Cystic fibrosis mucus

Water can bind to mucous glycoprotein (MGP) macromolecules and influence viscosity. Viscosity can be increased by dehydration of the mucus, as can adhesion of mucus-epithelium. In purulent sputum, the correlation between viscosity and dry weight of solids is poor and may explain why mucous glycoprotein content is a poor index of viscoelasticity in chronic bronchitis, bronchiectasis, and cystic fibrosis. Mucus s viscoelasticity increases with acidic pH (3), causing reduced mucociliary clearance. Its viscoelasticity is also dependent on the content of low molecular weight electrolytes. These properties reflect the polyelectrolyte nature of mucins (4-6). 

The gene defective in cystic fibrosis codes for CFTR (cystic fibrosis transmembrane condnctance regulator), a membrane protein that pumps CP out of cells. If this CP pump is defective, CP ions remain in cells, which then take up water from the surrounding mucus by osmosis. The mucus thickens and accumulates in various organs, including the lungs, where its presence favors infections such as pneumonia. Left untreated, children with cystic fibrosis seldom survive past the age of 5 years. 

A number of clinical symptoms characterize cystic fibrosis. Predominant among these is the presence of excess sodium chloride in cystic fibrosis patient sweat. Indeed, measurement of chloride levels in sweat remains the major diagnostic indicator of this disease. Another characteristic is the production of an extremely viscous, custard-like mucus in various body glands/organs that severely compromises their function. Particularly affected are ... 

The pancreas, in which the mucus blocks its ducts in 85 per cent of cystic fibrosis patients, causing pancreatic insufficiency. This is chiefly characterized by secretion of greatly reduced levels of digestive enzymes into the small intestine. 

Cystic fibrosis (CF) is a hereditary disease of abnormal fluid secretion. It affects cells of the exocrine glands, such as intestine, sweat glands, pancreas, reproductive tract, and especially the respiratory tract. The disease affects about 1 in 2500 infants of the Caucasian population to varying degrees of seriousness. Patients produce thickened mucus that is difficult to get out of the airway. This leads to chronic lung infection, which progressively destroys pulmonary function. 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Mucous airway obstruction. Mu-colytics, such as acetylcysteine, split disulfide bonds in mucus, hence reduce its viscosity and promote clearing of bronchial mucus. Other expectorants (e.g., hot beverages, potassium iodide, and ipecac) stimulate production of watery mucus. Acetylcysteine is indicated in cystic fibrosis patients and inhaled as an aerosol. Whether mucolytics are indicated in the common cold and whether expectorants like bromohexine or am-broxole effectively lower viscosity of bronchial secretions may be questioned. 

Mucolytic Adjuvant therapy for abnormal, viscid, or inspissated mucus secretions in chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis, primary amyloidosis of lung) acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis) pulmonary complications of cystic fibrosis tracheostomy care pulmonary complications associated with surgery use during anesthesia posttraumatic chest conditions atelectasis due to mucus obstruction diagnostic bronchial studies (bronchograms, bronchospirometry, bronchial wedge catheterization). 

Adjunctive treatment of viscid mucus secretions from chronic hronchopulmonary disease and for pulmonary complications of cystic fibrosis Nebulization Alert Bronchodilators should be given 15 min before acetylcysteine. 3-5 ml (20% solution) 3-4 times a day or 6-10 ml (10% solution) 3-4 times a day. Range 1-10 ml (20% solution) q2-6h or 2-20 ml (10% solution) q2-6h. ... 

F. Role in therapy Pulmozyme is a mucolytic enzyme used in the treatment of cystic hbrosis. Although it is not a cure, domase alfa is an effective mucolytic for adjunctive treatment. AU compliant patients with cystic fibrosis, irrespective of disease severity, who produce purulent sputum are potential candidates for Pulmozyme therapy. It is useful for liquefying the thick mucus secreted by cystic fibrosis patients, and causes both objective improvement (as measured by pulmonary function testing) and subjective symptomatic improvement. Pulmozyme reduces the frequency of respiratory infections requiring parenteral antibiotics and improves pulmonary function. 

Aerosolized DNase (dornase) is a therapeutic protein designed for alveoli delivery to achieve local effects in the deep lung. Aerosolized DNase is formulated as a pulmonary dosage form, targeted for deep-lung delivery to reduce opportunistic infections due to the increased viscosity of mucus in the lung that affects respiratory function in patients with cystic fibrosis. 

Chronic diseases include cystic fibrosis in which nasal mucus is thick and viscous as a result of abnormal chloride transport across the membrane of the epithelial cells, leading to reduced water secretion. Similarly, chronic sinusitis also reduces nasal mucociliary clearance due to an increase in the rheological properties of mucus. 

Genetic alterations or abnormalities of germ cells, some of which can be caused by toxicant exposure, can be manifested by adverse effects on progeny. The important health effects of these kinds of alterations may be appreciated by considering the kinds of human maladies that are caused by inherited recessive mutations. One such disease is cystic fibrosis, in which the clinical phenotype has thick, dry mucus in the tubes of the respiratory system such that inhaled bacterial and fungal spores cannot be cleared from the system. This results in frequent, severe infections. It is the consequence of a faulty chloride transporter membrane protein that does not properly transport Cl ion from inside cells to the outside, where they normally retain water characteristic of healthy mucus. The faulty transporter protein is the result of a change of a single amino acid in the protein. 

Cystic fibrosis is an autosomal recessive disease caused by mutations of the cystic fibrosis transmerobrane conductance regulator (CFTR) gene producing a dysfunctional chloride channel, normally located on the apical membrane of exocrine glands [16]. The disease manifests itself at an early age in the lung with accumulation of thick, sticky mucus and bacterial infections. These infections are followed by an inflammatory response, resulting in an Infiltration of neutrophils... 

Q5 Since a major problem in cystic fibrosis is production of very viscous mucus which is frequently infected, the cough reflex should not be completely suppressed. Failure to cough and at least partially clear the airways would cause secretions to be retained, forming obstruction and a focus for further infection. 

Patients with cystic fibrosis secrete very viscous mucus in the lung and suffer repeated lung infections. The pancreas is also affected and patients are deficient in pancreatic enzymes this reduces digestion and absorption of nutrients, so affecting growth. 

The viscous mucus in cystic fibrosis is difficult to clear from the lung patients need physical therapy and postural drainage to clear the airways. 

Cystic fibrosis (CF). Patients with CF generally suffer from bacterial infections in the lungs, which is associated with a heavy build-up of thick mucus. Antibiotics are generally prescribed but CF patients also require daily percussion therapy. DNA present in the mucous, which arises from dead white blood cells and bacterial cells, serves to cross link the mucous, changing it from a fluid gel to a semi-solid. The enzyme deoxyribonuclease (DNAase) hydrolyses extracellular DNA, and can be used usefully to alleviate this situation. 

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