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Advances in Inhaler Technology: Helping Patients Increase Adherence

Inhaler Use Problems – Where Are We Now?

Inhaler devices are used to deliver the majority of medications used in asthma and chronic obstructive pulmonary disease (COPD). However, despite the widespread availability of effective inhaler-based treatment options, disease control in asthma and COPD often remains suboptimal.1 This is often due, at least in part, to difficulties with adherence to prescribed treatment regimens and the complex steps required for effective inhaler use. Ideally, patients will adhere to their prescribed inhaler therapies at least 80% of the time; however, in real-life studies, adherence rates in asthma and COPD have ranged from 8 to 73%, and high rates of inhaler technique error have been observed.2 Lack of adherence can lead to serious health consequences. Data from a post-hoc analysis of the TOwards a Revolution in COPD Health (TORCH) trial found that patients with high adherence rates (>80%) had significantly lower mortality rates than patients with low adherence rates (11.3% vs 26.4%).3 In patients with asthma, poor adherence is considered an important risk factor for increased asthma exacerbations.4

Non-adherence in asthma and COPD is often multifactorial, and may take different forms.2 Poor adherence to inhaled therapy can be intentional or unintentional.4,5 Patients may believe that a particular medication is unnecessary or have concerns about side effects that lead them to avoid using the medication. Medication costs, social stigma, unrealistic expectations of treatment, and dissatisfaction with healthcare providers can also contribute to intentional non-adherence. In the case of unintentional non-adherence, patients may simply forget to take their medications as prescribed, or misunderstand directions for use. Other barriers to adherence may arise from the medications themselves. Patients may have difficulties with their specific inhaler device due to age or comorbidity or find the regimen burdensome due to the number of doses per day or different inhalers required.

Different medication classes serve different purposes in asthma and COPD treatment. Some classes, like short-acting beta agonists (SABAs) and short-acting muscarinic antagonists (SAMAs), are used for immediate relief of symptoms or “rescue therapy” (now termed “quick relief therapy”), while others, such as long-acting beta agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and inhaled corticosteroids (ICS), are used as maintenance/controller medications to decrease airway inflammation and facilitate long-term disease control.4,6 One of the most common types of non-adherence in both asthma and COPD is the overuse of rescue/reliever medications, which is often coupled with the underuse of maintenance/controller medications.5 Studies have found that patients with asthma adhere to ICS medications only 47 to 57% of the time.7 In COPD, one study found that adherence rates to a combination controller product were less than 23%.8 Patients are more likely to feel immediate symptom relief with short-acting quick reliever medications.9 This may lead them to rely on these medications more than their controller medications (which may not have immediately noticeable effects). Patients with mild asthma are especially prone to overuse of reliever medications, because symptoms are likely to be mild and infrequent, and traditionally, guidelines have supported as-needed reliever treatments as monotherapy in these patients. However, asthma is a disease of chronic airway inflammation, and this inflammation is usually present even in patients with mild symptoms. Overreliance on reliever medications has been associated with poor outcomes in asthma, including increased exacerbations, increased hospital admissions, and death.

Errors in inhaler technique are common among patients with asthma and COPD. It is estimated that more than two-thirds of patients make at least one error when using an inhalation device.6 Poor inhaler technique is often seen in elderly patients, as well as patients with multiple inhalation devices and/or lack of previous education on inhaler technique. Patients are often unaware that they have problems with incorrect technique.4 Poor technique can lead to poor disease control, increased adverse events, and increased risks of exacerbation, hospitalization, emergency department visits, and oral corticosteroid use.4,6,10 Although new and improved inhaler devices have been developed with the hopes of overcoming the problem of poor technique, there has been little to no sustained improvement in patients’ ability to use their inhaler devices correctly.11 Inhaler technique training has been shown to improve patient competence in inhaled medication administration; however, this training is often overlooked, or performed with insufficient follow-up over the long term.11,12

The Importance of Individualizing Inhaler Therapy

Pharmacotherapy in asthma and COPD is highly individualized, with inhaler-based regimens tailored to fit the patient’s specific needs. Patients with asthma and COPD often require multiple medications to manage their disease state effectively. The 2019 update of the Global Initiative for Asthma (GINA) guideline recommends a personalized approach to asthma management, with different therapies recommended based on level of asthma control and risk for exacerbations or other adverse outcomes.4 A combination of reliever and controller medications is generally recommended over the use of reliever medications alone, even in patients with mild asthma. Pharmacologic therapy for COPD is also highly individualized, depending on the patient’s exacerbation risk and symptom severity.6 Recent updates to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline have introduced eosinophil count as a biomarker to assist with individualizing COPD therapy. Combination therapy is commonly recommended for COPD patients with severe disease or disease that is not controlled on monotherapy regimens. Initial combination therapy may be beneficial for patients who present with severe symptoms and frequent or severe exacerbations (ie, GOLD Group D patients). Specifically, LABA/LAMA combination therapy should be considered for Group D patients who are highly symptomatic (ie, COPD Assessment Test [CAT] score >20), and LABA/ICS combination therapy should be considered for Group D patients with eosinophil counts ≥300 cells/mcL. Additionally, patients who do not achieve adequate disease control on monotherapy may benefit from escalation to dual or even triple combination therapy with drugs from different classes.

