Inhaler choice in primary practice

Over the next decade, chronic obstructive pulmonary disease (COPD) is expected to become the third most common cause of death in the world [1]. The rising prevalence of both COPD and asthma means treatment of obstructive airway diseases will continue to be a common management challenge for primary practitioners in ambulatory care settings, as well as clinicians in hospital settings. Guidelines for obstructive airway diseases rely increasingly on management with inhaled rather than oral or parenteral medications [2, 3]. The once ubiquitous quick-relief bronchodilator delivered by pressurised metered-dose inhaler (pMDI) has given way to a bewildering array of drugs, delivery devices, add-on devices (spacers) and drug/device combinations. Given the increasing importance and complexity of inhaler selection, this review has been undertaken with the goal of developing a simple algorithm or tool to guide inhaler choice for patients with COPD.

The majority of patients with COPD or asthma receive their respiratory care in a primary care practice setting: in North America, ∼80–85% of such patients receive care from a primary care practitioner alone and do not see a specialist [4, 5]. Visits to a primary practice are typically brief. For a patient with a respiratory disease, the 5- or 10-minute encounter could encompass diagnosis, assessment of control, review of medication usage, physical examination, measurement of lung function, prescription and education. For the older patient with COPD, common comorbidities might also be assessed. Due to time pressures, the selection of an inhaler device and training the patient in its correct use may be delegated explicitly or implicitly. A substantial proportion of patients may receive no inhaler instruction. In one primary practice audit of asthma management undertaken in Canada, 28% of 6,684 patients reported never having demonstrated their inhaler technique to a healthcare professional [6]. Moreover, physicians seem complacent about this neglect: 221 Canadian physicians who participated in the same practice audit estimated that 25% of their patients had never demonstrated their inhaler technique [6]. This Review focuses on the needs of the patient with COPD, but no inhaler choice algorithm intended for primary practice can remain practical if it ignores other diseases and age groups, and many principles of inhaler use in COPD patients are, fortunately, common to patients with asthma, as are the errors in inhaler technique [7]. Unfortunately, there is a dearth of inhaler research specific to patients with COPD and therefore it is necessary to extrapolate cautiously from research undertaken in patients with asthma, both stable and acutely ill.

PATIENT AND CAREGIVER KNOWLEDGE OF INHALERS

Numerous studies have identified sub-optimal inhaler technique as a common problem in patients with respiratory disease [8, 9]. Early studies clearly showed that patients struggled with conventional pMDIs. Although many errors in handling were detected by investigators, the most common was difficulty coordinating device actuation and inhalation [10]. Investigators working in referral centres, such as pulmonary function laboratories, have estimated that between 14–89% of patients seen for the first time will use their inhalers sub-optimally [9, 11]. On average, about one-third of patients assessed in a specialised centre do not use their inhaler to good advantage. However, if these studies are examined critically, it becomes clear that not all handling errors are crucial. For example, although failure to remove the cap from a pMDI before use will clearly render it useless, failing to shake the device before the second of two sequential inhalations may have little effect on drug delivery. Dry powder inhalers (DPIs) have been studied more recently [12, 13] and although they are thought to be easier to use than pMDIs, there are still potential problems when patients attempt to use them. Most importantly, some patients fail to generate inspiratory flow rates that are high enough to deliver sufficient drug to the lungs. This is certainly the case with most children <6 yrs of age. Many examples of DPI mishandling by adult and adolescent patients have also been reported [14, 15]. Some will hold the device in the wrong position when loading the dose or inhaling, and others may shake the device after priming it or tap some of the powder on to their hand to check that a dose has been dispensed, thereby dispersing the powder before it can be inhaled. Other patients may attempt to use an open-mouth inhalation technique with a DPI. As with pMDIs, some ways of mishandling a DPI may reduce efficacy slightly while others may render the device useless. In the literature, there is little consensus for any device as to what constitutes a crucial handling error.

How crucial different handling errors are may also depend upon the drug being delivered. In general, bronchodilators may be more resistant to improper inhaler use than inhaled corticosteroids (ICS), although this is difficult to assess clinically. This may be because recommended bronchodilator dosages are on the plateau of the dose–response curve so that even sub-optimal delivery results in a clinically meaningful, if not maximal, effect. Patients who do not notice an effect after one dose of bronchodilator often continue dosing until they do. In the case of β₂-agonists, an error resulting in poor deposition may be less crucial because the rich endobronchial microcirculation may redistribute absorbed drug.

