INTRODUCTION — Inhaler devices are the major method for delivery of medications for asthma and chronic obstructive pulmonary disease (COPD), but their effectiveness can be compromised if the patient uses the inhaler device incorrectly [1,2].
The magnitude of incorrect inhaler use has been well documented; in several studies, less than one-half of the patients used their inhaler correctly [3-13], with little to no improvement in rates of correct inhaler technique over the past 40 years [13]. Moreover, several investigators have reported low levels of adherence to inhaled therapy [14,15]. Errors in inhaler technique and poor adherence lead to poor control of asthma and COPD, with increased risk of hospitalization, emergency department visits, and oral glucocorticoid use [1,2,12,16]. In contrast, higher patient satisfaction with their inhaler device is associated with better adherence to therapy and improved clinical outcomes [17].
The use of inhaler devices by adults will be presented here. More general discussions of the delivery of inhaled medication via nebulizers and what patients need to know about their asthma are presented separately (table 1). (See "Delivery of inhaled medication in adults" and "Asthma education and self-management".)
TYPES OF INHALER DEVICES — Inhaler devices are used to deliver a variety of inhaled medications, including beta-agonists, anticholinergics, glucocorticoids, antibiotics, prostaglandin analogs, nicotine, insulin, mannitol, antipsychotics, and levodopa. Three main types of inhaler devices are available: the pressurized metered dose inhaler (pMDI), the dry powder inhaler (DPI), and the soft mist inhaler (SMI) [18-20].
Pressurized metered dose inhalers — pMDI devices usually consist of a pressurized canister, a metering valve and stem, and a mouthpiece actuator (picture 1). The pressurized canister contains the drug suspended in a mixture of propellants, surfactants, preservatives, flavoring agents, and dispersal agents. Following adoption of the Montreal Protocol, an international agreement to ban chlorofluorocarbons (CFCs), the CFC-free propellant hydrofluoroalkane (HFA)-134a has replaced CFC-containing devices [20-34]. pMDIs can be formulated as solutions, suspensions, or co-suspensions, with solutions typically having a finer aerosol particle size compared with suspensions [34,35]. Delivery of most aerosol medications to the lungs is comparable between HFA and CFC devices used in the past, although a few of the HFAs deliver a greater portion of the dose than the previous CFC pMDI [30,36-41].
The co-suspension technology platform overcomes some of the formulation challenges of combining respiratory drugs in suspension pMDIs [42]. This technology employs spray-dried porous phospholipid particles on which drug crystals are reversibly associated to achieve a more uniform suspension in propellant. pMDIs formulated with co-suspension technology provide more consistent drug delivery with single drugs, as well as dual and triple drug combinations [43,44]. Furthermore, these pMDIs are less influenced by patient-handling errors, such as the need for shaking prior to use.
A Redihaler is a breath-actuated pMDI that is activated quite differently from other pMDIs. The dose is ready for inhalation when the cap is opened. When the patient breathes in thorough the mouthpiece, a dose is delivered. The cap must be closed for the next dose. This device should not be shaken and there is no need for priming. The most widely available agent that is paired with a Redihaler is beclomethasone (brand name QVAR). The Redihaler cannot be used with a spacer or valved holding chamber.
Dry powder inhalers — DPIs are breath-actuated devices that deliver micronized drug particles with a mass median aerodynamic diameter (MMAD) of less than 5 micrometers, which usually are aggregated with larger carrier particles (such as lactose or glucose) (picture 2) [45-47]. Drug is delivered to the airways by the inhalation of air over a punctured capsule, blister, or reservoir [45-47]. DPIs have various designs and resistances, but generally, inspiratory flows of 30 to 60 L/minute are required to disaggregate and aerosolize the drug [48-50].
The controlling factor in a patient’s ability to effectively operate a DPI is the maximum inspiratory pressure they can achieve [51]. Inspiratory pressure generation is primarily dependent on the strength of the respiratory muscles [51,52]. While achieving an adequate maximum inspiratory pressure drop (or flow) is reassuring, optimal dosing from DPIs requires training of patients on the correct technique for each DPI [19].
