Nebulizer therapy: A modern treatment option for respiratory diseases

These include press-and-breathe or breath-activated metered aerosol inhalers, and breath-actuated dry powder inhalers. A major typical difficulty with the use of these devices is usually associated with the need to synchronize the activation of the inhaler and the patient’s breath.

Scientific research data demonstrate that only 33.2% of adults and 26% of children comply with a proper technique of inhalation (position the inhaler upwards, take a deep breath and simultaneously spray the drug with subsequent delay in breathing); while the optimal method of application, including preliminary shaking of the inhaler and only one spray of the drug – 22.1% of adults and 20% of children. Moreover, due to the propellant gas in their composition, the use of some metered dose inhalers may be associated with the risk of an apnea episode when the inhaler contacts the oral cavity. This, in turn, can also lead to unsafe application and increase the oro-pharyngeal exposure of the medication, increasing the likelihood of developing candidiasis and paradoxical bronchospasm (A.G. Chuchalin et al., 2006).

The choice of a metered aerosol inhaler is primarily defined by the peculiarities of the patient’s breathing. Both changes in the airways architectonics seen in certain conditions (e.g. emphysema, atelectasis, bronchiectasis) and violations in the respiratory movement coordination capacity make it necessary to choose an optimal way of drug delivery, which enables achieving the intensity of therapeutic effect and the rate of its onset, as well as minimizing the drug’s systemic effects (N.G. Kolosova, N.A. Geppe, 2011).

Nebulizer therapy is a modern inhalation therapy technique based on the conversion of liquid forms of drugs in a fine aerosol with certain characteristics through an air stream or an increase in kinetic energy of the solution; the method efficacy has been theoretically and practically proven in numerous studies (A.R. Tatarsky et al., 2007). The main purpose of nebulizer therapy is to deliver without breath synchronization the therapeutic dose of the drug in an aerosol form over a short period of time, usually for 5-10 minutes (O.V. Zaitseva, S.V. Zaitseva, 2008). Although nebulizers are expensive, nebulizer therapy is widespread in Europe almost every family uses a nebulizer to perform an inhalation.

The term «nebulizer» (from Latin ‘nebula’ – fog, cloud) was first used in the late 19th century to denote a device “converting liquid substance into an aerosol for medical purposes” (A.G. Chuchalin et al., 2006). Depending on the method of converting a liquid medication into an aerosol, there are three types of modern nebulizers, such as:

• jet (compressor, pneumatic) nebulizers, which use an air stream to generate an aerosol;
• ultrasonic nebulizers, operation principle of which is based on the use of the vibratory energy of a piezoelectric crystal;
• and membrane (mesh nebulizers) (O.V. Zaitseva, S.V. Zaitseva, 2008; A.G. Chuchalin et al., 2006; N.G. Kolosova, N.A. Geppe, 2011).

Compressor type nebulizers became the most widely used due to their lower cost and versatility (unlike ultrasonic nebulizers, in which some drugs (GCs, surfactants) can not be used due to the damaging effects of ultrasound, any drugs can be used in compressor nebulizers).

Efficacy of inhalation therapy

Drug delivery to the target organ of the respiratory system depends primarily on the aerosol dose deposited in different parts of the respiratory tract. To determine the dose, the following should be taken into account: an aerosol dispersion, the nebulizer specifications (the number of particles generated per time unit), the distribution density (the amount of the sprayed substance contained in 1 L of aerosol), vital capacity of the patient’s lungs and the loss of medication during inhalation (O.V. Zaitseva, S.V. Zaitseva, 2008).

It has been established that the fraction of particles larger than 10 µm won’t penetrate beyond the oropharynx; the fraction of 5-10 µm is deposited in the pharynx, larynx and trachea, 1-5 µm – in the lower respiratory tract, and 0.5-1µm –in the alveoli. A larger part of the spray volume is respirable particles (1-5 µm) of an optimal size to enter the airways (A.G. Chuchalin et al., 2006; N.G. Kolosova, N.A. Geppe, 2011).

Indispensable for the effective inhalation therapy is the observance of proper device application and its operation rules (A.R. Tatarsky et al., 2007).

Advantages of nebulizer therapy

The advantages of nebulizer therapy are:

• convenience and ease of performing inhalation, i.e. no need to coordinate a breath and the drug admission that provides natural breathing mode and allows to use nebulizers in patients who cannot use other types of inhalation therapy, such as the elderly, young children, patients in grave condition;
• promptness of the therapeutic effect;
• the ability to deliver a higher dose of the inhaled agent (e.g. in severe bronchial obstruction) and its continuous feed and, if necessary, to change the dose of a drug or combine with oxygen therapy;
• a high percentage of pulmonary deposition and, as a consequence, ensuring penetration of the agent in poorly ventilated areas of the bronchi;
• no propellant gas in the composition (N.M. Shmeleva, 2006; A.G. Chuchalin et al., 2006; O.V. Zaitseva, S.V. Zaitseva, 2008).

Among the undoubted advantages of nebulizer therapy in young children are the physiologic drug delivery to the respiratory tract; the non-invasiveness of the method; the possibility of obtaining pharmacological effects directly in the target organ while minimizing systemic effects and with almost complete absence of adverse effects; the possibility of achieving the maximum pharmacological activity of the drug by exposing to a larger surface area of the respiratory tract mucosa and, consequently, obtaining a prompt and prolonged therapeutic effect (N.D. Soroka et al., 2010).

