Treatment of chronic respiratory disorders, such as chronic obstructive pulmonary disease (COPD) and asthma, involves use of inhaled medication delivered directly to the desired site, with reduced medication doses and minimized systemic adverse effects compared with oral administration (Ibrahim, Verma, & Garcia-Contreras, 2015). Moreover, the chronic nature of COPD and asthma necessitates regular self-administration of drugs by inhalation, indicating that correct use of the inhaler by patients and effective delivery of the prescribed medication is critical. An incorrect technique, which has been shown to be common among patients with COPD and asthma, may lead to reduced delivery of medication to the lungs and reduced efficacy (Melani et al., 2011).
When assigning treatment to patients, little consideration may be given to the various available inhalers and the patients' ability to use them correctly, especially in children, older patients, those with more severe disease, and patients with cognitive impairment or impaired dexterity. Inhaler attributes should be considered along with patient preference, formulary considerations, adherence, and the likelihood of a favorable treatment outcome, which would result in decreased overall health care cost (Hodder & Price, 2009). Thus, effective disease control and treatment requires selection of an appropriate pharmacological agent, along with an appropriate inhaler for its delivery. Several types of inhalers are currently available for management of COPD and asthma, each offering distinct characteristics that necessitate careful consideration to tailor use to patients' needs.
The purposes of this article are to provide an overview of inhalation technology and inhaler characteristics in the treatment of COPD and asthma and to provide guidance on selecting an inhaler and matching the right inhaler to the right patient.
Guidelines available on inhaler use
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Global Initiative for Asthma (GINA) were launched as a collaborative effort between the National Heart, Lung, and Blood Institute and the World Health Organization. Both organizations comprise worldwide network of health care providers (HCPs), including nurse practitioners (NPs), and public health officials involved in disseminating information related to management of patients with COPD (GOLD, 2019) and asthma (GINA, 2018). The Global Initiative for Chronic Obstructive Lung Disease and GINA have proposed recommendations for diagnosis, management, and prevention of COPD and asthma, respectively. These recommendations translate scientific evidence for improved patient care and are based on either randomized controlled trials (RCTs) or real-world evidence (RWE) from clinical practice. Although RCTs enable evaluation of clinical outcomes, they also use strict inclusion and exclusion criteria for patients and, hence, may not always mimic real-world clinical practice. Data from RWE complement the data from RCTs and provide insights on effectiveness, safety, treatment patterns, and patient behavior in day-to-day clinical practice (NEHI, 2015).
Once a diagnosis of COPD or asthma is confirmed, recommendations from GOLD and GINA enable HCPs to make informed decisions related to choice of appropriate treatment. In fact, the guidance leads HCPs to the treatment that is most likely to benefit each patient, based on patient history, disease severity, and age. The recommendations have highlighted the importance of choosing the optimal inhaler, checking inhalation technique, and assessing adherence before considering step-up treatments, such as corticosteroids. However, detailed guidelines for matching an appropriate inhaler to patients' need and abilities are currently lacking (Dekhuijzen et al., 2014). With the aim of educating patients on correct use of inhalers, the American Thoracic Society published a chapter on how to use a metered dose inhaler (MDI) (Garvey, Fahy, Lareau, Braman, & Laube, 2014), which is one of the most commonly used inhalers that patients find difficult to use (Sanchis, Gich, Pedersen, & Aerosol Drug Management Improvement, 2016).
Principles of drug deposition in the lungs
The extent and pattern of drug deposition in the lungs affects the clinical outcome of treatment and is largely influenced by three parameters: the patient's inspiratory flow, the speed at which the aerosolized drug (fine spray or particle) is released, and the size of the inhaled drug particle (Labiris & Dolovich, 2003). Aerosols for inhalation usually contain a wide range of particle sizes.
Generally, particles with a mass median aerodynamic diameter (at which 50% of the particles are larger and 50% are smaller) <5 μ are easily respirable and are referred to as the fine particle fraction (FPF; less than particle size considered as the upper limit of respirable size) (Laube et al., 2011). Particle size is a determinant of the payload it can carry—a larger particle can carry more drug compared with a smaller particle; however, larger particles may not be easily respirable. This means that generation of a high FPF allows an inhaler to deposit more drug particles in areas of the lung, which are difficult to reach by particles having lower FPF, particularly the smaller airways and peripheral bronchioles. Particles >5 μ in diameter are more likely to be deposited in the oropharynx, while those between 2 and 5 μ are deposited throughout the bronchial tree (Bonini & Usmani, 2015). Depending on the size and velocity, particles are deposited by impaction, sedimentation, or diffusion. Deposition by impaction usually occurs in the upper airways of the lung, where air velocity is high and airflow is turbulent. Further down the airway, the air velocity decreases and particles largely precipitate out of the airflow by gravitational deposition of suspended particles (sedimentation) or by deposition of submicron-size particles (diffusion by Brownian motion) (Bonini & Usmani, 2015).
A patient's ability to synchronize inhalation with the release of the aerosol in pressurized MDIs (pMDIs) or generate sufficient airflow to deagglomerate the particles with dry powder inhalers (DPIs) is an important determinant of drug deposition in the lungs. One of the important factors influencing drug deposition in the lungs is inspiratory flow generated by the patient (Borgstrom, Bondesson, Moren, Trofast, & Newman, 1994); for example, achieving a high enough peak inspiratory flow rate (PIFR) through a DPI is needed to adequately disperse the drug before inhalation (Bonini & Usmani, 2015). Peak inspiratory flow rate (L/min), measured through an inhaler of specific airflow resistance, is the maximal airflow generated during an inspiratory cycle (Ghosh, Ohar, & Drummond, 2017) and depends on inhaler resistance and the patient's inhalation efforts (Mahler, 2017). A PIFR of <60 L/min is generally regarded as suboptimal (Mahler, 2017). In addition, minimal, suboptimal, and optimal PIFR values may vary by inhaler (Ghosh et al., 2017). Although patient-related factors such as advancing age (Loh, Peters, Lovings, & Ohar, 2017) and female gender (Mahler, Waterman, & Gifford, 2013) are associated with suboptimal PIFR, patients with COPD across all severity stages may have suboptimal PIFR (Loh et al., 2017). For patients with asthma or COPD, particularly those with suboptimal PIFR, a slow-moving velocity aerosol coupled with a smaller drug particle size (e.g., that produced by the slow-mist inhaler [SMI]) can help achieve effective (>50%) total deposition in the lungs and penetration into the distal airway tree (Brand, Hederer, Austen, Dewberry, & Meyer, 2008; Hochrainer et al., 2005; Pitcairn, Reader, Pavia, & Newman, 2005).
