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Delivery of inhaled medication in adults

Delivery of inhaled medication in adults
Authors:
Dean Hess, RRT, PhD, FAARC, FCCM
Rajiv Dhand, MD, FCCP, FACP, FAARC, FRSM, ATSF
Section Editor:
Anne E Dixon, BM, BCh
Deputy Editor:
Paul Dieffenbach, MD
Literature review current through: Nov 2022. | This topic last updated: Feb 08, 2022.

INTRODUCTION — The delivery of therapeutic aerosols is an important component of treatment for many respiratory disorders. The advantages of aerosolized therapy include delivery of medication directly to the site of action, potentially faster onset of action, and reduced systemic availability to minimize adverse effects of the medication.

The types and function of devices available for delivery of therapeutic aerosols are reviewed here. The education of patients regarding optimal inhaler technique and the role of these medications in the management of asthma and chronic obstructive pulmonary disease (COPD) are discussed separately. (See "The use of inhaler devices in adults" and "The use of inhaler devices in children" and "An overview of asthma management" and "Stable COPD: Initial pharmacologic management" and "COPD exacerbations: Management".)

OVERVIEW — The principal types of devices used to generate therapeutic aerosols are pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers (SMIs), and nebulizers [1-3]. pMDIs may be used with or without a spacer/valved holding chamber. Some breath actuated pMDIs (eg, QVAR Redihaler and others available outside the United States) overcome the problem of incoordination between actuation and inhalation that is commonly observed with pMDIs. Among nebulizers, three basic types have been developed, jet (also known as pneumatic), ultrasonic, and mesh. Jet nebulizer systems are typically less portable than pMDIs and DPIs. In the past, nebulizers were considered more expensive delivery devices; however, in some settings, hydrofluoroalkane (HFA) formulations of pMDIs, SMIs, and DPIs may be more expensive than the solutions used in a nebulizer.

Inhalation (or aerosol) therapy can be employed with a range of medications and devices. Examples include:

Inhaled beta agonist and muscarinic antagonist (anticholinergic) bronchodilators for chronic obstructive lung diseases (eg, asthma, COPD, bronchiectasis, bronchiolitis)

Inhaled glucocorticoids (also called inhaled corticosteroids or ICS) for asthma, eosinophilic bronchitis, and COPD

Inhaled antibiotics for prevention of Pneumocystis pneumonia and treatment of respiratory syncytial virus, cystic fibrosis, and bronchiectasis

Airway secretion modifying agents for cystic fibrosis

Inhaled pulmonary vasodilators for pulmonary hypertension [4]

Aerosol delivery of drugs (eg, opiates, insulin, levodopa, loxapine) may be used to treat some nonrespiratory diseases [5-7]

The advantages and disadvantages to each of the different types of aerosol delivery devices are listed in the table (table 1). The available evidence from systematic reviews and meta-analyses suggests equivalence among nebulizers, pMDIs, and DPIs for delivery of beta agonists and glucocorticoids when used correctly [8-15]. Thus, for spontaneously breathing patients without a tracheostomy, the selection of an aerosol delivery device is usually based upon the preference and convenience of the clinician and patient, the ability of the patient to use the device correctly, the durability of the device, and the cost of therapy rather than a clear superiority of one device over another [8]. However, in some situations, choice of device is determined by drug formulation, as some formulations require a particular delivery device, and patient interface factors, such as presence of a tracheotomy or mechanical ventilation.

The proper technique for using aerosol devices varies from one device to another and is a key component of optimal drug deposition and the desired therapeutic response. Understanding the correct use of aerosol delivery devices and providing patient education is a shared responsibility among all health care professionals participating in asthma or COPD management (eg, physicians, respiratory therapists, nurses, and pharmacists) [16]. Preferably, patients should use one type of inhaler device (either pMDIs, DPIs, or SMIs) for both reliever and maintenance therapy [17-19]. Inhaler technique for pMDIs and DPIs is discussed in detail separately. (See "The use of inhaler devices in adults" and "The use of inhaler devices in children".)

All the commonly employed aerosol delivery devices can be used to deliver medication to spontaneously breathing patients who can inhale orally. Only nebulizers and pMDIs can be used in patients who are intubated or have a tracheostomy; DPIs are not designed for use in these patients and adapters to connect SMIs in the ventilator circuit are not commercially available. Only nebulizers can be used with high flow nasal cannula.

IMPLICATIONS OF COVID-19 PANDEMIC — Delivery of aerosolized medication to treat bronchoconstriction is common in patients with respiratory viral infections, including coronavirus disease 2019 (COVID-19; due to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection). A potential problem is that nebulization significantly increases aerosol concentration in the patient’s vicinity (fugitive aerosols), particularly within one meter (approximately three feet) of the patient, and can provoke coughing or sneezing [20,21], raising the possibility that use of aerosolized therapies might disperse infectious bio-aerosols and cross-infect healthcare workers [22-24].

During a nebulizer treatment, the exhaled air from the patient passes over the reservoir in standard jet nebulizers potentially contaminating the reservoir with respiratory secretions. In modeling studies, jet nebulization led to 0.8 meter dispersion of the exhaled aerosol with more extensive dispersion in models with stiffer lungs mimicking severe lung injury [23]. Coughs provoked during nebulizer or inhaler therapy can disperse large respiratory droplets over approximately two meters, while smaller droplet nuclei can travel further. It is unclear whether nebulizer treatments can spread respiratory viruses by cough provoked by the treatment [20]. According to the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO), it is uncertain whether aerosols generated from nebulizer administration are infectious [25,26].

Interventions that may decrease the risk of virus spread during administration of inhaled medications include the following [27,28]:

Use a dry powder inhaler (DPI), soft mist inhaler (SMI), or pressurized metered dose inhaler (pMDI) to deliver respiratory medications instead of a nebulizer (when possible).

Use a mouthpiece rather than a mask for inhalation of the nebulized medication and place a filter on the exhalation port of the nebulizer and instruct the patient to seal their lips tightly around the mouthpiece during inhalation and exhalation. Commercially available systems are available to filter or scavenge fugitive aerosols (SafetyNeb, Exhalo Shield, Tavish filter mask, face tent attached to vacuum); whether or not such systems are necessary is yet to be determined.

Consider use of a breath synchronized nebulizer that only generates an aerosol during inhalation to minimize the release of medical aerosols [23].

Advise health care workers to stay two meters away from the infected patient during procedures that provoke cough or sneeze or generate an aerosol and to wear N95 or other respirators (eg, a powered air-purifying respirator [PAPR]), eye protection (eg, goggles or a disposable face shield that covers the front and sides of the face), gloves, and a gown [29-31]. Closing the door to the room during the treatment and a negative pressure room are additional considerations.