In addition, nebulizer therapy allows for a wide range of medicines and their combinations (two or more drugs). Nebulizers remain the only way to deliver to the respiratory tract some drugs, such as antibacterials and mucolytics, because there are no other metered dose inhalers for these groups of medications (N.G. Kolosova, N.A. Geppe, 2001; A.G. Chuchalin et al., 2006). The possibility of drug delivery over a long period (2-3 days) allows for an extensive use of nebulizer therapy in intensive care units and pulmonary in-patient departments. When using a nebulizer, the drug reaches the target organs even in the presence of bronchospasm. Anti-inflammatory drugs administered in the form of nebulizer therapy in severe bronchial asthma help reduce the daily doses of systemic GCs, and, in some cases, even completely replace them with the nebulizer administration (O.V. Zaitseva, S.V. Zaitseva, 2008). The nebulizer kit includes facial masks that allow using this device in infants and patients with pronounced bronchial obstruction (N.G. Kolosova, N.A. Geppe, 2011; O.V. Zaitseva, S.V. Zaitseva, 2008).

Indications for nebulizer therapy

Nebulizer therapy is indicated in acute and chronic respiratory diseases (ARVI, chronic obstructive pulmonary disease, acute and severe bronchial asthma, bronchiectatic disease, occupational pulmonary diseases, cystic fibrosis). Using a nebulizer is recommended in those cases when a prompt and effective delivery of the drug to the respiratory tract is required, including in post-operative patients and children (N.D. Soroka et al., 2010; A.G. Chuchalin et al., 2006; N.M. Shmeleva, 2006).

In paediatric practice, nebulizer therapy owes its advantages to the ease of use and the absence of both the emotional trauma to the child and the risk of post-injection complications; it is indicated in most respiratory diseases, including acute stenosing laryngotracheitis (pseudocroup). In the latter case, the treatment starts with the use of inhaled epinephrine, glucocorticosteroids, and furosemide through the pressured nebulizer (A.A. Sukharev, 2010). Given that the overwhelming majority of children cannot observe the proper technique of using metered dose inhalers, nebulizer therapy in these patients is the best treatment of choice (N.G. Kolosova, N.A. Geppe, 2011; O.V. Zaitseva, S.V. Zaitseva, 2008; N.D. Soroka et al., 2010).

Сlinical trials indicate that the use of a nebulizer in children rather promptly leads to improvements in their general condition, reduction or reversal of bronchial obstruction phenomena and reduced need in systemic glucocorticosteroids. Investigations showed that all the children who used other metered dose inhalers in a moderate to severe attack of bronchial obstruction required the administration of conventional treatment with systemic corticosteroids, whereas with nebulizer therapy there was a more pronounced bronchodilation, mainly at the level of small bronchi that was reliably confirmed by the favourable changes in the respiratory function indicators (O.V. Zaitseva, S.V. Zaitseva, 2008).

In recent years, publications have also emphasized that it is almost impossible to perform inhalation therapy in children and in debilitated or seriously ill patients without nebulizers (N.G. Kolosova, N.A. Geppe, 2011; A.G. Chuchalin et al., 2006).

Nebulizer therapy is expedient to be performed at the pre-hospital stage in various emergencies (e.g. asthma exacerbation). This can significantly improve the efficacy of pre-hospital treatment, halve the number of hospitalizations, reduce the number of repeated callings to doctor by 5 times, and greatly lower the costs of providing medical care to patients (A.L. Vertkin et al., 2008). Using a nebulizer at home for the early treatment of bronchial obstructive syndrome reduces the frequency of hospital admissions required (O.V. Zaitseva, S.V. Zaitseva, 2008).

For nebulizer therapy, solutions of modern bronchodilators and mast cell stabilizers are used (salbutamol, fenoterol, ipratropium bromide and combinations thereof); as well as anti-inflammatory drugs/topical GCs (budesonide and fluticasone as suspensions); mucolytics (ambroxol, acetylcysteine, sodium bicarbonate, Dornase alfa); antiseptics (Dekasan); antibacterial agents (acetylcysteine plus thiamphenicol, tobramycin, pentamidine); anti-TB drugs (isoniazid, rifampicin, ethambutol); immunomodulators (human leukocyte interferon); or antivirals (ACA). 0.9% sodium chloride solution is used as a universal solvent.

Absolute indications for nebulizer therapy include the following:

• inability to use any other inhalation device for drug delivery to the respiratory tract;
• the need for the drug to enter the lower respiratory tract;
• a prompt onset of therapeutic effect;
• inspiratory flow rate less than 30 L/min;
• the inability of the patient to hold the breath for more than 4 sec;
• impaired consciousness;
• the need to receive a high dose of the drug;
• patient preference (A.G. Chuchalin et al., 2006; A.R. Tatarsky et al., 2007).

Thus, nebulizer therapy is a modern way to deliver the drug to the respiratory tract, the efficacy and safety of its application is scientifically proven, including both in persons with severe somatic pathology and children. In some cases, the use of nebulizers is the only method providing drug delivery directly into the target organ.