Additional aspects that influence the effectiveness of DPIs include the formulation, oropharyngeal deposition, drug dissolution, and clearance mechanisms [47,53]. Notably, some powder formulations are extremely sensitive to moisture, and exposure to high ambient humidity could decrease generation of fine particles even with an adequate inspiratory airflow [54].
Soft mist inhalers — Soft mist inhalers (SMI) are propellant-free mechanical devices that are slightly larger than a conventional pMDI (picture 3) [55]. Rotating the lower half of the device compresses a spring and draws a measured amount of drug solution into the dosing system. After priming, the spring is released by pressing a button, creating pressure within the device that forces the liquid through a nozzle that has two narrow outlet channels (8 micrometers in diameter) etched using microchip technology [56]. The two fine jets of liquid produced by the channels converge at an optimized angle and their impact generates a fine mist that moves slowly (about 0.8 m/s) and lasts about 1.2 seconds [57]. Thus, the aerosol produced by an SMI has a low velocity and six times more sustained duration than a pMDI [58]. Dose delivery and particle fraction with an SMI are independent of inspiratory flow, and shaking is not necessary prior to using the device.
The lower velocity of the aerosol produced by an SMI decreases oropharyngeal deposition and enhances lung deposition [59]. The longer duration of the aerosol cloud increases the window for successful inhalation, thus reducing problems with coordination between actuation and inhalation [60]. These properties permit the nominal dose to be reduced. Combivent (20 micrograms ipratropium bromide and 100 micrograms albuterol) in an SMI was approved with the recommended dose of 1 inhalation four times per day being essentially one-half that delivered with a Combivent pMDI (2 puffs four times per day). Similarly, the increased lung deposition allows a reduction of the recommended daily dose of tiotropium bromide from 18 micrograms delivered from the HandiHaler DPI to 5 micrograms (2 puffs of 2.5 micrograms each) delivered by the SMI [61,62]. SMIs can be employed with a valved holding chamber (VHC) and a face mask in children [63]. Several formulations are available including ones containing short-acting bronchodilators, long-acting bronchodilators, and combinations.
SPACERS AND HOLDING CHAMBERS — Using a spacer or valved holding chamber (VHC) with a pressurized metered dose inhaler (pMDI) allows the velocity of particles to decrease before reaching the mouth, which decreases the amount of oropharyngeal deposition (picture 4) [20,64,65]. Use of a VHC also allows sequential actuation and inhalation as the aerosol is retained in the chamber after actuation of the pMDI. We typically prescribe a VHC for patients with difficulty coordinating actuation and inhalation and for those using pMDIs containing glucocorticoids, especially if the dose is in the medium to high range. Spacers are less expensive than VHCs and may be a better option in resource-limited settings, although they do not allow for sequential actuation and inhalation. Spacers and VHCs require a prescription from a clinician.
●Spacers – A spacer is usually an open-ended tube or bag that is of sufficient volume to allow the aerosol plume from the pMDI to expand and the propellant to evaporate. The spacer should be at least 100 to 700 mL in volume and should provide a distance of 10 to 13 cm between the pMDI nozzle and the mouth [66,67]. By dispersing the aerosol into the spacer, the individual medication droplets experience slight evaporative loss of the propellant, which decreases the droplet size and thereby decreases oral deposition of the aerosol. The spacer holds the medicine aerosol long enough for patients to inhale slowly and deeply (picture 4) [68]. Spacers can increase the bioavailability of inhaled medication [69]. However, the dose can be lost or diluted if the patient exhales into the spacer prior to inhalation of the dose.
●Valved holding chambers – The VHC is a specialized spacer that incorporates a one-way valve between the chamber and the mouthpiece. This design permits sequential actuation and inhalation as the aerosol is retained in the chamber after actuation of the pMDI. In addition, the valve prevents the exhaled breath from entering the chamber, so the aerosol medication is held in the chamber to allow a second or third inhalation, if needed. Commonly used VHCs include rigid devices, such as the AeroChamber, and plastic collapsible holding chambers, such as the InspirEase bag (picture 4). Upgrades to VHCs include improvements in valve design, visual feedback of inspiratory flow, an auditory alert if the patient inhales too quickly, and addition of an anti-static resin to the polymer from which the device is made [70].