Additional information about infection control during the COVID-19 pandemic is provided separately. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

PRESSURIZED METERED DOSE INHALERS (pMDI) — A pMDI consists of a pressurized canister, a metering valve and stem, and a mouthpiece actuator (picture 1) [32]. The canister contains the drug suspended in a pressurized mixture of propellants, surfactants, preservatives, flavoring agents, and dispersal agents. The propellent is hydrofluoroalkane (HFA) [33].

The medication-propellant mixture is released from the pMDI canister through the metering valve and stem into an actuator boot. Lung deposition ranges between 10 and 40 percent of the nominal dose in adults and is very technique-dependent. Some newer generation HFA-pMDIs have been formulated as ethanolic solutions, and they produce a finer aerosol spray with greater peripheral lung deposition and improved efficacy of drug delivery [34,35]. (See "The use of inhaler devices in adults", section on 'Pressurized metered dose inhalers'.)

Examples of medications available in a pMDI include short-acting beta agonists (SABAs) and long-acting beta agonists (LABAs) (table 2), ipratropium, a number of ICS alone and in combination with a LABA, and a triple combination with ICS-long-acting antimuscarinic agent (LAMA)-LABA (table 3 and table 4 and table 5 and table 6).

New pMDI technology incorporates micronized drug crystals that are co-suspended with porous phospholipid particles in the HFA propellant. The drug crystals form strong associations with the porous phospholipid particles, and the drug-to-porous-particle ratios employed minimize drug-drug interactions for multi-drug combinations within a single inhaler. Unlike conventional HFA pMDIs, no additional excipients, such as co-solvents or suspension stabilizers, are needed. This co-suspension technology was used in the development of a LAMA/LABA fixed-dose combination of glycopyrrolate-formoterol (Bevespi) and a triple combination of budesonide-glycopyrrolate-formoterol (Breztri) in a pMDI (table 5 and table 6)[36].

The correct techniques for priming and using a pMDI, cleaning the actuator, determining when the canister is empty, and deciding when to use a spacer or chamber device are discussed separately. (See "The use of inhaler devices in adults" and "The use of inhaler devices in children" and "Patient education: Inhaler techniques in adults (Beyond the Basics)".)

Difficulty precisely coordinating device actuation with inhalation leads to poor drug delivery, suboptimal disease control, and increased inhaler use [37]. Such problems might be overcome by employing a spacer/valved holding chamber or breath-actuated pMDI.

Spacer or valved holding chamber – A pMDI can be used with a spacer or valved holding chamber (VHC) to overcome problems related to incoordination between actuation and inhalation (picture 2). Spacer devices employ three basic designs: the open tube, the reservoir or VHC, and the reverse-flow design, in which the pMDI, placed close to the mouth, is fired in the direction away from the patient; adding a one-way valve creates a VHC. They can be used with a mouthpiece or mask, and anti-static devices reduce aerosol losses within the device. The use of these devices to improve aerosol delivery is discussed separately. (See "The use of inhaler devices in adults", section on 'Spacers and holding chambers'.)

Breath-actuated inhalers – Breath-actuated pMDI can help overcome problems with coordination of device actuation with inhalation. The efficacy of breath-actuated pMDIs matches the results with pMDIs in patients who are able to use pMDIs effectively [38]. However, in patients with incoordination of inhalation with device actuation, breath-actuated inhalers can improve efficacy of drug responses [39]. The breath-actuated pMDI for beclomethasone (QVAR RediHaler, available in the United States) does not need to be shaken or primed, but it cannot be used with a spacer or VHC.

DRY POWDER INHALERS (DPI) — Dry powder inhalers (DPIs) create medication aerosols by drawing air through a dose of powdered medication (picture 3) [40-42]. DPIs vary in the use of carrier molecules, internal resistance to airflow, threshold inspiratory flow needed for deaggregation of powder, particle size, and susceptibility to clumping in high ambient humidity.

Carrier molecules – The micronized particles are either in the form of loose aggregates or they are bound to larger carrier particles (usually lactose or glucose). To facilitate deposition in the lungs, drug particles are deagglomerated (dispersed) during inhalation. In DPIs that contain drug particles blended with carrier lactose particles, turbulent energy created in the inhalation channel of the DPI by the interaction of inspiratory airflow with the resistance of the DPI dissociates the drug particles from the carrier particles. This turbulent energy produces a pressure change that breaks up (deaggregates) the formulation and entrains the deaggregated drug particles in the inspiratory airflow [43]. The magnitude of the pressure change depends on the strength of the respiratory muscles, the degree of patient effort (ie, the force of the inhalation), and to a much lesser extent on disease severity [44].

Internal resistance to airflow – The internal resistance to airflow varies among DPIs over a broad range [2]. The turbulent energy created during inhalation is the product of the patient’s inhalation flow multiplied by the DPI’s resistance [43]. Thus, a DPI with a high resistance will require a lower inhalation flow to achieve a similar pressure difference, than a DPI with a lower resistance [44,45]. In general, as the patient's inspiratory effort increases, the flow through a given device increases and this translates into more effective aerosolization, greater particle dispersal (ie, reduced agglomeration of the particles), and a greater fine particle dose (FPD) [45]. DPIs with a high resistance tend to produce greater lung deposition than those with a lower resistance [43,44], but the clinical significance of this is not known.

Threshold inspiratory flow – For each DPI there is a minimum turbulent energy that must be achieved for sufficient deaggregation of the powder during an inhalation [46]. Young (pre-school) children with asthma [47] and patients with COPD [48] may have problems achieving minimum flows through some DPIs, especially if inhalation flow is reduced during exacerbations [49].

Particle size – DPIs produce aerosols in which most of the drug particles are in the respirable range; however, the distribution of particle sizes differs significantly among the various DPIs. These devices are either single-dose or multiple-dose. Multi-dose DPIs either contain a bulk formulation in a reservoir that is metered by the patient during use, or they contain pre-metered factory dispensed doses packaged inside blisters within the device. The single dose devices require the patient or caregiver to load a capsule of drug with each treatment, whereas the multiple dose devices typically contain a month’s supply of drug.

Humidity – High ambient humidity produces clumping of the powder, creating larger particles that are not as effectively aerosolized. DPI devices that use individually packaged capsules protect the powder from humidity and limit this effect. Patients should be instructed to exhale before inhaling through their DPI device. They should not exhale into the device, but rather exhale into the room. Also, any humidity that is introduced into the device will affect delivery of subsequent doses, especially for DPIs of the reservoir type [2]. For this reason, DPIs should be stored in a cool dry place.

