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The ADMIT series - Issues in Inhalation Therapy. 7) Ways to improve pharmacological management of COPD: The importance of inhaler choice and inhalation technique
Abstract
Since inhalation therapy will probably remain the preferred route of treatment for patients with chronic obstructive pulmonary disease (COPD), it is important to provide helpful information that may assist physicians and nurses in selecting the appropriate device(s) for individual patients as well as prescribing the correct medication. In line with the GOLD guidelines, the Aerosol Drug Management Improvement Team (ADMIT) propose a three-part "therapy adjustment strategy", which provides health care professionals with a way to monitor and check the delivery of inhaled medication. The strategy is a summation of the key principles behind the evidence-based management of stable COPD and exacerbations. It offers physicians a rapid and user-friendly overview of the requirements of COPD management starting with making the diagnosis and continuing with optimisation of therapy in follow-up appointments. It includes everything from check lists for disease assessment and recommendations for reducing risk factors to selecting the proper inhalers and continuous checking of compliance and correct inhaler technique. These practical COPD therapy adjustment algorithms have been used as part of an interactive online course developed by the ADMIT group (www.admit-online.info). The COPD "flash" video available at this web site offers suggestions on how to organise a complete doctor-patient consultation.
... The wide selection of available devices allows treatment to be tailored to the individual patient, but also complicates the decision on which device to choose. 10 Each type of inhaler requires a particular inhalation technique, which, if not mastered, can negatively affect drug delivery to the lungs. Alongside drug properties, key factors to consider include the inspiratory profile that a patient can achieve, as well as age, cognitive capacity and functional ability of the patient. ...
... 16 The importance of physician familiarity with a device has also been highlighted. 10 A Delphi consensus statement detailed some of the inhaler device selection factors judged to be most critical by experts in asthma and COPD: 17 consensus was achieved for the choice of inhalation device being as important as that of the active substance. For criteria influencing choice of inhaler device, patients' ability to use the device correctly scored highest with physicians. ...
... Considerations for appropriate device selection.10,13 ...
Inhaled therapies are the cornerstone of treatment in asthma and chronic obstructive pulmonary disease, and there are a multitude of devices available. There is, however, a distinct lack of evidence-based guidance for healthcare providers on how to choose an appropriate inhaler. This review aims to summarise recent updates on topics related to inhaler choice, and to offer practical considerations for healthcare providers regarding currently marketed devices. The importance of choosing the right inhaler for the right patient is discussed, and the relative merits of dry powder inhalers, pressurised metered dose inhalers, breath-actuated pressurised metered dose inhalers, spacers and soft mist inhalers are considered. Compiling the latest studies in the devices therapy area, this review focuses on the most common types of handling errors, as well as the comparative rates of incorrect inhalation technique between devices. The impact of device-specific handling errors on inhaler performance is also discussed, and the characteristics that can impair optimal drug delivery, such as inhalation flow rate, inhalation volume and particle size, are compared between devices. The impact of patient perceptions, behaviours and problems with inhalation technique is analysed, and the need for appropriate patient education is also highlighted. The continued development of technology in inhaler design and the need to standardise study assessment, endpoints and patient populations are identified as future research needs.
The reviews of this paper are available via the supplemental material section.
... [3,4,7] An optimal inhalation technique is essential to the inhaled drug being successfully deposited in the lungs. [3,[7][8][9][10][11][12][13][14][15] While proper deposition is partly dependent on the medication itself (e.g. type of inhaler device, particle size), it also relies on the patient performing a truly correct inhalation manoeuvre. ...
... type of inhaler device, particle size), it also relies on the patient performing a truly correct inhalation manoeuvre. [3,8,9] Thus, both inhalation technique and performance form integral parts of drug deposition within the lungs. [3,[6][7][8][9][10][15][16][17] It is widely accepted that optimal inhalation therapy can be hindered by poor patient adherence to treatment, whether it be intentional (patient's beliefs, doubts, fears of adverse effects) or non-intentional (when the patient forgets to use the inhaler device, or has no access to it). ...
... [3,8,9] Thus, both inhalation technique and performance form integral parts of drug deposition within the lungs. [3,[6][7][8][9][10][15][16][17] It is widely accepted that optimal inhalation therapy can be hindered by poor patient adherence to treatment, whether it be intentional (patient's beliefs, doubts, fears of adverse effects) or non-intentional (when the patient forgets to use the inhaler device, or has no access to it). [6,18] Importantly, even if the patient is willing and able to use the inhaler, a number of studies have identified that patient-related errors in inhalation techniques, particularly in those with COPD, are common and associated with reduced disease control. ...
Background
Inhalation errors frequently occur in patients receiving inhalation treatment, which can significantly impair treatment success. While this underscores the importance of inhalation training, the role of modern web-based instructional videos has not yet been investigated.
Methods
A randomized controlled trial using standardized checklists (10 items: preparation, N = 3, inhalation routine, N = 6, and closure of inhalation, N = 1) was carried out to determine the relative effects of web-based, device-specific videos versus standard personal instruction on reducing multiple (≥2) inhalation errors in severe COPD patients requiring hospitalisation. Investigators assessing inhalation errors were blinded to the intervention.
Results
Multiple handling errors were recorded at baseline in 152 out of 159 patients (95.6%). Each teaching method led to a similar reduction in errors (videos: from 4.2±1.6 to 1.5±1.5 errors; personal instruction: from 3.8±1.5 to 1.3±1.6; p<0.0001), although non-inferiority of web-based video teaching could not be confirmed statistically due to an unpredictably high number of patients in both groups still making multiple handling errors (44.0% versus 40.3%, mean difference 3.7%; 95%CI [-12.0–19.4%]).
Conclusion
Multiple inhalation errors regularly occur in severe COPD patients requiring hospitalisation. Web-based video teaching is capable of reducing inhalation errors. However, compared to personal instruction non-inferiority could not be established. This was due to an unexpectedly high number of patients with persisting inhalation errors despite training.
Trial registration
Clinical trial Registration: German Clinical Trial Register, DRKS 00004320.
