Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031350 (pharyngitis)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Respiratory symptoms, recurrent infectious exacerbations, and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. Purulent secretions contain high concentrations of extracellular DNA, a viscous material released by leukocytes. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase or Pulmozyme), the human enzyme was cloned, sequenced, and expressed. In in vitro studies, rhDNase has been shown to reduce the viscoelasticity, reduce the adhesiveness, and improve the mucociliary transportability of cystic fibrosis sputum. In short-term phase 1 and phase 2 clinical trials, rhDNase has been shown to be safely tolerated and to improve the FEV1, FVC, and symptoms of dyspnea. A long-term placebo-controlled phase 3 study was performed in 968 adults and children (> or = 5 years) with cystic fibrosis to determine the effect of rhDNase on the risk of respiratory exacerbations requiring parenteral antibiotics and on the FEV1. Compared with placebo-treated patients, patients treated with rhDNase once daily or twice daily experienced a reduced risk of respiratory exacerbations by 28% (p = 0.04) and 37% (p = 0.01), respectively, and had a mean improvement in FEV1 of 5.8% (p < 0.01) and 5.6% (p < 0.01), respectively. Compared with placebo-treated patients, patients treated with rhDNase spent 2.7 fewer days receiving parenteral antibiotics (p = 0.04) and spent 1.3 fewer days in the hospital (p = 0.06) over the 6-month treatment period. Inhalation of rhDNase did not cause anaphylaxis but was associated with upper airway symptoms (ie, voice alteration, hoarseness, pharyngitis) that were generally mild and transient. In conclusion, aerosol administration of rhDNase was safely tolerated, reduced the risk of infectious exacerbations requiring parenteral antibiotics, and improved pulmonary function and patient well-being.
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PMID:Aerosolized recombinant human DNase I for the treatment of cystic fibrosis. 784 16

The major causes of morbidity and mortality in cystic fibrosis (CF) are the obstruction and damaged airways that result from the accumulation of viscid and infected secretions. Dornase alfa, also called recombinant human DNase I (rhDNase), cleaves extracellular DNA, which is present in inordinately high concentrations in purulent CF airway secretions. Dornase alfa has been found to increase the pourability and reduce the viscoelasticity of CF sputum in vitro and, in an animal model, to increase its mucociliary transportability. Short-term (10-day) Phase I and II clinical trials showed dornase alfa to be safe and effective in improving pulmonary function in clinically stable CF patients with mild to moderate pulmonary disease (FVC > or = 40% of predicted value). A long-term (24-week) Phase IIB clinical trial demonstrated the importance of administering dornase alfa daily to maintain its efficacy. A large-scale, long-term, Phase III clinical trial, consisting of a 24-week double-blind period and a 24-week open-label extension, confirmed these findings and further demonstrated that dornase alfa reduces the incidence of respiratory tract infectious exacerbations requiring parenteral antibiotic therapy. Dornase alfa also decreased the rate of hospitalizations, the number of days missed from work or school, and the frequency of CF-related symptoms. Adverse events were limited to upper airway irritation (i.e., voice alteration, laryngitis, pharyngitis), rash, chest pain, and conjunctivitis. These manifestations generally were mild and transient, and they did not limit the use of dornase alfa. A small proportion (2 to 4%) of patients developed serum antibodies to dornase alfa, but no patient developed anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aerosolized dornase alfa (rhDNase) for therapy of cystic fibrosis. 788 98