INTRODUCTION — The delivery of aerosolized medication is an important component of treatment for many respiratory disorders and is a critical aspect of asthma management in children. Glucocorticoids, bronchodilators, antibiotics, and mucolytic agents can be administered via aerosol using a range of aerosol-generating devices [1-4]. In addition, indications for aerosol therapy will broaden as novel macromolecular medications are delivered via the respiratory tract for the treatment of both pulmonary and systemic disorders [5,6]. (See "Delivery of inhaled medication in adults".)
The delivery of aerosolized medication to infants and children is complicated by anatomic and physiologic differences in their respiratory systems compared with adults [7-9]. Thus, a basic knowledge of the uses and limitations of aerosol delivery systems, the properties of effective aerosols, and the anatomic considerations affecting aerosol delivery in infants and children is essential to the optimal use of this therapeutic modality [10,11]. An overview of the delivery of inhaled medication in children will be presented here; specific aspects of medication delivery using nebulizers, pressurized metered dose inhalers (MDIs), and dry powder inhalers (DPIs) are discussed separately. (See "Use of medication nebulizers in children" and "The use of inhaler devices in children".)
ADVANTAGES OF AEROSOLIZED DRUG DELIVERY — There are several advantages to delivering drugs by aerosol rather than systemically:
●Delivery of agents directly to their sites of action decreases the dose required for therapeutic effect.
●Faster onset of action (compared with intravenous delivery) of bronchodilating medications allows more rapid reversal of acute bronchoconstriction.
●Reduced systemic bioavailability minimizes side effects.
TYPES OF AEROSOL DELIVERY DEVICES — Three types of aerosol delivery devices are widely employed in the management of children with respiratory disease (table 1A-B):
●Nebulizers, which use a jet flow of driving gas, ultrasound, or vibrating membrane to aerosolize medications
●Pressurized metered dose inhalers (MDIs)
●Dry powder inhalers (DPIs)
Specific issues related to the use of these devices are discussed separately. (See "Use of medication nebulizers in children" and "The use of inhaler devices in children".)
LUNG DISEASES MANAGED USING AEROSOL THERAPY — A wide range of pediatric disorders can be treated effectively using aerosol therapy as a central component of management. Examples include:
●Obstructive airway diseases, including asthma, congenital emphysema, bronchiectasis, and bronchiolitis
●Processes that result in acute upper airway obstruction, usually croup or postextubation upper-airway edema
●Chronic lung diseases, including bronchopulmonary dysplasia and cystic fibrosis
●Infectious diseases, including Pneumocystis jirovecii (previously carinii) pneumonia (treatment and prophylaxis), respiratory syncytial virus infection, and some pulmonary fungal infections [12-15]
Less common indications for aerosol therapy include intractable cough, which may respond to inhaled lidocaine, and administration of analgesia in the setting of palliative care, using inhaled morphine [16,17]. In the future, aerosol delivery of gene constructs could be an important component of therapy for genetic diseases [5].
PROPERTIES OF AN IDEAL AEROSOL THERAPY DEVICE — The ideal aerosol delivery device varies depending upon the medication to be administered and the clinical situation. To maximize the advantages of inhaled medications described above, the device selected should:
●Deliver an adequate dose of medication to the lungs
●Minimize oropharyngeal deposition
●Minimize systemic side effects
●Match the needs of the patient
●Be simple for the patient to use
●Be cost effective
FACTORS AFFECTING DRUG DEPOSITION — A number of factors influence the ultimate amount of medication delivered to the appropriate anatomic region within the lung.
Properties of the device — Devices vary greatly in their efficiencies in delivering particles to the lungs. From 6 to 60 percent of the total dose of medication is delivered to the peripheral airways when these devices are used optimally [18]. (See "Delivery of inhaled medication in adults".)
Aerosol properties — Aerosol particles are characterized by their mass median aerodynamic diameter (MMAD) [19,20]:
●Particles with MMAD less than 0.8 micrometers generally are exhaled.