Just as medication regimens in asthma and COPD are individualized, inhaler device selection must also be individualized, taking the patient’s ability and preference into account, as well as factors like access and cost.4,6 Of note, both GINA and COPD guidelines recommend assessing inhaler technique and adherence before changing therapy, as lack of response may be due to incorrect inhaler technique or poor adherence to the prescribed regimen. Therefore, in order to provide effective therapy for patients with COPD and asthma, it is essential to facilitate proper adherence by addressing patient-specific barriers and educating patients on proper inhaler technique.

Guideline Updates and Recommendations on Inhaled Therapies

GOLD Guideline Use in Practice and Updates for 2019

The GOLD guideline offers recommendations for medication management in COPD.6 However, clinical implementation of these recommendations has historically been poor.13 A retrospective study of Veterans Affairs prescribing from 2005 to 2010 found that only 19% of patients with COPD were treated according to the recommendations in the 2004 iteration of the GOLD guideline.14 Other retrospective studies have found that adherence to the 2011 and 2017 GOLD recommendations was approximately 36%.15,16 A recent study of prescribing at 2 outpatient primary care offices noted that the medication regimens used to manage COPD were heterogeneous, and frequently out of alignment with the GOLD guideline recommendations.17 In this study, only 42% of patients received any form of LAMA therapy; 62% of patients received a regimen that incorporated ICS, despite concerns that have been expressed about routine ICS use in this patient population.

Potential barriers to guideline adherence in COPD may include a lack of familiarity with GOLD guideline recommendations, as well as a lack of clarity in the guideline recommendations themselves.17 Prescribers may also have chosen to modify therapy outside of the guideline recommendations to address patient-specific symptoms and exacerbation rates.16 The 2017 iteration of the GOLD guideline relied on baseline disease severity/GOLD group to make recommendations for both initial and follow-up treatment.6 The 2019 update of the GOLD guideline presents modified algorithms for initial and follow-up pharmacologic management of COPD. Initial therapy recommendations are still based on the patient’s GOLD group at diagnosis; however, follow-up therapy recommendations only consider dyspnea symptoms, exacerbations, and the patient’s current therapeutic regimen. They do not take the patient’s baseline GOLD group status into account. This approach may be more helpful for individualizing treatment in patients with COPD who are already on maintenance medication. In most cases, these new algorithms recommend escalating therapy by adding a new agent from a different class. For example, in patients with insufficient control of exacerbations on LABA or LAMA monotherapy, the guideline recommends escalating to combination LABA/LAMA therapy, or combination LABA/ICS therapy if the patient has eosinophil counts ≥300 cells/mcL (or eosinophil counts ≥100 cells/mcL plus ≥2 moderate exacerbations or ≥1 hospitalization for COPD). De-escalation of ICS therapy should be considered for patients who contract pneumonia, ICS non-responders, and patients who did not have an appropriate indication for ICS originally.

2019 GINA Guideline Updates and Implementation Toolbox

Patients with asthma typically require medications for both as-needed symptom relief and long-term disease control. Recent updates to the GINA guideline emphasize the importance of controller therapy even in patients with mild asthma.4 These patients may not need a controller medication on a daily basis, but should still take a controller medication whenever therapy for immediate symptom relief is administered. Monotherapy with a SABA as needed is no longer recommended for adults and adolescents with mild asthma; instead, formoterol/ICS or SABA with ICS is recommended for reliever therapy. Of note, the only LABA/ICS combination recommended for quick relief use is formoterol/ICS. Formoterol has a more rapid onset of action than other LABAs (such as salmeterol), which allows it to be effective as quick relief therapy. Implementing this guideline change may be difficult if patients do not understand the purpose behind each component of their therapeutic regimen. Adherence to this therapeutic regimen may also be challenging if patients are not able to take both medications using a single inhaler device.