... The amount of drug delivered to the area is determined by the patient's inhalation flow [1]. Therefore, the patients' inhalation flow pattern is one of the significant determinants for clinical performance of inhalation therapy [2][3][4]. However, incorrect use of inhaler device by patient has been a major problem, which spoils the benefits of inhalation therapy [3]. ...
... Therefore, the patients' inhalation flow pattern is one of the significant determinants for clinical performance of inhalation therapy [2][3][4]. However, incorrect use of inhaler device by patient has been a major problem, which spoils the benefits of inhalation therapy [3]. Many studies for dry powder inhalers (DPI) have demonstrated that a high inhalation flow rate is required to disperse the micronized drug particle [5][6][7]. ...
... Inhalation instruction plays an important role in inhalation therapy for asthma and COPD because therapeutic efficacy of inhalation medicine is influenced by the patient's inhalation technique [3,[30][31][32][33]. Therefore, it is an urgent issue to develop inhalation instruction tools for a large variety of inhalation devices [12]. ...
The patients' inhalation flow pattern is one of the significant determinants for clinical performance of inhalation therapy. However, the development of inhalation flow meters for various inhalation devices has been unable to keep up with the increasing number of newly launched inhalation devices. In the present study, we developed simple attachment orifices for the inhalation flow pattern monitoring system, which are suitable for all commercial inhalers, and investigated the efficacy of the system on the clinical inhalation instruction for patients co-prescribed dry powder inhaler (DPI) and soft mist inhaler (SMI). First, we constructed simple attachment orifices that were adjusted for 13 commercial inhalers, and examined the correlation between orifice and inhalation device. Second, the inhalation flow patterns (peak inspiratory flow rate, PIFR; inhalation duration time, DT) of patients prescribed a combination of DPI and SMI were monitored before and after inhalation instruction. The inhalation resistance of commercial inhalers are listed in the following order; Twincaps® > Handihaler® > Swinghaler® = Clickhaler® > Twisthaler® > Turbuhaler® > Jenuair® > Diskus® = Ellipta® > Diskhaler® > Breezhaler® > Respimat® = pMDI. The pressure drop via orifice was significantly correlated with that via the commercial inhaler. For the confirmation, all participants achieved the DPI criterion of PIFR. On the other hand, 4 participants (6 clinical visits) of 10 experimented participants could not achieve the essential criterion of DT (> 1.5 sec) for SMI, but all participants improved their duration time after inhalation instruction by pharmacists (P<0.05). In the present study, we successfully developed simple attachment orifice suitable for 13 commercial inhalation devices. These data suggested that our simple attachment orifices for the inhalation flow pattern monitoring system can detect patients with inadequate inhalation patterns via SMI.
... Despite the recommendations of both the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (21) and The National Institute for Health and Care Excellence (NICE) (22) in the United Kingdom that training in the use of inhalers is vital there is ample evidence that it is often absent or at least, infrequent (23,24). In this scenario, 'ease of use' assumes even greater significance if the patient is to reap the benefits of full compliance with dosage instructions. ...
... There is extensive evidence that training in the handling of maintenance inhalers is far from universal (23,24) in which case it can be argued that the more intuitive and easier to handle an inhaler is, the more likely it will be that patients will comply with dosage instructions and so benefit from improved disease control, clinical outcomes and quality of life. ...
Background:
Good compliance in chronic obstructive pulmonary disease (COPD) is of 'paramount importance' in reducing the occurrence of acute exacerbations, hospitalisation and mortality and in improving quality of life. However, a number of studies have confirmed that long-term compliance is low and often associated with difficulties in handling maintenance inhalers. Therefore, the easier an inhaler is to use, the more likely the patient will comply with handling instructions and so, optimise control of the condition. A research study was undertaken comparing the maintenance inhalers BreezhalerTM (BH-available in combination with Ultibro, Seebri and Onbrez from Novartis) and RespimatTM (RM-available in combination with Spiriva, Spiolto and Striverdi from Boehringer Ingelheim).
Methods:
The research was conducted among 240 maintenance inhaler-naive participants who before handling the inhalers were asked to indicate how important they felt it was that an inhaler offered each of a list of 22 handling-related attributes. They then handled each inhaler on three separate occasions familiarising themselves with the correct handling procedure by consulting respective 'Instructions for use' and short training videos. Following the handling process, participants rated the individual inhaler against each of the 22 attributes and finally expressed their preference between the two on a number of key handling-related attributes and indicated which they preferred overall.
Results:
A significant majority of participants preferred BH to RM overall. BH was rated statistically superior on 20 of the 22 handling-related attributes particularly those participants rated most highly including dosing confidence, 'easy to use' and 'easy to learn'.
Conclusions:
Significantly more participants were confident that BH would deliver a full dose of medication and was easier to learn and use. These attributes are crucial for achieving improved patient compliance. As a result, BH offers an opportunity for improved symptom control in the maintenance treatment of COPD.
... Despite the recommendations of both the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (21) and The National Institute for Health and Care Excellence (NICE) (22) in the United Kingdom that training in the use of inhalers is vital there is ample evidence that it is often absent or at least, infrequent (23,24). In this scenario, 'ease of use' assumes even greater significance if the patient is to reap the benefits of full compliance with dosage instructions. ...
... There is extensive evidence that training in the handling of maintenance inhalers is far from universal (23,24) in which case it can be argued that the more intuitive and easier to handle an inhaler is, the more likely it will be that patients will comply with dosage instructions and so benefit from improved disease control, clinical outcomes and quality of life. ...
Background and aims
Difficulties and errors in the use of maintenance inhalation devices in COPD are common and can result in loss of control and an increased risk of exacerbations, hospitalisation and death. In this research, participants handled the Breezhaler® (BH) device (Novartis) and the Respimat® (RM) device (Boehringer Ingelheim) assessing each against a number of handling-related device attributes and against each other, to reveal their preferred device.
Method
240 maintenance device-naive respondents across Australia, Brazil, Germany and Japan handled each device in a randomised order. Prior to handling the devices, participants ranked 22 handling-related device attributes according to their perception of importance for use. Participants familiarised themselves with the correct handling procedure for each device by consulting relevant ‘Instructions for Use’ and short training videos. After device-handling, participants indicated their level of agreement with pre-defined handling attributes on a 7-point scale from ‘I do not agree at all’ to ‘I completely agree’. In addition and after having handled both devices, participants expressed their preference for one device over the other by splitting 100 points between them.
