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)

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormal ciliary structure and function and impaired mucociliary clearance. Because patients with PCD use cough clearance as an airway defense mechanism, we tested the hypothesis that aerosolized uridine-5'-triphosphate (UTP) would improve clearance during cough by its actions to stimulate Cl- secretion and mucin release by goblet cells. We measured clearance during cough in 12 patients with PCD (ages 14 to 71 yr, FEV1 43% to 89% predicted) in a double blind, randomized, crossover study after aerosolization of a single dose of UTP (5 mg/ml, 3.5 ml) or vehicle (0.12% saline, 3.5 ml). Clearance during cough (whole lung) was quantified during and after a series of controlled coughs by measuring the clearance of [99mTc]Fe2O3 particles via gamma camera scanning over 120 min. Safety parameters were recorded during and after drug delivery. Aerosolized UTP improved whole-lung clearance during cough as compared with vehicle (from 0 to 60 min: 0.40 +/- 0.07%/min [UTP] versus 0.26 +/- 0. 04%/min [vehicle] [mean +/- SEM], p = 0.01), and from 0 to 120 min: 0.38 +/- 0.05%/min [UTP] versus 0.25 +/- 0.04%/ min [vehicle], p = 0. 02). Aerosolized UTP is safe, with no serious adverse effects. Whole-lung clearance during cough in patients with defective ciliary function is enhanced after inhalation of UTP.
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PMID:Effect of aerosolized uridine-5'-triphosphate on airway clearance with cough in patients with primary ciliary dyskinesia. 1039 Mar 92

To investigate the influence of erdosteine, a new homocysteine-derived expectorant, on airway clearance we studied the effects of the drug on the viscosity of mucin, on the mucociliary transport rate in quails, on airway secretion in rats and on the cough reflex in guinea-pigs. The active metabolite of erdosteine, M1 (10 microM to 1 mM), significantly reduced the viscosity of porcine stomach mucin. Erdosteine by itself did not reduce viscosity. Erdosteine significantly promoted mucociliary transport in quails and increased airway secretion in rats. The effect was still apparent 24h after administration. Erdosteine significantly suppressed citric acid-induced cough reflexes in guinea-pigs but did not suppress mechanical stimuli-induced cough reflexes. Erdosteine suppressed the reduction of the recovery volume of bronchoalveolar lavage fluid and albumin leakage into the fluid in citric acid-exposed guinea-pigs. These results indicate that erdosteine removes sputum by reducing its viscosity, and by promoting mucociliary transport and sustained enhancement of airway secretion. It also suppressed the chemical stimulation-induced cough reflex and plasma leakage into the airway. These results suggest that erdosteine is an excellent expectorant with several modes of action.
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PMID:Mucolytic and antitussive effects of erdosteine. 1050 37

The aerosol route is attractive for the delivery of mucoactive medications. Mucoactive medications include mucolytics, which depolymerize polymers of mucin (classic mucolytics) or DNA/actin (peptide mucolytics), mucokinetic agents, which increase cough clearance, mucoregulatory medications, which decrease abnormal mucus secretion, and expectorants and ion channel modifiers. Despite the widespread use of these medications, there are few well conducted studies and thus few data clearly supporting (or failing to support) their use. This will change as our understanding of mucociliary physiology and pharmacology increases and as well designed and well powered clinical trials are conducted with appropriate outcome measurements. Effective mucoactive therapy should make a profound impact on the care of patients with chronic bronchitis, asthma, cystic fibrosis, and inflammatory airways disease, and will be essential for the effective delivery of gene therapy vectors and bioactive peptides to the airway epithelium.
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PMID:Evaluating the efficacy of mucoactive aerosol therapy. 1130 34