The effect of humidity and the need for a tight seal for breath actuation makes all DPIs inefficient for use in patients with a tracheostomy or endotracheal tube.

Examples of medications available in a DPI include short-acting beta-agonists (SABA) (table 2), inhaled glucocorticoids (also called inhaled corticosteroids or ICS; eg, budesonide, fluticasone, mometasone) (table 3), long-acting beta agonists (LABA; eg, formoterol, indacaterol, salmeterol) (table 7), long-acting muscarinic antagonists (LAMA; eg, aclidinium, glycopyrronium, tiotropium, umeclidinium) (table 8), and combinations such as LABA/ICS (table 4), LABA/LAMA (table 5), and LABA/LAMA/ICS (table 5). The use of DPI devices is discussed separately. (See "The use of inhaler devices in adults", section on 'DPI technique' and "The use of inhaler devices in children", section on 'Dry powder inhalers'.)

SOFT MIST INHALERS — Soft mist inhalers (SMI; eg, Respimat) are aerosol delivery devices that have been formulated to aerosolize solutions through microelectronic dosimetric systems. When an SMI is manually primed (rotation of the lower half of the device compresses a spring), a measured amount of drug solution is drawn up into the dosing system. Pressing a button releases the spring, and the buildup of pressure forces the liquid through a nozzle structure within a uniblock that has two narrow outlet channels etched using microchip technology. The two jets of solution converge and the impact generates a soft mist aerosol for approximately 1.2 seconds.

The SMI aerosol has a high fine particle fraction, a low velocity, and more sustained duration than a pMDI [50,51]. The device has a dose indicator. Once the dose indicator reaches the red zone it alerts the patient that approximately 30 doses remain in the device. The device locks after all the doses have been actuated.

The SMI technology achieves a two-to-three fold higher pulmonary deposition than a pMDI [52,53]. Accordingly, the efficacy of a given dose of medication is higher when administered by SMI compared with conventional pMDIs [54].

Depending on geographic location, a variety of bronchodilators are available via SMI, including ipratropium, combination ipratropium-albuterol, tiotropium, combination tiotropium-olodaterol, and olodaterol alone.

NEBULIZERS — The three basic types of nebulizer devices are jet (also known as pneumatic), ultrasonic, and mesh. Nebulizer performance is affected by both technical and patient-related factors (table 9) [55,56].

Jet nebulizers — The basic design of jet (pneumatic) nebulizers has changed little over the past 25 years (figure 1). Jet nebulizers are often considered interchangeable. However, differences in performance among nebulizers produced by various manufacturers have been reported [57,58]. Some nebulizers deliver the dose of medication in a shorter time, while others deliver a more accurate dose or have less drug wastage. These differences may not be important for delivery of inhaled bronchodilators, but may be significant for more expensive medication formulations where precise dosing is required. (See 'Nebulizers for specific medications' below and 'Enhanced nebulizer designs' below.)

Mechanism — The operation of a jet nebulizer requires an air compressor or a pressurized gas supply (eg, compressed air, oxygen), which acts as the driving force for liquid atomization. Compressed gas is delivered as a jet through a small orifice, generating a region of negative pressure above the medication reservoir. The solution to be aerosolized is first entrained, or pulled into the gas stream (Venturi effect), and then sheared into a liquid film. This film is unstable, and rapidly breaks into droplets due to surface tension forces.

A baffle placed in the aerosol stream allows formation of smaller droplets and recycling of larger droplets into the liquid reservoir. The aerosol of respirable particles is entrained into the inspiratory gas stream inhaled by the patient.

Technique — The correct technique for use of a nebulizer is described in the table (table 10) [59].

Factors affecting drug delivery — A number of factors determine the efficiency of a nebulizer system, including the respirable dose, nebulization time, dead volume of the device, and the gas used to drive the nebulizer.

Respirable dose – The most important characteristic of nebulizer performance is the respirable dose delivered to the patient. The respirable dose is a function of the mass output of the nebulizer and the size of the droplets produced. Droplet size is usually reported as mass median aerodynamic diameter (MMAD), which is the median diameter around which the mass of the aerosol is equally divided. Droplet size should be 2 to 5 µm for airway deposition (eg, bronchodilator administration) and 1 to 2 µm or smaller for parenchymal deposition (eg, drugs intended for absorption into the bloodstream such as pulmonary vasodilators).

Nebulization time – Nebulization time, the time required to deliver a dose of medication, is determined by the volume of drug to be delivered and the flow of the driving gas into the nebulizer. The larger the volume and the lower the flow, the longer the nebulization time. Nebulization time is an important determinant of patient compliance with completing a full dose in the outpatient setting. In addition, a reduction in nebulization time may decrease the need for clinical supervision in hospitalized or emergently-treated patients.

During nebulization, the solution within the nebulizer becomes increasingly concentrated as water evaporates from the solution. Thus, on a per breath basis, more medication is delivered late in the course of a treatment. Patients should be encouraged to continue the treatment until there is no further pooling of medication in the bottom of the reservoir; nebulizer sputtering is a good sign that the treatment is complete. Continuing treatment after sputtering is of limited value.

Dead volume – The volume of medication trapped inside the nebulizer, and therefore not available for inhalation, is referred to as the dead volume of the device. The dead volume is typically in the range of 1 to 3 mL. Increasing the amount of solution within the nebulizer (the fill volume) reduces the proportion of the dose lost as dead volume. Although nebulizer output increases with a greater fill volume, this also results in an increase in nebulization time. Considering both factors, an initial nebulizer fill volume of 4 to 5 mL is typically used [58]. The maximum fill volume of the nebulizer is manufacturer-determined; most do not exceed 5 mL, but some accept a volume as great as 10 mL. Unit dose ampules of bronchodilators (eg, albuterol and ipratropium) are typically 2.5 to 3 mL, which may not be ideal in terms of the proportion of dead volume to the total dose. However, the value of adding additional diluent to minimize the dead volume effect has not been studied.

Unit dose ampules of antibiotics (eg, tobramycin) are 5 mL, which may be more suitable to minimize the dead volume effect. When combining drug solutions in the nebulizer to minimize the time required for treatment, it is important to avoid a drug volume that exceeds the labeled maximum volume of the nebulizer and to avoid any incompatibility issues of the drugs [60].

Driving gas – Increasing the flow of the driving gas results in an increase in nebulized output and a reduction in particle size. A flow of 6 to 8 L/min is usually selected to optimize drug delivery [58,61]. When a compressor is used to power the nebulizer, instead of compressed air or oxygen from a wall device, the selected compressor should provide an adequate flow rate for drug aerosolization and delivery [62-64].