Results
Participants perceived BH to be superior to RM on 20 of 22 and similar on 2 of 22 handling-related device attributes (Figure 1). Participants found BH more intuitive to use (69:31), easier to use (60: 40) and offering higher confidence that the full dose has been taken (58:42). Finally, there was a preference for BH over RM (56:44).
Conclusions
The consistently higher preference for BH regarding device handling-related attributes and its position as the preferred device suggest that it offers an opportunity for improved compliance and therefore improved control of COPD.
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Abstract P287 Figure 1 Assessment of the devices against 22 devices handling-related attributes
... There have already been calls for more careful consideration to be given to the choice of prescribed inhaler devices in COPD. 29 The Aerosol Drug Management Improvement Team suggested a strategy in 2011, 29 which offered physicians guidelines for various aspects of COPD management, including choice of inhaler. A previous study found that physicians usually base inhaler choices on the age, skills and physical capacity of their patients. ...
... There have already been calls for more careful consideration to be given to the choice of prescribed inhaler devices in COPD. 29 The Aerosol Drug Management Improvement Team suggested a strategy in 2011, 29 which offered physicians guidelines for various aspects of COPD management, including choice of inhaler. A previous study found that physicians usually base inhaler choices on the age, skills and physical capacity of their patients. ...
Background
Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques. Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique. Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known.
Aims
To compare clinical outcomes of COPD patients who use devices requiring similar inhalation technique with those who use devices with mixed techniques.
Methods
A matched cohort design was used, with 2 years of data from the Optimum Patient Care Research Database. Matching variables were established from a baseline year of follow-up data, and two cohorts were formed: a “similar-devices cohort” and a “mixed-devices cohort”. COPD-related events were recorded during an outcome year of follow-up. The primary outcome measure was an incidence rate ratio (IRR) comparing the rate of exacerbations between study cohorts. A secondary outcome compared average daily use of short-acting beta agonist (SABA).
Results
The final study sample contained 8,225 patients in each cohort (mean age 67 [SD, 10], 57% males, 37% current smokers). Patients in the similar-devices cohort had a lower rate of exacerbations compared with those in the mixed-devices cohort (adjusted IRR 0.82, 95% confidence interval [CI] 0.80–0.84) and were less likely to be in a higher-dose SABA group (adjusted proportional odds ratio 0.54, 95% CI 0.51–0.57).
Conclusion
COPD patients who were prescribed one or more additional inhaler devices requiring similar inhalation techniques to their previous device(s) showed better outcomes than those who were prescribed devices requiring different techniques.
... COPD is the fourth most com-mon global cause of death. Its prevalence is expected to increase and is primarily related to tobacco smoking, affecting 5-10% of the adult population [2][3][4]. It is characterized by airflow limitation or airway obstruction that is only partially reversible, and is usually relentlessly progressive in nature. ...
... Patients frequently fail to exhale fully before inhalation. Other common errors are high inspiratory flows, not shaking the device before use, and stopping inspiration when the spray reaches the throat [4,9,16]. Sometimes patients put the mouthpiece into their mouths, which prevents them from getting a good inhalation. ...
Background:
An appropriate inhalation technique and adherence to treatment are both critical determinants of the success of chronic obstructive pulmonary disease (COPD) management. We have observed that up to 75% of patients do not use a successful inhalation technique. Knowledge evaluation and frequent reassessment of inhaler use, together with education of patients and healthcare professionals, can significantly improve the benefits that patients with COPD will derive from inhaler therapy. The objective of this study is to test the efficacy of two educational interventions to improve inhalation techniques in patients with COPD.
Methods:
Multicenter randomized controlled trial with 296 patients diagnosed with COPD selected by a non-probabilistic method of sampling from seven Spanish Primary Care Centers. The patients will be divided into three groups by block randomization. The three groups are: 1) control; 2) Intervention A; and 3) Intervention B. The control group will comprise patients with no explanations or written information; the Intervention A group will comprise patients to whom we give written information only; and the Intervention B group will comprise patients to whom we give written information plus instructor training. Every patient in each group will be visited four times during the year of the study at the health centers.
Discussion:
Our hypothesis is that the application of educational interventions (A or B) in patients with COPD who use inhaler therapy will increase the number of patients who perform a correct inhalation technique by at least 25%. We will evaluate the effectiveness of these interventions on patient inhalation technique improvement, where feasible within the context of clinical practice.
... Greater emphasis for more careful consideration to be given to the choice of prescribed inhaler devices in COPD has been called for in the literature. 33 The results from this study provide evidence to support changes to potential refinement of inhaler-specific checklists, as patients with COPD seem to be prone to a mismatch between their inhaler technique and prescribed inhaler device. This potential mismatch should be a further consideration when HCPs are prescribing (additional) inhaler therapies. ...
Background
Patients with chronic obstructive pulmonary disease (COPD) may be prescribed multiple inhalers that require different techniques for optimal performance. Mixing devices has been associated with poorer COPD outcomes suggesting that it leads to inappropriate inhaler technique. However, empirical evidence is lacking.
Aims
Compare the nature and frequency of dry powder inhaler (DPI) technique errors in patients with COPD using (1) a single DPI or (2) mixed-devices (a DPI and pressurised metered dose inhaler (pMDI)).
Methods
Data from the PIFotal study—a cross-sectional study on Peak Inspiratory Flow in patients with COPD using a DPI as maintenance therapy, capturing data from 1434 patients on demographic characteristics, COPD health status and inhaler technique—were used to select 291 patients using mixed-devices. Frequency matching based on country of residence and DPI device type was used to select 291 patients using a DPI-only for comparison. Predetermined checklists were used for the evaluation of DPI video recordings and complemented with additional errors that were observed in ≥10%. Error proportions were calculated for the (1) individual and total number of errors, (2) number of critical errors and (3) number of pMDI-related errors.