Retention of aerosol within the chamber of a VHC for a finite time post pMDI actuation produces a finer aerosol because of impaction of large particles and partial evaporation of propellant from the aerosol droplets [71].
Several issues are important to the correct use of a VHC. Only one actuation should be placed into the chamber for each inhalation, as multiple actuations into the chamber reduces the overall amount of drug inhaled [72]. The time between actuation and inhalation should be as short as possible because the aerosol is lost to the walls of the device due to gravitational sedimentation, inertial impaction, and electrostatic charge [72,73]. MDIs that generate fine particle aerosols, such as HFA-beclomethasone dipropionate, may be less affected by a delay in inhalation from a VHC [41,73].
Electrostatic charge can be minimized by washing the device in detergent, rinsing, and allowing it to air dry. However, the relative effects of detergent coating can vary depending on the VHC and pMDI formulations [74,75]. Alternatively, multiple doses may be actuated into a new spacer before use to minimize the static charge. VHCs made of nonelectrostatic materials are available, but these are costlier. Observations from retrospective, real-life studies in patients with asthma suggest that use of antistatic VHCs could improve clinical outcomes (such as exacerbation rates, time to first exacerbation, need for emergency department visits) compared with use of MDIs with nonantistatic spacers [76].
Despite the variety and popularity of spacer devices, little information is available on their relative performance [64,77]. In general, larger-sized spacers appear more effective than smaller ones, but proper technique remains important for obtaining optimal drug delivery (table 2 and table 3) [78,79]. A point of controversy is whether or not a VHC is necessary for delivery of nonsteroid drugs when the patient demonstrates good technique with the pMDI alone, as the use of the chamber adds cost and complexity [80]. (See "Delivery of inhaled medication in adults".)
COMMON PROBLEMS WITH INHALER DEVICES — The main problems with the use of inhaler devices, such as metered dose and dry powder inhalers, are upper airway deposition and poor coordination between actuation and inhalation. A less common problem is that of an insufficient breath-hold after inhalation of the medication. Poor adherence with use of inhalers compromises the effectiveness of inhaled therapies in patients with asthma and COPD.
Upper airway deposition — Metered dose inhalers (MDIs) tend to spray out medication more quickly than the patient can inhale. In addition, some patients do not inhale long enough after actuation of the device. As a result, a substantial amount of the medication is deposited in the back of the throat or on the tongue. Oropharyngeal deposition results in inefficient medication delivery and, with inhaled glucocorticoids, may cause hoarseness and thrush. It has been estimated that, in most patients, only about 10 percent of the dose reaches the lungs, while 80 percent remains in the oropharynx, although this varies depending on the preparation and delivery device [4,39,40,81-83].
Use of hydrofluoroalkane (HFA) MDIs may diminish oropharyngeal deposition as they tend to deliver a greater proportion of the actuated dose to the airways in the lungs and less to the oropharynx compared with chlorofluorocarbon (CFC) MDIs [39-41,82,84].
Another way to address this problem is to add a spacer device or valved holding chamber (VHC), which can decrease the oral deposition of medicine [4,67]. In a study comparing HFA and CFC formulations of beclomethasone with and without a VHC or large volume spacer, the VHC and spacer decreased oropharyngeal deposition from approximately 80 to 20 percent [41]. (See 'Spacers and holding chambers' above.)
Actuation-inhalation coordination — The other major cause of inefficient delivery of inhaled medications is lack of coordination between actuation and inhalation. The use of a VHC allows the patient to sequentially activate the inhaler into the chamber and then inhale the medication. In addition, dry powder inhalers (DPIs) that contain the medication in the form of a powder are breath actuated. The force of the patient's inhalation draws the powder into the lungs (picture 2) [53,72]. (See "Delivery of inhaled medication in adults", section on 'Dry powder inhalers (DPI)'.)
