Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.25.1 (deoxyribonuclease)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify factors influencing lung dose of aerosolized recombinant human deoxyribonuclease (rhDNase I), we used gamma camera and filter techniques to measure deposition in 15 clinically stable patients with cystic fibrosis (CF) (five males and 10 females, age 6-31 yr, mean 16.9) who were on chronic daily therapy. Total and regional deposition were correlated with breathing pattern, pulmonary function, demographic factors, and disease severity. In addition, the effects of each patient's measured lung dose on pulmonary function was estimated by stopping the drug and observing changes in spirometry over a 2-wk follow-up period. After discontinuance of the drug, all patients reported worsening of dyspnea and difficulty producing sputum. There was a significant decrease in FEV1 (% predicted, mean +/- SE, 86.9% +/- 5.57 to 77.8% +/- 5.73, p < 0.005), but all patients completed the study. In some patients, as much as 48% of the deposited aerosol was found in the pharynx (range 0.0 to 0.30 mg, mean 0.089 mg +/- 0.029), and pharyngeal deposition correlated negatively with tidal volume (r = -0.696, p < 0.006) and age (r = -0.743, p < 0.005). For the lungs, deposition ranged between 0.16 mg and 0.78 mg of the 2.5 mg nebulizer dose (mean 0.47 +/- 0.04 mg) and correlated negatively with FEV1 (% predicted, r = -0.611, p = 0.0152). However, the spirometric decrements following cessation of therapy did not correlate with the lung dose of the drug. Analysis of regional deposition within the lungs indicated a wide range of distribution between central and peripheral zones. In conclusion, the deposition pattern of rhDNase I aerosols in patients with CF is largely influenced by respiratory physiology, which itself depends upon age and severity of lung disease. As the patients grow there is a decrease in upper airway deposition and more particles are presented to the lungs where those patients with more airways disease have enhanced pulmonary deposition. Upper airway deposition of rhDNase I is significant, especially in younger patients, and may be related to laryngeal side effects.
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PMID:RhDNase I aerosol deposition and related factors in cystic fibrosis. 937 91

Recombinant human deoxyribonuclease (rhDNase) has been shown to reduce sputum viscoelasticity and to improve lung function in patients with cystic fibrosis (CF). The aim of this study was to determine whether airway inflammation would decrease after administration of rhDNase. Twenty patients with CF and chronic suppurative lung disease inhaled 2.5 mg of rhDNase daily for 1 month. Before and after the 1-month trial, lung function was measured and sputum was obtained, either after spontaneous expectoration or after sputum induction with hypertonic saline. Sputum total cell and differential counts were measured using techniques previously described. The mean age of the patients was 16.8 years (range, 6.7-27.5). After 1 month of rhDNase, mean FEV1 increased from a baseline of 62.3% predicted to 70.8% (P= 0.02, paired t test); and FVC increased from 74.4% to 83.9% predicted (P=0.007). No significant differences were found in sputum cytology before or after rhDNase (median total cell counts 16.0 x 10(6)/ml vs. 19.3 x 10(6)/ml, P=0.68). Thirteen patients had a 10% or greater increase in FEV1 after rhDNase (responders). Initial lung function was less in responders than in nonresponders (53.5% vs. 78.6%, P=0.007). There was no significant change in total cell count and neutrophil count after rhDNase in either responders or nonresponders. We conclude that airway inflammation, as measured by total cell counts in sputum, was a prominent feature in cystic fibrosis, and neutrophils were the dominant inflammatory cells. Although the administration of rhDNase resulted in significant improvements in FEV1, there was no evidence of accompanying changes in airway inflammation.
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PMID:Airway inflammation after treatment with aerosolized deoxyribonuclease in cystic fibrosis. 972 59

Recombinant human deoxyribonuclease (rhDNase) has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis (CF), but its long-term effect on airway inflammation remains unknown. In this study, we used bronchoalveolar lavage (BAL) to investigate the long-term effect of rhDNase on inflammation in patients with CF having mild lung disease. A total of 105 patients with CF (> or =5 years of age) having normal lung function were randomized to receive rhDNase (2.5 mg/day) or no rhDNase. Patients with a normal percentage of neutrophils in BAL fluid at baseline were not randomized and served as the control group. The percentage of neutrophils in the pooled BAL sample was similar in both randomized groups at baseline. A significant increase in neutrophils was observed over the 3-year study period in both untreated patients and control subjects, whereas neutrophils remained unchanged in patients treated with rhDNase. Elastase activities and interleukin-8 concentrations also increased in untreated patients and remained stable in patients on rhDNase. We conclude that in patients with CF, an increase in neutrophilic airway inflammation is found that is positively influenced by rhDNase treatment.
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PMID:Effect of treatment with dornase alpha on airway inflammation in patients with cystic fibrosis. 1468 61

