UMLS:C0010200 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce the viscosity of purulent cystic fibrosis (CF) respiratory mucus, to improve pulmonary function and to reduce the risk of respiratory tract infectious exacerbations, but its effect on mucus transportability has not so far been investigated. The dose-dependent effect of rhDNase was analysed in vitro on mucus transport rate (tr) by ciliary activity and by simulated cough (cough transport (ct)), as well as on mucus viscosity and surface properties. Purulent CF sputa (n = 15) were incubated for 30 min at 37 degrees C with either rhDNase at three different concentrations (final concentrations 0.2, 2 or 20 micrograms.ml-1 of mucus) or placebo. No significant dose-dependent effect of rhDNase on the mucociliary transport rate was observed when the samples wer statistically analysed together. However, in the larger group of mucus samples (n = 11) with a low initial mucociliary transport rate, the latter was improved at each rhDNase concentration (tr0.2 = 0.69, tr2 = 0.88 and tr20 = 0.87) as compared to placebo (trp = 0.58). In the smaller group of mucus samples (n = 4) with high initial transport rate, a decrease in mucociliary transport rate was observed, particularly at the highest concentration rhDNase assayed, i.e. 20 micrograms.ml-1 of mucus (tr20 = 0.58) as compared to placebo (trp = 0.86). The mucus cough transport was increased by rhDNase (ct0.2 = 25 mm, ct2 = 27.5 mm and ct20 = 31 mm) as compared to placebo (ctp = 23.5 mm).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dose-dependent in vitro effect of recombinant human DNase on rheological and transport properties of cystic fibrosis respiratory mucus. 778 81

The airway secretions which line the respiratory tract form a biphasic layer composed of an aqueous 'sol' layer and a more superficial 'gel' layer. In the sol layer, also described as the 'periciliary' layer or 'airway surface fluid', the cilia beat and relax. The lubricant sol layer enables the gel mucus present at the tips of the cilia to be transported by the ciliary beating of the ciliated cells. Due to difficulties with sampling, little is known about the physical and biochemical properties of the sol layer. The gel layer is composed of high molecular weight glycoproteins (mucins) linked with proteins and lipids. They form a gel network with a high water content (95%) and rheologic and physical properties (viscoelasticity, adhesivity) adapted in normal conditions to protect the airway mucosa, particularly through mucociliary transport. The adhesive properties of mucus, which are influenced by its lipid composition and degree of hydration, are very important in controlling the efficacy of mucus transport through ciliary activity and coughing. An intermediate viscosity and elasticity is required for optimal mucociliary transport. In obstructive airway diseases, either of genetic origin, such as cystic fibrosis (CF), or acquired (acute or chronic bronchitis), and particularly during inflammatory and infectious episodes, mucus dehydration is associated with an increase in secreted or transudated molecules and with marked augmentation of DNA content. These abnormalities contribute to the increased viscosity and adhesivity of the airway secretions and are responsible for their abnormally low transport rate by ciliary activity and for inefficient cough clearance. In view of these alterations in the physical and functional properties of CF airway secretions, pharmacologic approaches should aim to rehydrate the mucus and to restore normal mucociliary or cough transport by stimulating chloride ion secretion (i.e. using UTP or ATP associated with amiloride in order to block sodium ion and water reabsorption). During acute episodes of infection, recombinant human DNase (rhDNase) may rapidly prevent mucus stasis by improving its rheologic properties. Lubrication of the mucus at the sol phase interface by 'surfactant' therapy may also represent a very promising therapeutic perspective to reduce the hyperviscosity and hyperadhesivity of airway secretions.
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PMID:Physical and functional properties of airway secretions in cystic fibrosis--therapeutic approaches. 779 36

A 56-year-old man was transferred to our department from the department of oral surgery, with a high fever and a cough. He had inhaled a fibrinolysin-deoxyribonuclease mixture (Elase) to treat inflammation in the oral cavity after resection of an oral tumor. A chest X-ray film showed diffuse patchy shadows in both lung fields. Bronchoalveolar lavage fluid had an abnormally high number of lymphocytes and transbronchial lung biopsy revealed interstitial infiltration by lymphocytes and histiocytes, with granulomatous lesions. The patient was treated with steroids, and his clinical condition improved markedly. He accidentally inhaled the drug again, and the coughing and fever began again. The drug lymphocyte stimulation test was positive only for the fibrinolysin-deoxyribonuclease mixture. Based on these findings, we diagnosed pneumonitis induced by this fibrinolysin-deoxyribonuclease mixture. To our knowledge, this is the first reported case of pneumonitis caused by this fibrinolysin-doxyribonuclease mixture.
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PMID:[Pneumonitis in a patient who inhaled a fibrinolysin-deoxyribonuclease mixture]. 858 26

Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce in vitro the viscosity and to improve the transport capacity of purulent respiratory mucus in cystic fibrosis. During episodes of exacerbation of chronic bronchitis, the patients generally expectorate purulent mucus. Purulence of mucus is associated with an increased deoxyriboneucleic acid (DNA) concentration. We analyzed in vitro the potential effect of rhDNase on chronic bronchitis mucus transport by the ciliary activity (frog palate model) and by simulated cough (cough machine model), as well as the effect on mucus viscosity (controlled stress rheometer) and surface properties (contact angle). Purulent sputa collected from patients with chronic bronchitis (n = 15) during an episode of exacerbation were incubated for 30 min at 37 degrees C with either rhDNase at two different concentrations (final concentration 2 or 4 micrograms.mL-1) or placebo. The median mucociliary transport rate was significantly improved by rhDNase from 0.68 with placebo to 0.79 and 0.83 with 2 and 4 micrograms.mL-1 of rhDNase, respectively. A significant improvement in mucus cough transport was also induced by rhDNase from 25.5 mm with placebo to 27.0 mm with either 2 or 4 micrograms.mL-1 rhDNase. These improvements in mucus transport capacity were associated with alterations in the physical properties of the mucus. The mucus median control viscosity (511.4 Pa.s) and median contact angle (0.85 rd) significantly decreased to 112.5 Pa.s and 0.74 rd, respectively, in the presence of 4 micrograms.mL-1 of rhDNase. These findings demonstrate that recombinant deoxyribonuclease may exert a beneficial effect on mucus clearance in vitro by altering the viscosity and surface properties of the purulent chronic bronchitic sputum samples.
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PMID:Effects of rhDNase on purulent airway secretions in chronic bronchitis. 872 43

Atelectasis occurs frequently in patients with spinal cord injury (SCI). Impaired cough leads to ineffective clearance of secretions. If the secretions cannot be cleared and become thick and purulent, atelectasis may occur. Recombinant human DNase (rhDNase) has been shown to decrease purulent sputum viscosity in vitro. We report two SCI patients with respiratory failure due to recurrent atelectasis from purulent secretions in whom conventional treatment methods had failed. Administration of rhDNase resulted in successful resolution of atelectasis. These results suggest the need for a controlled clinical trial.
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PMID:Resolution of recurrent atelectasis in spinal cord injury patients with administration of recombinant human DNase. 881 75

The objective of this study was to evaluate the individual and combined effects of Nacystelyn (NAL) and rhDNase in vitro on the rheological properties of cystic fibrosis (CF) sputum. Sputum samples were collected from 11 CF patients and subjected to the following protocols: 1) negative control sample without any treatment; 2) positive control sample incubated with 0.02 ml of normal saline; 3) incubation of CF sputum with 0.02 mL DNase (25 micrograms/mL in normal saline) at 37 degrees C to achieve 2.5 micrograms/g final sputum concentration (approximately 100 nM); 4) incubation of CF sputum with 0.02 mL NAL (30.9 micrograms/mL in normal saline) at 37 degrees C to achieve 3.09 micrograms/g final sputum concentration (10 microM); and 5) combination of protocols 3 and 4 with half the concentration of each drug. The samples in protocols 2 through 5 were incubated for 30 minutes at 37 degrees C. For each protocol, spinnability by filancemeter and viscoelasticity (log G*) by magnetic microrheometer were measured at baseline and 30 minutes. Treatment of the sputum with rhDNase alone or NAL alone decreased spinnability more than control treatment with saline. Combining NAL with rhDNase at half the concentration of each drug significantly decreased spinnability more than either treatment by itself. There were no significant changes in log G* or the derivative parameters, mucociliary clearability index (MCI) and cough clearability index (CCI). The enhanced reduction in sputum spinnability by the combination of NAL and rhDNase indicates additative effects between these two mucolytic treatments. These results suggest that combined treatment with rhDNase and NAL should be considered as a potential therapy for CF patients.
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PMID:Reduction in viscoelasticity in cystic fibrosis sputum in vitro using combined treatment with nacystelyn and rhDNase. 889 54

Nebulized recombinant human DNase (rhDNase) reduces sputum viscosity, improves pulmonary function, and results in a small reduction in acute respiratory exacerbations requiring intravenous antibiotics in many patients with cystic fibrosis (CF). rhDNase is now recommended for use in CF patients with moderately severe suppurative lung disease. A 14-year-old girl with suppurative lung disease [forced expiratory volume in 1 second (FEV1) 69% and forced vital capacity (FVC) 81% predicted] secondary to Kartagener's syndrome and severe gastroesophageal reflux had worsening spirometry together with intractable gastrointestinal symptoms over the previous 18 months despite conventional treatment. She was, therefore, started on 2.5 mg rhDNase once daily. Her cough lessened and the volume of sputum decreased within 72 hours of commencement of treatment; this improvement was strongly associated with a dramatic reduction in gastrointestinal symptoms. Spirometry after 4 weeks of treatment demonstrated a 20% improvement in FEV1 and a 13% improvement in FVC. These improvements have been maintained after 4 months of rhDNase therapy. The use of rhDNase should be considered in patients with Kartagener's syndrome and a multicenter trial may be justified.
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PMID:Clinical benefit from nebulized human recombinant DNase in Kartagener's syndrome. 890 3

