Why is mucolytic therapy necessary for cystic fibrosis?
An increase in the viscosity of bronchial secretions in the respiratory system plays a key role in the formation of a chronic bronchopulmonary inflammatory process in patients with cystic fibrosis (CF). Already at an early age, a large number of neutrophils, free neutrophil elastase, DNA and interleukin-8 are detected in the bronchoalveolar lavage of patients. Drugs that have a mucolytic effect dilute the secretion of the upper and lower respiratory tract and thereby reduce its viscosity.
What mucolytics are used to treat cystic fibrosis?
Today, the following mucolytic drugs are used for cystic fibrosis:
Dornase alpha
Dornase alfa – a drug for inhalation – is a purified solution of recombinant human deoxyribonuclease. The mechanism of its action consists in the splitting of extracellular DNA molecules that accumulate in the bronchial secretion as a result of the breakdown of neutrophils, macrophages and bacterial cells and increase its viscosity.
Hypertonic NaCl solution
An increase in the concentration of salt in the bronchial secretion leads to its active moistening and improvement of the function of mucociliary transport. To improve compliance when using a hypertonic solution in the optimal therapeutic concentration – 7% – various additives were studied, including hyaluronic acid, which provides protection of the mucous membrane of the respiratory tract from the irritating effect of the hypertonic solution.
Inhaled mannitol
Mannitol is a mucoactive drug from the group of hyperosmolar drugs or rehydrators. Under its influence, the water component of bronchial secretion increases, compensating for the defect of chlorine channels caused by the CFTR gene. This leads to an improvement in sputum removal, a significant increase in pulmonary function indicators, and a decrease in the frequency of bronchopulmonary exacerbations.
N-acetylcysteine
The effect of acetylcysteine is related to the ability of its sulfhydryl groups to break the disulfide bonds of acidic mucopolysaccharides of sputum, which leads to depolarization of mucoproteins and a decrease in mucus viscosity.
Ambroxol
Amroskol activates the movement of the cilia of the epithelium, restores mucociliary transport, stimulates the formation of bronchial secretion of reduced viscosity due to changes in the structure of mucopolysaccharides.
What devices to use for inhalation?
The most common are metered-dose aerosol inhalers, metered-dose powder inhalers, and nebulizers.
Modern methods of drug delivery include the nebulizer, which converts the liquid form of the drug (solution, suspension) into an aerosol using compressed air. During nebulization, aerosol particles are formed that contain drug molecules. An important role in the inhalation process is played by particles smaller than 5 μm, the so-called respirable aerosol fraction, which is deposited in small bronchi and bronchioles. In most nebulizers, the respirable fraction is at least 60% of the produced aerosol.
One of the important factors for achieving the optimal peripheral concentration of the drug aerosol and reducing its deposition in the oropharynx is the reduction of the inspiratory flow rate. This can be achieved by using nebulizers with an option to control the inhalation power, which limits the patient’s inhalation power to a level of no more than 30 l/min.
The use of low-flow compressors (6 l/min) with nebulizers with adjustable aerosol supply helps to reduce the loss of the drug – dispersion in the environment – and increases the effectiveness of therapy.
Nebulizer inhalation can be carried out in continuous or intermittent mode using an air flow interrupter. This not only allows you to exclude the loss of medication, but also makes it possible to combine inhalation with kinesitherapy techniques or a positive oscillator resistance device on exhalation (flutter).