Mucus and sputum: what drug therapy works?
Mucus is secreted from surface goblet cells and submucosal glands. It is composed of water, proteins and mucins. Mucins are the primary airway gel-forming proteins with attached oligosaccharide (sugar) side chains. On the other hand, sputum contains respiratory tract, oropharyngeal and nasopharyngeal secretions, as well as bacteria and products of inflammation, including DNA.
The more purulent the sputum the less likely it is to contain mucin, and it has similar composition to pus. Mucoative agents have been used for years to treat sputum; however, most have not been shown to be effective.
N-acetylcysteine - There are several categories of mucus-controlling drug therapy that can be used, including mucolytics, expectorants and mucokinetic agents. Mucolytics are agents that degrade polymers in secretions. The two most common mucolytics on the market today are dornase alfa (Pulmozyme) and N-acetylcysteine (NAC), commonly referred to as Mucomyst.
As a mucolytic, aerosolized NAC has been used in the treatment of conditions associated with viscous mucus secretions such as COPD, although this is not an approved use of the drug. A second use of NAC is as an antidote to reduce hepatic injury with acetaminophen overdose. The drug is given orally for this use.
Currently, there are no data that demonstrate that oral or aerosolized NAC is effective therapy for any lung disease. Data suggest that it may be harmful. The reason that NAC is ineffective may be due to the fact that NAC only affects the mucin polymer structure leaving DNA and debris intact, resulting in secretions that are still viscid.
The most serious complication with NAC is bronchospasm due to its acidity (pH 2.2). This is more common in asthmatic patients and is less common when using the 10 percent, rather than the 20 percent, solution. The risk can be reduced by pretreatment with a bronchodilator. If this is done, a bronchodilator with rapid onset should be used.
NAC is incompatible in mixture with the following antibiotics and should not be combined in physical solution: sodium ampicillin, amphotericin B, erythromycin, tetracyclines and aminoglycosides. Agents that are not compatible will have a change in color, clarity or odor.
Dornase Alfa - Dornase alfa reduces extracellular DNA and binding polymers to reduce viscosity. Dornase alfa is a recombinant form of the human DNase I enzyme, which digests extracellular DNA material. In February 1994 the Food and Drug Administration approved dornase alfa for general use in treating the abnormally tenacious DNA-containing sputum seen in cystic fibrosis.
Dornase alfa is indicated for the management of CF, to reduce the frequency of respiratory infections requiring parenteral antibiotics, and to improve or preserve pulmonary function in these subjects. The bulk of respiratory secretions in CF are due to the presence of DNA from necrosing neutrophils present during chronic respiratory infections and inflammation. The use of Dornase alfa may produce side effects.
Common side effects with use of the drug have included voice alteration, pharyngitis, laryngitis, rash, chest pain and conjunctivitis. Other less common side effects reported include increased cough, dyspnea, pneumothorax, hemoptysis, rhinitis and sinusitis, flu syndrome and malaise, gastrointestinal obstruction, hypoxia and weight loss. Contraindications include hypersensitivity to the medication.
Iodide-containing agents such as supersaturated potassium iodide (SSKI) are generally considered to be expectorants. They are thought to stimulate the secretion of airway fluid. However, studies have not been favorable in increasing pulmonary function studies or changing sputum properties.
Sodium Bicarbonate - Sodium bicarbonate is a base that has occasionally been used as a mucoactive agent. Increasing the bronchial pH, sodium bicarbonate weakens the bonds between the side chains of mucus, resulting in lowering the mucus viscosity and elasticity. Sodium bicarbonate has not been clinically demonstrated to improved airway mucus clearance.
Guaifenesin - Guaifenesin is an expectorant, which like SSKI, stimulates airway fluid. It has not been demonstrated to be clinically effective in randomized controlled trials.
Mucokinetic agents increase cough clearance by increasing expiratory airflow or by reducing adhesive forces of sputom. Bronchodilators are the most common agents in this category. Beta-agonists are known to increase ciliary beat; however, this has little to no effect on mucus. The main effect of bronchodilators is to increase expiratory flow. But theses agents, when used in large quantities such as in continuous nebulization, may in fact increase mucus production, especially in patients that with severe asthma.
Hypertonic saline has been used for a number of years to induce sputum samples. However, lately it has been used to treat patients with excessive sputum production. A number of studies have found that it has improved pulmonary function studies in CF patients and non-CF bronchiectasis. Although it has been reported that hypertonic saline is not as effective as dornase alfa, CF patients should continue to be treated with dornase alfa.
A number of physical factors affect secretion clearance in patients. In acute airway diseases this may cause mucus hypersecretion, and cough is the primary mechanism for secretion clearance from the airways.
During a normal cough, expiratory airflow increases along with an increased turbulence in the airway allowing secretions to be moved to the trachea. In COPD, narrowing airways may close prematurely, trapping gas, reducing expiratory flow rates and limiting the effectiveness of the cough. The use of techniques to keep airways open and increase expiratory airflow will be of benefit to pulmonary patients.
Simple techniques such as deep breathing and forced expiratory technique (huff cough) may be used to increase airflow and clear mucus. Because breathing is so important, a good exercise plan can be used to increase expiratory flow. Positive airway pressure (PAP) techniques are used to expand the lungs which may be used to for lung recruitment.
The use of PAP with oscillation of the airway (Flutter or Acapella) are novel approaches that may work but have not been well-studied. Newer devices such as the Quake and Lung Flute, both of which use oscillation of the airway, have been introduced to the market.
The vest uses oscillation of the chest wall to mobilize secretions. Studies show that frequency of oscillations is the most important factor in its effectiveness. It is recommended to keep the oscillation frequency between 10 and 15 Hz for the duration of therapy. Clinical studies have found the vest is effective for secretion clearance in CF patients. It has not been established if the vest is effective in other lung disease.
By Douglas Gardenhire MS, RRT-NPS
Douglas Gardenhire is a veteran therapist, author, educator and the Director of Clinical Education in the RC Program at Georgia State University.
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|Title Annotation:||RESPIRATORY PHARMACOLOGY|
|Publication:||FOCUS: Journal for Respiratory Care & Sleep Medicine|
|Date:||Jul 1, 2009|
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