Controller Inhalers: Overview of Devices, Instructions for Use, Errors, and Interventions to Improve Technique

Abstract

Inadequate inhaler technique in persistent asthma is frequently reported. However, there is little consensus on inhaler checklists, and critical elements of technique are not uniformly described. In addition, inhaler error rates and risk factors for poor technique are variable across studies. This Clinical Commentary Review summarizes the literature on inhaler design, use, and interventions to improve technique. Our aim is to help clinicians identify patients with poor inhaler technique, recognize the most important errors, and correct technique using evidence-based interventions.

INTRODUCTION

Asthma is a serious chronic disease affecting one in twelve Americans.¹ For those with persistent asthma, the use of a controller inhaler improves symptoms and lung function, and decreases the need for systemic corticosteroids and emergency department visits. Despite advances in care, asthma exacerbation prevalence in the United States appears to be increasing.¹ It is estimated that over one-third of children and one-half of adults with asthma have uncontrolled disease.² Poorly-controlled asthma confers higher morbidity and mortality, and contributes disproportionately to high healthcare costs related to asthma. Inhalers providing both controller and reliever medications comprise essential delivery devices. However, inhaler technique is complex, involves many steps, and has often been observed to be inadequate.^3–6 Inhaler misuse is among the most important modifiable risk factors for uncontrolled asthma and can be corrected in a single clinic visit. Therefore, ensuring proper inhaler technique is an essential component of routine asthma management.

Herein we provide an overview of inhaler devices and checklists with a focus on controller inhalers and their accessories. We then discuss the research on inhaler errors. We conclude with a summary of interventions to improve technique. We do not cover atopy, environmental exposures, adherence, or other risk factors for uncontrolled asthma. Side effects of medications used in inhalers are outside the scope of this review.

INHALER DEVICES

Inhaled medication, delivered to the lungs with minimal systemic absorption, represented a major advancement in the treatment of chronic lung diseases, including asthma. This mode of delivery presented a new challenge for pharmaceutical companies, clinicians, and patients. Inhalation requires the use of a complex device, and demands user coordination and dexterity for effective delivery. Controller inhalers are available as metered dose inhalers (MDI) and dry powder inhalers (DPI). Both types are FDA-approved for long-term asthma control for patients four years of age and older, and high-quality randomized controlled trials have shown equivalent efficacy.⁷ Some controller inhalers are also available in nebulizer form, but nebulized delivery currently has little role in long-term asthma control in older children and adults.

The first pressurized MDI was introduced in 1956, comprised of a pressurized canister containing drug and propellant, a metering valve and stem, and an actuator (Figure 1). A major development in MDI design was the transition from chlorofluorocarbon (CFC) to hydrofluoroalkane (HFA) propellant in the late 1980s.⁸ CFC canisters contained drug in suspension with propellant, whereas some modern HFA canisters have drug and propellant in solution, offering several advantages over its predecessor. Drug in suspension does not dissolve and therefore requires shaking prior to use, whereas a solution is a homogeneous mixture and does not require shaking. Additionally, the shaking of a device containing drug in suspension does not resuspend drug collected in the metering apparatus. This results in the first actuation delivering less medication than successive actuations.⁹ Solution-based devices avoid this problem. Finally, actuated drug in solution produces a smaller particle size (i.e. extrafine), resulting in greater lung deposition^10,11 and better disease outcomes.¹² Table 1 lists some common HFA inhalers in suspension versus solution and the corresponding particle sizes.

Figure 1. Components of a metered dose inhaler (MDI).

Schematic of an MDI used with permission from the American Thoracic Society and OurDesigns, Inc.

Table 1.

Formulations of some HFA (hydrofluoroalkane) controller inhalers.

Inhaler	Type	Formulation	Particle Size
Beclomethasone dipropionate (Qvar)	ICS	Solution	Extrafine
Ciclesonide (Alvesco)	ICS	Solution	Extrafine
Fluticasone propionate (Flovent)	ICS	Suspension	Standard
Budesonide and formoterol fumarate dihydrate (Symbicort)	ICS/LABA	Suspension	Standard
Fluticasone propionate and salmeterol (Advair HFA)	ICS/LABA	Suspension	Standard
Mometasone furoate and formoterol fumarate dihydrate (Dulera)	ICS/LABA	Suspension	Standard

Modern DPIs arrived later, first reaching market in 2006. DPIs are an alternative design delivering powder to the lungs via self-actuation, obviating the need to coordinate actuation and inhalation. DPIs consist of a chamber for holding drug powder, a dispersion apparatus, and a mouthpiece for inhalation (Figure 2). DPIs are more flow-dependent than MDIs, with most requiring forceful inhalation for maximum efficacy.^13,14 As a result, DPIs are not recommended for children younger than four years due to insufficient inspiratory flow in this age group,¹⁵ and may not be appropriate for use in the elderly, the cognitively-impaired, or those with chronic obstruction pulmonary disease (COPD).¹⁶

Figure 2. Components of a dry powder inhaler (DPI).