Technology associated with the use of inhalation devices
Inhalation technology has significantly evolved since the importance of inhaling medicated vapors was recognized; however, a major advancement in inhaled drug delivery was marked by the dispersal of medicated droplets into fine particles for inhalation (i.e., nebulization). The initial atomizers (predecessors to nebulizers) were associated with poor delivery of inhaled medication to the lungs (Nikander & Sanders, 2010). The full history of developments in therapeutic aerosol delivery, leading to the currently available inhalers, has been reviewed (Stein & Thiel, 2017).
Nebulizers use energy (pneumatic or ultrasonic) to generate a respirable aerosol plume from an aqueous drug solution or suspension (Lavorini, Fontana, & Usmani, 2014). Most nebulizers are bulky and result in drug loss during exhalation; however, they are considered appropriate for older patients with COPD or asthma and children with asthma (Ari & Fink, 2011) because the patient does not need to coordinate inhalation with device actuation. The development of a mesh-based portable nebulizer—the I-neb Adaptive Aerosol Delivery (AAD) System—has allowed for efficient drug delivery by synchronizing aerosol delivery with the patient's breathing pattern (Dhand, 2010). However, with the AAD system, patients need to use different discs for different formulations; patients who need to inhale multiple drugs can get confused when switching operation modes of the device. In addition, drugs administered by the I-neb AAD system cannot be mixed together, leading to prolonged inhalation times for multiple inhaled medications (Dhand, 2010).
The currently available portable inhalers for pulmonary drug delivery are categorized as pMDIs, DPIs, and SMIs (Figure 1). Not all classes of inhaled drugs are available in all types of inhalers.
In contrast to nebulizers that use an alternate energy source, pMDIs use propellants for aerosolizing the drug solution. The earliest pMDIs consisted of drug dissolved in a mixture of ethanol and chlorofluorocarbons (CFCs). However, because of their damaging environmental impact, CFC-based propellants were phased out and replaced with hydrofluoroalkane propellants (Stein & Thiel, 2017). Subsequently, suspension-based formulations were developed for delivery of drugs that were unstable in ethanol. Pressurized MDIs are among the most widely used inhalers, but a major limitation associated with their use is that patients need to coordinate inhalation with inhaler actuation, which can lead to insufficient drug delivery (Roche & Dekhuijzen, 2016) or drug impaction in the oropharynx (Usmani, Biddiscombe, & Barnes, 2005).
Development of breath-actuated pMDIs, such as the Easi-Breathe and the Autohaler, overcame the need for coordination; these devices release the drug only in response to the patient's inhalation (Stein, Sheth, Hodson, & Myrdal, 2014). Studies have shown that patients prefer breath-actuated pMDIs over pMDIs that need coordination (Lenney, Innes, & Crompton, 2000). The Easi-Breathe and Autohaler are actuated at inspiratory flow rates of around 20 and 30 L/min, respectively, and only <5% of patients have been unable to generate the threshold inspiratory flow for actuation of the Autohaler (Fergusson, Lenney, McHardy, & Crompton, 1991; Lenney et al., 2000).
The most commonly reported problem associated with the use of pMDIs is lack of actuation–inhalation coordination and stopping inhalation because of the initial reaction to the cold blast of MDI propellant on the back of the throat (i.e., cold Freon effect) (Virchow et al., 2008).
They use micronized dry powder formulations for drug delivery to the lungs, offering greater stability than liquid formulations. However, this also creates the challenge of protecting the dry powder from environmental moisture if the DPI has a reservoir for multiple doses (Hoppentocht, Hagedoorn, Frijlink, & de Boer, 2014). Based on how a breath-actuated DPI stores and dispenses the drug, they are divided into three categories: single-unit dose inhalers (each dose is loaded before inhalation; e.g., Breezhaler, known as Neohaler in the United States), multidose reservoir inhalers (entire supply of drug is preloaded; e.g., Turbuhaler), and multiunit dose inhalers (single doses are individually sealed and released on actuation; e.g., Diskus).
Dry powder inhalers are also categorized as active or passive, depending on whether they use the patient's inspiratory flow (Chan, Wong, Zhou, Leung, & Chan, 2014). Most DPIs are passive and breath actuated, using the energy generated by the inspiratory flow to deagglomerate the drug particles for release in the form of respirable fine particles (Chan et al., 2014). The inspiratory maneuver of the patient creates a pressure drop (a measure of patient's inspiratory effort) within the inhaler, which drives the airflow. This airflow is dependent on two important factors: the ability to generate the airflow and the intrinsic resistance offered by the DPI to the airflow. Because breath-actuated DPIs release the drug only on inhalation, patients do not need to coordinate inhalation with actuation, thus overcoming a major limitation of pMDIs (Chan et al., 2014). The need for breath actuation also presents complications that may be influenced by patient or inhaler characteristics. Not all patients, such as children, older patients, or those with more severe airflow limitation, may be able to produce the minimum turbulent energy required to create a fine particle mass; higher inspiratory flow rates generated by a patient (most likely with a low-resistance DPI) will lead to higher drug particle velocity, resulting in higher oropharyngeal drug deposition. These particles are consequently swallowed, leading to potential systemic side effects (Demoly, Hagedoorn, de Boer, & Frijlink, 2014). Conversely, lower inspiratory flow rate generated by a patient (most likely with a high-resistance DPI) may result in inadequate drug deagglomeration for effective delivery to the lungs. Moreover, some patients may be unable to generate sufficient airflow through a high-resistance DPI.