Gas density – The density of the gas powering the nebulizer affects nebulizer performance. For example, the inhaled mass of albuterol is significantly reduced when a nebulizer is powered with a mixture of helium and oxygen (heliox). Accordingly, in the rare situation that the nebulizer is powered with heliox, the flow to the nebulizer is increased by 50 percent to 9 to 12 L/min [65]. Heliox may improve aerosol delivery to the lower respiratory tract, because the decrease in gas density results in creation of smaller particles; however, the clinical benefit of this approach is unclear [66-71]. (See "Physiology and clinical use of heliox".)

Breathing pattern – The breathing pattern of the patient affects the amount of aerosol deposited in the lower respiratory tract. Airflow obstruction increases the need for inhaled bronchodilator therapy, but can decrease the effectiveness of that treatment. To improve aerosol penetration and deposition in the lungs, the patient should be encouraged to use a slow breathing pattern with a normal tidal volume and an occasional deep breath [16].

Nebulizer/compressor combination – When nebulizers are employed in the home, their performance is dependent on the choice of compressor that is used to drive the nebulizer. The flow rate of gas that drives the nebulizer is not the same as the flow rate from the compressor, which is usually higher [72]. The nebulizer/compressor combination employed must provide adequate flow rate and volume output from the nebulizer in an acceptable time period. Moreover, the aerosol generated should have an acceptable range of respirable particles [73]. Matching a nebulizer with a compressor is important for optimal performance and to ensure that the aerosol produced is therapeutic. (See 'Nebulizers for specific medications' below.)  

Continuous nebulization — For patients with acute exacerbations of asthma, nebulized bronchodilators can be administered continuously, rather than intermittently at scheduled intervals [1]. (See 'Asthma exacerbation' below.)

One problem with continuous nebulization is the need for refilling the standard, small volume nebulizer every 10 to 15 minutes. Strategies to avoid frequent refilling of the nebulizer chamber for continuous nebulization include use of an infusion pump connected to the nebulizer and use of a large volume nebulizer [55,74]. The usual dose for continuous nebulization of albuterol is 10 to 15 mg/hour. Albuterol 0.5 percent (5 mg/mL) is available in a preservative-free 20 mL bottle [75-77]. This solution is diluted in respiratory saline to achieve a total volume of 4 to 5 mL in the nebulizer reservoir. Benzalkonium chloride, the preservative used in some multidose preparations of albuterol, may cause bronchoconstriction or delay resolution of bronchoconstriction in some patients [76,78,79].  

In general, drug delivery over time by continuous nebulization appears similar to that with frequent intermittent nebulization, although some large volume nebulizers may not provide as consistent a flow as a small volume nebulizer [80-82].


Examples of nebulizers for continuous aerosolized bronchodilators include the HEART Nebulizer (Westmed) and the AirLife Misty Finity (Vyaire), Flo-Mist (Smiths Medical), and Hope (B&B Medical Technologies) [82]. The driving gas flow for these large volume nebulizers should follow the manufacturers’ specifications.

Increasingly common is the use of a mesh nebulizer with an infusion pump for continuous aerosol treatment (figure 2). This can be used with a facemask or inline with a ventilator. Such a set-up is used not only for continuous aerosol bronchodilator delivery for acute asthma, but also for continuous epoprostenol inhalation for selective pulmonary vasodilation in critically ill patients.


Continuous aerosolized bronchodilators can be administered via high flow nasal cannula (HFNC), rather than the traditional facemask [83,84]. This approach has the advantage of being better tolerated by the patient and less likely to be interrupted due to removal of the face mask. When aerosols are delivered via a nebulizer and HFNC, the ratio of HFNC gas flow to patient’s inspiratory flow is critical; the optimal inhaled dose is achieved with the HFNC gas flow set at about 50 percent of patient’s inspiratory flow. (See 'Patients using high flow nasal cannula' below.)

Mesh nebulizers — Several manufacturers have developed aerosol devices that use a mesh or plate with multiple apertures to produce a liquid aerosol (figure 3) [85]. The solution or suspension of medication is forced through the mesh to produce an aerosol, without need for an internal baffling system or compressed air source [86]. A common feature of these devices is their ability to generate aerosols with a high fine-particle fraction, which results in more efficient drug delivery compared to conventional nebulizers.

Examples of mesh nebulizers include the eFlow (Pari), Aeroneb Solo and Aeroneb Go (Aerogen), MicroAIR/NE-U22 (OMRON), InnoSpire Go (Philips) and the I-neb (Respironics) (picture 4). These nebulizers are portable, battery-operated, and have minimal residual medication volume [85]. Another advantage to mesh technology is the ability to deliver expensive formulations with precise dosing and minimal wastage [87] such as the Altera Nebulizer System for administration of aztreonam, the Magnair for administration of glycopyrrolate, and the Lamira for administration of amikacin, each of which utilizes the eFlow technology. Some mesh nebulizers can be used with a holding chamber (eg, Aerogen Ultra).

The I-neb nebulizer uses mesh technology combined with Adaptive Aerosol Delivery (ADD). ADD monitors the patient's breathing pattern and injects a programable dose of the aerosol at the beginning of inhalation [88]. This improves the likelihood of the aerosol penetrating deep into the respiratory tract. This nebulizer is used specifically for the administration of iloprost (Ventavis) inhalation solution for the treatment of pulmonary arterial hypertension (figure 4). (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy".)

In general, mesh nebulizers are more light-weight and portable than jet nebulizers. Mesh nebulizers usually deliver the medication dose more quickly than jet nebulizers and could reduce the duration of each nebulizer treatment. However, the speed of medication delivery is influenced by the position of the nebulizer. Under laboratory conditions, the Omron vibrating mesh nebulizer has a comparable drug delivery to a conventional jet nebulizer only when the Omron is in a vertical position [89]. The time to deliver the same dose is three times longer when the Omron is in the horizontal position, rather than vertical or slightly tilted.

Blockage of the minute apertures with drug particles, especially when suspensions are aerosolized, can impair performance. Thus, manufacturer’s recommendations for cleaning the device should be followed meticulously. Cleaning is required after each treatment, and more extensive disinfection or sterilization needs to be performed on a regular basis. One study reported that the Aerogen Solo mesh nebulizer was often randomly interrupted with a wide range of retained volumes, so the chamber should be checked to ensure that the full dose has been delivered [90].