A) Schematic of a Diskus^® DPI, and B) Schematic of a Diskhaler^®. Images used with permission from asthma.ca.

In the early 1990s, patent filings for MDIs and DPIs grew rapidly, introducing most of the inhalers available today.⁸ The removal of CFC inhalers resulted in fewer inexpensive generic inhalers.¹⁷ Meanwhile, new inhaled corticosteroids (ICS), long-acting beta₂-agonists (LABA), anticholinergics, and combination therapies were developed for use.⁸ The number of devices on the market increased dramatically, and many became highly profitable,⁸ while prices steadily increased. In the past several years, the first generic controller inhalers were released to market. At the same time, patent filings in the inhaler industry remain high, as manufacturers propose more effective or user-friendly inhaler designs. Thus, with the growing number of brands with ever-new designs, it is no wonder that it is difficult for patients and clinicians to keep up with using devices and teaching correct use, respectively.

SPACERS AND FACE MASKS

Spacers and valved holding chambers (VHC) are attachments for MDIs. A VHC is a spacer with a one-way valve to prevent accidental exhalation into the device and loss of actuated drug. The National Asthma Education and Prevention Program Expert Panel Report (EPR) 3 recommends VHCs over simple spacers due to more clinical trials showing efficacy.¹⁵ No specific MDI-spacer combination is FDA-approved.

The EPR 3¹⁵ and the Global Initiative for Asthma (GINA)¹⁸ recommend MDIs with spacers for children four and five years of age or younger, respectively, and for older individuals who cannot perform correct MDI technique. An exception is for breath-actuated MDIs, which are not designed to be used with spacers. As young children can only adequately perform tidal breathing and not breath holding, GINA¹⁸ recommends five-to-ten breaths from the spacer, per actuation, for this age group. Spacers offer some advantages. After actuation, particles remain in the spacer for several seconds during which inhalation can take place.¹⁹ As a result, spacers may “correct” for poor coordination of actuation and inhalation.^20,21 Coordination is still required while using a spacer, as a more than two-second delay between actuation and inhalation decreases drug delivery.²² Also, spacers trap large particles, while smaller, respirable particles are inhaled.²³ Finally, spacers slow particles, possibly allowing more medication to reach the lungs rather than deposit in the oropharynx. However, a real-life clinical benefit of spacers has not been conclusively demonstrated. In 2017, Guilbert and colleagues²⁴ assessed asthma outcomes in adolescent and adult asthma patients using MDIs with or without spacers. Spacers did not improve patients’ asthma exacerbation rates with either standard or extrafine-particle HFA inhalers. Notably, because extrafine-particle inhalers release smaller and lower-velocity particles, spacers may offer less benefit.^25–28

Spacers may increase or decrease drug delivery depending on its size and shape and corresponding MDI.^14,29 Spacer material also affects drug delivery. Most spacers are constructed of plastic, which accrue electrostatic charge and attract drug particles. An exception is the Nebuchamber, a metal spacer. Plastic spacers that are pre-washed prior to initial use have lower static voltage³⁰ and allow for better drug delivery. ^31–33 The EPR 3 recommends rinsing plastic VHCs once a month.¹⁵ “Priming” a spacer by actuating into a spacer several times before inhalation may also enhance medication delivery,^{30,32,34–36} but is wasteful of medication.

Young children are often unable to use spacers’ mouthpieces, and the EPR 3 recommends VHCs with face masks for all children under four years.¹⁵ However, newborns³⁷ and some infants under two years³⁸ may be unable to generate enough inspiratory pressure to open the spacer valves, so clinicians should observe children using the devices correctly. Alternatives in young children are to use simple spacers or nebulizers. Face masks result in less lung deposition compared to spacers,³⁹ likely because nasal inhalation traps particles. Therefore, children should be transitioned to spacers when able.