Generally, patients have a greater preference for low-resistance DPIs over those with a higher intrinsic resistance to airflow (Van Der Palen, Eijsvogel, Kuipers, Schipper, & Vermue, 2007). To achieve the same inspiratory flow with the two types of inhalers, a patient may need to exert a significantly higher inspiratory effort while inhaling through a high-resistance inhaler compared with a low-resistance inhaler. Evidence suggests that patients can inhale most comfortably through an inhaler when the pressure drop produced in the DPI is up to 4 kPa (Behara, Larson, Kippax, Stewart, & Morton, 2012). Data from in vitro studies indicate that for most DPIs, the pressure drop created by inhalation (at flow rates above ∼70 L/min) exceeds 4 kPa (Ciciliani, Langguth, & Wachtel, 2017), suggesting that patients may feel uncomfortable when inhaling through most DPIs, particularly the high-resistance devices. This raises the question of the level of comfort of inhalation experienced by patients when using their inhalers, which should be kept in mind when prescribing the medication. In general, patients feel most comfortable while inhaling their medication through an inhaler that allows drug delivery independent of their inspiratory effort, such as an SMI. Among the currently available DPIs, the Breezhaler is reported to offer low airflow resistance and consistent drug delivery (Colthorpe, Voshaar, Kieckbusch, Cuoghi, & Jauernig, 2013). Some commonly used breath-actuated DPIs include Ellipta, Diskus, and Breezhaler.
Active DPIs use an alternate energy source for drug deagglomeration and therefore do not rely on the patient's ability to generate airflow, thus allowing for greater consistency in drug delivery (Chan et al., 2014). An active DPI may use varied means to deagglomerate drug particles, and flow sensors are designed to detect patient inspiration that triggers release of the drug for inhalation; for example, sensors in Inspiromatic (currently under clinical investigation) can detect flow rates ≥6 L/min (Inspiromatic, 2014). Other manufacturers, such as Occoris (currently under clinical investigation), use an external engine for deagglomerating the drug particles that can be attached to any available DPI (Berkenfeld, Lamprecht, & McConville, 2015).
Currently, the only available SMI is the Respimat slow-mist inhaler; the term “slow mist” is used to describe the speed of aerosol generation and characteristics of the aerosol cloud. The SMI technology was developed to overcome the limitations of the available inhalers (pMDIs and DPIs) by avoiding use of propellants, minimizing the need for coordination, reducing inspiratory effort for inhalation, and allowing for consistent delivery of drug aerosol to the lungs. The introduction of Respimat provided a significant technological advancement in inhaler design for delivery of respiratory medicine. Characteristics such as much slower velocity of the aerosol (slow mist; 0.8 m/second, which is ∼3–10 times slower than a pMDI) (Dalby, Eicher, & Zierenberg, 2011) and longer spray duration (1.5 seconds versus 0.15–0.36 seconds for pMDIs) (Hochrainer et al., 2005) improved the delivery of inhaled drugs. The majority of the aerosol (>60%) released by Respimat lies within the easily respirable FPF of ≤5 μ, which accentuates sedimentation of particles in the smaller bronchi and bronchioles (Wachtel, Kattenbeck, Dunne, & Disse, 2017). Together, these characteristics simplify the need for coordinating inhaler actuation and inhalation while allowing for consistent dose delivery to the lungs and reduced oropharyngeal drug deposition. The greater efficiency in delivery of inhaled medication has also allowed reduction of the nominal drug dose without loss of clinical efficacy in asthma and COPD (Dalby et al., 2011; Hohlfeld et al., 2014; Kilfeather et al., 2004). In addition, inhaler handling studies have shown that Respimat provides efficient drug delivery and can be effectively used by all patients, irrespective of age (toddlers to seniors) (Kamin et al., 2015) or level of bronchoconstriction.
Although the design features of the Respimat inhaler considerably minimize the need for coordination versus pMDIs, patients still need to coordinate inhalation with actuation. Some patients with impaired dexterity may find it difficult to twist the base before use for actuation.
Inhaler attributes that influence patient perception and compliance with treatment
Patients, including those with respiratory disorders, generally show the highest adherence to oral therapy (Cohn, 2003). Thus, for patients to persist with the inhaled treatment, the inhaler must have attributes that enhance their experience. Unfortunately, persistence with inhalation medication is a significant problem among patients with asthma and COPD and is associated with greater health care utilization costs (Mäkelä, Backer, Hedegaard, & Larsson, 2013). It is reported that only 40%–60% of patients with COPD adhere to the prescribed treatment (Restrepo et al., 2008). Moreover, patients find it difficult to work around the various characteristics of different inhalers (Stevens, 2003) and demonstrate poor technique, independent of the device used (Molimard et al., 2003).
Factors that affect adherence to treatment could be related to patient characteristics (e.g., disease severity, age, and cognitive impairment) (Turan, Turan, & Mirici, 2017), inhaler attributes (e.g., ease of use during breathing difficulty) (Hawken et al., 2017), or the treatment regimen (e.g., dosing schedule and route of administration) (Cohn, 2003). Patients with chronic respiratory disorders such as COPD or asthma who switch medications or take multiple medications would benefit from inhaling the medications, including combinations, through the same inhaler. This may result in improved compliance and reduced flare-ups (Kew, Karner, Mindus, & Ferrara, 2013).
