To date, the most effective treatment available for asthma is the regular use of inhaled medications, which delivers the medication directly to the lungs and allows for optimal efficacy and safety.12,94,95 The efficacy of inhaled treatment is partly dependent on the correct use of inhalers, a common issue reported by patients and clinicians. There are many products and devices available on the market for delivering a variety of drugs from different classes. However, the inhalation technique varies between products and this increases the chance of administration-related error and, consequently, reduces the ability to control the disease, especially if multiple inhalers are being used.96,97 This issue is reflected in multiple studies that have assessed patient preferences for attributes of inhalers; studies frequently cited ease of use, functionality, and instructions that are simple and easy to follow as aspects of an inhaler that are important to patients.94,98,99 Of the many types of inhalers, pressurized MDIs and dry powder inhalers are most commonly used for the treatment of asthma.12,94,100
The product under review is QMF administered via the Breezhaler, which is an inhalation-driven, single-dose dry powder inhaler with active ingredients dispersed in a lactose monohydrate excipient.101
A supplemental literature search was completed by CADTH for studies that assessed asthma patient preferences for, and use of, the Breezhaler device in an effort to evaluate Breezhaler performance in comparison to other available products in terms of device preference, ease of use, and device satisfaction. The following describes the studies identified, in addition to one observational study submitted by the sponsor that included patients with COPD.
The first is an observational study (N = 333) that included outpatients with asthma (n = 175) and COPD (n = 158); the study assessed patients’ usability and preference of the Breezhaler, Genuair, and Handihaler devices via the Handling Questionnaire, a validated questionnaire used to assess the determinants of choice and patient usability of inhaler devices in diseases of airflow limitation. Patients were divided into three groups. One group (n = 127) tested all three devices, another (n = 110) compared the Breezhaler and the Genuair, and the last group (n = 96) tested the Breezhaler and the Handihaler devices. The Handling Questionnaire was administered to all three groups. Within this study, a nurse demonstrated the functioning of the device, after which patients described their first impressions of the device. Then, patients prepared the actuation of the device and the nurse recorded technical errors made. Lastly, both patients and nurses recorded their preferences and comments on device functionality. Of the patients who tested all three devices, approximately 50% preferred the Genuair, with only 5% saying they preferred the Breezhaler. The Breezhaler was least preferred in terms of appearance, comfort, safety, and convenience. According to the patients and nurses, the Breezhaler was the most problematic; 50% of patients perceived that they made a mistake in preparing the Breezhaler while 90% of nurses perceived that patients made a mistake, and 80% of patients were still unable to use the Breezhaler after the first demonstration. The mean number of patient attempts to prepare the first proper inhalation was 1.5, 2.5, and 2.6 for the Genuair, Breezhaler, and Handihaler, respectively (Genuair versus Breezhaler; P < 0.0001). It took a mean of 12 minutes (SD = 0.6 minutes) to teach patients how to correctly use the Breezhaler compared to approximately five minutes (SD = 0.4 minutes) for the Genuair and six minutes (SD = 0.5 minutes) for the Handihaler. This included the nurse’s explanation and the maneuvres the patient had to perform to prepare the device. Patient age was a contributing factor where older patients needed more attempts to perform the first proper inhalation and more time to learn how to use the device; their success rate was lower. The Breezhaler device was the least favourite of the three evaluated even when an asthma-only subgroup was analyzed.102
The second study is an observational study (N = 333) that evaluated patient preference of the Breezhaler, Genuair, and Respimat devices in asthma and COPD patients. It is published by the same authors of the previous study and has a very similar study design. In this study, the Handling Questionnaire informed that the Breezhaler was the least liked by patients, and was perceived by patients and nurses as the most difficult to use. Here, the Breezhaler was the device that took the most attempts to prepare the first actuation (2.6 ± 1.1 versus 1.6 ± 0.8 for Genuair and 1.6 ± 1.0 for the Respimat; P < 0.0001 for Breezhaler versus Genuair and Breezhaler versus Respimat). As well, 82%, 44.3%, and 37.6% of patients were unable to prepare the Breezhaler, Genuair, or Respimat, respectively, on their first attempt. The persisting trait of the Breezhaler device as the least favourite and most difficult to use device was evident even when an asthma-only subgroup of the population was analyzed.103