●Particles with MMAD of 0.8 to 2 micrometers are optimal for alveolar deposition, which occurs largely as a result of gravitational sedimentation [7,21].
●Particles with a MMAD between 2 and 5 micrometers are optimal for deposition in the lower airway and are deposited largely by inertial impaction with airway structures.
●Particles with a MMAD greater than 5 micrometers are deposited largely in the oropharynx.
Properties of medication to be delivered — The ultimate effect of the dose is dependent upon the site of deposition of the drug within the lung, the rate of drug clearance from the airway, and the site of action of the medication [18]. To be effective, drugs must be able to withstand the shear forces required to generate the aerosol and often must penetrate the mucus layer and airway mucosa to reach their target receptors or cells [5].
Disease state and ventilatory pattern — Anatomic and pathologic factors, as well as ventilatory patterns, alter the efficiency of aerosolized drug delivery. Aerosol particles may be deposited in the central, rather than lower, airways in diseases that are associated with decreased airway caliber such as asthma. In a study of infants with acute bronchiolitis, only 1.5 percent of aerosolized drug released from the nebulizer was deposited in the lung and 0.6 percent penetrated to the peripheral airways [22]. Partly for this reason, bronchodilators are not routinely recommended for treatment of bronchiolitis. However, most of this information is based upon studies of inhalers containing chlorofluorocarbon (CFC) propellants. Penetration into peripheral airways appears to be better with the hydrofluoroalkane propellants (HFAs) that have replaced CFCs, even in patients with significant obstructive airway disease [23].
Diseases causing mucus plugging or atelectasis, such as cystic fibrosis, may lead to reduction and marked heterogeneity in the distribution of particle deposition. Other factors such as tidal volume, breath-holding time, respiratory rate, and nose versus mouth breathing can dramatically alter the deposition of aerosolized particles in the lungs [7,24].
Patient technique, acceptance, and preference — Improper technique is a common cause for a suboptimal response to aerosolized medication, and poor understanding or acceptance may lead to noncompliance. Rapid inspiration from metered dose inhalers (MDIs) may increase inertial impaction of droplets in the central airways and decrease lung delivery [24]. Patient education is essential for the effective use of any aerosol delivery device [1]. Furthermore, patient factors such as weakness, severe arthritis or contractures, and altered mental status may mandate the use of specific delivery devices.
SPECIAL CONSIDERATIONS IN INFANTS AND YOUNG CHILDREN — The deposition of medication in peripheral airways and alveoli is reduced in infants and young children, presumably due to their smaller airways, faster respiratory rates, and lower tidal volumes, which combine to lower the resident time of small particles in the airway [7-9,25,26].
Dose — Data suggest that drug deposition in children older than five to six years of age is similar to that observed in adults, and identical doses in children and adults result in similar plasma concentrations [18,27]. Thus, aerosol doses generally do not need to be decreased, except possibly in very young children. However, it is probable that variability exists based upon the specific medication used, drug delivery technique (tidal volume breathing compared with inspiratory breath hold), and delivery device employed.
The output of the aerosol-generating device may exceed inspiratory flow rate in children younger than six months of age, resulting in the loss of air entrainment (mixing of inspired air with nebulizer output) and a higher concentration of drug delivered [26]. Overall, this effect can lead to a higher inhaled dose per kilogram of body weight in the infant younger than six months of age, increasing the possibility of side effects, although increased side effects have not been reported in this age group, nor are there recommendations to decrease any drug dose because of this effect.