Respiratory tract secretions consist of mucus, surfactant, and periciliary fluid. The airway surface fluid is present as a bilayer, with a superficial gel or mucous layer and a layer of periciliary fluid interposed between the mucous layer and the epithelium. A thin layer of surfactant separates the mucous and periciliary fluid layers. The mucous layer extends from the intermediate airway to the upper airway and is approximately 2-10 microm thick in the trachea. Airway mucus is the secretory product of the goblet cells and the submucosal glands. It is a nonhomogeneous, adhesive, viscoelastic gel composed of water, carbohydrates, proteins, and lipids. In health, the mucous gel is primarily composed of a 3-dimensional tangled polymer network of mucous glycoproteins or mucin. Mucin macromolecules are 70-80% carbohydrate, 20% protein, and 1-2% sulfate bound to oligosaccharide side chains. The protein backbones of mucins are encoded by mucin genes (MUC genes), at least 8 of which are expressed in the respiratory tract, although MUC5AC and MUC5B are the 2 principal gel-forming mucins secreted in the airway. Mucus is transported from the lower respiratory tract into the pharynx by air flow and mucociliary clearance. Expectorated sputum is composed of lower respiratory tract secretions along with nasopharyngeal and oropharyngeal secretions, cellular debris, and microorganisms. Disruption of normal secretion or mucociliary clearance impairs pulmonary function and lung defense and increases risk of infection. When there is extensive ciliary damage and mucus hypersecretion, airflow-dependent mucus clearance such as cough becomes critically important for airway hygiene.
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PMID:Physiology of airway mucus clearance. 1208 46

The airway mucosa responds to infection and inflammation in a variety of ways. This response often includes surface mucous (goblet) cell and submucosal gland hyperplasia and hypertrophy, with mucus hypersecretion. Products of inflammation, including neutrophil-derived deoxyribonucleic acid (DNA) and filamentous actin (F-actin), effete cells, bacteria, and cell debris, all contribute to mucus purulence and, when this mucus is expectorated it is called sputum. Mucoactive medications are intended to serve one of 2 purposes; either to increase the ability to expectorate sputum or to decrease mucus hypersecretion. Mucoactive medications have been classified according to their proposed mechanisms of action. Increased knowledge of the properties of mucus has given us tools to better understand the mechanisms of airway disease and mucoactive therapy. Expectorants are thought to increase the volume or hydration of airway secretions. Systemic hydration and classic expectorants have not been demonstrated to be clinically effective. Modifiers of airway water transport are being clinically investigated as expectorants. Mucolytics degrade polymers in secretions. The classic mucolytics have free thiol groups to degrade mucin. Peptide mucolytics break pathologic filaments of neutrophil-derived DNA and actin in sputum. Nondestructive mucolysis includes mucin dispersion by means of charge shielding. Mucokinetics are medications that increase mucociliary efficiency or cough efficiency. Cough flow can be increased by bronchodilators in patients with airway hyperreactivity. Abhesives such as surfactants decrease mucus attachment to the cilia and epithelium, augmenting both cough and mucociliary clearance. Mucoregulatory agents reduce the volume of airway mucus secretion and appear to be especially effective in hypersecretory states such as bronchorrhea, diffuse panbronchiolitis, and some forms of asthma. Mucoregulatory agents include anti-inflammatory agents (indomethacin, glucocorticosteroids), anticholinergic agents, and some macrolide antibiotics. Classifying mucoactive agents should help us to develop and evaluate new types of therapy and to better direct therapy toward the patients who are most likely to benefit.
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PMID:The pharmacologic approach to airway clearance: mucoactive agents. 1208 52

Defective expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) airway epithelial cells are associated with airway mucus hypersecretion, inflammation and infection that begin early in life and lead, at an advanced stage of the disease, to severe airway obstruction with hyperviscous and adhesive airway mucus. Whether the abnormalities of airway mucus are already present at birth before infection is debatable. In CF, the impaired Cl(-) and HCO(3)(-) secretion associated with increased epithelial Na(+) absorption results in dehydration of airway mucus, decreased antimicrobial functions and impaired mucociliary clearance. Alterations in antibacterial peptide function, as well as the increased mucin expression and secretion (MUC 5AC and MUC 5B), are important biochemical factors responsible for the propensity for infection in CF airways. Alterations in mucin and lipid composition induce an increased viscosity and adhesiveness to the airways that can affect the mucociliary and cough transport. The increased content of pro-inflammation cytokines such as interleukin-8 (IL-8) suggest that, before infection, airway inflammation occurs very early in CF. The development of non-invasive techniques and humanised animal models (xenografts) represents a major opportunity to identify early abnormalities in CF airway mucus.
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PMID:Airway mucus in cystic fibrosis. 1229 57