Ultrasonic nebulizers — Ultrasonic nebulizers consist of a power unit and transducer, with or without an electric fan [55,91]. The power unit converts electrical energy to high-frequency ultrasonic waves. A piezoelectric element in the transducer vibrates at the same frequency as the applied wave. Ultrasonic waves are transmitted to the surface of the solution to create an aerosol. The droplets produced by these devices have a slightly higher MMAD than droplets from a jet nebulizer [92]. A fan is used to deliver the aerosol to the patient, or the aerosol is evacuated from the nebulization chamber by the inspiratory flow of the patient.

Small volume ultrasonic nebulizers (eg, Beetle Neb, Lumiscope, Minibreeze) are commercially available for delivery of bronchodilators. Advantages of ultrasonic nebulization are quieter medication delivery and shorter treatment time than the jet nebulizers. Reported problems include poor battery life and overheating. A potential issue with the use of ultrasonic nebulizers is drug inactivation by increased temperature of the solution during ultrasonic nebulization. Drug inactivation has not been shown to occur with the medications in solution that are commonly delivered using this system (eg, bronchodilators). Additionally, ultrasonic nebulizers create aerosol droplets from the surface of the liquid. In suspensions, such as budesonide, the drug particles tend to settle and ultrasonic nebulizers are inefficient for aerosolization of suspensions.

The Optineb is an ultrasonic nebulizer used to deliver treprostinil inhalation solution for the treatment of pulmonary hypertension. The device is specific for the delivery of treprostinil and prompts the patient to use correct inhalation technique.

Enhanced nebulizer designs — Newer technologies for nebulizer design address issues of medication conservation, speed of delivery of medication, portability, battery power, and administration of specialized medications. With the traditional nebulizer design, an aerosol is generated throughout the patient's respiratory cycle. This results in considerable waste of aerosol during exhalation. Newer designs reduce aerosol waste during the exhalation phase (picture 5).

Breath-enhanced nebulizers, such as the Pari LC, are designed to allow release of more aerosolized medication during inhalation than exhalation. With this design, exhaled gas is routed out the expiratory valve in the mouthpiece and aerosol is contained in the nebulizer chamber during the expiratory phase.

The Circulaire nebulizers reduce waste from a constant-output nebulizer by attachment of a storage bag with a one-way valve in the mouthpiece connector. During the expiratory phase, aerosol generated by the nebulizer is collected in the bag and delivered to the patient on the subsequent inhalation.

The AeroEclipse nebulizer has a breath-actuated valve that triggers aerosol generation only during inhalation, eliminating the need for a storage bag or reservoir [93]. A randomized controlled trial has reported benefit for the use of this nebulizer compared to a jet nebulizer in a pediatric emergency department setting [94].

Mouthpieces and facemasks — Inhaled aerosols from nebulizers can be administered using a mouthpiece or a facemask, although the mouthpiece interface is generally preferred.

Bronchodilator response appears similar with either interface, and some have argued that the selection of patient interface should be based upon patient preference. Significant facial and eye deposition of aerosol can occur when a face mask is used, especially in young children [95]. Eye deposition is of particular concern when aerosolized anticholinergic agents (eg, ipratropium) are administered, as this can result in blurring of vision, pupil dilation, and worsening of narrow angle glaucoma. When a facemask is used, it is important to instruct the patient to inhale through the mouth to minimize nasopharyngeal deposition of medication.

AEROSOL DELIVERY IN SPECIAL SITUATIONS

Mixing nebulized medications — Some patients need more than one nebulized medication, such as one or more bronchodilators or a bronchodilator plus glucocorticoid or hypertonic saline. Certain preparations are compatible and can be mixed into a single nebulizer treatment, thus improving patient convenience. However, caution is necessary as certain mixtures are incompatible due to changes in particle size or other characteristics. As an example, hypertonic sodium chloride is compatible with budesonide, but not with albuterol, formoterol, ipratropium, or fluticasone. A listing of compatible and incompatible solutions is provided in the table (table 11).

When mixing nebulized medications, freshly opened, single use formulations should be used.

Nebulizers for specific medications — Drug formulation can affect nebulizer performance, and some drug preparations are only approved for delivery with specific nebulizers (table 12) [96-99]. Examples of medications that should be delivered only by an approved nebulizer include budesonide suspension, iloprost, pentamidine, ribavirin, DNase I, tobramycin, aztreonam, treprostinil, glycopyrrolate, revefenacin, and liposomal amikacin, as described below.

Budesonide - Budesonide is prepared as a suspension for nebulization. It can be administered via jet or mesh nebulizers, but not by an ultrasonic nebulizer. (See 'Ultrasonic nebulizers' above.)

Iloprost – Iloprost requires use of a nebulizer with an Adaptive Aerosol Delivery (AAD) system that controls the dosage of drug by use of a specialized disc and metering chambers. Two types of nebulizer are acceptable, the vibrating mesh nebulizer I-neb AAD (Respironics) and the jet nebulizer Prodose AAD (Respironics) [88]. The AAD metering chambers can deliver a pre-set volume ranging from 0.25 to 1.4 mL with a residual of about 0.1 mL. The drug is only delivered during inspiration and requires that the patient be conscious and breathing spontaneously [100,101].

The I-neb AAD delivers aerosol via two modes of inspiration: the tidal breathing mode, in which the aerosol is delivered during the first 50 percent of the patient’s inspiration or a new target inhalation mode (TIM) which guides the patient to a slow and deep inspiration. Typical inspiratory flows are reduced to approximately 20 L/min by introduction of a high-resistance mouthpiece. The device provides feedback (by a vibration signal) to gradually lengthen the duration of inspiration with each breath, until the inhalation time matches a target inhalation time. At this time, aerosol generation occurs over >70 percent of the inspiration. The device remembers this breathing pattern and gives a vibratory feedback at the same point in each successive breath and for all future treatments. The slow and deep breathing combined with AAD greatly enhances drug delivery and pulmonary deposition compared to tidal breathing [100,101].

Pentamidine – Specially constructed small-volume jet nebulizers, such as the Respirgard II, are used when it is necessary to prevent contamination of the ambient environment with the aerosolized drug (eg, pentamidine) [55]. The Respirgard II is fitted with one-way valves and filters to minimize gross contamination of the environment. (See "Treatment and prevention of Pneumocystis infection in patients with HIV", section on 'Patients with a sulfa allergy'.)

Ribavirin – A specialized jet nebulizer is used to allow the safe delivery of aerosolized ribavirin, which is potentially teratogenic. The Valeant Small-Particle Aerosol Generator (SPAG-2) is designed specifically to aerosolize ribavirin. It consists of a nebulizer and drying chamber that reduces the MMAD to about 1.3 µm, which optimizes drug delivery to distal airspaces. The SPAG-2 is used with a scavenging system to minimize contamination of the ambient environment. (See "Respiratory syncytial virus infection: Treatment", section on 'Ribavirin'.)

