symptomatic asthmatics aged 18-55 years presenting to an Emergency Department with an FEV(1) < 60% predicted after 2 nebulized albuterol and ipratropium treatments were included. Patients were randomized into one of three nebulized rhDNAse treatment groups of 2.5, 5.0 or 7.5 mg, or placebo. Standardized bronchodilator therapy was continued throughout the protocol and the FEV(1) at 6 h was the primary study endpoint.
  
  
  RESULTS
  50 patients were enrolled. There were no significant differences in FEV(1)% predicted between the rhDNAse and placebo patients at any of the post-randomization time points. The dose of rhDNAse administered did not influence response. In a post-hoc stratification, patients with the lowest pre-randomization FEV(1) tended to improve more from rhDNAse, particularly at times 60 and 120 min post-randomization.
  
  
  CONCLUSIONS
  In this pilot study rhDNAse did not cause clinical improvement among severely ill adults refractory to standardized care. The observed trend to higher FEV(1) among the most severely obstructed patients is an exploratory finding that may warrant further study. This clinical trial was registered as NCT00169962 under the name "Study of Pulmozyme to Treat Severe Asthma Episodes".
authors.affiliation: Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, New York, USA. aresilv@aol.com
authors.forename: Robert A
authors.initials: RA
authors.lastname: Silverman
authors.forename: Finbar
authors.initials: F
authors.lastname: Foley
authors.forename: Resul
authors.initials: R
authors.lastname: Dalipi
authors.forename: Myriam
authors.initials: M
authors.lastname: Kline
authors.forename: Martin
authors.initials: M
authors.lastname: Lesser
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D003850:Deoxyribonuclease I / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005100:Expectorants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D005100:Expectorants; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I