As inhalation technology has evolved, inhalers have become more diverse in their capabilities. This has highlighted the need for patients to use their inhalers correctly, regardless of their skill and ability, particularly as patient care transitions from clinic to home settings. Studies investigating human factors and patient preferences have driven development of devices such as insulin pumps (Schaeffer, 2012). Such user-assisted approaches, involving consideration of human factors, were used in the development of Respimat.
Inhaler attributes that may be preferred by patients and HCPs and may lead to improvement in persistence of use and compliance to treatment include:
- Intuitiveness (Virchow, Weuthen, Harmer, & Jones, 2014): instinctive design that facilitates ease of understanding about the sequence of steps needed to use an inhaler.
- Easy to teach, learn, and use (Molimard & Colthorpe, 2015): design features that simplify inhaler use (e.g., fewer steps involved in the dispensing of the medication).
- Portable and compact: easy to carry and is hand-held.
- Ability to provide feedback on correct use (Molimard & Colthorpe, 2015): provides confirmation that the dose has been taken completely and correctly.
- Dose counter (Hawken et al., 2017): reminds patients if they need to refill or replace their inhaler.
- Patient satisfaction (Molimard & Colthorpe, 2015): overall patient perception and preference associated with the attributes of an inhaler.
- Comfort of inhalation (Hawken et al., 2017): reduced effort for inhalation (e.g., less intrinsic airflow resistance offered by an inhaler enhances comfort of inhalation).
- Environment-friendly (Molimard & Colthorpe, 2015): reduced or minimal harm to the environment (e.g., avoids use of propellants or is recyclable).
Inhalation technique and inhaler handling
Data from RCTs comparing inhaled treatments use stringent inclusion criteria (e.g., all patients can use the inhalers correctly if using correct inhalation techniques). This is not representative of the real-world scenario because patients do not always receive training on how to use their inhaler correctly. Treatment guidelines recommend that physicians should regularly check correct inhaler use by patients; however, 39%–67% of HCPs do not adequately train their patients (Fink & Rubin, 2005).
Although a prerequisite for a favorable outcome of inhaled treatment is that patients use the correct inhaler technique (Table 1), available data indicate that most patients cannot use their inhalers correctly. Real-world evidence suggests that the proportion of patients who commit at least one error is higher with pMDIs (76%) than with breath-actuated pMDIs (49–55%) (Molimard et al., 2003). A systematic analysis of the available literature showed that between 4% and 94% of patients with asthma or COPD did not use their DPI correctly, and approximately, a quarter of them never received adequate training on inhaler use (Lavorini et al., 2008). It is known that lack of proper training for inhaler use and incorrect technique may lead to reduced lung deposition and inadequate bronchodilation, which may lead to poor disease control (Lindgren, Bake, & Larsson, 1987). Using the correct technique not only ensures that the patient receives the full prescribed dose of medication but also improves adherence, clinical outcomes, quality of life, and health care resource utilization in patients with COPD and asthma (Bosnic-Anticevich et al., 2017; Price et al., 2017). A quantitative assessment of errors related to inhaler use is therefore very important to ensure that HCPs can assign the right inhaler to the right patient.
A systematic review of articles published between 1975 and 2014 assessing inhaler use in asthma and COPD concluded that incorrect inhaler use was unacceptably high and had not improved in the past 40 years (Sanchis, Gich, & Pedersen, 2016). Among all the inhalers, the highest average frequency of errors was associated with the use of pMDIs. Moreover, addition of holding chambers to MDIs was not shown to substantially reduce errors. The authors also observed that error rates with DPIs were only lower than with pMDIs, with almost one third of patients making errors in dose preparation, expiration, and inspiration, thus affecting drug delivery (Sanchis et al., 2016).
Another systematic review and meta-analysis of inhaler error in patients with asthma and COPD showed that both the overall errors (50–100%) and critical errors (14–92%) were high for all inhalers (Chrystyn et al., 2017). However, the authors also concluded that the level of evidence currently available is insufficient to assess differences in error rates between different inhaler devices. It is important to note that critical errors with inhaler use have been shown to be associated with an increased rate of severe COPD exacerbations (Molimard et al., 2017).
In addition to inhaler attributes, factors related to patient characteristics and demographics have also been shown to influence the error rates associated with inhaler use. Higher error rates have been observed in older patients (Chorão, Pereira, & Fonseca, 2014; Melani et al., 2011), female patients (Chorão et al., 2014), patients with lower levels of education (Chorão et al., 2014), obese patients (Westerik et al., 2016), and in patients with COPD versus patients with asthma (Souza, Meneghini, Ferraz, Vianna, & Borges, 2009). Other factors that may influence error frequency associated with inhaler use include training (Sestini et al., 2006), length of time the patient has been using the inhaler (Batterink, Dahri, Aulakh, & Rempel, 2012), and use of multiple inhalers (Rootmensen, van Keimpema, Jansen, & de Haan, 2010).
Role of NPs in training patients in inhaler technique
Imparting instructions on inhaler use can help ensure that patients use proper technique while using their inhalers. Unfortunately, only a small proportion of patients receive information on inhaler use, and an even smaller proportion of these patients have their technique reviewed over time (Basheti, Reddel, Armour, & Bosnic-Anticevich, 2005). However, it is important that NPs do not rely only on written and/or verbal communication but also use a step-by-step demonstration of the use of the inhaler along with periodic reassessment (Lavorini, Levy, Corrigan, Crompton, & Group, 2010). The most effective training technique has been reported to be written and verbal instruction, along with physical demonstration (Bosnic-Anticevich, Sinha, So, & Reddel, 2010). Because poor adherence to inhaled medication is associated with suboptimal disease control (Mäkelä et al., 2013), treatment guidelines stress the importance of checking the inhalation technique and educating patients on the correct technique if needed (GOLD, 2019). According to a survey conducted in Spain, only 14% of physicians demonstrated adequate knowledge of inhaled therapy, and only 28% of the physicians checked the inhalation technique of the patient before prescribing a new drug–device combination (Plaza et al., 2012). Educational programs designed to train the trainer have been shown to be effective in improving their competence (Basheti, Armour, Reddel, & Bosnic-Anticevich, 2009; Kim et al., 2009). It is important to involve the patient in the selection of the inhaler and consider their preference (Hodder & Price, 2009) because it may affect the outcome of the inhaled treatment. In addition, NPs should be sure to involve the patient when changing the inhaler. It has been suggested that switching a patient's inhaler without their consent could reduce their self-control over good disease management, potentially damaging the doctor–patient relationship and increasing the burden on resource utilization (Doyle et al., 2010).