Although there are many papers that describe patients' handling of inhalation devices, fewer focus on their preference for different devices. Most studies of preference are performed somewhat crudely and typically use unvalidated scoring systems for assessing preference. In some studies, patients seem to prefer a new inhaler over an existing device for reasons that bear little relevance to its efficacy, such as novelty, colour or shape. In addition, companies with a commercial interest in the device under test have sponsored a large majority of these papers. The subject of measuring preference is dealt with in an accompanying paper in this Review [16].

Given our increasing reliance on inhaled medications as the foundation of care for asthma and COPD, and the well-known phenomenon of patient inhaler mishandling, a well-established educational approach for prescribing inhalers to patients could be expected. Regrettably, studies suggest that many caregivers are unfamiliar with correct inhaler technique [17, 18]. Although physicians are the least adept of caregivers at handling inhalers, even respiratory ward nurses and respiratory therapists may make mistakes in device technique, particularly with newer devices. Pharmacists charged with dispensing inhalers may also have difficulty instructing patients correctly [19, 20].

SPECIAL CONSIDERATIONS IN COPD

Patients with COPD may present special problems when the prescribing physician comes to select an inhalation device. Most obviously, the majority of patients with COPD are advanced at the time of diagnosis. Their severe expiratory airflow limitation is typically accompanied by decreased inspiratory capacity, hyperinflation and respiratory muscles that work at a mechanical disadvantage. All of these factors combine to reduce inspiratory flow rates, which could diminish lower airway deposition of drug if inhaled from a DPI. Most DPIs are designed to ensure that drug delivery is adequate even at relatively low inspiratory flow rates and that the device offers little resistance to the struggling patient [21]. However, devices vary in their flow characteristics, with some requiring higher pressure drops to disperse the powder into particles of respirable size [22]. Most COPD patients are middle-aged or older and some of the more severely affected patients are elderly. Although advanced age alone is not thought to be a major factor in how patients handle an inhaler device [23], the comorbidities suffered by COPD patients in advanced age should be considered when choosing an inhaler, as they may markedly affect handling. For example, patients with arthritis will struggle with pMDIs because actuation (pressing on the canister) may be difficult. Similarly, patients with neuromuscular disease may have handling or inhalation problems [23].

The greatest challenge for inhaler selection in COPD is determining efficacy. By definition, patients with COPD are less responsive to bronchodilators than patients with asthma. The effect of an inhaled bronchodilator in an asthma patient can be demonstrated in only a few minutes using spirometry. In the patient with COPD, spirometric changes are much smaller and vary from day to day. Guyatt et al. [24] have shown clearly that the response to inhaled β₂-agonists on any given day is a poor guide to responsiveness on any other day. Even longer-term responses to potent systemic agents such as oral corticosteroids are challenging to interpret and may bear little relationship to the patients' responses to ICS over time. In the absence of rapidly and easily measured spirometric outcomes, most clinicians rely upon subjective patient responses to guide bronchodilator prescription. ICS prescriptions for the COPD patient tends to be guided by general principles and the clinician's assessment of exacerbation rate. More recently, end-points used in clinical trials have included increased inspiratory capacity, reduced dynamic hyperinflation, improved exercise tolerance or decreased exacerbation rate. Such outcomes, however, are not currently validated as practical assessments for use by a prescribing primary care physician.

The decreased inspiratory and expiratory flow rates and decreased inspiratory capacity of the COPD patient may also pose problems for the practitioner attempting to evaluate correct inhaler technique. A recent study has compared patient handling of a conventional and a breath-actuated pMDI in elderly patients, half of whom had never used an inhaler [25]. Inhaler handling was monitored in a conventional subjective fashion (by trained technologists), and by a simple inhalation-monitoring device that recorded when device actuation occurred and measured inspiratory volume. The authors discovered that trained technologists sometimes failed to notice inadequate technique; patients who appeared to inhale adequately were inhaling too rapidly, too slowly or with inadequate volume. Even when such errors are imperceptible to the trained observer, an objective monitoring device can detect them readily. Although such devices have become available for use in office settings, this remains uncommon, with the risk that inadequate inhaler technique may go undetected.

THE FUNDAMENTALS OF INHALER CHOICE

Several general principles of inhaler selection and use can be derived from the medical literature and have recently been reviewed in detail by a joint committee of the American College of Chest Physicians (ACCP) and the American College of Asthma, Allergy and Immunology (ACAAI) [26].