The GINA implementation toolbox offers some strategies to overcome barriers in asthma management and optimize inhaler-based therapy.18 In this document, common patient questions are answered, including those pertaining to the need for maintenance controller therapy. It is important to engage patients in empathetic discussions to determine any barriers to adherence, including forgetfulness, lack of confidence in inhaler technique, concerns about side effects, and perceived medication utility. Patients who have trouble remembering to take their maintenance medications may benefit from setting reminders, keeping their inhaler in a place where it is readily visible, or associating inhaler use with a regular habit (such as leaving for work). In order to ensure that patients use their inhalers correctly, the implementation toolbox recommends referring patients for a brief show-and-tell inhaler training with a pharmacist, nurse, asthma educator, or respiratory therapist. If these resources are unavailable, online video demonstrations of inhaler technique can also be useful.

Improving Inhaler Adherence

As discussed above, non-adherence in asthma and COPD is a complex problem that may arise from a number of different factors.4,5 Interventions to improve adherence should therefore be tailored to address the specific factors contributing to non-adherence. In order to identify these factors and understand the reasons behind a patient’s medication-taking behavior, it is important to engage patients in open, nonjudgmental discussions about their medication therapy.4 Asking questions in an empathetic manner and acknowledging that incomplete adherence often occurs can encourage patients to be more honest about their medication-taking behaviors.

Patients who are unintentionally non-adherent may benefit from strategies that focus on patient education, medication-taking routines/reminders, and regimen simplification.5 Patient education helps to clarify the role of each medication (ie, how and when each medication should be taken). Text messages and audiovisual medication reminders improve adherence to ICS therapy in the short term, and dose reminders, in combination with other interventions, increase medication adherence in COPD. However, the long-term benefits of reminder-based strategies are unknown. Patients may begin to suffer from “alert fatigue” if they receive frequent notifications, and health-related notifications may be lost among the other types of notifications that patients receive on their smartphones. Establishing a routine for medication administration may be useful for patients who struggle to remember their inhaler medications. Strategies may include keeping the medication in a visible location, integrating inhaler use into an established morning or evening routine, and carrying the controller medication on their person at all times. Finally, simplification of medication regimens may be helpful for increasing adherence. For example, in COPD, data have shown that adherence rates drop with each additional incremental dose per day, from 43% with once daily dosing to 37%, 30%, and 23% with twice daily, three times daily, and four times daily dosing, respectively.19 A number of fixed-dose combination inhalers are available for the management of asthma and COPD; using these combination inhalers may help to decrease the number of drugs and doses that must be taken each day. Another strategy for regimen simplification is ensuring that all inhaled medications require similar inhalation techniques. A study in patients with COPD found that patients who used multiple inhaler devices with similar inhalation techniques had fewer exacerbations and less SABA use than patients who used multiple inhaler devices with mixed inhalation techniques.20

Patients who are intentionally non-adherent may not benefit from the types of interventions discussed above, unless their beliefs regarding inhaler therapy are also addressed.5 Shared decision-making for medication/dose choice has been shown to improve patient adherence and outcomes in asthma.4 This approach involves eliciting the patient’s treatment preferences/goals, and discussing the risks and benefits of different treatment options with the patient to arrive at a mutually agreeable treatment plan.5 Motivational interviewing techniques may be useful to increase intrinsic motivation in patients who are ambivalent about making the behavioral changes required for inhaler adherence, although evidence from the literature is limited. One randomized controlled trial found that motivational interviewing was effective for increasing adherence in COPD as part of a multifactorial intervention.

Role of Digital Inhaler Systems

Digital inhaler systems may also have a role in facilitating and monitoring adherence to inhaler-based therapies. A number of digital inhaler systems that measure adherence and/or technique are currently available or in development.2 Most of these systems use external add-on devices; commercially available examples of these include Hailie (Adherium, NZ) and Propeller (Propeller Health, USA).2,21,22 These add-on devices attach to the patient’s inhaler and record information about medication usage (ie, date, time, number of puffs taken). The devices are paired with smartphone apps that allow patients to view their medication use data and receive reminders about missed doses. The data from these devices may be useful to facilitate discussions between patients and healthcare providers about inhaler usage. However, most add-on devices are limited in their ability to measure inhalation-related parameters and provide specific feedback on the patient’s inhalation technique.2 No add-on devices that measure inhalation-related parameters are commercially available at this time, although several of these devices have been developed and used in clinical trials. One example of such a device is the electronic inhaler compliance assessment (INCA) device.

