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)

Failure to clear mucus normally is a critical event in the pathogenesis of chronic bronchitis (CB). A unifying concept for the failure to clear mucus from airway surfaces has emerged that focuses on an abnormally high mucin-to-airway surface liquid volume ratio. At a certain level, a high mucin-to-volume ratio is associated with loss of the periciliary liquid layer and adhesion of the mucus layer to the cell surface. Adherent mucus becomes a stimulus for irritation and cough and is the nidus for bacterial infection. Therapeutic approaches for clearing mucus from CB airways should focus on restoring the balance of mucin and water. Pharmacologic blockade of the epithelial Na+ channel, which is rate-limiting for volume absorption from airway surfaces, constitutes a novel therapeutic target. Studies of mucus clearance both in sheep models and human subjects demonstrate that blockade of the epithelial Na+ channel is associated with an acceleration of mucus clearance, suggesting that epithelial Na+ channel blockade may indeed constitute a rational form of therapy for CB.
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PMID:Relationship of airway epithelial ion transport to chronic bronchitis. 1611 15

A 5-year-old, intact male Italian Spinone dog was presented for progressive, severe dyspnea and coughing. Thoracic radiographs revealed a large mass in the right cranial thorax. Fine needle aspiration of the mass yielded a highly cellular sample containing dense clumps of oval to spindle-shaped mesenchymal cells with distinct intracytoplasmic vacuolation, consistent with lipoblasts and lipocytes. Cell clusters were associated with abundant eosinophilic matrix, which was identified as mucin, based on Alcian blue staining. At exploratory thoracotomy, the mass was found to be nonresectable, and the dog was euthanized. Histologic sections of the multilobular mass had discrete regions of variable cellular differentiation, including highly cellular areas of pleomorphic cells, areas of spindle cells and lipoblasts in a myxoid background, and areas of well-differentiated lipogenic cells. The histologic diagnosis was myxoid liposarcoma. The thoracic cavity is a rare site for liposarcoma in the dog. The cytologic features of lipoblasts together with a mucopolysaccharide matrix were useful for distinguishing the myxoid variant of liposarcoma from other forms of liposarcoma and myxoid sarcomas.
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PMID:Matrix "blues": clue to a cranial thoracic mass in a dog. 1613 77

Clearance of mucus is an important function of the airways to maintain hygiene. In disease, persistent inflammation leads to excessive production of mucus, with high viscoelasticity and adhesivity, which is not easily transported by cilia or cough interactions. Accumulated mucus in the airways can lead to airway obstruction, bacterial colonisation, and recurrent infections, resulting in poor quality of life and increased morbidity and mortality. Hyperosmolar agents have the potential to alter the physical properties of mucus and facilitate its clearance by increasing the water in the airway lumen and by reducing the entanglements of the mucin network. Clinical studies using radioaerosols, and imaging with a gamma camera, have demonstrated that hypertonic saline (HS; 3-14.4%) and mannitol (300-400 mg) increase clearance of mucus acutely in patients with mild asthma, bronchiectasis, and cystic fibrosis (CF). Further, in sputum studies, a reduction in the viscoelastic properties, surface tension and spinnability and an increase in the hydration of mucus have been measured in response to HS, mannitol, and other sugars. Inhalation of mannitol (400 mg) twice daily over 2 weeks improved the quality of life significantly in patients with bronchiectasis. Inhalation of 7% HS, four times daily, over 2 weeks improved significantly the baseline mucus clearance rate and lung function in CF patients. In addition, inhalation of 7% HS twice daily over 12 months showed similar results to the short-term studies without a change in the bacterial load in CF patients. Further studies of the long-term clinical effect of hyperosmolar agents are needed.
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PMID:Hyperosmolar agents and clearance of mucus in the diseased airway. 1655 Dec 21