Patient outcomes can be influenced significantly by the quality of nursing care particularly because NPs spend more time with patients than any other HCP (DeLucia, Ott, & Palmieri, 2009). An RCT of 191 patients with COPD and asthma found that inclusion of a nursing care program at a pulmonary outpatient clinic resulted in significantly lower exacerbation rates compared with the control group (odds ratio = 0.35; p = .04) (Rootmensen et al., 2008). Nurse practitioners can therefore play a key role in not only designing education/training programs for patients but also evaluating inhaler attributes to assess the best delivery device for the patient based on their preference and characteristics, along with ensuring that patients adhere to their treatment.
Supplemental Digital Content 1 (Table S1, http://links.lww.com/JAANP/A36) lists the commonly used inhaled medications for asthma and COPD, including links to instructions on the correct use of the inhalation devices.
Digital technology and inhaled medications
Use of digital technologies, such as telehealth, provides a means of administering general disease management and education to patients for self-management, while also allowing the possibility of remote monitoring to identify trends and triggers for treatment adjustment (Himes & Weitzman, 2016) (Figure 2). An example of this technology, currently under development, is the VeriHaler device, which consists of a microphone coupled to the inhaler and uses an algorithm (that removes background noise) to assess information related to PIFR, timing of inhalation and actuation of dose, and delivery of the formulation through the device (Sagentia, 2018). The device also records time and date of inhaler usage to monitor compliance.
Information transmitted to an application on a smartphone can allow the NP and the patient to discuss actionable items and how to improve inhaler performance or switch devices altogether. It is expected that as digital technology evolves, patients will be more empowered to take control of their condition and revolutionize health care by shifting the care model from NP monitoring to self-monitoring at home.
The number of drug–device combinations is expected to grow as patent protection on several marketed therapies expires, which makes choosing the right inhaler for the right patient a very important task. When selecting an inhaler, HCPs must consider a range of patient characteristics, including age, cognitive function, dexterity, inspiratory capacity, and concomitant medication. Treatment decisions may be made based on a perspective of cost and effectiveness, such as choosing pMDIs (Brocklebank et al., 2001), but it is also important to consider patient preference and beliefs when prescribing a medication.
Data on lung deposition of the inhaled medication may help differentiate one inhaler from another; however, such studies do not always include comparisons with other drugs or inhalers, limiting the generalizability of such data. It is however very useful for the HCP to know the lung deposition data for the inhaler being prescribed.
Although the importance of correct inhaler technique and adherence to the prescribed treatment is highlighted in most guidelines, general awareness of their importance remains poor (Fink & Rubin, 2005). An algorithm for selecting an appropriate inhaler for a patient with COPD or asthma has been proposed and included the following considerations based on ability of patients to perform conscious inhalation, generate sufficient inspiratory flow, and coordinate breathing with inhaler actuation (Figure 3) (Dekhuijzen et al., 2013).
Although the algorithm is an empirical proposal that needs experimental validation, it is important to note that characteristics of the SMI make it an appropriate choice for all patients who are capable of conscious inhalation, irrespective of their age, severity, or ability to coordinate breathing with device actuation or generating sufficient inspiratory flow. Although SMIs such as Respimat represent a significant advancement in inhalation technology, it is important to focus on training and education, so that patients can appreciate the attributes of the chosen inhaler and are able to use it correctly.
Measures such as implementation of training programs, patient involvement in decision-making, and regular monitoring of inhaler technique hold significant importance because patient perception may be influenced by factors other than the inhaler (e.g., adverse events associated with the inhaled medication). With the large array of devices currently available to the prescribing physician, it is increasingly important to understand factors such as comfort of inhalation that can influence patient preference and the likelihood of the inhaler being used correctly.
Acknowledgments:The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. The authors received no direct compensation related to the development of the manuscript. Writing, editorial support, and formatting assistance were provided by Praveen Kaul and Roderick Sayce of Cactus Communications, which was contracted and compensated by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) for these services. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.
Arcapta®Neohaler®. (2017). Prescribing information. Retrieved from https://www.arcapta.com/Arcapta-Prescribing-Information.pdf
Ari A., Fink J. B. (2011). Guidelines for aerosol devices in infants, children and adults: Which to choose, why and how to achieve effective aerosol therapy. Expert Review of Respiratory Medicine, 5, 561–572.
Basheti I. A., Armour C. L., Reddel H. K., Bosnic-Anticevich S. Z. (2009). Long-term maintenance of pharmacists' inhaler technique
demonstration skills. American Journal of Pharmaceutical Education, 73, 32.
Basheti I. A., Reddel H. K., Armour C. L., Bosnic-Anticevich S. Z. (2005). Counseling about turbuhaler technique: Needs assessment and effective strategies for community pharmacists. Respiratory Care, 50, 617–623.
Batterink J., Dahri K., Aulakh A., Rempel C. (2012). Evaluation of the use of inhaled medications by hospital inpatients with chronic obstructive pulmonary disease. The Canadian Journal of Hospital Pharmacy, 65, 111–118.
Behara S. R., Larson I., Kippax P., Stewart P., Morton D. A. (2012). Insight into pressure drop dependent efficiencies of dry powder inhalers. European Journal of Pharmaceutical Sciences, 46, 142–148.
Berkenfeld K., Lamprecht A., McConville J. T. (2015). Devices for dry powder drug delivery to the lung. AAPS PharmSciTech, 16, 479–490.