In December 2018, the first “smart” inhaler, the ProAir Digihaler, was approved by the Food and Drug Administration (FDA).2 This albuterol inhaler uses integrated sensors to measure the dates and times of administered doses, as well as the peak inhalation flow and inhaled volume achieved during each use. These data are subsequently transmitted to the linked smartphone app; healthcare providers may discuss data with the patient, and use it to help patients improve inhaler technique. The ProAir Digihaler has initially been made available in a small number of health systems; a national launch of the product is anticipated in 2020.23 A Digihaler formulation of fluticasone/salmeterol was also approved in July 2019, with widespread commercial availability expected in 2020.24

Digital feedback on inhaler use may help encourage appropriate use and improve patient outcomes. In a pragmatic randomized controlled study of 495 asthma patients, a digital inhaler system was used to track SABA use.25 In the intervention arm, patients and their providers had access to SABA use data during the trial. These data were not accessible for patients who were assigned to the control arm. The mean number of daily SABA uses per person decreased more in the intervention arm (-0.41 uses per day vs -0.31 uses per day in the control arm; p < 0.001). Additionally, patients in the intervention arm had greater increases in the percentage of SABA-free days. Patients who had poor asthma control initially had greater improvements in Asthma Control Test scores when they had access to digital data. In 2018, an open label, single-arm study by Merchant and colleagues also examined the impact of a digital inhaler system.26 The system was used to record data on SABA and controller medication use in 224 asthma patients. Healthcare providers viewed this data and incorporated it into their clinical decision-making process. After this digital technology was implemented, the number of asthma-related emergency department visits per 100 patient-years significantly decreased, from 11.6 to 5.4 visits per 100 patient-years. Combined emergency department visits and hospitalization events also decreased, from 13.4 to 5.8 events per 100 patient-years. Mean SABA use decreased significantly (from 0.68 puffs/day to 0.16 puffs/day), and the controller-to-total medication ratio improved significantly, indicating that patients shifted away from reliever medication use and toward more consistent controller use. Electronic inhaler adherence monitoring has also been studied in children with uncontrolled asthma. In a randomized controlled trial of 90 patients aged 6 to 16 years, ICS adherence rates were higher among patients who received electronic adherence monitoring with reminders and clinician feedback (70% vs 49% with usual care).27 Asthma Control Questionnaire scores were not significantly different between groups at 12 months, but fewer hospital admissions were seen in the group that received electronic monitoring (0.0254 per 100 patient-days vs 0.129 per 100 patient-days).

Increased reliever medication use (as measured by digital inhaler systems) has been correlated with acute exacerbations.2 Therefore, digital inhaler data could potentially be used for the identification and early management of impending exacerbations, although more studies are required to confirm utility in this setting. A retrospective pre-post analysis of 39 patients with COPD and high healthcare utilization (defined as ≥1 hospitalization or emergency room visit in the year prior to enrollment) found that, when electronic inhaler monitoring was used as part of a disease management program, COPD-related healthcare utilization decreased from a mean of 3.4 visits per year to a mean of 2.3 visits per year.28 The electronic monitoring system identified patients who did not use their controller medications for 4 consecutive days, as well as patients who displayed increased quick relief inhaler use. These patients were contacted by providers, and engaged in open-ended conversation with the aim of encouraging adherence and detecting exacerbations in their early stages.

Pharmacist-Led Strategies for Improving Inhaler Use

Pharmacists can help ensure that patients are matched to an appropriate inhaler device, and facilitate adherence through inhaler technique training and education. Pharmacist interventions have been shown to increase adherence to inhaled therapies.12 For example, in a randomized, 3-month study of COPD patients, a protocol-based pharmacist intervention was associated with significant improvements in inhaler technique, maintenance medication adherence, and hospitalization rates when compared with usual care.29 It is important to note that a single education session is not sufficient to promote adherence and improve inhalation technique in the long term.12 Adherence and technique tend to fall off over time, so repeat assessment and education are crucial. Pharmacists dispensing inhaled medications should not assume that other healthcare providers are providing this routine education and assessment. Many healthcare professionals, including physicians, are not familiar enough with available inhaler devices to provide appropriately detailed education; thus, inhaler device education may be poorly taught in physicians’ offices, or overlooked due to perceived time constraints.11 One survey of pulmonologists found that only 54% of pulmonologists discuss inhaler device options with patients, and only 53% screen for physical or cognitive impairments that impact device choice.30 Only 43% were knowledgeable in teaching patients how to use inhalers.