Insufficient breath-hold — The usual advice is for a 5 to 10 second breath-hold at the end of inhalation from either a pMDI or a DPI. In support of this recommendation, a study examining the effect of breath-hold on drug delivery from HFA pMDIs containing beclomethasone found that lung deposition was reduced by 16 percent with a 1 second versus a 10 second breath-hold [41].
Poor adherence to inhaler use — Lack of adherence to the prescribed therapy is more prevalent among patients with asthma or COPD compared with patients with other chronic diseases [85]. In patients with asthma or COPD, nonadherence rates to inhaled medications have been reported in as high as 50 to 80 percent [15,16]. A variety of factors, both unintentional and intentional, contribute to poor adherence by patients [15,86]. The Ascertaining Barriers to Compliance taxonomy identifies lack of adherence to either failure to initiate therapy; poor implementation due to infrequent use, incorrect inhaler technique or incorrect dose; or lack of persistence leading to early discontinuation after initiation [87]. This classification helps to identify possible reasons for nonadherence among patients and adopt an individualized approach to address them more effectively.
Nonadherence to inhaled therapies diminishes symptom control in patients with asthma or COPD leading to an increase in acute exacerbations and hospitalizations, unnecessary escalation of treatment, and greater morbidity and mortality [85]. Assessment of adherence is complex. Measures of adherence that were used in the past, such as patient self-reports or canister weighing, tend to overestimate inhaler use [88,89]. Introduction of electronic monitoring devices ("Smart Inhalers") allows collection of real-time and objective data on inhaler use that reliably detects nonadherence by patients [90], but several issues must be resolved before their use can be implemented in routine clinical practice [91]. Interventions to improve adherence with inhaled therapy have a positive impact on clinical outcomes of patients. Achieving good (>80 percent) adherence with inhaler use is associated with significant reductions in health care utilization (less exacerbations, hospitalizations, and emergency department visits), improvements in lung function and quality of life, and decrease in the economic and societal impact of asthma and COPD [16,92,93].
TEACHING INHALER USE SKILLS — The National Asthma Education Program (NAEP) recommends that patients be taught inhaler use in the following manner [94]:
●The clinician should first demonstrate the steps on the checklist.
●The patient then practices in front of the clinician so that errors may be corrected.
●The patient's technique should be evaluated periodically and corrections made as necessary.
●Patients should be positively reinforced for correct inhaler technique. Instructions should be reviewed and repeated over time to reinforce the correct inhaler technique [95].
At follow-up visits, the best way to assess if a patient uses the inhaler correctly is to observe the patient. There are a number of published checklists or criteria for correct use of the various types of inhalers (table 2 and table 3 and table 4 and table 5) [3,4,94,96]. (See "Patient education: How to use your metered dose inhaler (adults) (The Basics)" and "Patient education: How to use your dry powder inhaler (adults) (The Basics)" and "Patient education: How to use your soft mist inhaler (adults) (The Basics)" and "Patient education: Inhaler techniques in adults (Beyond the Basics)".)
pMDI technique — Important teaching points to emphasize regarding use of pMDI devices include shaking the pMDI before each actuation to ensure consistency of dosing from one actuation to the next and priming the pMDI (wasting four doses, depending on the specific device) before initial use and if it has not been used in two weeks or longer [97-101].
For administration technique for a specific inhaler, refer to the package insert provided by the manufacturer. The following basic steps for using a pMDI are provided in the table and patient information handout (table 2). (See "Patient education: How to use your metered dose inhaler (adults) (The Basics)".)
pMDI inhalers must be cleaned on a regular basis to prevent medication build up and blockages. Most manufacturers recommend cleaning the mouthpiece at least once per week. To clean the pMDI:
●Remove the medication canister and cap from the mouthpiece. Do not wash the canister or immerse it in water.
●Clean the top and bottom of the plastic mouthpiece by running warm tap water through them for 30 to 60 seconds.
●Shake off excess water and allow the mouthpiece to dry completely (overnight is recommended).
●Replace the canister in the mouthpiece when dry.
