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)

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

Many of the proteins associated with innate immunity in the upper respiratory tract are to be found localized into mucus gels and the mucin-rich surface layers of the epithelium and the cilia. Mucus is a relatively dilute suspension of such macromolecules being around 2-4% solids in normal induced sputum. These proteins scavenge, immobilise and/or kill pathogens and at the same time immobilize them into the mucus. Mucus is moved from the lung by the mucociliary clearance mechanisms or by cough. Some 190 proteins are readily detectable in sputum by proteomics methods and about 100 in bronchial air-liquid interface culture secretions. This cell culture system mimics the surface ciliated phenotype of the large airways very well and about 85 secreted proteins are common to both culture and sputum secretions. The major single protein by weight in cell culture secretions is MUC5B and in sputum a mixture of MUC5B and MUC5AC. The three epithelial mucins MUC1, 4 and 16 are also detectable in both secretions. In this paper the roles that these molecules play in protecting and stabilising the ciliated surface and building the gel will be discussed. The role of water and ion homeostasis is particularly crucial in mucus gel formation and evidence is gathering that it is perturbation of hydration mechanisms that may play into defective mucus leading subsequently to stasis and mechanical problems.
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PMID:Innate immunity and mucus structure and function. 1727 93

The biophysical properties of airway secretions are largely determined by the polymeric components. In normal airway mucus, the gel-forming mucins, MUC5AC and MUC5B, are responsible not only for the viscoelastic properties essential for clearance and protecting the airway epithelium from invaders and water evaporation. With chronic airway infection, inflammatory cell necrosis leads to a predominance of polymeric DNA and F-actin. There is almost no mucin in the sputum of patients with established cystic fibrosis lung disease. Sputum viscoelastic and surface properties determine how well secretions can be cleared by cilia or cough. In this mini-Symposium on Airway Clearance in Cystic Fibrosis, the physiology of CF secretion structure and rheology is discussed in the context of medications and physical maneuvers for enhancing sputum clearance.
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PMID:Mucus structure and properties in cystic fibrosis. 1741 72

In health, the airways are lined by a layer of protective mucus gel that sits atop a watery periciliary fluid. Mucus is an adhesive, viscoelastic gel, the biophysical properties of which are largely determined by entanglements of long polymeric gel-forming mucins, MUC5AC and MUC5B. This layer entraps and clears bacteria and inhibits bacterial growth and biofilm formation. It also protects the airway from inhaled irritants and from fluid loss. In diseases such as cystic fibrosis there is almost no mucin (and thus no mucus) in the airway; secretions consist of inflammatory-cell derived DNA and filamentous actin polymers, which is similar to pus. Retention of this airway pus leads to ongoing inflammation and airway damage. Mucoactive medications include expectorants, mucolytics, and mucokinetic drugs. Expectorants are meant to increase the volume of airway water or secretion in order to increase the effectiveness of cough. Although expectorants, such as guaifenesin (eg, Robatussin or Mucinex), are sold over the counter, there is no evidence that they are effective for the therapy of any form of lung disease, and when administered in combination with a cough suppressant such as dextromethorphan (the "DM" in some medication names) there is a potential risk of increased airway obstruction. Hyperosmolar saline and mannitol powder are now being used as expectorants in cystic fibrosis. Mucolytics that depolymerize mucin, such as N-acetylcysteine, have no proven benefit and carry a risk of epithelial damage when administered via aerosol. DNA-active medications such as dornase alfa (Pulmozyme) and potentially actin-depolymerizing drugs such as thymosin beta(4) may be of value in helping to break down airway pus. Mucokinetic agents can increase the effectiveness of cough, either by increasing expiratory cough airflow or by unsticking highly adhesive secretions from the airway walls. Aerosol surfactant is one of the most promising of this class of medications.
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PMID:Mucolytics, expectorants, and mucokinetic medications. 1759 30

Ginkgo biloba has long been used in ancient China for the treatment of cough, asthma, and other lung diseases. However, the active constituents in G. biloba for pulmonary disease treatment remain unclear. The objective of this study was to evaluate the anti-inflammatory active constituents in G. biloba and clarify their associated molecular mechanisms. The biological effects of different G. biloba extracts were evaluated in an ovalbumin-induced allergic mouse model. Anti-inflammatory compounds were present in the ethyl acetate phase of the extract, which were analysed by HPLC-MS. Biflavones were identified as the main compounds, which were further evaluated by docking calculations. Leukocyte elastase showed a high fit score with ginkgetin, one of the identified biflavones. The lowest binding free energy was -6.69 kcal mol-1. The effects of biflavones were investigated in vivo and in vitro. Ginkgetin markedly suppressed the abnormal expression of the Akt and p38 pathways in human neutrophil elastase (HNE)-stimulated A549 cells. Biflavones also decreased MUC5AC mRNA expression in HNE-stimulated A549 cells and the allergic mouse model. Inflammatory cells (neutrophils) and cytokines (IL-8) also decreased in mice treated with biflavones. The results suggest that G. biloba biflavones could inhibit the activity of leukocyte elastase. This in turn implicates G. biloba as a functional food for the treatment of airway inflammation.
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PMID:Evaluation of the anti-inflammatory properties of the active constituents in Ginkgo biloba for the treatment of pulmonary diseases. 3094 5

Periostin may serve as a biomarker for type-2-mediated eosinophilic airway inflammation in asthma. We hypothesised that type-2 cytokine IL-13 induces airway epithelial expression of periostin, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 on periostin expression in BEAS-2B and air-liquid interface (ALI)-differentiated primary bronchial epithelial cells (PBECs). Additionally, effects of recombinant human periostin on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. In bronchial biopsies and induced sputum from asthma patients and healthy controls, we analysed periostin single cell gene expression and protein levels.IL-13 increased POSTN expression in both cell types, which was accompanied by EMT-related features in BEAS-2B. In ALI-differentiated PBECs, IL-13 increased periostin basolateral and apical release. Apical administration of periostin increased the expression of MMP9, MUC5B and MUC5AC In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus controls. Higher protein levels of periostin, expressed in epithelial and subepithelial layers, was confirmed in bronchial biopsies from asthma patients compared to healthy controls. Although sputum periostin levels were not higher in asthma, levels correlated with eosinophil numbers and coughing up mucus.Periostin expression is increased by IL-13 in bronchial epithelial cells and higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of periostin increased epithelial expression of mucin genes, supporting the relationship of periostin with type-2 mediated asthma and mucus secretion.
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PMID:Periostin: contributor to abnormal airway epithelial function in asthma? 3290 87