Some pharmacist-led strategies have incorporated the use of digital inhaler systems. A randomized controlled trial examined the impact of a pharmacist-driven intervention on inhaler technique and adherence in asthma.31 The intervention in this trial incorporated the use of digital technology and personalized biofeedback. An INCA device was attached to the salmeterol/fluticasone maintenance inhaler devices of 152 adult patients. These patients were randomized to receive inhaler technique training informed by their INCA data (biofeedback group), inhaler technique training using a checklist to correct any observed errors (demonstration group), or usual care (control group). Training/education according to group assignment took place at the end of months 1, 2, and 6. The primary outcome measure was actual adherence, which considered both attempted adherence (ie, whether the patient attempted to take their medication at the correct time) and technique adherence (ie, whether critical errors in inhaler technique were made at the time of administration, as measured by INCA data). The biofeedback group had higher rates of actual adherence than the demonstration group during month 2 (62.8% vs 44.7%) and month 6 (60.8% vs 44.2%), although differences during month 6 were not statistically significant. Actual adherence rates in the biofeedback group were significantly better than those seen in the control group at both time points (rates of actual adherence in the control group were 38.2% and 33.2% during months 2 and 6, respectively). These results suggest that digital inhaler systems can assist pharmacists in providing personalized, patient-specific inhaler education. However, more data are required to determine the clinical impact of these digital inhaler systems in the context of pharmacist-led interventions.

Digital devices may also assist pharmacists in the selection of an appropriate inhaler device for a given patient. In a small observational study, pharmacists used data from aerosol inhalation monitors to test patients’ abilities to use various types of inhaler devices.32 If testing demonstrated that the patient’s current inhaler device was inappropriate, the pharmacist recommended specific device changes based on patient respiratory ability. After inhaler optimization (which could include other interventions in addition to device optimization), patients demonstrated improvements in respiratory symptoms. Further research is required to delineate the effect of aerosol inhalation monitor assessment on patient outcomes.

Inhaler Device Selection and Education

Inhaler devices can be classified into 4 broad categories: pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), slow mist inhalers (SMIs), and nebulizers.33 This program will primarily focus on pMDIs, DPIs, and SMIs. A given medication may not be available in all types of inhaler devices. Table 1 summarizes the available inhaler devices for the medications and fixed-dose combination products used in asthma and COPD.4,6,34 When possible, it is beneficial to ensure that the same type of inhaler device is used to deliver all of a patient’s inhaled medications.33 Using multiple inhaler device types can be confusing for patients, potentially resulting in poor inhaler technique and critical errors in inhaler use. The use of multiple inhaler devices with different inhalation techniques has been shown to worsen clinical outcomes in COPD and asthma patients.10

Table 1. Inhaled Medications Used in Asthma and COPD.4,6,34
Generic Drug Name Inhaler Device Types Available
SABAs
Albuterol pMDI, DPI (RespiClick), digital DPI (Digihaler)a, inhalation solution
Levalbuterol pMDI, inhalation solution
LABAs
Arformoterol inhalation solution
Formoterol inhalation solution
Indacaterol DPI (Neohaler)
Olodaterol SMI (Respimat)
Salmeterol DPI (Diskus)
SAMAs
Ipratropium pMDI, inhalation solution
LAMAs
Aclidinium DPI (Pressair)
Glycopyrrolate DPI (Neohaler), inhalation solution
Revefenacin inhalation solution
Tiotropium DPI (HandiHaler), SMI (Respimat)
Umeclidinium DPI (Ellipta)
SABA/SAMA Combinations
Albuterol/ipratropium SMI (Respimat), inhalation solution
LABA/LAMA Combinations
Formoterol/aclidinium DPI (Pressair)
Formoterol/glycopyrrolate pMDI
Indacaterol/glycopyrrolate DPI (Neohaler)
Olodaterol/tiotropium SMI (Respimat)
Vilanterol/umeclidinium DPI (Ellipta)
ICS
Beclomethasone breath-actuated pMDI (RediHaler)
Budesonide DPI (Flexhaler), inhalation solution
Ciclesonide pMDI
Fluticasone furoate DPI (Ellipta)
Fluticasone propionate pMDI, DPI (Diskus, RespiClick)
Mometasone pMDI, DPI (Twisthaler)
LABA/ICS Combinations
Formoterol/budesonide pMDI
Formoterol/mometasone pMDI
Salmeterol/fluticasone propionate pMDI, DPI (Diskus, RespiClick, Inhub), digital DPI (Digihaler)a
Vilanterol/fluticasone furoate DPI (Ellipta)
LABA/LAMA/ICS Combinations
Vilanterol/umeclidinium/fluticasone furoate DPI (Ellipta)
aFDA-approved, with anticipated commercial availability in 2020.

Abbreviations: DPI, dry powder inhaler; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; pMDI, pressurized metered-dose inhaler; SABA, short-acting beta agonist; SAMA, short-acting muscarinic antagonist; SMI, slow mist inhaler.