Bonini M., Usmani O. S. (2015). The importance of inhaler
devices in the treatment of COPD
Research and Practice, 1.
Borgstrom L., Bondesson E., Moren F., Trofast E., Newman S. P. (1994). Lung deposition of budesonide inhaled via turbuhaler: A comparison with terbutaline sulphate in normal subjects. The European Respiratory Journal, 7, 69–73.
Bosnic-Anticevich S., Chrystyn H., Costello R. W., Dolovich M. B., Fletcher M. J., Lavorini F., Price D. B. (2017). The use of multiple respiratory inhalers requiring different inhalation techniques has an adverse effect on COPD
outcomes. International Journal of Chronic Obstructive Pulmonary Disorder, 12, 59–71.
Bosnic-Anticevich S. Z., Sinha H., So S., Reddel H. K. (2010). Metered-dose inhaler technique
: The effect of two educational interventions delivered in community pharmacy over time. Journal of Asthma
, 47, 251–256.
Brand P., Hederer B., Austen G., Dewberry H., Meyer T. (2008). Higher lung deposition with Respimat Soft Mist inhaler
than HFA-MDI in COPD
patients with poor technique. International Journal of Chronic Obstructructive Pulmonary Disease, 3, 763–770.
Brocklebank D., Ram F., Wright J., Barry P., Cates C., Davies L., White J. (2001). Comparison of the effectiveness of inhaler
devices in asthma
and chronic obstructive airways disease: A systematic review of the literature. Health Technology Assessment, 5, 1–149.
Chan J. G., Wong J., Zhou Q. T., Leung S. S., Chan H. K. (2014). Advances in device and formulation technologies for pulmonary drug delivery. AAPS PharmSciTech, 15, 882–897.
Chorão P., Pereira A. M., Fonseca J. A. (2014). Inhaler
devices in asthma
-an assessment of inhaler technique
and patient preferences. Respiratory Medicine, 108, 968–975.
Chrystyn H., van der Palen J., Sharma R., Barnes N., Delafont B., Mahajan A., Thomas M. (2017). Device errors in asthma
: Systematic literature review and meta-analysis. NPJ Primary Care Respiratory Medicine, 27, 22.
Ciciliani A. M., Langguth P., Wachtel H. (2017). In vitro dose comparison of Respimat® inhaler
with dry powder inhalers for COPD
maintenance therapy. International Journal of Chronic Obstructructive Pulmonary Disease, 12, 1565–1577.
Cohn R. C. (2003). A review of the effects of medication delivery systems on treatment adherence
in children with asthma
. Current Therepeutic Research, Clinical and Experience, 64, 34–44.
Colthorpe P., Voshaar T., Kieckbusch T., Cuoghi E., Jauernig J. (2013). Delivery characteristics of a low-resistance dry-powder inhaler
used to deliver the long-acting muscarinic antagonist glycopyrronium. Journal of Drug Assessment, 2, 11–16.
Dalby R. N., Eicher J., Zierenberg B. (2011). Development of Respimat®
Soft mist inhaler
and its clinical utility in respiratory disorders. Medical Devices, 4, 145–155.
Dekhuijzen P. N. (1998). Inhaler
therapy for adults with obstructive lung diseases: Powder or aerosol? Nederlands tijdschrift voor geneeskunde, 142, 1369–1374.
Dekhuijzen P. N., Bjermer L., Lavorini F., Ninane V., Molimard M., Haughney J. (2014). Guidance on handheld inhalers in asthma
guidelines. Respiratory Medicine, 108, 694–700.
Dekhuijzen P. N., Vincken W., Virchow J. C., Roche N., Agusti A., Lavorini F., Price D. (2013). Prescription of inhalers in asthma
: Towards a rational, rapid and effective approach. Respiratory Medicine, 107, 1817–1821.
DeLucia P. R., Ott T. E., Palmieri P. A. (2009). Performance in nursing. Review of Human Factors and Ergonomics, 5, 1–40.
Demoly P., Hagedoorn P., de Boer A. H., Frijlink H. W. (2014). The clinical relevance of dry powder inhaler
performance for drug delivery. Respiratory Medicine, 108, 1195–1203.
Dhand R. (2010). Intelligent nebulizers in the age of the internet: The I-neb adaptive aerosol delivery (AAD) system. Journal of Aerosol Medicine Pulmonary Drug Delivery, 23, iii–v.
Doyle S., Lloyd A., Williams A., Chrystyn H., Moffat M., Thomas M., Price D. (2010). What happens to patients who have their asthma
device switched without their consent? Primary Care Respiratory Journal, 19, 131–139.
Fergusson R. J., Lenney J., McHardy G. J., Crompton G. K. (1991). The use of a new breath-actuated inhaler
by patients with severe airflow obstruction. The European Respiratory Journal, 4, 172–174.
Fink J. B., Rubin B. K. (2005). Problems with inhaler
use: A call for improved clinician and patient education. Respiratory Care, 50, 1360–1374.
Garvey C., Fahy B., Lareau S., Braman S., Laube B. (2014). Using your metered dose inhaler
(MDI). American Journal of Respiratory and Critical Care Medicine, 190, P5–P6.
Ghosh S., Ohar J. A., Drummond M. B. (2017). Peak inspiratory flow rate in chronic obstructive pulmonary disease: Implications for dry powder inhalers. Journal of Aerosol Medicine Pulmonary Drug Delivery, 30, 381–387.
GINA. (2018). Global strategy for asthma
management and prevention. Retrieved from http://ginasthma.org/
GOLD. (2019). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Retrieved from http://goldcopd.org/
Hawken N., Torvinen S., Neine M. E., Amri I., Toumi M., Aballéa S., Roche N. (2017). Patient preferences for dry powder inhaler
attributes in asthma
and chronic obstructive pulmonary disease in France: A discrete choice experiment. BMC Pulmonary Medicine, 17, 99.