Results
The study sample contained 582 patients (mean (SD) age 69.6 (9.4) years, 47.1% female). DPI technique errors were common, but not significantly different between the groups. The majority of patients made at least one critical error (DPI-only: 90.7% vs mixed-devices: 92.8%). Proportions of total, ‘pMDI-related’ and critical errors did not significantly differ between the groups.
Conclusion
The nature and frequency of inhaler technique errors did not substantially differ between patients prescribed with a single DPI and mixed-devices. Currently, ‘pMDI-related errors’ in DPI use are not accounted for in existing checklists.
Trial registration number
ENCEPP/EUPAS48776.
... The key issues to consider when choosing an inhaler is the device(s) with which the patient is already familiar or already using, the patient's preference, their ability to use the device correctly, the availability of devices that can deliver the desired drug, the convenience and portability of available devices, and the familiarity of the physician with potential devices. 28 The opposing breathing techniques needed to correctly use pMDIs and DPIs means that their concurrent use has obvious disadvantages and is discouraged. ...
The mainstay of the pharmacological management of asthma and chronic obstructive pulmonary disease (COPD) is the use of inhaled drugs. This route enables drugs to be delivered to the site of their action, minimising the risk of adverse effects caused by systemic absorption. Drugs that can be administered by the inhaled route include the most commonly prescribed drugs for asthma and COPD, namely short and long-acting β2 agonists and anticholinergic drugs and corticosteroids. There are two main types of inhalers: pressurised metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). pMDIs were introduced in the mid-20th century. The active drug is held in suspension or solution in a canister with a propellant. Proper use of pMDIs requires the patient to apply a series of techniques correctly: i) fire the device, releasing the aerosol very shortly after the initiation of inspiration; ii) inspire slowly and deeply; and iii) hold their breath. Many patients find this procedure difficult. Modifications and add-ons include breath-activated pMDIs and spacers and valved holding chambers; these help to obviate some of the problems with pMDIs. DPIs are breath-activated devices. Following priming, which is different for each device, the aerosol is generated by the patient taking a deep, rapid inspiration. This de-aggregates the powdered drug from its carrier. A prolonged breath-hold is then required. Many studies have shown that errors that may impair the effective delivery of the drug to the lungs, including critical errors, are very common with both pMDIs and DPIs. Such inhaler misuse has been shown to be associated with poorer symptom control and more frequent emergency department attendances. Errors in the use of inhalers can be a consequence of device-related factors, patient-related factors, and health professionalrelated factors. Minimising inhaler misuse requires the prescribing physician to choose, in cooperation with the patient, the most suitable device for the individual patient. Education and training with subsequent monitoring and re-training are thereafter crucial. There remains a need for more user-friendly devices, which provide constant doses of the active agent, in addition to built-in dose counters and patient feedback.
... With so many inhaler device options available, prescribers have a complicated decision to make in choosing an inhaler for their patients [25], not only because of the number of different inhalers but also because of the complex array of factors which impact on patient use of/ satisfaction with and preference for different products, including patient perceptions and beliefs [12,23]. Reviews have been conducted to give prescribers guidance on the selection of inhalers [26][27][28]; however, there is little evidence of GPs using these guidelines in practice. ...
Introduction:
Correct inhaler technique is essential for the optimal delivery of inhaled medicines and the successfully management of respiratory conditions. The general practitioner (GP), the prescriber of inhaled medicines, plays a crucial role in educating patients on inhaler technique. However, in the real-world setting, there are barriers. For the GP, it is time and competence and for the patient, it is their ability to recognise inhaler technique as an issue and their ability to maintain correct inhaler technique over time. This study aimed to determine GPs' experience, skills and priority placed on inhaler technique and to identify factor(s) associated with inhaler technique competence.
Methods:
This cross-sectional observational study design surveyed GPs' perspectives on inhaler use and preferences for inhaler prescribing within their practice setting. GP inhaler technique was assessed. GPs were recruited through an established network of GP practices. Data collected include (i) practice demographics, (ii) inhaler technique opinions and experience, (iii) inhaler prescribing preferences and (iv) inhaler education history data. Data were analysed descriptively and multivariate logistic regression modelling was used to explore the relationship between outcomes and GPs' ability to use devices correctly.
Results:
A total of 227 GPs completed the inhaler survey. Sixty-three percent of GPs reported receiving previous inhaler education and 73.3% educated or checked their patients' inhaler technique; 64.5% felt they were somewhat competent in doing so. GPs who reported not demonstrating inhaler technique believed that a pharmacist or a practice nurse would do so. When prescribing new inhaler devices, GPs considered the disease being treated first and then patient's experience with inhalers; they often already have an inhaler preference and this was related to familiarity and perceived ease of use. For GPs, inhaler competence was not associated with their previous inhaler education or the priority placed on inhaler technique.
Conclusion:
GPs do recognise the importance of inhaler technique in respiratory management but their technique can be better supported with regular educational updates to inform them about new inhalers and management practices and to support appropriate inhaler choices for their patients.
... It was repeatedly recommended that the patient's ability to generate an adequate PIFR through an inhaler device should be taken into consideration when choosing inhaler device on prescriptions. 2,3 Optimal PIFR was considered as the main requirement of successful inhaled therapy. It significantly differs according to the inhaler-device resistance. ...
Aim of work
Suboptimal peak inspiratory flow rate (PIFR) is highly prevalent in chronic obstructive pulmonary disease (COPD) patients owing to the mismatch of their own PIFR with the corresponding inhaler-device resistance. This study aimed to evaluate aerosol drug-delivery and short-term clinical outcomes of suboptimal PIFR in COPD subjects
Methods
Twenty optimal and suboptimal COPD subjects were crossed-over in this prospective, randomized, controlled, open label study. They were tested for urinary salbutamol amount (USAL30) and spirometric response 30 min post study-dose (200 µg salbutamol) through Aerolizer® and Handihaler® after assessment of their own PIFR through In-Check™ Dial G16. Urine-samples were extracted through solid phase extraction and assayed through a high performance liquid chromatography (HPLC) method.