Different types of inhaler devices require different inhalation techniques for effective use.33 Pressurized metered-dose inhalers deliver medication using a propellant; therefore, it is not necessary for patients to generate a strong inspiratory flow in order to receive an adequate dose. However, most pMDIs do require the ability to coordinate the actuation of the inhaler with inhalation. If actuation and inhalation are not coordinated properly, the drug will deposit in the oropharyngeal area, rather than the lungs. This may increase the risk of local side effects, including oral thrush if the inhaled medication is a corticosteroid. Patients who have difficulty with the coordination required for pMDI use may benefit from the use of a spacer chamber, or a breath-actuated pMDI.18,33 Breath-actuated pMDIs automatically coordinate actuation with inhalation.33 Patients seal their lips around the device and inhale to trigger device actuation.

Unlike pMDIs, DPIs do not require hand-breath coordination, because the dose is delivered using the power of the patient’s own inspiratory flow.33 However, most DPIs require a minimum peak inspiratory flow rate of 30 L/min for effective use, and peak inspiratory flow rates over 60 L/min are considered optimal for medication delivery. Different types of DPI devices are available, but all DPIs require patients to load each dose.34 Patients may be required to insert a separate capsule each time they take a dose, or they may need to manipulate the device in some way so that the next dose is advanced.

A third type of inhaler device, the SMI, delivers medication in the form of a fine aerosol mist.33 As with pMDIs, some coordination between device actuation and inhalation is necessary for effective drug delivery. Nebulizers, the final type of inhaler device, do not require a strong inspiratory flow or good hand-breath coordination; medication is delivered in a fine mist that is generated by the motor of the nebulizer device. However, nebulizer devices are generally more inconvenient and time-consuming to use than other inhaled medication delivery options, and many medications are not available as inhalation solutions.

When selecting an inhaler device for a patient, it is important to consider patient-specific issues such as dexterity, cognition, and vision. Elderly patients may have physical difficulty performing the maneuvers necessary to use their inhaler.10 Handgrip and manual dexterity may be significantly reduced by comorbid conditions, such as osteoarthritis, joint pain, stroke, and muscle weakness. Patients with cognitive or vision impairment may have difficulty attaching pMDIs to spacers, and patients with facial weakness or missing teeth may have trouble forming a firm seal around the mouthpiece during inhaler use. In children, the physical size of the device may pose a problem, and young patients may lack the necessary manual dexterity, finger strength, or hand-breath coordination to properly actuate and use the inhaler device. Insufficient inspiratory flow can be a barrier to DPI use in both elderly patients and young children. If patients are unable to breathe in with sufficient force, drugs delivered via DPI may not deposit adequately in the lungs. Inspiratory flow meters and training devices, such as AIM (Aerosol Inhalation Monitor) or In-Check DIAL, can be used to measure a patient’s inspiratory flow rate and assess their ability to use a given type of inhaler device.36 Table 2 provides a general overview of potentially appropriate inhaler device options based on patient age, coordination ability, and inspiratory flow.10,36 In the case of DPIs, it may also be useful to review the instructions for use for the specific device being considered, as some devices may be easier for patients to manipulate than others.

Table 2. Inhaler Device Options Based on Age, Patient Coordination, and Inspiratory Flow.10,34,36
Age Inspiratory Flow Coordination Device Options
Adult (≥13 years) ≥30 L/min Good pMDI, DPIa, ba-pMDI, SMI
Poor pMDI + spacer, DPIa, ba-pMDI, SMI
<30 L/min Good pMDI ± spacer, ba-pMDI, SMI
Poor pMDI + spacer, ba-pMDI, SMI, nebulizer
6 to 12 years - - Nebulizer, pMDI + spacer, DPIa, ba-pMDI, SMI
4 to 5 years - - Nebulizer, pMDI + spacer, ba-pMDI (5 years), some DPIsa
Birth to 4 years - - Nebulizer, pMDI + spacer and mask
aAge recommendations for individual DPI devices vary. Consult the prescribing information for the specific DPI under consideration. Individual patient ability should also be considered, particularly in younger patients.

Abbreviations: ba-pMDI, breath-actuated metered-dose inhaler; DPI, dry powder inhaler; pMDI, pressurized metered-dose inhaler; SMI, slow mist inhaler.