Himes B. E., Weitzman E. R. (2016). Innovations in health information technologies for chronic pulmonary diseases. Respiratory Research, 17, 38.
Hochrainer D., Hölz H., Kreher C., Scaffidi L., Spallek M., Wachtel H. (2005). Comparison of the aerosol velocity and spray duration of Respimat Soft Mist inhaler
and pressurized metered dose inhalers. Journal of Aerosol Medicine, 18, 273–282.
Hodder R., Price D. (2009). Patient preferences for inhaler
devices in chronic obstructive pulmonary disease: Experience with Respimat Soft mist inhaler
. International Journal of Chronic Obstructive Pulmonary Disease, 4, 381–390.
Hohlfeld J. M., Sharma A., van Noord J. A., Cornelissen P. J., Derom E., Towse L., Disse B. (2014). Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. Journal of Clinical Pharmacology, 54, 405–414.
Hoppentocht M., Hagedoorn P., Frijlink H. W., de Boer A. H. (2014). Technological and practical challenges of dry powder inhalers and formulations. Advanced Drug Delivery Reviews, 75, 18–31.
Ibrahim M., Verma R., Garcia-Contreras L. (2015). Inhalation drug delivery devices: Technology update. Medical Devices: Evidence and Research, 8, 131–139.
Kamin W., Frank M., Kattenbeck S., Moroni-Zentgraf P., Wachtel H., Zielen S. (2015). A handling study to assess use of the Respimat® Soft Mist Inhaler
in children under 5 years old. Journal of Aerosol Medicine Pulmonary Drug Delivery, 28, 372–381.
Kew K. M., Karner C., Mindus S. M., Ferrara G. (2013). Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler
maintenance for chronic asthma
in adults and children. The Cochrane Database of Systematic Reviews Electronic Resource, CD009019.
Kilfeather S. A., Ponitz H. H., Beck E., Schmidt P., Lee A., Bowen I., Hesse C. (2004). Improved delivery of ipratropium bromide/fenoterol from Respimat Soft Mist Inhaler
in patients with COPD
. Respiratory Medicine, 98, 387–397.
Kim S. H., Kwak H. J., Kim T. B., Chang Y. S., Jeong J. W., Kim C. W., Jee Y. K. (2009). Inappropriate techniques used by internal medicine residents with three kinds of inhalers (a metered dose inhaler
, diskus, and turbuhaler): Changes after a single teaching session. Journal of Asthma
, 46, 944–950.
Labiris N. R., Dolovich M. B. (2003). Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. British Journal of Clinical Pharmacology, 56, 588–599.
Laube B. L., Janssens H. M., de Jongh F. H., Devadason S. G., Dhand R., Diot P., Chrystyn H. (2011). What the pulmonary specialist should know about the new inhalation therapies. The European Respiratory Journal, 37, 1308–1331.
Lavorini F., Fontana G. A., Usmani O. S. (2014). New inhaler
devices - the good, the bad and the ugly. Respiration; International Review of Thoracic Diseases, 88, 3–15.
Lavorini F., Levy M. L., Corrigan C., Crompton G., Group A. W. (2010). The ADMIT series - issues in inhalation therapy. 6) Training tools for inhalation devices. Primary Care Respiratory Journal, 19, 335–341.
Lavorini F., Magnan A., Dubus J. C., Voshaar T., Corbetta L., Broeders M., Crompton G. K. (2008). Effect of incorrect use of dry powder inhalers on management of patients with asthma
. Respiratory Medicine, 102, 593–604.
Lenney J., Innes J. A., Crompton G. K. (2000). Inappropriate inhaler
use: Assessment of use and patient preference of seven inhalation devices. EDICI. Respiratory Medicine, 94, 496–500.
Lindgren S., Bake B., Larsson S. (1987). Clinical consequences of inadequate inhalation technique in asthma
therapy. European Journal of Respiratory Diseases, 70, 93–98.
Loh C. H., Peters S. P., Lovings T. M., Ohar J. A. (2017). Suboptimal inspiratory flow rates are associated with chronic obstructive pulmonary disease and all-cause readmissions. Annals of the American Thoracic Society, 14, 1305–1311.
Mahler D. A. (2017). Peak inspiratory flow rate as a criterion for dry powder inhaler
use in chronic obstructive pulmonary disease. Annals of the American Thoracic Society, 14, 1103–1107.
Mahler D. A., Waterman L. A., Gifford A. H. (2013). Prevalence and COPD
phenotype for a suboptimal peak inspiratory flow rate against the simulated resistance of the Diskus®dry powder inhaler
. Journal of Aerosol Medicine Pulmonary Drug Delivery, 26, 174–179.
Mäkelä M. J., Backer V., Hedegaard M., Larsson K. (2013). Adherence
to inhaled therapies, health outcomes and costs in patients with asthma
. Respiratory Medicine, 107, 1481–1490.
Melani A. S., Bonavia M., Cilenti V., Cinti C., Lodi M., Martucci P., Gruppo Educazionale Associazione Italiana Pneumologi O. (2011). Inhaler
mishandling remains common in real life and is associated with reduced disease control. Respiratory Medicine, 105, 930–938.
Molimard M., Colthorpe P. (2015). Inhaler
devices for chronic obstructive pulmonary disease: Insights from patients and healthcare practitioners. Journal of Aerosol Medicine Pulmonary Drug Delivery, 28, 219–228.
Molimard M., Raherison C., Lignot S., Balestra A., Lamarque S., Chartier A., Girodet P. O. (2017). Chronic obstructive pulmonary disease exacerbation and inhaler
device handling: Real-life assessment of 2935 patients. The European Respiratory Journal, 49. doi:10.1183/13993003.01794-2016.
Molimard M., Raherison C., Lignot S., Depont F., Abouelfath A., Moore N. (2003). Assessment of handling of inhaler
devices in real life: An observational study in 3811 patients in primary care. J Aerosol Med, 16, 249–254.