Treatment with recombinant human deoxyribonuclease I (rhDNase) is currently used as therapy for cystic fibrosis (CF) lung disease. Hypertonic saline (HS) acts as an expectorant promoting mucus secretion and augmenting the volume of sputum. We evaluated the individual and combined effects of HS and rhDNase in vitro on the viscoelasticity of CF sputum. Sputum samples were collected from nine CF patients to use for in vitro testing. Aliquots of CF sputum (0.20 to 0.40 g) were subjected to the following protocols: (1) negative control sample without any treatment; (2) positive control sample, adding 10% volume of normal saline (0.9% NaCl); (3) application of hypertonic saline (HS-3% NaCl); (4) combining approximately 100 nM concentration of rhDNase with protocols 2 and 3. The samples in protocols 2 through 4 were incubated for 30 min at 37 degrees C. For each protocol, CF sputum was analyzed at baseline and at 30 min for spinnability by filancemeter and viscoelasticity by magnetic microrheometry. Spinnability decreased for the sputum samples that were treated with rhDNase, in combination with either HS or normal saline. Treatment with HS alone and combined treatment with rhDNase and HS decreased log G* (the principal viscoelasticity index) to the same degree. Saline alone and rhDNase in normal saline both increased the predicted cough clearability of the sputum; however, the combined treatment with rhDNase and hypertonic saline had the best overall effect on cough clearability. The change in predicted mucociliary clearability, although greatest after HS, was not significant. These in vitro results suggest that combined treatment with rhDNase and HS should be evaluated further as a potential mucotropic approach to augment the clearance of purulent sputum in CF lung disease.
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PMID:Rheology of cystic fibrosis sputum after in vitro treatment with hypertonic saline alone and in combination with recombinant human deoxyribonuclease I. 923 Jul 43

Cystic fibrosis (CF) is caused by mutation in the gene for the CF transmembrane conductance regulator which leads to massive, abnormally viscous, purulent sputum, chronic destructive endobronchitis and early death. Purified recombinant human (rh) DNase can digest extracellular DNA and its inhalation in these patients significantly improves lung function. To evaluate the poorly understood mechanisms, saliva protected sputum from patients treated with and without rhDNase were evaluated. Therapy with rhDNase resulted in a soluble sputum fraction that had a higher percentage of phosphatidylethanolamine, a phospholipid present mainly in cellular membranes, a much lower percentage of phosphatidylcholine, but a higher surface activity. The rigidity was significantly lower and the ratio of viscosity in proportion to elasticity increased. All these data are consistent with an increased clearability of the sputum by coughing, but not by mucociliary activity. Thus the interaction of inhaled rhDNase with the purulent mucus and the endobronchial inflammatory processes may induce changes that result in rheological properties favoring clearance of sputum by cough.
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PMID:Recombinant human DNase (rhDNase) influences phospholipid composition, surface activity, rheology and consecutively clearance indices of cystic fibrosis sputum. 934 29

Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases or airway malacia. Use of positive pressure to maintain airway patency in these children allows cephalad clearance of secretions. Patients with segmental atelectasis, particularly related to asthma, may benefit from intrapulmonary percussive ventilator, positive expiratory pressure, or PDPV. Prevention of postoperative atelectasis is particularly well suited to positive expiratory pressure, which is not as painful as techniques using oscillations. Neurologically abnormal patients who are unable to cooperate with any active method are also treated using intrapulmonary percussive ventilator, PDPV, and suctioning, if necessary. Musculoskeletal abnormalities, muscular dystrophies, myasthenia gravis, poliomyelitis, or other similar diseases require stabilization of bellows function. Optimizing ventilation in patients with such abnormalities may require positive pressure ventilation either during sleep or continuously. Externally applied pressure, such as with the In-Exsufflator or the cyclically inflated pneumatic belt, can augment the patient's own efforts and is sometimes helpful. Normalizing the vital capacity and functional residual capacity typically helps to improve the ability to cough and clear secretions. Assisted cough devices or maneuvers are described in other papers by Bach and Hill. Not all patients who have weak muscles require nocturnal or continuous support, and may benefit from positive expiratory pressure mask treatments. Further studies are sorely needed for this population. Long-term controlled trials are urgently needed to help establish the best types of treatment for patients with CF and bronchiectasis. Such studies will become more complicated by the introduction of new treatments, such as DNase and other therapies that alter secretions, and may begin to change mucociliary or cough clearance. The selection of appropriate outcome measures is central to studying these questions, and it is unclear which are the most important. (ABSTRACT TRUNCATED)
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PMID:Noninvasive clearance of airway secretions. 939 Aug 86

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