Inhalation treatment of respiratory conditions such as asthma and COPD is the predominant mode of therapy for the simple and logical reason that applying pharmacological agents to the target organ reduces the drug dose, maintains good efficacy, as well as reduces potential systemic adverse effects. To this end, there are now multiple systems for delivering therapeutic agents either as single or fixed dose combinations of two or three agents. The focus of this article is on the delivery devices and potential challenges with multiple device options rather than the therapeutic agents. It is important to recognize that even the best therapeutic agents cannot be effective unless they are delivered to the correct target organ or site.
Given the wealth of treatment and delivery options, it is surprising that treatment of COPD remains less than optimal and reported rates of device use errors remain high (Sanchis J et al. 2016, Molimard et al. 2017). This topic has been broadly discussed in the latest Global Initiative for Obstructive Lung Disease (GOLD 2021) report, with an emphasis on effective training and appropriate device selection for COPD patients. In a recent study, only 23% of patients discharged from the hospital demonstrated appropriate use of dry powder inhalers (Sulaiman et al. 2017). It is important to note that despite significant improvements in device design and a greater understanding of drug delivery issues, such as aerodynamics of particle flow as well as optimal particle size for pulmonary delivery, device error rates have remained high for decades (Sanchis et al. 2016). It is now well-recognized that education and training are key components of proper inhaler use, which requires regular assessment and the implementation of the “teach back” method (Dantic 2014). The importance of continued assessment is highlighted by the observation that the training effect does not persist (Press et al. 2016).
Inhalation delivery options. In general, there are four drug delivery options—pressurized metered dose inhalers (pMDI), dry powder inhalers (DPI), soft mist inhaler (SMI), and nebulizers. Except for the SMI, there are multiple variants of pMDIs, DPIs, and nebulizers. Irrespective of device type, instructions for use (IFU) is provided by the manufacturers in the Prescribing Information or on the product label. The IFU is a stepwise guide to the proper use of a device and is an additional resource for the user to help with proper use of the device. The importance of training and education of caregivers and patients as well as continued assessment cannot be overemphasized.
What are the causes of handheld inhalation device use errors? All approved devices are designed and rigorously tested to deliver pre-defined drug doses to the lungs according to the IFU. Nevertheless, errors remain unacceptably high, particularly in COPD patients, who tend to be elderly and may suffer from lack of dexterity, lack of coordination to actuate the device and inhale at the same time or suffer cognitive challenges that negatively impact comprehending or remembering instructions. Device use errors generally fall into critical or non-critical categories. Critical errors are those that prevent any drug from getting into the lungs. Often, missing seemingly simple steps lead to significant errors such as not shaking a pMDI device prior to use (to resuspend drug particles in the canister). All handheld devices require certain breathing maneuvers for successful drug delivery to the lungs. DPIs require the patient to generate sufficient and consistent inspiratory flow (device dependent) during inhalation to release the powder from the device, move the disaggregated particles in an airstream through the oral cavity, and finally deposit the drug into the lungs. With pMDIs, the propellent in the canister provides the energy to deliver the drug but the “explosive” nature of each actuation causes impaction of the drug in the oral cavity if a spacer is not used. These devices require actuation and breath coordination otherwise the dose is mostly wasted. The SMIs release the medication as a gentler mist so the patient does not have to generate the inspiratory energy, but there is still the requirement for coordinated actuation and breathing to achieve effective drug delivery. All handheld devices have a breath holding requirement (about 10 seconds) according to the IFU in order to allow for the drug particles to land on the airway wall rather than be exhaled. This is often very difficult for a COPD patient who is short of breath already and may not be able to achieve this step effectively. An important consideration is the fact that all handheld devices are designed for one or two actuations per dose, which means that if that dose is missed or wasted due to an error, the patient is without medication until the following dose.
Handheld device use errors have consequences in terms of disease management, and several large studies have shown the association of poor outcomes as a result of device use errors (Molimard et al. 2017, Van der Palen et al. 2016) and increased health resource utilization (Roggin et al. 2016). A further complicating factor is that most patients are prescribed multiple medications which are in different device types, so the burden is on the patient to remember how to use each device type effectively. This is a significant challenge for many COPD patients.
Nebulizers. Nebulizers are an important drug delivery option and can be used in any COPD patient. Nevertheless, this option is commonly reserved for hospitalized patients or those who are unable to use handheld devices. Traditional jet nebulizers are cumbersome and not generally portable, as they are dependent on a source of pressurized air, although many jet nebulizers are now made small enough to be portable and user-friendly. Advances in nebulizer design and function have made use of piezo-electric and vibrating membrane technologies to reduce the size of nebulizers and make them portable and silent (Martin & Finlay, 2015, Pham et al. 2017). Irrespective of nebulizer type, there are some important differences compared with handheld devices, which should be considered when deciding on selecting a device type for a patient. Inhaling medication from a nebulizer does not require any special respiratory maneuver by the patient who continues to breath normally (tidal breathing) through the mouthpiece. There is no requirement for breath holding, as per handheld devices. Importantly, nebulization occurs over several minutes (two to 10 minutes, depending on the device), which allows the patient to take many breaths of the drug mist, therefore increasing the probability that drug will get into the lungs. This is particularly important in frail patients who are most susceptible to incorrect use of handheld devices and usually have poor lung function. It is important to assess the physical, physiological, and psychological status of a patient prior to recommending a device type (Patel 2017) particularly in nursing home or long-term care residents.
Take home message. Inhalation drug delivery is the most logical and appropriate means of treating lung disease. The challenge is to ensure that patients receive the device type that they can use and to ensure that the devices are used correctly over a long period of time. In this respect, device selection must consider the patient’s capability to learn and activate the device correctly and to periodically reassess the inhalation technique. Some patients don’t have the capability to correctly use any handheld devices. The recommendation in such cases would be to switch to a nebulizer, which may require a caregiver who would set up and clean the equipment or device.
The range of inhalation devices (DPI, pMDI, SMI, and nebulizer) have various attributes; device selection should depend on specific requirements of each COPD patient
Regular training in inhalation technique is important for treatment to remain effective
Inhalation device technique (and adherence to therapy) should be assessed before determining that the current therapy is insufficient
Patients who do not master a technique may require a change in inhalation device
Switching a device without adequate patient training may negatively affect adherence and, over time, may impact disease control
In patients who are not able to use handheld devices, nebulizers are an important option
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