DNase I (Dornase alfa) – Inhaled DNase I (Dornase alfa) is administered to patients with cystic fibrosis using the Pulmo-Aide, Pari-Proneb, Mobilaire, Porta-Neb, or Pari Baby jet nebulizer systems. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Inhaled airway clearance agents'.)

Tobramycin – Inhaled tobramycin is administered over 20 minutes using a handheld jet nebulizer (PARI-LC PLUS). It cannot be combined with other inhaled medications. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Inhaled tobramycin'.)

Aztreonam – Inhaled aztreonam is administered using the Altera Nebulizer System, which uses mesh nebulizer technology. (See 'Mesh nebulizers' above and "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Inhaled aztreonam lysine'.)

Treprostinil – Inhaled treprostinil is used to treat pulmonary arterial hypertension (PAH; WHO Group I) in patients with NYHA class III symptoms. It is delivered with the Optineb ultrasonic nebulizer. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy".)

Glycopyrrolate – Glycopyrrolate, a long-acting muscarinic antagonist (LAMA), is available as an inhalation solution (Lonhala), administered twice daily with a specialized portable vibrating mesh nebulizer. The sealed drug vial can only be used with the Magnair device system and the treatment time is two to three minutes [102]. (See "Role of muscarinic antagonist therapy in COPD", section on 'Glycopyrronium'.)

Revefenacin – (Yupelri) inhalation solution is the only once-daily, nebulized bronchodilator for maintenance treatment of COPD [103,104]. Revefenacin is a LAMA and is nebulized with a standard jet nebulizer connected to a compressor. (See "Role of muscarinic antagonist therapy in COPD", section on 'Revefenacin'.)

Amikacin – Amikacin (Arikayce) liposome inhalation suspension is delivered once daily with the Lamira mesh nebulizer system. During nebulization, approximately 70 percent of the amikacin dose remains encapsulated within liposomes while approximately 30 percent of the dose is released as free amikacin. Nebulized amikacin is indicated for patients who remain culture positive after six months of multi-drug treatment for Mycobacterium avium complex (MAC) [105,106]. (See "Treatment of Mycobacterium avium complex pulmonary infection in adults", section on 'Efficacy of alternative agents'.)

Asthma exacerbation — Two issues that arise when choosing an aerosol delivery system for bronchodilator medication during exacerbations of asthma are whether to use an MDI or a nebulizer and whether to use continuous or intermittent nebulization for hospital-based treatment. These choices are typically based on the severity of the exacerbation and also clinician and patient preference (algorithm 1). (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management".)

For patients who have an asthma exacerbation that is mild to moderate in severity (eg, mild to no dyspnea at rest and peak expiratory flow ≥40 percent of predicted), administration of the beta 2-agonist albuterol via a pMDI (2 to 6 puffs for treatment at home, 4 to 8 puffs for emergency room or hospital treatment) combined with a spacer or chamber device (eg, Aerochamber, Optichamber Diamond, Vortex) results in comparable improvements in lung function compared to nebulizer delivery, although the actual dose delivered by a pMDI is much lower (table 2). Similar results with pMDIs have been reported in patients with severe exacerbations, but only a small number of such patients have been studied. Generally, nebulizer treatments (every 20 minutes or continuous) are preferred for more severe asthma exacerbations. (See "Acute exacerbations of asthma in adults: Emergency department and inpatient management", section on 'Nebulizer versus MDI'.)

For patients with severe asthma exacerbations (eg, dyspnea at rest, accessory muscle use, retractions, forced expiratory volume in one second or peak expiratory flow <40 percent predicted), beta agonists are often administered continuously (eg, albuterol 5 to 15 mg/hour) rather than intermittently [16,107,108]. This method of bronchodilator administration is equally effective compared to frequent intermittent nebulization [8,109].

Several studies have established the safety of continuous nebulization, even when high doses (eg, 20 mg/hour of albuterol) are used [55,107,110]. However, continuous nebulization of albuterol (10 mg/hour) in healthy adults has been associated with a decrease in serum potassium of 0.5 mmol/L (95% CI: -0.72 to -0.28 mmol/L), which could be clinically important in patients with a low potassium level prior to therapy [111].

Continuous nebulization may be most beneficial in patients with the most severe pulmonary dysfunction [107]. The specialized delivery systems adapted for continuous nebulization are described above. (See 'Continuous nebulization' above.)

Patients with tracheostomy — Techniques have been developed for the delivery of aerosol medication by nebulizer or pMDI to patients with a tracheostomy tube who are not ventilator dependent (picture 6) [112]. Two systems are available for delivery of nebulized medication: either a mask can be placed over the tracheostomy opening or the nebulizer chamber can be attached to the tracheostomy tube using a T-piece made of ventilator tubing and a connector. The T-piece approach is preferred because more aerosol medication is directed into the tracheostomy tube.

For delivery of a pMDI aerosol, the canister is removed from its usual plastic actuator and inserted into an actuator/spacer that is attached by T-shaped connector to the tracheostomy tube. This actuator/spacer is the same as that used for patients on mechanical ventilation (picture 7). The caregiver actuates the pMDI into the spacer and the patient inhales the aerosol through the tracheostomy tube.

Adaptors have not been developed for effective administration of medication from DPIs into tracheostomy tubes [113].

Mechanically ventilated patients — A number of factors affect aerosol delivery during mechanical ventilation (table 13) [114-125]. One major factor is that humidification of inhaled gas decreases aerosol deposition by approximately 40 percent due to increased particle drug deposition in the ventilator circuit. For this reason, increased dosage of medication is often required to achieve a therapeutic effect in mechanically ventilated patients.

Inhaled medications can be delivered to patients receiving mechanical ventilation using either a pMDI or a nebulizer [117,118]. A DPI is inefficient for delivery of a dry powder during mechanical ventilation because ventilator circuit humidification impairs aerosol formation.

Metered dose inhaler — A special actuator is needed to adapt the pMDI into the ventilator circuit (picture 7) [126,127]. The size, shape, and design of these actuators have a major impact on drug delivery to the patient. A pMDI with a chamber results in a four- to six-fold greater delivery of aerosol than MDI actuation into a connector attached directly to the endotracheal tube, or into an in-line device that lacks a chamber [117]. When using a pMDI during mechanical ventilation, it is important to synchronize actuation with inspiratory airflow to optimize drug delivery. Properly used, a pMDI may deliver a more consistent dose than a nebulizer [128].