Once an appropriate inhaler device is selected, it is important to train patients on the proper use of the chosen device. The GOLD guideline notes that education and training in inhaler device technique is absolutely essential.6 Proper technique should be demonstrated when the inhaler is first prescribed, and inhaler technique should be reassessed at every visit to ensure that patients continue to use it correctly. The GINA guideline similarly states that inhaler skills training is essential for all patients with asthma to ensure that selected medications can work as intended.4

Problems with inhaler technique may be related to inspiratory flow, inhalation duration, coordination, dose preparation, exhalation maneuvers prior to inhaler use, and breath-holding following dose inhalation.6 A meta-analysis of studies in US COPD patients found that 86.7% of patients made at least 1 error in the use of their pMDI, and 76.8% of patients performed over 20% of the device use steps incorrectly.37 The most common errors in pMDI technique were failing to attach a spacer when required (78.1%), failing to exhale fully (away from the inhaler) before use (65.5%), failing to hold breath for 5 to 10 seconds (41.9%), inhaling too fast and too deeply (39.4%), failing to exhale after inhalation (35.9%), and failing to shake the inhaler before use (34.2%). Certain errors in inhaler technique may be more critical than others. In asthma patients, the CRITIKAL study revealed that some errors in inhaler technique are significantly associated with poor symptom control and/or increased exacerbations.38 The most common errors in the CRITIKAL study were generally related to inhalation effort. With pMDIs, inspiratory flow was not slow/deep enough in 47.2% of patients, while up to 38.4% of patients using DPIs had insufficient inhalation effort. For pMDIs, 3 errors were associated with poor symptom control in multivariable analyses: lack of device knowledge or incorrect second dose preparation, timing, or inhalation; exhaling into the inhaler or not holding it upright; and actuating the device prior to inhalation. Failure to inhale slowly and deeply was not associated with uncontrolled asthma. For DPIs, insufficient inspiratory effort was associated with uncontrolled symptoms and increased exacerbations.

Although different devices may be more or less prone to certain types of error, there is no device that is completely error-proof.6 In order to ensure correct technique, patients should receive an initial explanation and demonstration of their specific inhaler device. Verbal instruction, combined with a physical demonstration of the device, is the most effective technique for training patients on inhaler use.9 Videos may be used to supplement these trainings, but a randomized study in inhaler-naïve volunteers found that direct instruction on inhaler technique from a pharmacist was more effective than written materials or video demonstrations for improving inhaler competency.39 The pharmacist-provided education in this study was limited to a 2-minute time period, demonstrating that effective patient education can be accomplished in a relatively short period of time. Use of the teach-back method during education sessions can help ensure that patients understand the proper way to use their inhaler device.40 Integration of tools that provide real-time, interactive sensory feedback on the patient’s inhaler performance may also help improve patient recall of optimal technique.10 Inhaler technique tends to fall off with time if it is not reassessed, so checking inhaler technique at every visit and retraining patients as necessary is essential.4,6 Steps for appropriate inhaler use are demonstrated in the accompanying video: however, it is important to note that each inhaler device is different, and even among inhaler devices within the same broad category, the instructions for use may differ. Always consult the instructions for use that correspond to the patient’s specific inhaler device.