INHALER CHECKLISTS

Inhaler checklists, lists of steps that must be taken to inhale a medication properly, are provided by inhaler manufacturers and committee guidelines. Information for patients on inhaler use is made available by the American Thoracic Society, the Center for Disease Control, the American Academy of Allergy, Asthma & Immunology, and other organizations. A review of these manufacturer pamphlets and materials yields a list of some common checklist steps for MDIs and DPIs, listed in Table 2. Basheti and colleagues⁵² describe the history of checklists in a review, noting that checklists were originally validated in 1982 and were later shown to be effective training tools for improving asthma control. There is considerable variation in checklists, and study investigators derive checklists from multiple sources including manufacturers’ leaflets, committee guidelines, and previous studies.⁵² Not all checklist steps are generated from research demonstrating their importance for drug deposition or asthma control. The grading of inhaler technique based on checklists is not standardized.

Table 2.

Common MDI and DPI inhaler checklists derived from committee guidelines and manufacturers’ instructions.

MDI technique*	DPI technique
Expose mouthpiece/remove cap15,40–47	Expose mouthpiece/remove cap48–50
Canister shaken (if medication in suspension)15,40–42,44–46	Cock the trigger or twist base (prepare medication)48–50
If first use or if several days have elapsed since last use, prime inhaler by releasing actuations into the air43–46	Inhaler is not tilted, tipped, or shaken after preparing dose49
Hold inhaler upright40–47	Exhale before inhalation48–50
Exhale before actuating inhaler15,40–47	Does not exhale into device48,50
Actuate inhaler at the start of inhalation15,40–47	Hold inhaler horizontally while inhaling49
Inhalation takes place over 3–5 seconds, or slow and deep inhalation40–47	Inhale quickly and deeply48–50
Hold breath for 5–10 seconds15,40–47	Hold breath for 6–10 seconds49
Actuate only once per inhalation15,40–45,47	Replace cap/click shut48–50
If instructed to take a second puff, wait 15–30 seconds before second actuation15,40,44–46
Replace cap40,42–47

^*See validated checklist by Press et al.⁵¹ for a similar set of instructions for MDIs with the use of a spacer.

INHALER ERRORS RATES

Inhaler errors are common, but research on error rates among asthma and COPD patients is inconsistent. Our group found that most patients in a cohort of adults with uncontrolled asthma had zero errors when graded with common checklist steps,⁵³ but prior reviews and meta-analyses suggest that around half of patients up to a large majority are error-prone.^3–6 Error rates for MDIs and DPIs are similar but may be slightly higher for MDIs.^3,4 However, inter-study heterogeneity is high.^3,54 Mahon and colleagues⁵⁴ noted the lack of a standardized definition of correct inhaler technique, further complicated by a range of inhalers used across studies and a variety of means of assessing technique. Systematic reviews of error rates in children are similarly inconclusive.^4,43 Reviews have identified exhalation before inhalation and adequate breath hold as commonly failed steps.^3,4 The CRITIKAL study⁵⁶ assessed fourteen steps of technique, more than is assessed using common checklists, and additional frequent errors included improper head tilt and incorrect second dose preparation, timing, or inhalation.

Patient characteristics associated with technique in some studies are shown in Table 3. Barbara and colleagues⁵ found higher error rates in older adults in a systematic review. Other characteristics associated with poorer technique in some studies are female sex,^57–60 lower educational attainment and/or socioeconomic status,^{58,60,61,67–69} and COPD.⁷⁰ Lack of training in inhaler use^61,68,71 and the simultaneous use of MDIs and DPIs^70–72 predict higher error rates. In a review of studies in children,⁵⁵ asthma knowledge and self-efficacy were associated with better technique.^75–80 Research is conflicting on whether younger or older children have poorer technique.^55,81 Patients’ beliefs about the necessity of using an inhaler⁶⁰ and motivation to achieve asthma control⁷³ predict better technique, although inhaler preference is not associated with technique.^58,60,73,82 Importantly however, patients’ satisfaction with their inhalers is associated with inhaler adherence,⁸³ and self-reported adherence is positively correlated with maintenance of correct inhaler technique over time.⁷⁴ Notably, confidence in technique does not reflect an ability to demonstrate correct technique.⁷³ In the pediatric population, inhaler self-management is an important ability for school-age patients, and similarly, parents’ and children’s confidence in inhaler self-carry skills are poorly predictive of readiness to self-carry.⁸⁴ In one study of schoolchildren, parents and children identified asthma knowledge, inhaler characteristics (e.g. portability), and easy access to inhalers as facilitating inhaler carry and use.⁸⁵

Table 3.

Patient characteristics associated with poor technique.