The following technique has been proposed for using pMDIs in mechanically ventilated adult patients [129]:

Shake the pMDI vigorously

Place canister in the actuator of a cylindrical spacer situated in the inspiratory limb of ventilator circuit (picture 7)

Actuate the pMDI once only with the onset of inspiration by the ventilator

Repeat actuations after 15 seconds until the total dose is delivered

Helium-oxygen mixtures affect aerosol deposition, and in vitro modeling has reported a 50 percent increase in deposition of albuterol from a pMDI during mechanical ventilation when heliox was used as the driving gas [130]. However, heliox can interfere with the functioning of flow sensors and oxygen levels when delivered through some ventilators, and care must be taken if this approach is employed with a ventilator that is not approved for heliox administration [131-133]. (See "Physiology and clinical use of heliox", section on 'Instrument recalibration'.)

The use of a heat and moisture exchanger (HME) in the ventilator circuit can filter out the aerosol when a pMDI (or nebulizer) is used. Commercially available devices can be used to bypass the HME when a pMDI is used (picture 8 and picture 9). Alternatively, the HME must be removed from the circuit when the aerosol is delivered [134].

Nebulizer — The optimal methods for delivery of nebulized medication to mechanically ventilated patients are not well-established. Delivery of a large tidal volume, use of an end-inspiratory pause, and use of a slow inspiratory flow affect aerosol delivery by jet nebulizer but not by a pMDI [114]. Nebulizer performance can be optimized by placing the nebulizer 30 cm from the endotracheal tube, rather than at the Y-piece, because the inspiratory ventilator tubing acts as a spacer. In a simulation model, delivery of albuterol via mesh nebulizer was two to four times greater than with a jet nebulizer, and placement of the mesh nebulizer in the ventilator tubing on the ventilator side of the humidifier, rather than closer to the patient, increased drug delivery [119].

Operating the nebulizer only during inspiration is more efficient for aerosol delivery compared with continuous aerosol generation throughout the respiratory cycle. When a breath-actuated nebulizer is used, the delivered dose increases by more than five-fold. In addition, when the humidifier is bypassed the delivered dose increases by a factor of nearly four [115].

Disadvantages of jet nebulizer use during mechanical ventilation include circuit contamination due to opening the ventilator tubing circuit, decreased ability of the patient to trigger the ventilator, and the associated increases in tidal volume and airway pressure due to nebulizer flow. Valved T-piece devices are commercially available and commonly used to allow the nebulizer to be inserted within the ventilator circuit without disconnecting the patient from the ventilator, thus avoiding interruption of mechanical ventilation for nebulizer insertion and removal (picture 10). (See "The ventilator circuit".) A filter in the expiratory limb during the nebulizer treatment protects the expiratory valve and flow/pressure monitors.

The mesh nebulizer can be used effectively during mechanical ventilation and is placed between the ventilator outlet and the heated humidifier [119,135]. Unlike the jet nebulizer, the mesh nebulizer remains in the ventilator circuit and does not interfere with ventilator function (eg, no additional gas flow, no effect on triggering). (See 'Mesh nebulizers' above.)

Choice of device — Although the jet nebulizer is less efficient than the pMDI during mechanical ventilation, the nebulizer can deliver a greater cumulative dose to the lower respiratory tract [136]. Thus, nebulizers and pMDIs produce similar therapeutic effects in mechanically ventilated patients [137]. The use of a pMDI for routine bronchodilator therapy in ventilator-supported patients has been preferred because of the problems associated with the use of nebulizers, including contamination and triggering difficulty, as well as increased pressure and volume delivery. However, use of a mesh nebulizer avoids several of the problems of the jet nebulizer and performs comparably to pMDIs. Compared with the pMDI, the mesh nebulizer is a convenient and efficient delivery method in mechanically ventilated patients [138].

Aerosol delivery by pMDI is easy to administer, involves less personnel time than a nebulizer, provides a reliable dose of the drug, and is free from the risk of bacterial contamination. When a pMDI is used with an in-line spacer, the ventilator circuit does not need to be disconnected with each treatment; this may reduce the risk of ventilator-associated pneumonia. This also prevents the loss of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). (See "The ventilator circuit" and "Ventilator management strategies for adults with acute respiratory distress syndrome".)

Patients receiving noninvasive ventilation — Aerosol therapy can also be administered during noninvasive positive pressure ventilation (NIV), using devices adapted for inline administration (picture 11) [139-143]. Effective delivery of albuterol by MDI during NIV using a specialized spacer has been reported in patients with exacerbations of chronic obstructive pulmonary disease (COPD) [144]. When delivering aerosol therapy during NIV, the aerosol generator should be placed between the leak port and the interface. (See "Acute exacerbations of asthma in adults: Home and office management" and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

Patients using high flow nasal cannula — The high flow nasal cannula is increasingly used for hypoxemic respiratory failure and can also be used for aerosol delivery in the intensive care unit (ICU) [145,146]. The results of in vitro studies suggest that aerosols can be delivered by HFNC, and there is anecdotal experience suggesting benefit [83]. When aerosols are delivered via a nebulizer and HFNC, the ratio of HFNC gas flow to patient’s inspiratory flow is critical; optimal inhaled dose is achieved with the HFNC gas flow set at about 50 percent of patient’s inspiratory flow [147]. At high flows, the amount of aerosol delivery is likely to be very low [83,84]. In one study, pulmonary drug delivery through the high-flow nasal cannula was about 1 to 4 percent of the amount placed in the nebulizer, with a higher efficiency for a mesh nebulizer than a jet nebulizer [17]. However, in a separate study of 26 subjects with COPD, the physiologic response to inhaled bronchodilator was similar for mouthpiece and nasal cannula at a flow of 35 L/minute [148]. In 42 stable asthma and COPD patients with known positive responses to 400 mcg albuterol via pMDI and spacer, the bronchodilator response to albuterol 1.5 mg via a vibrating mesh nebulizer and HFNC with gas flow of 15 to 20 L/min was similar to that achieved with albuterol 400 mcg by pMDI with spacer [147,149]. The lower deposition with high flow nasal cannula might also be overcome by increasing the dose [83]. A pMDI, SMI, or DPI device cannot be used with high flow nasal cannula. (See "Continuous oxygen delivery systems for the acute care of infants, children, and adults", section on 'Nasal cannula'.)

Home use — Prescription of a nebulizer for home use is usually not necessary for patients with asthma or COPD due to the efficacy of pMDIs and DPIs for delivery of bronchodilator medications. However, some patients (eg, those with difficulty mastering the technique of pMDIs) may have a better response to a nebulizer. The decision to prescribe a nebulizer for home use is made on a case-by-case basis. Careful instructions are provided regarding indications for coming to the emergency department if one or two nebulizer treatments do not result in reduced symptoms.