●Release one puff from the inhaler into the room away from the patient’s face.
●Replace the mouthpiece cover.
pMDI technique with spacer/chamber — Spacers and valved holding chambers are accessory devices that reduce oropharyngeal deposition of pMDI-delivered drug, improve distal delivery, and minimize the importance of hand-breath coordination. New spacer/chamber devices may have a static charge on the inside surface and thus be less effective when it is new compared with after use or washing [102-104]. Washing the device with dishwashing detergent prior to initial use and then allowing it to air dry eliminates this static charge [105,106].
For a specific spacer/chamber, refer to the package insert provided by the manufacturer. The general technique for using a pMDI with spacer or valved holding chamber is detailed in the table and patient information handout (table 3) [66,107]. (See "Patient education: How to use your metered dose inhaler (adults) (The Basics)", section on 'How do I use an inhaler with a spacer?'.)
Discharging multiple doses into the chamber prior to a single inhalation will markedly reduce the amount of respirable drug available compared with individual actuation-inhalation cycles, so this practice should be discouraged [77,108,109].
Although the powder residue that is deposited on the wall of the chamber is not harmful, the spacer/chamber should be cleaned periodically, approximately every one to two weeks when the spacer/chamber is used daily. Wash the spacer/chamber with warm water and dilute dishwashing detergent. Washing with water alone causes an electrostatic charge to develop, reducing the effectiveness of the spacer [105,106]. After washing, air dry the spacer/chamber before the next use.
DPI technique — There are many different proprietary dry powder inhaler (DPI) devices, each of which load the initial dose differently. For a specific inhaler, refer to the package insert provided by the manufacturer. The basic steps for using a DPI are provided in the table and the patient information handout (table 4) [66,107]. (See "Patient education: How to use your dry powder inhaler (adults) (The Basics)".)
DPIs come in two main types (picture 2):
●Multiple-dose devices, which usually contain enough doses for one month (eg, Handihaler, Diskus, Flexhaler, Ellipta, Pressair, Respi-Click, Digihaler). Among the multiple-dose devices, the method for moving the medication containing powder into the holding chamber is either depressing a lever, opening the cap, or twisting a part of the canister. The RespiClick and Digihaler devices resemble the pMDI in appearance.
●Single-dose devices (picture 2) (eg, tiotropium [Spiriva Handihaler], insulin [Afrezza], levodopa [Inbrija], tobramycin [Tobi PodHaler], mannitol [Bronchitol], treprostinil [Tyvaso]), require placement of a capsule or a cartridge in the device immediately before each treatment. DPI capsules should NOT be swallowed.
Patients will need instructions for and demonstration of the correct use of the specific device they are prescribed. The key points to emphasize are storing the DPI device at room temperature in a dry place, inhaling the medication forcefully and deeply, and not exhaling into the canister [48,49,110-112]. The humid exhaled air can cause the powder to clump, impairing aerosolization and reducing drug delivery to the airways.
The delivery systems and use of inhaled insulin for diabetes and inhaled tobramycin powder for cystic fibrosis are discussed separately. (See "Inhaled insulin therapy in diabetes mellitus" and "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Inhaled tobramycin'.)
DPIs should not be washed with soap and water, as this can cause the medication to clump. The mouthpiece can be cleaned with a dry cloth as needed.
The In-Check DIAL is a hand-held device to measure inspiratory flow. It is intended to accurately simulate the resistance of a variety of DPIs to enable clinicians to train patients for the proper inspiratory technique, considering force and flow, to achieve optimal deposition in the lungs. Whether or not the use of this device improves patient technique for the use of inhalers is yet to be determined [113-115].
Digihalers (eg, ProAir [albuterol], ArmonAir [fluticasone], AirDuo [fluticasone-salmeterol]) are DPIs with built-in sensors that provide objective data about when the inhaler is used and what inspiratory flow the patient generated. Wireless technology sends the information to the companion mobile app. The mobile app also reminds patients to check their dose counter.