Characteristic
Female57–60
Elderly5
Poorly controlled disease61–66
Low income and/or socioeconomic status58,60,61,67–69
COPD70
Lack of prior inhaler training61,68,71
Simultaneous use of MDIs and DPIs70–72
Lack of belief in the necessity of using an inhaler60
Low motivation to achieve disease control73
Lack of adherence with inhaler over time74
Less asthma knowledge*55
Less self-efficacy*55

^*in children

CRITICAL INHALER ERRORS

Poor inhaler technique is associated with worse asthma (and COPD) control in children^86,87 and adults.^62,88 Incorrect use of rescue inhalers may also lead to poor symptom control and overuse of controller medication.⁸⁹ Critical errors are those errors thought to affect drug deposition and/or disease control, and therefore are considered to be especially important in patients with poor symptom control. Unfortunately, the definition of a critical error varies considerably between studies, and the errors labeled as critical often differ and usually are not based on empirical data.⁶² Some earlier studies used empiric methods to evaluate the effect of inhaler technique steps on lung deposition. Then in 2017, the CRITIKAL study by Price and colleagues⁵⁶ was the first to identify associations between checklist steps and disease control. Tables 4 and 5 list checklist steps that are associated with drug deposition and/or disease control based on a search of the relevant literature.

Table 4.

Studies evaluating critical inhaler steps for MDIs as defined by lung deposition or disease control

Preparatory step	Affects drug delivery	Affects symptoms or disease control
Inhaler step
Expose mouthpiece/remove cap
Cannister shaken (if medication in suspension)	Everard (1995)9
If first use or if several days have elapsed since last use, prime inhaler by releasing actuations into the air	Dewsbury (1996)30
	Kenyon (1998)32
	Janssens (1999)36
	Mitchell (2007)35
Head tilted so that chin is slightly upward
Hold inhaler upright		Price (2017)56*
Exhale before actuating inhaler	Hindle (1993)90
Does not exhale into inhaler		Price (2017)56*
Actuate inhaler at the start of inhalation	Newman (1991)91	Price (2017)56
	Farr (1995)92
Inhalation takes place over 3–5 seconds, or slow and deep inhalation		Al-Showair (2007)102
	Newman (1980)93
	Newman (1981)94
	Dolovich (1981)95
	Newman (1982)96
	Lawford (1983)97
	Hindle (1993)90
	Newman (1995)98
	Pavia (1995)99
	Farr (1995)92
	Heyder (2004)100
	Tomlinson (2005)101
Hold breath for 5–10 seconds	Newman (1980)93
	Newman (1982)96
	Hindle (1993)90
Correct second dose preparation and timing		Price (2017)56†
Replace cap after use

^*study combined the errors “exhaled into the inhaler or did not hold inhaler upright”

^†study combined the errors “lack of device knowledge or incorrect second dose preparation, timing or inhalation”

Table 5.

Studies evaluating critical inhaler steps for DPIs as defined by lung deposition or disease control

Inhaler step	Affects drug delivery	Affects symptoms or disease control
Expose mouthpiece/remove cap		Price (2017)56
Cock the trigger or twists base (prepares medication)	Meakin (1995)103
Inhaler is not tilted, tipped, or shaken after preparing dose		Price (2017)56
Head tilted so that chin is slightly upward
Seal lips around mouthpiece		Price (2017)56
Hold inhaler horizontally while inhaling	Kondo (2017)104
Exhale before inhalation
Does not exhale into device	Meakin (1995)103
	Holmes (2015)105
	Sulaiman (2017)106
Hold inhaler horizontally while inhaling
Inhale quickly and deeply	Pedersen (1986)107	Price (2017)56
	Pederson (1990)108
	Engel (1992)109
	Newman (1991)110
	Borgström (1994)111
	Pitcairn (1994)112
	Palander (2000)113
	Sulaiman (2017)106
	Olsson (1996)114
Hold breath for 6–10 seconds	Horváth (2017)115
Replace cap/click shut

PROVIDER TEACHING OF INHALER TECHNIQUE

Committee guidelines recommend that providers review and evaluate inhaler technique at each clinic visit.^15,18 This recommendation is supported by research showing that inhaler technique proficiency can decline over an eight-week period,¹¹⁶ and that inhaler technique can be corrected in minutes.^117–119 Press and colleagues have shown in several studies that the teach-to-goal method, wherein patients repeatedly demonstrate technique until mastery is achieved, is effective.^51,120–123 However, many clinicians perceive a lack of time in clinic, with one study showing that half of pediatric providers view time as a barrier to routinely reviewing inhaler technique.¹²⁴ In this study, two-thirds of providers reported only assessing technique when patients’ asthma was uncontrolled. Many providers, including physicians, do not know or cannot demonstrate correct technique.^125–128