In brief summary, pMDIs are convenient for delivering a wide variety of drugs to a broad spectrum of patients. The crucial steps in technique appear to be inhalation from functional residual capacity or residual volume, timed to coincide with device actuation and at a reasonably slow and steady inspiratory flow rate. A breath-hold of 5–10 seconds may increase drug deposition but may not be crucial for efficacy. For patients who have trouble coordinating inhalation with device actuation, the use of a spacer (with a valve) may obviate this difficulty, though most of these devices are cumbersome to store and transport. The use of spacers, however, is mandatory for infants and young children. DPIs are usually easier for patients to handle and a growing number of drug types are available in several DPI formats. The key issue for dry powder inhalation is adequate inspiratory flow rate. The most severely ill patients and the very young may not be candidates for a DPI. Gas-driven nebulisers can be used by almost any patient, in a variety of clinical settings from the home to the intensive care unit for the intubated and ventilated patient. However, nebulisers are more expensive, cumbersome and relatively time-consuming to use, compared with handheld devices. Most gas-driven nebulisers require time for dose preparation and loading, and ∼20 minutes for inhalation. These attributes can and should limit the use of nebulisers whose effect can be matched by handheld devices in almost all clinical settings.

A new type of device that further expands the range from which physicians can choose is the soft mist inhaler. Such inhalers use a variety of means other than compressed gas, to produce a very fine liquid aerosol (a “soft mist”) from a handheld device. In the case of the Respimat® Soft Mist^TM Inhaler (Boehringer Ingelheim & Co. KG, Ingelheim, Germany), for example, a metered dose of drug solution is forced by the energy of a compressed spring through a nozzle system (the “uniblock”), producing two fine jets of liquid that converge at a preset angle and collide to generate the soft mist [27]. Respimat® Soft Mist^TM Inhaler appears to be easy to use: dosing requires a single inhalation and produces greater lower airway deposition than conventional pMDIs [28]. Although a wide range of compounds have yet to be tested in soft mist inhalers, available studies on Respimat® Soft Mist^TM Inhaler suggest that the high lung deposition enables the desired clinical effect to be achieved with lower nominal doses and without propellant or adjuvants that might provoke adverse effects [29–34].

POSSIBLE APPROACHES TO INHALER SELECTION

Relatively little research has been carried out on how primary practitioners select inhalers. Anecdotal evidence suggests that many practitioners choose to become familiar with a single type of inhaler and prescribe it exclusively. Certainly, for many years in Western nations, the pMDI was the most commonly prescribed handheld inhaler. The obvious drawbacks to the “one size fits all” approach are that either patients will use the selected device sub-optimally or that the compound best suited to the patient's therapeutic needs will not be available in the selected device. Some physicians prescribe more than one type of inhaler, but delegate the task of monitoring inhaler technique to others. If the responsibility is delegated explicitly to an asthma educator, the treatment outcomes are likely to be reasonable [18]. Often, though, the delegation is implicit and the intended education and monitoring may not happen. As noted above, pharmacists charged with the task of dispensing inhalers may be unfamiliar with their use and may be ill-equipped to teach their optimal use to patients [19]. A better strategy would be for physicians to become familiar with more than a single inhaler and, ideally, with all the available inhalers that their patients may need. The ability to prescribe more than one type of inhaler will allow primary practitioners to select the one best suited to their patient's needs; implicitly, the physician will require a method for selecting this device.

QUESTIONS THAT NEED TO BE ANSWERED

Although much of the respiratory community is aware that patient use of inhalers is often sub-optimal, there are many unanswered questions about the selection of inhalation devices. There is clearly a need to determine the impact of inhaler choice on compliance and clinical outcome. Literature in the asthma field suggests that sub-optimal inhaler technique is associated with poor outcome [38], but less is known about the impact of inhaler choice and inhaler handling on outcome in patients with chronic obstructive pulmonary disease. Similarly, little is known about the effect of patient preference for a given inhaler type on treatment outcomes. As already stated, it will be challenging to select outcomes that are feasible for use in the primary practice setting to determine whether inhaler choice for a chronic obstructive pulmonary disease patient has been successful. Once this is done, however, it will be possible to test the value of a checklist, such as that proposed above, to guide primary practitioners in device selection for patients with chronic obstructive pulmonary disease and possibly for patients with other respiratory diseases.

SUMMARY

1. Primary practitioners should familiarise themselves with the characteristics of several inhalers and choose a device that a chronic obstructive pulmonary disease patient can use correctly and that will be of benefit to them.

2. The selection of a device for a chronic obstructive pulmonary disease patient may be influenced by patient comorbidities as well as by the patient's ability to handle the device and perform the necessary inhalation manoeuvres.

3. When selecting a device for the patient with respiratory disease, the primary practitioner should check that it is affordable and that the patient can handle it correctly. The patient's and physician's preferences should also be taken into account.

4. The patient's ability to handle a device should be assessed by the practitioner or other trained professional. They should also assess whether the patient can properly prepare and actuate the device, take an adequate inspiration and coordinate actuation of a pressurised metered-dose inhaler with inspiration.