Soft mist inhaler technique — Soft mist inhalers (SMI) include the Combivent Respimat, Spiriva Respimat, Striverdi Respimat, and Stiolto Respimat [116]. These inhalers all use the same Respimat device (picture 3); the basic steps for using an SMI are provided in the table and the patient information handout, as well as the package insert (table 5). (See "Patient education: How to use your soft mist inhaler (adults) (The Basics)".)
Notably, the recommended dose of Combivent is 1 inhalation four times daily, whereas for Spiriva, Striverdi, and Stiolto, 2 puffs once daily are recommended. The SMI does not need to be shaken; priming is done by twisting the clear plastic base before each dose. If the clear plastic base springs back after turning, it was probably not turned until it clicked. When the patient puts their lips on the mouthpiece, the device should be horizontal and pointed towards the pharynx, not the roof of the mouth. The patient's lips should not cover the air vents on the side of the mouthpiece.
SMIs have an indicator on the side that shows the number of inhalations remaining. When the SMI is empty, the clear base will no longer turn. SMIs should be cleaned once per week by wiping the mouthpiece inside and out with a clean, damp cloth. The SMI can be used with a spacer or VHC [63,117].
Determining when an inhaler device is empty — It is important for the patient to be able to determine when an pMDI canister is empty. All pMDIs are now manufactured with integrated dose counters [118]. This has made obsolete methods that were recommended in the past [119,120]. (See "Patient education: Inhaler techniques in adults (Beyond the Basics)".)
DPI devices have counters that display the number of puffs remaining or use individual capsules or cartridges that can be counted. SMIs have integrated dose counters. Patients should be instructed to observe the dose counter and to replace the inhaler as indicated.
MECHANICALLY VENTILATED PATIENTS — The administration of inhaled medications to mechanically ventilated patients requires special attention because of the propensity for deposition of the medication on ventilator tubing and the endotracheal tube. The methods for delivering inhaled medications to mechanically ventilated patients are discussed separately. (See "Delivery of inhaled medication in adults", section on 'Mechanically ventilated patients'.)
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: Inhaler techniques in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Inhaler devices – Inhaler devices are used to deliver a variety of inhaled medications, most commonly beta-agonists, anticholinergics, and glucocorticoids. Three main types of inhaler devices are available, the pressurized metered dose inhaler (pMDI) (picture 1), the dry powder inhaler (DPI) (picture 2), and the soft mist inhaler (SMI) (picture 3). (See 'Types of inhaler devices' above.)
●Common problems with inhaler devices – Common problems with inhaler usage are deposition of medication in the oropharynx, poor coordination of actuation and inhalation, and insufficient breath-hold after inhalation. Correct technique for using inhaler devices delivers the medication to the airways of the lung with minimal oropharyngeal deposition, leading to better airway responses. Furthermore, poor adherence with inhaler use compromises the effectiveness of inhaled therapies in patients with asthma and COPD.
(See 'Common problems with inhaler devices' above.)
●Strategies to improve inhaled drug delivery – For patients who have difficulty with proper pMDI technique and for those who are using glucocorticoid-containing pMDIs, use of a spacer device or valved holding chamber reduces oropharyngeal deposition and improves coordination of actuation and inhalation. DPI and SMI inhalers are additional methods to address actuation-inhalation problems. (See 'Actuation-inhalation coordination' above.)
●pMDI technique – The basic steps for using a pMDI are provided in the tables (table 2 and table 3) and in the Patient education handout. (See "Patient education: How to use your metered dose inhaler (adults) (The Basics)".)
●DPI and SMI technique – The basic steps for using a DPI or an SMI are provided in the tables (table 4 and table 5) and also in the Patient education handouts. (See "Patient education: How to use your dry powder inhaler (adults) (The Basics)" and "Patient education: How to use your soft mist inhaler (adults) (The Basics)".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William Bailey, MD, who contributed to earlier versions of this topic review.
7 : Knowledge of and technique for using inhalation devices among asthma patients and COPD patients.
12 : Inhaler mishandling remains common in real life and is associated with reduced disease control.
71 : In vitro evaluation of nonconventional accessory devices for pressurized metered-dose inhalers.
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