Typically, jet nebulizers are provided for patients with asthma or COPD unless the patient is willing to pay extra for a smaller, more portable mesh nebulizer. For patients requiring specialized medications such as budesonide suspension, iloprost, pentamidine, ribavirin, DNase I, tobramycin, aztreonam, and treprostinil the selection of a nebulizer device depends on the requirements of the particular medication, as described above. (See 'Nebulizers' above.)

With a jet nebulizer, the patient also needs an air compressor in addition to the nebulizer, tubing, and mouthpiece. Although the nebulizer is disposable, many patients re-use it multiple times before replacing. Proper cleaning and air-drying of the nebulizer chamber and mouthpiece are needed to prevent bacterial and fungal colonization and also contamination by allergens, such as dust mites, cockroach, and dander. The plastic tubing and medication chamber should be stored in a plastic bag between uses. Once or twice a week, the nebulizer (figure 1) should be disassembled, washed in soapy tap water, and disinfected with either a 1.25 percent acetic acid (white vinegar) mixture or a quaternary ammonium compound at a dilution of 1 ounce to 1 gallon of sterile distilled water. The acetic acid soak should be at least 1 hour, but a quaternary ammonium compound soak needs only 10 minutes. However, patients with asthma should avoid breathing the fumes of these cleaning agents.

Ultrasonic and mesh nebulizers should be cleaned and disinfected per the manufacturer’s specifications. Acetic acid should not be reused, but the quaternary ammonium solution can be reused for up to one week.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic obstructive pulmonary disease" and "Society guideline links: Asthma in adolescents and adults".)

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 dry powder inhaler (adults) (The Basics)" and "Patient education: How to use your metered dose inhaler (adults) (The Basics)" and "Patient education: How to use your soft mist inhaler (adults) (The Basics)")

Beyond the Basics topics (see "Patient education: Asthma symptoms and diagnosis in children (Beyond the Basics)" and "Patient education: Inhaler techniques in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Available devices

Four principal types of devices are used to deliver inhaled medications: pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers (SMIs), and nebulizers. A comparison of delivery devices for inhaled medications is provided in the table (table 1). (See 'Overview' above.)

A pMDI consists of a pressurized canister, a metering valve and stem, and a mouthpiece actuator (picture 12) [32]. DPIs create aerosols by drawing air through a dose of powdered medication (picture 3). SMIs produce a fine particle, slow moving aerosol (picture 13). The correct techniques for using pMDIs, DPIs, and SMIs are reviewed separately. (See 'Pressurized metered dose inhalers (pMDI)' above and "The use of inhaler devices in adults" and "The use of inhaler devices in children".)

The most commonly-used type of nebulizer is the jet (or pneumatic) nebulizer (figure 1); mesh and ultrasonic nebulizers are also available. Nebulizer performance is affected by technical factors, such as mechanism of aerosol generation and drug formulation (not all medications can be used with all nebulizers), as well as patient-related factors (table 9). (See 'Nebulizers' above.)

With all of the standard nebulizers, patients should be encouraged to use a slow breathing pattern with an occasional deep breath. We generally favor the use of mouthpieces over face masks, as the latter are associated with some facial and eye deposition of aerosol. (See 'Mouthpieces and facemasks' above.)

Mesh nebulizers force a solution or suspension of medication through a mesh to produce an aerosol, without need for an internal baffling system or compressed air source. These devices are quiet, portable, and able to generate aerosols with a high fine-particle fraction, resulting in more efficient drug delivery. (See 'Mesh nebulizers' above.)

Ultrasonic nebulizers transmit ultrasonic waves to the surface of the solution to create an aerosol, which is delivered to the patient by a fan or by the inspiratory flow generated by the patient’s breath. They are quieter than jet nebulizers, but cannot be used to deliver a drug in suspension. (See 'Ultrasonic nebulizers' above.)

Newer nebulizer designs to reduce drug wastage include breath-actuated devices that deliver the majority of the medication during inhalation and storage bag nebulizers. (See 'Enhanced nebulizer designs' above.)

Options for specific patient situations

For spontaneously breathing patients, pMDIs, DPIs, and nebulizers are all effective for treatment of asthma and chronic obstructive pulmonary disease (COPD) when used correctly. Thus, we advise selecting a delivery device based upon the desired beta agonist or glucocorticoid, convenience, cost, clinician and patient preferences, and the patient’s ability to use the device correctly (table 1). (See 'Overview' above.)

For patients with a mild to moderate exacerbation of asthma, beta-2 agonists (eg, albuterol) may be administered either by nebulizer or by pMDI combined with a spacer or chamber device. For patients with a severe exacerbation of asthma not requiring mechanical ventilation, we suggest delivery of inhaled beta-2 agonists by nebulizer rather than pMDI (Grade 2C). Use of a nebulizer for a severe asthma exacerbation may be intermittent (every 20 to 30 minutes) or continuous. The doses of beta-2 agonists for these applications are provided in the table (table 2). (See 'Asthma exacerbation' above and 'Continuous nebulization' above.)

Some drug preparations are only approved for delivery with specific nebulizers due to factors such as preventing contamination of the ambient environment, achieving greater precision in dosing, or preventing medication degradation by the aerosol technology. Examples of medications requiring specific nebulizers include budesonide, iloprost, pentamidine, ribavirin, DNase I, tobramycin, aztreonam, treprostinil, glycopyrrolate and liposomal amikacin (table 12). (See 'Nebulizers for specific medications' above.)

Administration of medication aerosols by pMDI or nebulizer to a spontaneously breathing patient with a tracheostomy tube requires use of adaptive devices; examples are provided in the figure (picture 6). (See 'Patients with tracheostomy' above.)

For mechanically-ventilated patients who require aerosol medication, we suggest the use of pMDIs, combined with a specialized spacer that is placed in the ventilator tubing (picture 7), or a mesh nebulizer, rather than a jet nebulizer (Grade 2C). The pMDI method is technically easier than jet nebulizer treatments, involves less personnel time, provides a reliable dose of the drug, and reduces the risk of bacterial contamination that can occur with a nebulizer. Inhaled medications can also be delivered effectively to patients receiving noninvasive positive pressure ventilation (NIV). (See 'Mechanically ventilated patients' above.)

Accumulating evidence supports the use of a nebulizer for aerosol delivery with high flow nasal cannula. (See 'Patients using high flow nasal cannula' above.)

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