We performed a retrospective analysis of potential prognostic markers in 260 patients with surgically resected stage I and II non small-cell lung cancer (NSCLC) with a minimum 5-year follow-up. Cox proportional hazard models and Wilcoxon tests were employed to analyze the effect of patient characteristics on survival and disease-free survival (DFS). In the univariate analysis, the following were significant predictors of shorter overall survival: N-stage (N1 vs N0) (p<0.001); T-stage (T2 vs T1) (p<0.001); antigen A (loss vs presence) (p<0.01); cough (present vs absent) (p=0.01); bcl-2 expression (positive vs negative) (p=0.03); age (>63.5 vs <63.5) (p=0.03); mucin (positive vs negative) (p<0.03). The following were significant predictors of shorter DFS: N-stage (p<0.001); T-stage (p=0.001); loss of antigen A (p=0.01); mucin expression (p<0.01); cough (p=0.02); Ki-67 expression (p=0.02) and negative bcl-2 expression (p=0.03). Analysis of survival difference for histologic subtype, degree of differentiation, aneuploidy, %S-phase, codon 12 K-ras mutation, and immunohistochemistry staining for Lewisy, p53, Rb, microvessel count, HER2, E-cadherin and neuroendocrine markers did not reach statistical significance. In multivariate analysis, the following predicted for shorter overall survival: N-stage (p<0.01), antigen A (p=0.01), age (p<0.01), and bcl-2 (p=0.05); and for DFS, N-stage (p<0.01), antigen A (p<0.01), Ki-67 (p=0.03), mucin (p=0.04) and T-stage (p=0.05). Of all the clinical-pathological, proliferative, and biological markers studied, only a few carried independent prognostic significance.
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PMID:Prognostic markers in resected stage I and II non small-cell lung cancer: an analysis of 260 patients with 5 year follow-up. 1472 52

Although there has been impressive progress in the elucidation of the genetic and molecular basis of cystic fibrosis (CF), the pathogenesis of CF lung disease remains obscure. The elucidation of the pathogenesis of CF lung disease requires both a full description of normal innate airway defence and how absent function of the cystic fibrosis transmembrane regulator protein (CFTR) adversely perturbs this activity. Recent data have linked the abnormal ion transport properties of CF airway epithelia to depleted airway surface liquid (ASL) volume, reflecting the combined defects of accelerated Na+ transport and the failure to secrete Cl-. Depletion of a specific compartment of the ASL, i.e. the periciliary liquid (PCL), appears to abrogate both cilia-dependent and cough clearance. Subsequent to PCL depletion, mucus adheres to airway surfaces and persistent mucin secretion generates the formation of "thickened" mucus plaques and plugs, which become the nidus for bacterial infection. The paucity of liquid in these plaques/plugs, and the hypoxia in this environment, appear to promote biofilm bacterial infection. Therapeutic agents that restore airway surface liquid volume, i.e. blockers of Na+ transport, initiators of Cl- transport and osmolytes, are reviewed, as are strategies that may be required to use volume-restoring agents safely in patients with cystic fibrosis.
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PMID:New concepts of the pathogenesis of cystic fibrosis lung disease. 1473 47

The epithelial cells lining the airways serve protective functions. The "barrier function" of the epithelium protects the individual from damage by inhaled irritants. The epithelium produces mucins which become hydrated and form a viscoelastic gel which spreads over the epithelial surface. In healthy individuals inhaled foreign materials become entrapped in the mucus and are cleared by mucociliary transport and by coughing. In many chronic inflammatory airway diseases, however, excessive mucus is produced and is inadequately cleared, leading to mucous obstruction and infection. At present there is no specific treatment for hypersecretion. However, the discovery that an epidermal growth factor receptor (EGFR) cascade is involved in mucin production by a wide variety of stimuli suggests that blockade may provide specific treatment for hypersecretory diseases. EGFR pathways have also been implicated in the repair of damaged airway epithelium. The roles of EGFR in airway epithelial cell hypersecretion and epithelial damage and repair are reviewed and future potential treatments are suggested.
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PMID:Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium. 1551 78

Two Japanese females complained of cough and bronchorrhea for which chest radiographs showed infiltrate in the lungs. The patients were subsequently diagnosed as having bronchioloalveolar carcinoma by transbronchial lung biopsy. After receiving systemic chemotherapy, their symptoms were slightly improved. A few months later, their bronchorrhea and dyspnea worsened, and they were then treated with gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor. Bronchorrhea and dyspnea were improved within 24 h after treatment with gefitinib where the improvement was evident after 6 h for one patient and 24 h for the other patient. Thereafter, their radiological findings showed gradual improvement. Rapid relief of bronchorrhea preceded the improvement seen by the radiological findings. These observations suggest that gefitinib may inhibit mucin production as well as exert anti-proliferative activity against bronchioloalveolar carcinoma.
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PMID:Novel effects of gefitinib on mucin production in bronchioloalveolar carcinoma; two case reports. 1594 98


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