Respiratory pattern — Normal tidal breathing results in the most efficient delivery to the airways. Crying markedly reduces aerosol delivery to the lungs; therefore, in general, aerosols should not be administered to crying children [28,29]. An alternative in these infants and children is to administer aerosols while they are sleeping [30]. However, lung deposition of aerosolized drugs may be reduced in a nose-breathing sleeping infant [31]. Furthermore, a "real-life" feasibility study of aerosol delivery via metered dose inhaler (MDI) and masked holding chamber to sleeping infants and young children found that aerosol delivery during sleep offered no advantage for most children due to frequent awakenings associated with poor cooperation and difficulty with the proper placement of the mask due to sleep position [32]. Thus, aerosol administration during sleep may be tried for uncooperative infants and children, but parents should be informed that the success rate may be low.
Breath-actuated devices and dry powder inhalers (DPIs) should be avoided in infants and toddlers due to their inability to generate an adequate inspiratory flow rate to reliably aerosolize the medication [18]. (See "The use of inhaler devices in children".)
Interface — The interface between the aerosol-generating device and the patient is an important, and often overlooked, component of effective therapy. Administration of aerosols by a mouthpiece rather than a facemask is generally preferred due to improved drug delivery to the lungs by as much as twofold [33]. However, most children will not be able to reliably breathe through a mouthpiece until approximately four years of age, and patient technique with a mouthpiece must be assessed prior to switching from a facemask [34]. In addition, delivery by facemasks or mouthpieces has been shown to provide similar clinical responses when administering bronchodilators in children with acute asthma [35] or nebulized budesonide in chronic asthma [36]. Finally, delivery of fluticasone propionate via an MDI with an antistatic valved holding chamber is similar when using either a mouthpiece or facemask in children up to nine years of age, and both are associated with higher delivery compared with direct actuation into the mouth [37]. These devices may be associated with higher systemic concentrations of glucocorticoids and an increased risk of side effects, particularly with higher drug doses. Thus, doses should be adjusted to the lowest that maintains asthma control.
Poor patient cooperation leads many parents to use blow-by techniques for aerosol delivery. However, removing the facemask just 1 cm from the face may reduce the inspired dose by approximately 50 percent, and a 2 cm distance results in an 80 percent reduction [24]. When a facemask is used either with a spacer or nebulizer, it should be placed snugly and tightly fitted over the face, as even a small leak may reduce the inhaled mass of drug to <0.5 percent of the total dose [38].
The nose is an efficient filter for particles in aerosol. Thus, when using a facemask, any nose breathing is associated with increased deposition in the upper airway [24,39]. This may lead to more systemic side effects due to greater drug absorption from the upper airway. In addition, this can reduce drug efficacy because of decreased deposition in the lower respiratory tract [1,35].
Specific aspects of aerosolized medication delivery using nebulizers, MDIs, and DPIs are presented separately. (See "Use of medication nebulizers in children" and "The use of inhaler devices in children".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: How to use your child's dry powder inhaler (The Basics)" and "Patient education: How to use your child's metered dose inhaler (The Basics)")
●Beyond the Basics topics (see "Patient education: Asthma inhaler techniques in children (Beyond the Basics)" and "Patient education: Asthma symptoms and diagnosis in children (Beyond the Basics)")
SUMMARY
●There are three main types of aerosol delivery devices used in the management of children with respiratory disease: nebulizers, pressurized metered dose inhalers (MDIs), and dry powder inhalers (DPIs). (See 'Types of aerosol delivery devices' above.)
●Factors that affect drug deposition include properties of the device, aerosol particle, and medication and patient factors such as disease state, ventilatory pattern, and administration technique. (See 'Factors affecting drug deposition' above.)
●In general, aerosol doses do not need to be decreased except possibly in very young children. (See 'Dose' above.)
●Normal tidal breathing results in the most efficient delivery to the airways. Crying markedly reduces aerosol delivery to the lungs. A better option in children who tend to cry with administration is to give the aerosolized drug while they are sleeping. (See 'Respiratory pattern' above.)
●Administration of aerosols by a mouthpiece rather than a facemask is generally preferred due to improved drug delivery to the lungs. Blow-by techniques significantly decrease the inspired dose. (See 'Interface' above.)