Results
Mean USAL30 was significantly higher in the optimal group than the suboptimal group (P = 0.001). There was no significant difference in Δ FEV1% predicted and Δ FVC% predicted between optimal and suboptimal groups, with higher values in optimal Aerolizer® and Handihaler® than suboptimal groups.
Conclusion
Suboptimal PIFR was associated with a significantly lower drug-delivery in COPD subjects at hospital discharge, and a slightly lower pulmonary function response 30 min post-bronchodilation if compared to optimal PIFR.
... Inspiratory-capable digital inhalers add a physiological measure to the drug usage data around exacerbations. Similar to peak expiratory flow, peak inspiratory flow (PIF) is responsive to bronchodilators [81] and decreases during exacerbations [74,76,82]. Air trapping and airflow obstruction are important mechanisms for reducing PIF [83,84]. ...
Impressive advances in inhalation therapy for patients with asthma and chronic obstructive pulmonary disease (COPD) have occurred in recent years. However, important gaps in care remain, particularly relating to poor adherence to inhaled therapies. Digital inhaler health platforms which incorporate digital inhalers to monitor time and date of dosing are an effective disease and medication management tool, promoting collaborative care between clinicians and patients, and providing more in-depth understanding of actual inhaler use. With advances in technology, nearly all inhalers can be digitalized with add-on or embedded sensors to record and transmit data quantitating inhaler actuations, and some have additional capabilities to evaluate inhaler technique. In addition to providing an objective and readily available measure of adherence, they allow patients to interact with the device directly or through their self-management smartphone application such as via alerts and recording of health status. Clinicians can access these data remotely and during patient encounters, to better inform them about disease status and medication adherence and inhaler technique. The ability for remote patient monitoring is accelerating interest in and the use of these devices in clinical practice and research settings. More than 20 clinical studies of digital inhalers in asthma or COPD collectively show improvement in medication adherence, exacerbation risk, and patient outcomes with digital inhalers. These studies support previous findings about patient inhaler use and behaviors, but with greater granularity, and reveal some new findings about patient medication-taking behaviors. Digital devices that record inspiratory flows with inhaler use can guide proper inhaler technique and may prove to be a clinically useful lung function measure. Adoption of digital inhalers into practice is still early, and additional research is needed to determine patient and clinician acceptability, the appropriate place of these devices in the therapeutic regimen, and their cost effectiveness.
Video: Digital Inhalers for Asthma or Chronic Obstructive Pulmonary Disease: A Scientific Perspective (MP4 74535 kb)
... 33 Besides, factors relating to optimal prescription, taking into account patients' preferences 34 and interventions on behaviour modification (for example, stimulation of self-management and inhalation techniques), are equally important and may add to patients' capacity of acting in a more adherent behaviour. 35 In addition, enhancing health-care providers' education and communication skills may be beneficial. 36 Targeting these interventions on non-adherent patients is expected to improve cost effectiveness. ...
BACKGROUND: With a growing availability of different devices and types of medication, additional evidence is required to assist
clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence
with long-acting β2-agonists (LABAs).
AIMS: To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and
switching patterns with LABAs.
METHODS: A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose
inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD
patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using
pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and
switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities.
RESULTS: In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multipledose
inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%)
salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio:
0.98, 95% confidence interval: 0.76–1.26, P = 0.99). Over 80% re-started or switched medication.
CONCLUSIONS: There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence
with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers
or medication within 1 year.
... (1)(2)(3)(4) It is, therefore, often recommended, that the patient's ability to generate an appropriate inhalation flow through a DPI should be checked. (1,4,5) The inspiratory flow rate for DPIs is device specific (6) and must overcome the device's internal resistance. (1) For each DPI device, a minimum flow rate must be exceeded to guarantee an acceptable drug release and deposition in the lung. ...
Background:
Inhalation of medications is the cornerstone in the treatment of patients with lung diseases. A variety of inhalation devices exists and each device has specific requirements to achieve optimum inhalation of the drug. The goal of this study was to establish a clear overview on performance requirements of standard inhalation devices that should be met by the patient's breathing power and to develop a new method to measure the individual performance data.
Materials and methods:
An optimum and still acceptable required breathing power (P in watts) was calculated for each device with the aid of individual device flow rates (determined by a literature search) and the flow resistances (by measuring the pressure drop over the different inhalation devices). For the in vivo part of the study, peak inspiratory flow and peak inspiratory pressure drop were measured in 21 adult patients with asthma or chronic obstructive pulmonary disease and healthy volunteers and the peak inspiratory power (PIPO in watts) was calculated.
Results:
Nearly no power is needed to achieve optimum results when using pressurized metered dose inhalers. For dry powder inhalers, the required power depends on the specific inhalation device.
Conclusions:
Inhalation devices impose differing demands on the inspiratory breathing power of patients. To ensure adequate use of the different devices, a cheap and simple assessment of patients' PIPO may be one option.
... 8,10,[17][18][19] Provider inhaler knowledge is not only important for patient education when initially prescribing inhalers but is critical in the selection of devices that might best suit an individual patient to improve their opportunity for correct use and to identify inhaler technique errors in patients with poorly controlled COPD. 10,20 Incorrect inhaler technique by patients occurs in up to 90% of patients with COPD. 1,2,[5][6][7]11,21 Correct inhaler technique is critical in the management of COPD because inhaled drug effectiveness requires appropriate delivery to the correct anatomic location for maximal physiologic ben- Fig. 4. COPD assessment test scores before inhaler education and at follow-up. ...
Background:
Although inhaled medications are effective therapies for COPD, many patients and providers use them incorrectly.
Methods:
We recruited providers who prescribe inhalers or teach inhaler technique and assessed their use of metered-dose inhalers (MDIs), various dry powder inhalers (DPIs), and Respimat using predefined checklists. Then they watched tablet-based multimedia educational videos that demonstrated correct inhaler technique by a clinical pharmacist with teach-back from a patient and were re-evaluated. We also recruited patients with COPD and assessed their use of their prescribed inhalers and then retested them after 3-6 months. Baseline and follow-up respiratory symptoms were measured by the COPD Assessment Test.