In patients with cystic fibrosis (CF), the poor clearance of airway secretions promotes recurrent cycles of pulmonary infection and inflammation. In recent years, novel drugs have been developed to alter the properties of the secretions in an attempt to aid chest physiotherapy in improving airway clearance. Once-daily nebulised recombinant human deoxyribonuclease (rhDNase; dornase alfa; Pulmozyme) is the most widely used mucoactive therapy in patients with CF. It has been shown to reduce the viscoelasticity of sputum from patients with CF and enhance the clearance of secretions. Clinical trials have shown rhDNase to be a well tolerated treatment that improves pulmonary function and reduces respiratory exacerbations. However, the response to treatment is heterogeneous and only a proportion of patients with CF actually benefit from the treatment. At present, we are unable to predict which patients will benefit from rhDNase. Many CF centers have developed formal n-of-1 trials of treatment to find out who benefits and to justify prescribing the agent. rhDNase is an expensive therapy and is mainly used in patients over the age of 5 years with moderate to severe lung disease. However, studies have shown that rhDNase may be useful in patients with milder lung disease. Comparisons with another mucoactive drug, hypertonic saline, have shown rhDNase to be more effective. Recently, it has been shown that giving rhDNase on an alternate-day basis, rather than daily, is equally effective, potentially reducing costs and treatment time.
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PMID:The use of human deoxyribonuclease (rhDNase) in the management of cystic fibrosis. 1598 99

Chronic rhinosinusitis (CRS) is highly prevalent in patients with cystic fibrosis (CF) and accounts for significant morbidity and contribution to CF lung disease. Mutations of the cystic fibrosis transmembrane regulator gene occur with increased prevalence in patients with CRS without CF, suggesting some contribution to CRS pathophysiology. Nasal polyps (NPs) occur with increased prevalence in patients with CF of all ages and have a more neutrophilic appearance with fewer eosinophils and increased submucosal glandular elements in comparison to NPs from patients without CF. Mainstays of medical treatment include isotonic saline irrigations and topical intranasal glucocorticoids, with some evidence that topical intranasal glucocorticoids reduce NP size. Although inhaled hypertonic saline (7%) has been widely studied as a mucolytic agent for CF lung disease, there are no reports of its use in CF CRS. Mucolytics have also not been studied as a treatment for CRS in CF, and most evidence does not support their use for CF lung disease. Nasally nebulized dornase alfa (recombinant human deoxyribonuclease) following sinus surgery shows promise for treatment. Other unproven therapies include addition of baby shampoo to isotonic saline to potentially thin mucus and help prevent biofilm formation. There are no data to support the use of low-dose oral macrolide antibiotics or the use of prophylactic oral antibiotics for CRS in patients with CF. However, there is some support for the use of topical antibiotics, including colistimethate sodium or tobramycin, administered as a sinus irrigation or antral lavage in patients following sinus surgery when susceptible bacteria are cultured. Key components of CF sinus surgical management include extensive surgery to ensure that the maxillary, frontal, sphenoid, and ethmoid sinuses are all widely opened with smoothing of bony overhangs to prevent mucus retention and bacterial recolonization, postoperative meticulous daily nasal irrigations, and appropriate use of culture-directed topical antibiotics. There are no data yet on whether CF-targeted therapies, including ivacaftor or ivacaftor combined with lumacaftor, have an impact on CF CRS.
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PMID:Chronic Rhinosinusitis in Patients with Cystic Fibrosis. 2739 75

Although destructive airway disease is evident in young children with cystic fibrosis (CF), little is known about the nature of the early CF lung environment triggering the disease. To elucidate early CF pulmonary pathophysiology, we performed mucus, inflammation, metabolomic, and microbiome analyses on bronchoalveolar lavage fluid (BALF) from 46 preschool children with CF enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) program and 16 non-CF disease controls. Total airway mucins were elevated in CF compared to non-CF BALF irrespective of infection, and higher densities of mucus flakes containing mucin 5B and mucin 5AC were observed in samples from CF patients. Total mucins and mucus flakes correlated with inflammation, hypoxia, and oxidative stress. Many CF BALFs appeared sterile by culture and molecular analyses, whereas other samples exhibiting bacterial taxa associated with the oral cavity. Children without computed tomography-defined structural lung disease exhibited elevated BALF mucus flakes and neutrophils, but little/no bacterial infection. Although CF mucus flakes appeared "permanent" because they did not dissolve in dilute BALF matrix, they could be solubilized by a previously unidentified reducing agent (P2062), but not N-acetylcysteine or deoxyribonuclease. These findings indicate that early CF lung disease is characterized by an increased mucus burden and inflammatory markers without infection or structural lung disease and suggest that mucolytic and anti-inflammatory agents should be explored as preventive therapy.
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PMID:Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis. 3094 66