Clinicians can improve patients’ inhaler technique, including in young children¹²⁹ and older adults.¹³⁰ Physical demonstration using an inhaler is the standard intervention for improving technique, and is effective.¹⁸ Clinicians should observe patients demonstrating their inhaler technique, and this may be particularly useful in children, the elderly, the cognitively impaired, and others at risk for inhaler errors.¹⁵ One study showed that the elderly had persistence of poor technique even after training,¹³¹ highlighting the need for repetitive self-demonstration of inhaler use in these patients. Interventions tend to improve technique after the intervention and at follow-up, and consistent teaching over time can improve technique incrementally.^55,116 In a Cochrane Review of randomized controlled trials, Normansell and colleagues¹³² examined interventions to improve technique in children and adults with asthma. Most interventions successfully improved technique, including face-to-face verbal training sessions with or without the use of a demonstration inhaler, the use of multimedia (e.g. an educational video), and the use of training devices that provides visual or audio feedback to the patient. Conclusions in the Cochrane Review were limited by variable interventions and outcome measures across studies. Table 6 lists interventions shown to improve inhaler technique in some studies.

Table 6.

Interventions to improve technique

Intervention
Face-to-face teaching129,133–138
Teach-to-goal method51,120–123
Use of multimedia (e.g. an instructional video or computer program)134,139–141
Use of a training device that provides visual or audio feedback102,142
Repetitive teaching over time55,116

TECHNOLOGY-BASED TECHNIQUE EVALUATION AND SKILLS EDUCATION

Technology offers innovative approaches for evaluating and improving inhaler technique. Telemedicine can provide effective face-to-face training.^133,143,144 Locke and colleagues¹⁴⁴ used the teach-to-goal method to provide inhaler instruction via video telemedicine. Patients demonstrated improvement in technique for MDIs, DPIs, and soft mist inhalers, and this improvement persisted for two months after the first session. These findings suggest that telemedicine has the potential to improve asthma care in patients for whom distance or cost preclude routine clinic visits, and thereby target patients who are disproportionately affected by asthma. However, despite evidence of benefit, telemedicine for subspecialty care is still uncommon.¹⁴⁵

Some electronic devices have been developed to enable providers and patients to evaluate adherence and technique during routine inhaler use. Such devices may minimize the observer bias present in face-to-face assessment of technique. Costello and colleagues developed an inhaler compliance assessment (INCA) biofeedback device that attaches to DPIs and provides feedback to providers on adherence and steps of technique,^146–148 and has been shown to improve adherence, technique, and outcomes.^147,148 Notably, the device is effective in patients with severe, uncontrolled asthma.¹⁴⁷ Other devices are available for use with MDIs, and some devices provide real-time feedback to patients.¹⁴⁹ Despite the promising applications of electronic devices, their usage is not widespread. More research is needed to assess the benefits of electronic devices in community settings.

CONCLUSIONS

Considerable advances have been made in the treatment of asthma, but poor inhaler technique remains an intractable and consequential problem. Research has generally been limited by inconsistency in devices studied, inhaler checklists used, and definitions of adequate technique. With many different designs constantly evolving, and new devices being marketed, it is difficult to develop checklists and difficult for patients and clinicians to keep up with the appropriate techniques. Furthermore, while many studies have assessed lung deposition as an indicator of proper inhaler technique, few studies have examined the effect of technique on asthma control. In addition to refining inhaler design and clarifying the most important checklist steps, future research must continue to address the challenges to improving technique. Sequential educational sessions to reinforce correct technique is likely effective, but is understudied,¹⁵⁰ and may be perceived as impractical in a busy clinical environment. Ongoing research in inhaler design and use, and in durable educational interventions aimed at the most vulnerable patients, is needed to ensure optimal drug delivery of inhaled medication.

Abbreviations used

CFC

Chlorofluorocarbon

COPD

Chronic obstructive pulmonary disease

DPI

Dry powder inhaler

EPR

Expert Panel Report

GINA

Global Initiative for Asthma

HFA

Hydrofluoroalkane

ICS

Inhaled corticosteroid

INCA

Inhaler compliance assessment

LABA

Long-acting beta₂-agonist

MDI

Metered dose inhaler

VHC

Valved holding chamber