Results:
Fifty-eight providers and 50 subjects participated. For all providers, correct inhaler technique (reported as percentage correct steps) increased after the videos: MDI without a spacer (72% vs 97%) MDI with a spacer (72% vs 96%), formoterol DPI (50% vs 94%), mometasone DPI (43% vs 95%), tiotropium DPI (73% vs 99%), and Respimat (32% vs 93%) (before vs after, P < .001 for all comparisons). Subjects also improved their inhaler use technique after viewing the educational videos: MDI without a spacer (69% vs 92%), MDI with a spacer (73% vs 95%), and tiotropium DPI (83% vs 96%) (before vs after, P < .001 for all comparisons). The beneficial effect of this educational intervention declined slightly for subjects but was durably improved after several months. COPD Assessment Test scores did not demonstrate any change in respiratory symptoms.
Conclusions:
A tablet-based inhaler education tool improved inhaler technique for both providers and subjects. Although this intervention did show durable efficacy for improving inhaler use by patients, it did not reduce their respiratory symptoms.
... A major limitation of the methodology used to assess the technique of inhaler use, direct observation, is that it involves a subjective visual assessment of the individual's technique during inhaler use, which means that it is not easy to assess the inspiratory flow rate, which can be low in patients with obstructive lung disease. 12 In addition, observation does not assess how well the patients use their inhaler when they are not under observation. ...
Background:
Cross-sectional observational studies suggest that between 50% and 60% of patients misuse a dry powder inhaler, whereas studies with electronic monitors indicate that patients sometimes overuse/underuse their inhalers. It is not known what impact errors and erratic use have on inhaler adherence.
Objectives:
The purpose of this study was to longitudinally quantify when and how patients adhered to a twice-daily preventer treatment by using a novel acoustic recording device attached to an inhaler (INhaler Compliance Assessment).
Methods:
Patients with a history of asthma or chronic obstructive pulmonary disease (n = 123) from primary care and community pharmacies were given an INhaler Compliance Assessment-adapted inhaler for 1 month. Analysis of the audio files provided quantitative information on time and technique of inhaler use.
Results:
Data were available for 103 patients. Twenty-one patients (20%) used their inhaler in the correct manner at the correct interval. There were 5045 audio files with attempted inhalations, of which 1204 had technique errors (24%). Errors included inadequate flow (27%), drug priming without inhalation (19%), exhalation into the inhaler (18%), and multiple inhalations (25%). On average, participants made errors 20% of the time. Of 60 doses expected to be taken in a month per person, on average 49 doses (82%) were attempted and when errors were accounted for, the average number of actual doses taken was 34 doses (57%; P < .01) comparing attempted to actual doses.
Discussion:
These data highlight that ineffective and irregular inhaler use is common and when combined in a single calculation indicate that only 20% of participants used their inhaler correctly and on time.
... A variety of methods may subsequently be used to control the timing of the aerosol generation and dispersion processes (35). The precise form of the inhalation flow rate-time curves that patients generate when using a DPI is therefore of importance in determining the eventual deposition profile of the inhaled aerosol in the respiratory tract (37)(38)(39). This is true regardless of how the medication delivery function is controlled. ...
Current pharmacopeial methods for in vitro orally inhaled product (OIP) performance testing were developed primarily to support requirements for drug product registration and quality control. In addition, separate clinical studies are undertaken in order to quantify safety and efficacy in the hands of the patient. However, both laboratory and clinical studies are time-consuming and expensive and generally do not investigate either the effects of misuse or the severity of the respiratory disease being treated. The following modifications to laboratory evaluation methodologies can be incorporated without difficulty to provide a better linkage from in vitro testing to clinical reality: (1) examine all types of OIP with patient-representative breathing profiles which represent normal inhaler operation in accordance with the instructions for use (IFU); (2) evaluate OIP misuse, prioritizing the importance of such testing on the basis of (a) probability of occurrence and (b) consequential impact in terms of drug delivery in accordance with the label claim; and (3) use age-appropriate patient-simulated face and upper airway models for the evaluation of OIPs with a facemask. Although it is not necessarily foreseen that these suggestions would form part of future routine quality control testing of inhalers, they should provide a closer approximation to the clinical setting and therefore be useful in the preparation for in vivo studies and in improving guidance for correct use.
... 11 The results of our study may be explained by a distinct deterioration of inhalation technique derived from arthritis or decreases in muscular strength, vision, dexterity, and cognitive function, among other factors with increasing age. 8,17 Logistic analysis has shown that age and the count of inhalation device are significant factors that lead to diminished inhalation technique, even when the type of inhalation device is taken into account (Table 3). Although it has been previously reported that the type of the inhalation device, in addition to age, causes a difference in the performance of the inhalation technique, 12 this divergence seems to be attributable to individual patients or to differences in the method of evaluation. ...
Background:
There is no systematic analysis to identify problems involved with instruction on inhalation therapy for elderly patients. We conducted a nationwide questionnaire survey for patients and medical professionals.
Methods:
A questionnaire survey was conducted of adult patients on inhaled drugs (ages 18-92 years, 820 individuals) and medical professionals (pharmacists or nurses) who provided instruction on inhalation therapy to these patients in 23 institutions in Japan to investigate the technique and the level of understanding (knowledge) of the inhalation therapy. Changes in the recognition of performance of inhalation technique and inhalation knowledge with increasing age were analyzed.
Results:
According to patients' subjective assessment, there was no deterioration in the performance of the inhalation technique or loss of the knowledge with increasing age. On the other hand, medical professionals' objective assessment revealed a significant loss of both inhalation technique and knowledge with increasing age. Not many elderly patients noticed their own problems themselves, revealing a great perception gap between elderly patients and medical professionals. Thus, there was concern that patients would unconsciously practice the inhalation procedure improperly. On the other hand, in comparison with non-elderly patients, elderly patients were less resistant to continuation of therapy, suggesting that they would be more likely to accept instruction on inhalation therapy.
Conclusions:
Elderly patients are apt to assume that they "understand well", therefore, in order to recognize and close the perception gap between elderly patients and medical professionals, it is necessary to provide them with more aggressive (frequent) instructions on inhalation therapy.