The third study was a prospective, single-centre, observational study (N = 216) that evaluated the number of instructions necessary to minimize errors in pressurized MDIs, Turbuhaler, Breezhaler, Respimat, and Ellipta in patients with asthma (n = 135) and COPD (n = 81). All the devices tested required at least three instructions to minimize the error rate to 10% or less. Of the patients who tested the Breezhaler device (n = 32; three patients had asthma and 29 patients had COPD), around 60%, 20%, and 3% made a mistake in overall handling and device inhalation after one set, two sets, and three sets of pharmacist instructions on device use, respectively. This was largely similar to all the other devices tested. This study illustrates that three sets of instructions may be necessary to teach patients about proper Breezhaler use.104
Additionally, an observational study (N = 2,935) that evaluated handling errors of inhaler devices in patients with COPD — including the Breezhaler — was submitted by the sponsor.105 A total of 876 patients used the Breezhaler device, 452 used Diskus, 598 used Handihaler, 422 used a pressurized MDI, 625 used Respimat, and 420 used Turbuhaler. (Note: Patients may have used more than one type of inhaler). Correct use of the devices was assessed by 212 general practitioners and 50 respirologists. The Breezhaler had the greatest proportion of patients making no errors at 36.5% (95% CI, 33.3 to 39.7), followed by the Turbuhaler at 30.5% of patients (95% CI, 26.1 to 34.9) without an error. The worst performing device was the Handihaler at 10.7% of patients (95% CI, 8.2 to 13.5) without an error. Correspondingly, the Breezhaler was associated with the fewest patients (15.4%) making critical errors in administration, followed by Diskus (21.2%), Handihaler (29.3%), Turbuhaler (32.1%), pressurized MDIs (43.8%), and Respimat (46.9%). It should be noted that the first three studies outlined earlier included both asthma and COPD patients, and the study provided by the sponsor was only on patients with COPD. No studies were identified that assessed Breezhaler device preference in asthma patients only. There are differences in baseline characteristics of asthma patients versus COPD patients. For example, asthma patients tend to be younger than COPD patients and typically have fewer comorbidities that could influence uptake of instructions and the use of an inhaler device.102 A younger population is one that can exert more physical strength and dexterity related to their inhaler technique. In a study published by Ciciliani et al. (2019) evaluating finger strength and its relation to patient device satisfaction, the authors found that finger strength differed between the age groups evaluated (five years to 17 years, 18 years to 64 years > 65 years), but all age groups had sufficient finger strength to operate the Breezhaler. Moreover, participants expressed dissatisfaction related to “the inhaler buttons did not move once pressed” for all the inhalers tested except for the pressurized MDIs. Generally, participants with arthritis reported that the hand position required to operate the Breezhaler was uncomfortable and the elderly preferred larger devices while children preferred smaller devices (like the Breezhaler). Overall, patients were the least satisfied by the Breezhaler when compared to the Respimat, Aerolizer, Genuair, Diskus, Ellipta, Handihaler, Turbuhaler, and Atrovent.106 The study on patients with COPD that was identified by the sponsor did not control for factors such as health literacy and prior device training, which may influence proper inhaler technique. Moreover, it only included patients with COPD, who were older (mean age of 65.4 years). Therefore, the generalizability of the results of this study to Canadian patients with asthma may be limited.
These studies, when taken together, suggest that the Breezhaler device may be the least preferred device by patients with asthma. There are conflicting data on whether the device requires the most instruction and attempts to prepare correctly in order to deliver a dose with no critical errors. Larger comparative studies in patients with asthma are required to draw concrete conclusions about the ease of use and patient preferences related to the Breezhaler device.