CASE 1: A 64-year-old, otherwise healthy woman was referred to the surgery clinic for a presumed umbilical hernia. On physical examination, a cutaneous nodule was noted on the umbilical region and the patient was referred to the dermatology clinic. The patient was reexamined and an erythematous nodule was observed in the umbilicus measuring 2.5 cm in diameter. The patient denied pain, change in bowel habits, or weight loss. There were no other abdominal masses, no sign of ascites, and no regional lymphadenopathy. A skin biopsy from the nodule showed mucinous adenocarcinoma. Immunohistochemical staining was positive for carcinoembryonic antigen, and negative for cytokeratin (CK)7 and CK20. These results were consistent with a Sister Mary Joseph's nodule and led to the diagnosis of an occult colon carcinoma. The patient had no risk factors for colorectal carcinoma. The patient underwent surgery in another hospital, and died 3 months after the initial diagnosis of Sister Mary Joseph's nodule. CASE 2: A 73-year-old woman was referred to the dermatology clinic for evaluation of a painful, ulcerated, 3-cm lesion in the umbilicus (Figure 1). She was otherwise asymptomatic. A skin biopsy showed neoplastic glandular cells infiltrating among collagen bundles (Figure 2). Stainings for mucin and for CK7 were positive, while staining for CK20 was negative. An abdominopelvic CT scan demonstrated a 3.5-cm space-occupying lesion in the liver. Results of gastroscopy, colonoscopy, chest computed tomographic (CT) scan, and mammography were normal. Serum levels of the tumor-associated protein CA125 were elevated to 164 units, while those of CA 19-9 and carcinoembryonic antigen were within normal range. A gynecologic examination and a transvaginal ultrasound were normal. The patient had no personal or family history of any malignancy or any risk factors for developing a carcinoma. The patient was scheduled for a palliative resection of the umbilical nodule, combined with a laparoscopic inspection in search of the undetected primary tumor. She refused surgery and was lost to follow-up. She died 4 months after the initial diagnosis of umbilical metastasis. CASE 3: A 51-year-old man was aware of a silent mass in his umbilicus for 2 years without seeking medical advice. Following 2 weeks of increasing pain in this area, he was referred to the emergency room for a suspected incarcerated umbilical hernia. Surgery revealed a mass attached to the fascia and peritoneal fat. The mass was removed and diagnosed as a poorly differentiated adenocarcinoma, staining positively for carcinoembryonic antigen, and negatively for CK20, CK7, prostate-specific antigen, and prostatic acid phosphatase. Both gastroscopy and colonoscopy failed to detect the primary tumor. An abdominopelvic CT scan was normal, but a CT scan of the chest disclosed a nodule measuring 2.5 x 1.5 cm in the lower lobe of the right lung. On bronchoscopy, it was found to be an invasive adenocarcinoma, consistent with a primary tumor of the lung. The patient was a heavy smoker (45 pack-years). The patient received 4 cycles of combined chemotherapy with carboplatine and gemcitabine, with no improvement. A month later, the patient complained of abdominal pain. Following demonstration of intra-abdominal spread of disease by CT scan, a second line chemotherapy was instituted with paclitaxel. A month later the patient's condition deteriorated and he complained of cough, sweating, and pain along the right leg. A bone scan revealed bone metastases in the right femur and left tibia. Two weeks later he was admitted to the hospital with intestinal obstruction and underwent laparotomy. He had massive intra-abdominal spread of cancer and ascites. Only a palliative colostomy was performed. The patient died 3 weeks later, 9 months after the diagnosis of adenocarcinoma of the lung. The clinical data on the three patients are summarized in Table I.
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PMID:Sister Mary Joseph's nodule as a presenting sign of internal malignancy. 1695 43

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

Exposed to a diverse array of potentially noxious agents, the respiratory tract is protected by a highly developed innate defense system. Physiologically regulated epithelial ion and water transport coordinated with mucin secretion, beating cilia, and cough results in continuous flow of fluid and mucus over airway surfaces toward the larynx. This cleansing action is the initial and perhaps most quantitatively important innate defense mechanism. Repeated lung infections and eventual respiratory insufficiency characteristic of human cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) illustrate the consequences of impaired mucus clearance. Altered mucus clearance likely contributes to the initiation, progression, and chronicity of other airway diseases characterized by inflammation and mucous secretory cell hyper/metaplasia that afflict millions worldwide, including chronic obstructive pulmonary disease (COPD). This review concisely discusses the pathophysiology of human diseases characterized by genetic defects that impair mucus clearance. It then explores animal models in which components of the mucus clearance system have been disrupted. These models firmly establish the importance of mucus clearance for respiratory health, and will help elucidate disease mechanisms and therapeutic strategies in CF, PCD and COPD.
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PMID:Cystic fibrosis and other respiratory diseases of impaired mucus clearance. 1732 80

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

Mucus accumulation in the lower airways is a key feature of cystic fibrosis (CF) lung disease. The major component of mucus in CF is not mucin derived from mucus producing cells but rather pus that includes viscous material such as polymerized DNA derived from degraded neutrophils. This has important implications for mucolytic therapy aiming to improve mucus clearance from the airways, since degradation of mucin may not be a suitable treatment strategy. In addition, thinning of secretions may not always be beneficial, since it may negatively affect certain aspects of mucus transport such as cough clearance. While inhaled N-acetylcysteine has been used as a mucolytic drug in CF for decades, there is little evidence that it has any beneficial effect. Dornase alfa has been shown to reduce pulmonary exacerbations and improve lung function and is currently the only mucolytic agent with proven efficacy in CF. Newer agents targeting other components of CF mucus, such as filamentous actin, are currently in development. Ultimately, drugs that are mucokinetic, which preserve viscoelasticity, rather than mucolytic may prove to be beneficial for CF lung disease in the future.
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PMID:Mucolytics in cystic fibrosis. 1741 75

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

Cough clears off foreign bodies from the airways and maintains bronchial clearance when mucociliary transport is defective. Cough requires intact inspiratory muscles to inflate the lung up to 80 % of vital capacity and sound expiratory muscles to generate pressure against a closed glottis. Two mechanisms are required to facilitate proximal mucus transport: 1. Constriction of the cartilage containing airways caused by anterior bulging of the pars membranacea due to high air-flow velocity. 2. Thixotropia of the sputum. This feature changes mechanical properties in a way that sputum viscosity decreases with motion. Thixotropia is caused by the complex mucin-structure of the mucus.
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PMID:[Physiology and physiopathology of cough]. 1831 76


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