... The misuse of inhalers is a significant problem in asthma and COPD because it is associated with reduced therapeutic drug effects leading to a lack of control both symptoms and disease [7][8][9][10]. If patients are prescribed a treatment without proper training, a less than optimal therapeutic effect results [10,11]. ...
Background
Chronic obstructive pulmonary disease (COPD) accounts for 10–12 % of primary care consultations, 7 % of hospital admissions and 35 % of chronic incapacity related to productivity. The misuse of inhalers is a significant problem in COPD because it is associated with reduced therapeutic drug effects leading to lack of control of both symptoms and disease. Despite all advice, health care professionals’ practice management of inhalation treatments is usually deficient. Interventions to improve inhaler technique by health care professionals are limited, especially among primary care professionals, who provide the most care to patients with COPD. The aim of this study is to evaluate the efficacy of an educational intervention to train general practitioners (GPs) in the right inhalation technique for the most commonly used inhalers.
Methods/design
We are conducting a pragmatic cluster randomised controlled trial. The sample population is composed of 267 patients diagnosed with COPD using inhalation therapy selected from among those in 20 general practices, divided into two groups (control and intervention) by block randomisation at 8 primary care centres. The sample has two levels. The first level is patients with COPD who agree to participate in the trial and receive the educational intervention from their GPs. The second level is GPs who are primary health care professionals and receive the educational intervention. The intervention is one session of the educational intervention with a monitor given to GPs for training in the right inhalation technique. The primary outcome is correct inhalation technique in patients. Secondary outcomes are functional status (spirometry) and quality of life. The follow-up period will be 1 year. GPs will have two visits (baseline and at the 1-year follow-up visit. Patients will have four visits (at baseline and 3, 6 and 12 months). Analysis will be done on an intention-to-treat basis.
Discussion
We carried out three previous clinical trials in patients with COPD, which showed the efficacy of an educational intervention based on monitor training to improve the inhalation technique in patients. This intervention is suitable and feasible in the context of clinical practice. Now we are seeking to know if we can improve it when the monitor is the GP (the real care provider in daily practise).
Trial registration
ISRCTN Registry identifier ISRCTN93725230. Registered on 18 August 2014.
... 43 Importantly, selection of a proper inhaler in agreement with patients' preferences is a key issue for achieving best possible control of patients with obstructive lung diseases. [44][45][46] Our study has obvious limitations. We do not know the reversibility when, for example, a pMDI with or without a spacer would have been used in the same patients. ...
The choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result. On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics. In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio,70% in chronic obstructive pulmonary disease [COPD];,80% in asthma) were included (n=121, age: 57.8±17.3 years). Bronchodilator reversibility (American Thoracic Society/European Respiratory Society criteria) was tested in patients with COPD (n=63) and asthma and COPD overlap syndrome (ACOS; n=12). Forty-six asthmatics served as controls. Reversibility was tested with 400 μg salbutamol dry powder inhaler (Buventol Easyhaler, Orion Pharma Ltd, Espoo, Finland). Demographic data and patients’ perceptions of Easyhaler compared with β2-agonist pressurized metered dose inhalers (pMDIs) were analyzed. American Thoracic Society/European Respiratory Society guideline defined reversibility was found in 21 out of 63 COPD patients and in two out of 12 ACOS patients. Airway obstruction was more severe in COPD patients as compared with controls (mean FEV1 and FEV1% predicted both P,0.0001). Average response to salbutamol was significantly lower in COPD patients compared with asthma controls (P,0.0001). Reversibility was equally often found in smokers as in never-smokers (33% vs 34%). Nonreversible COPD patients had higher mean weight, body mass index, and FEV1/FVC compared with reversible COPD patients. Most patients preferred Easyhaler and defined its use as simpler and more effective than use of a pMDI. Never-smokers and patients with asthma experienced Easyhaler somewhat easier to use than smokers and patients with COPD. In conclusion, a substantial part of patients with COPD or ACOS showed reversibility to salbutamol dry powder inhaler. Nonreversible patients with COPD were characterized by higher weight and body mass index, and a higher FEV1/FVC ratio. Most patients preferred Easyhaler compared with a pMDI.
... 7 Despite the importance of inhaled therapies in the management of COPD, incorrect inhalation technique is common among patients with COPD [8][9][10] and is thought to be a key reason for reduced disease control in COPD. 11,12 Issues relating to incorrect inhaler technique may also be worsened because many patients with COPD require multiple inhaled therapies (e.g., short-acting bronchodilators, long-acting bronchodilators, inhaled corticosteroids), which are often administered via separate inhalers that require distinct inhalation techniques for optimal use. 5,8,13 Ensuring that patients with COPD always use the correct technique is key to achieving maximal benefit from inhaled therapies. ...
Background:
The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD).
Aims:
To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use.
Methods:
Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication. The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire). Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device.
Results:
Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years). Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs. 27.3%; P<0.001). Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs. 5.3, respectively; P<0.001). After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs. 3.3%, respectively).
Conclusions:
Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler. The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler.
... 33 Besides, factors relating to optimal prescription, taking into account patients' preferences 34 and interventions on behaviour modification (for example, stimulation of self-management and inhalation techniques), are equally important and may add to patients' capacity of acting in a more adherent behaviour. 35 In addition, enhancing health-care providers' education and communication skills may be beneficial. 36 Targeting these interventions on non-adherent patients is expected to improve cost effectiveness. ...
Background:
With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs).
Aims:
To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs.
Methods:
A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities.
Results:
In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76–1.26, P=0.99). Over 80% re-started or switched medication.
Conclusions:
There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year.
... This disease may also negatively influence the ability to properly use a dry powder inhaler because of the need to consistently provide adequate inspiratory airflow to disperse and deliver the drug properly. 53,54 The use of a nebulizer to administer inhaled medications may improve drug delivery in patients who are unable to effectively use handheld inhalers. Nebulizers are well received by patients with COPD, 55-57 because they require only tidal breathing, 58 which facilitates adherence. ...
Background:
Chronic obstructive pulmonary disease (COPD) affects an estimated 14% of adults in the United States between the ages of 40 and 79 years. This progressive disease is characterized by persistent airflow limitation. The management of patients with COPD is focused on reducing risk factors, relieving symptoms, and preventing exacerbations.