NEHI. (2015). The network for excellence in health education. Real world evidence: A new era for health care innovation. The network for excellence in health innovation. Retrieved from http://www.nehi.net/writable/publication_files/file/rwe_issue_brief_final.pdf
Nikander K., Sanders M. (2010). The early evolution of nebulizers. Medicamundi, 54.
Pitcairn G., Reader S., Pavia D., Newman S. (2005). Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler
compared to deposition by metered dose inhaler
or by Turbuhaler dry powder inhaler
. Journal of Aerosol Medicine, 18, 264–272.
Plaza V., Sanchis J., Roura P., Molina J., Calle M., Quirce S., Murio C. (2012). Physicians' knowledge of inhaler
devices and inhalation techniques remains poor in Spain. Jounal of Aerosol Medicine Pulmonary Drug Delivery, 25, 16–22.
Price D. B., Roman-Rodriguez M., McQueen R. B., Bosnic-Anticevich S., Carter V., Gruffydd-Jones K., Chrystyn H. (2017). Inhaler
errors in the CRITIKAL study: Type, frequency, and association with asthma
outcomes. Journal of Allergy Clinical Immunology Practice, 5, 1071–1081 e1079.
Restrepo R. D., Alvarez M. T., Wittnebel L. D., Sorenson H., Wettstein R., Vines D. L., Wilkins R. L. (2008). Medication adherence
issues in patients treated for COPD
. International Journal of Chronic Obstructive Pulmonary Disorder, 3, 371–384.
Roche N., Dekhuijzen P. N. (2016). The evolution of pressurized metered-dose inhalers from early to modern devices. Journal of Aerosol Medicine Pulmonary Drug Delivery, 29, 311–327.
Rootmensen G. N., van Keimpema A. R., Jansen H. M., de Haan R. J. (2010). Predictors of incorrect inhalation technique in patients with asthma
: A study using a validated videotaped scoring method. Journal of Aerosol Medicine Pulmonary Drug Delivery, 23, 323–328.
Rootmensen G. N., van Keimpema A. R., Looysen E. E., van der Schaaf L., de Haan R. J., Jansen H. M. (2008). The effects of additional care by a pulmonary nurse for asthma
patients at a respiratory outpatient clinic: Results from a double blind, randomized clinical trial. Patient Education and Counseling, 70, 179–186.
Sagentia. (2018). Verihaler: Connected health system for monitoring adherence
. Retrieved from https://www.sagentia.com/case-study/verihaler/
Sanchis J., Gich I., Pedersen S., & Aerosol Drug Management Improvement Team (ADMIT). (2016). Systematic review of errors in inhaler
use: Has patient technique improved over time? Chest, 150, 394–406.
Schaeffer N. E. (2012). The role of human factors in the design and development of an insulin pump. Journal of Diabetes Science Technology, 6, 260–264.
Seebri®Neohaler®. (2018). Prescribing information. Retrieved from https://www.seebri.us/Seebri-Prescribing-Information.pdf
Sestini P., Cappiello V., Aliani M., Martucci P., Sena A., Vaghi A.; Associazione Italiana Pneumologi Ospedalieri Educational, G. (2006). Prescription bias and factors associated with improper use of inhalers. Journal of Aerosol Medicine, 19, 127–136.
Souza M. L., Meneghini A. C., Ferraz E., Vianna E. O., Borges M. C. (2009). Knowledge of and technique for using inhalation devices among asthma
patients and COPD
patients. Jornal brasileiro de pneumologia, 35, 824–831.
Stein S. W., Sheth P., Hodson P. D., Myrdal P. B. (2014). Advances in metered dose inhaler
technology: Hardware development. AAPS PharmSciTech, 15, 326–338.
Stein S. W., Thiel C. G. (2017). The history of therapeutic aerosols: A chronological review. Journal of Aerosol Medicine Pulmonary Drug Delivery, 30, 20–41.
Stevens N. (2003). Inhaler
devices for asthma
: Choice and technique. Professional Nurse, 18, 641–645.
Turan O., Turan P. A., Mirici A. (2017). Parameters affecting inhalation therapy adherence
in elderly patients with chronic obstructive lung disease and asthma
. Geriatrics & Gerontology International, 17, 999–1005.
Usmani O. S., Biddiscombe M. F., Barnes P. J. (2005). Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. American Journal of Respiratory and Critical Care Medicine, 172, 1497–1504.
Utibron®Neohaler®. (2018). Prescribing information. Retrieved from https://www.utibron.com/Utibron-Prescribing-Information.pdf
Van Der Palen J., Eijsvogel M. M., Kuipers B. F., Schipper M., Vermue N. A. (2007). Comparison of the diskus inhaler
and the HandiHaler regarding preference and ease of use. Journal of Aerosol Medicine, 20, 38–44.
Virchow J. C., Crompton G. K., Dal Negro R., Pedersen S., Magnan A., Seidenberg J., Barnes P. J. (2008). Importance of inhaler
devices in the management of airway disease. Respiratory Medicine, 102, 10–19.
Virchow J. C., Weuthen T., Harmer Q. J., Jones S. (2014). Identifying the features of an easy-to-use and intuitive dry powder inhaler
and chronic obstructive pulmonary disease therapy: Results from a 28-day device handling study, and an airflow resistance study. Expert Opinion on Drug Delivery, 11, 1849–1857.
Wachtel H., Kattenbeck S., Dunne S., Disse B. (2017). The Respimat® development story: Patient-centered innovation. Pulmonary Therapy, 3, 19–30.
Westerik J. A., Carter V., Chrystyn H., Burden A., Thompson S. L., Ryan D., Price D. B. (2016). Characteristics of patients making serious inhaler
errors with a dry powder inhaler
and association with asthma
-related events in a primary care setting. Journal of Asthma
, 53, 321–329.