Inhaler Types
Type Manufacturer Brand/Generic Website
Breath-Actuated Inhaler (BAI)
RediHaler Teva Respiratory Qvar/ beclomethasone dipropionate HFA https://www.qvar.com/redihaler/how-to-use-qvar-redihaler
Dry Powder Inhaler (DPI)
Digihaler Teva Respiratory ProAir/albuterol https://www.proairdigihaler.com/globalassets/proair_digihaler/Proair_Digihaler_IFU.pdf
Diskus GSK    
    Advair/ fluticasone propionate and salmeterol https://www.advair.com/how-to-use-advair.html
    Flovent/ fluticasone propionate https://www.flovent.com/about-flovent-diskus/how-to-use.html
    Serevent/ salmeterol https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Serevent_Diskus/pdf/SEREVENT-DISKUS-PI-MG-IFU.PDF
    Advair/ fluticasone propionate and salmeterol https://www.advair.com/how-to-use-advair.html
Ellipta GSK    
    Anoro/umeclidinium and vilanterol https://www.anoro.com/about-anoro/how-to-use-anoro/
    Arnuity/fluticasone furoate https://www.arnuity.com/about-arnuity/how-to-use-arnuity.html
    Breo/fluticasone furoate and vilanterol https://www.mybreo.com/asthma/how-to-use-breo-ellipta.html
    Incruse/ umeclidinium https://www.incruse.com/how-to-use-incruse.html
    Trelegy/ fluticasone furoate/umeclidinium/vilanterol https://www.trelegy.com/how-to-use-trelegy/
Flexhaler AstraZeneca Pulmicort/ budesonide http://www.pulmicortflexhaler.com/asthma-control/pulmicort-flexhaler-instructions.html
Handihaler BI Spiriva/ tiotropium https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Spiriva/Spiriva.pdf#page=15
Inhub Mylan Wixela/ fluticasone propionate/salmeterol https://www.wixela.com/en/how-to-use
Neohaler Sunovion    
    Arcapta/ indacaterol https://www.arcapta.com/Arcapta-Prescribing-Information.pdf#page=11
    Seebri/ glycopyrrolate https://www.seebri.us/instructions-for-using-seebri.html
    Utibron/ indacaterol and glycopyrrolate https://www.utibron.com/Utibron-Prescribing-Information.pdf#page=11
Pressair Almirall, S.A., AstraZeneca Tudorza/ aclidinium bromide https://www.tudorza.com/using-tudorza/taking-tudorza/
RespiClick Teva Respiratory    
    Airduo/ fluticasone propionate and salmeterol https://hcp.myairduo.com/using-airduo#instructions-for-use
    ArmonAir/ fluticasone propionate https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208798s000lbl.pdf
    ProAir/albuterol http://hcp.proair.com/Pdf/ProAir_RespiClick_Patient_Information_Leaflet.pdf 
Twisthaler Merck Asmanex/mometasone furoate https://www.asmanex.com/asmanex-twisthaler/
Metered-Dose Inhaler (MDI)
  Teva Respiratory ProAir/ albuterol sulfate http://hcp.proair.com/hfa/pdf/ProAirDoseCounter-Prescribing-Information.pdf
  Merck Proventil HFA/ albuterol sulfate https://www.merck.com/product/usa/pi_circulars/p/proventil_hfa/proventil_hfa_doseindicator_ppi.pdf
  GSK, generic Ventolin/ albuterol sulfate https://www.ventolin.com/about-ventolin-hfa/how-to-use.html
  AstraZeneca Symbicort/ budesonide and formoterol fumarate dihydrate https://www.mysymbicort.com/asthma/about-symbicort/how-to-use-your-inhaler.html
  AstraZeneca Alvesco/ ciclesonide https://www.alvesco.us/About-Alvesco/#how
  Armstrong Primatene Mist/ epinephrine https://www.primatene.com/pdf/how-to-use-inhaler.pdf
  GSK Flovent HFA/ fluticasone propionate https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Flovent_HFA/pdf/FLOVENT-HFA-PI-PIL-IFU.PDF#page=29
  GSK Advair/ fluticasone propionate and salmeterol https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Advair_HFA/pdf/ADVAIR-HFA-PI-PIL-IFU.PDF#nameddest=PIL
  AstraZeneca Bevespi Aerosphere/ glycopyrrolate and formoterol https://www.bevespi.com/how-to-use-bevespi-inhaler.html
  BI Atrovent HFA/ipratropium https://www.atrovent.com/img/HOW_TO_USE_ATROVENT_PC-AT-0056-CONS.pdf
  Sunovion, generic Xopenex/levalbuterol https://www.xopenexhfa.com/how-to-use.html
  Merck Asmanex HFA/ mometasone furoate https://www.merck.com/product/usa/pi_circulars/a/asmanex/asmanex_ppi.pdf
  Merck Dulera/ mometasone furoate and formoterol fumarate dihydrate https://www.dulera.com/what-is-dulera/inhaler-instructions/
Slow-Mist Inhaler (SMI)
Respimat BI    
    Combivent/ ipratropium bromide and albuterol https://www.combivent.com/your-respimat-inhaler/video
    Spiriva/ tiotropium bromide https://www.spiriva.com/copd/starting-spiriva/how-to-use-spiriva-respimat
    Stiolto/ tiotropium bromide and olodaterol https://www.stiolto.com/stiolto-respimat/how-to-use-stiolto-respimat
    Striverdi/ olodaterol https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Striverdi%20Respimat/striverdi.pdf
Italicized products only have written directions for product use. BAI- Breath-actuated inhalation aerosol; HFA- hydrofluoroalkane; DPI- Dry powder inhaler; GSK- GlaxoSmithKline; BI- Boehringer Ingelheim; Merck- Merck & Co., Inc.; MDI- metered dose inhaler; Sunovion- Sunovion Pharmaceuticals Inc.; Armstrong- Armstrong Pharmaceuticals Inc.; SMI- slow mist inhaler

Conclusion

Non-adherence is a long-standing problem in asthma and COPD. Poor adherence may be intentional or unintentional, and a wide variety of factors can contribute to a patient’s non-adherence. In order to improve adherence to inhaled therapies, it is important to engage patients in honest discussions about their medication use, and tailor interventions to address patient-specific adherence challenges. Additionally, it is important to ensure that patients are using correct inhaler technique. Digital inhaler systems have the potential to assist providers with the optimization of inhaler-based therapy. These devices can monitor patient adherence and, in some cases, provide data related to the patient’s inhaler technique. These data can be used to facilitate patient-provider discussions and identify the need for regimen changes or further patient education.

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