Objective:
To examine the peer-reviewed literature on the impact of maintenance therapy on the direct treatment costs of patients with COPD in the United States.
Methods:
PubMed was searched for articles written in English that were published between 2000 and 2013, using the search terms "COPD," "economics," "exacerbation," "maintenance," and related terms. Articles reporting the results of longitudinal studies of the costs associated with the management of patients with COPD, the costs associated with hospitalizations for acute exacerbations of COPD, and randomized clinical trials evaluating the effects of maintenance therapy on the incidence of COPD exacerbations were included in this review.
Results:
The search identified a total of 277 articles, and 11 of these articles were deemed appropriate for inclusion in this review. The direct healthcare costs for patients with COPD increased by 38% between 1987 and 2007, and continued to increase by approximately 5% annually between 2006 and 2009. The costs associated with hospital admissions for patients with COPD accounted for the largest absolute increase ($2289 per admission in constant 2007 US dollars). Recent estimates suggest that the aggregate costs associated with the treatment of acute exacerbations are between $3.2 billion and $3.8 billion, and that annual healthcare costs are 10-fold greater for patients with COPD associated with acute exacerbations than for patients with COPD but without exacerbations. The results of 2 large clinical trials of maintenance therapy, including a long-acting cholinergic antagonist or a long-acting beta-2 agonist, showed a 16% to 17% reduction in the incidence of exacerbations compared with placebo. Nevertheless, maintenance therapy remains underutilized, with only 30% to 35% of patients with COPD in private and public health insurance plans receiving prescriptions for maintenance therapy.
Conclusions:
The treatment of acute exacerbations of COPD remains the major driver of increasing healthcare costs associated with this condition. The appropriate use of maintenance therapy has been shown to reduce the incidence of exacerbations and has the potential to reduce overall costs associated with the management of patients with COPD.
... However, opening the blister packs that contain the medication capsules is one of the most difficult aspects of DPI use for elderly patients. 33 Once the capsule is loaded, DPIs typically require eight steps for appropriate utilization, 34 four of which are commonly associated with errors (failure to exhale before actuation, 34 failure to do a deep and rapid inhalation, 34,35 lingual blockage of the mouthpiece, 34 failure to hold the breath after inhaling). Patients who are cognitively impaired with neurologic alterations, frail, or simply unable to follow instructions, are likely to be more prone to these errors. ...
Chronic obstructive pulmonary disease (COPD) is common in older people, with an estimated prevalence of 10% in the US population aged ≥75 years. Inhaled medications are the cornerstone of treatment for COPD and are typically administered by one of three types of devices, ie, pressurized metered dose inhalers, dry powder inhalers, and nebulizers. However, age-related pulmonary changes may negatively influence the delivery of inhaled medications to the small airways. In addition, physical and cognitive impairment, which are common in elderly patients with COPD, pose special challenges to the use of handheld inhalers in the elderly. Health care providers must take time to train patients to use handheld inhalers and must also check that patients are using them correctly on a regular basis. Nebulizers should be considered for patients unable to use handheld inhalers properly. What follows is a review of issues associated with COPD and its treatment in the elderly patient.
The inhalation performance of a dry powder inhaler (DPI) depends on the inhalation patterns of patients, inhalation particle characteristics and inhalation devices. In capsule-based DPIs, the capsule plays an important role in the dispersion of inhalation particles. The present study investigated the effects of inner physical properties of capsules on drug release from capsules-based DPIs with high resistance device. Atomic force microscopy (AFM) was used to evaluate the capsule physical properties, such as the capsule inner structure and surface potential, of three capsules with different compositions (G-Cap, PEG/G-Cap, and HPMC-Cap). As a model dry powder for capsule-based DPIs, the dry powder in Spiriva® Inhalation Capsules containing tiotropium bromide was used. Inhalation performance was evaluated using a twin-stage liquid impinge and Handihaler® (flow rate 30 l/min). The results indicated that the capsule inner surface presented with numerous valleys and mountains, regardless of the capsule type. Furthermore, the valley and mountain areas on the capsule inner surface showed a significantly higher or lower surface potential. Following inhalation of capsule-based DPIs, the drug remained in the valleys on the capsule inner surface; however, no significant difference was observed in the drug release from capsule and lung drug delivery. Therefore, inhalation performance in capsule-based DPIs when a high resistance device, such as Handihaler®, is used at an appropriately flow rate is not markedly affected by the physical properties of the capsule inner surface due to capsule composition.
The Delphi survey in Slovakia aimed to assess the use of inhalation devices in asthma and chronic obstructive pulmonary disease. The experts consider the choice of inhalation device as important as that of active substances. For patients, the ease of use is important. The experts discourage inhalation device interchangeability. Pharmacists or health insurance companies cannot switch inhalation devices without medical consultation. The consequences may be misuse, low adherence, lower pulmonary deposition and more exacerbations/poorer control of the respirátory disorder.
Riassunto
Introduzione. Una scorretta tecnica inalatoria è frequente e spesso causa di ridotta deposizione polmonare del
farmaco inalato. Al fine di ridurre il problema del loro inadeguato utilizzo, i produttori hanno recentemente introdotto
alcuni inalatori innovativi, ma se questo stia effettivamente migliorando la situazione nella vita reale non è chiaro.
Materiali e metodi. Confronto di due studi multicentrici osservazionali svolti nel 2001 e nel 2008, ciascuno
condotto in una ampia popolazione di pazienti italiani, per lo più affetti da asma o BPCO, e già esperti all’uso
domiciliare di inalatori, durante una visita pneumologica ambulatoriale. I soggetti arruolati hanno fornito informazione
sul loro trattamento inalatorio domiciliare con questionario standardizzato e hanno mostrato la loro
tecnica inalatoria con tutti gli erogatori usati a domicilio.
Risultati. Il primo studio ha incluso 1.404 soggetti (età media 57 anni; 45% maschi, 55% femmine; 48% asmatici,
39% BPCO), di cui 1.056 e 721 rispettivamente stavano usando inalatori pressurizzati e polveri inalatorie. La
seconda indagine ha arruolato 1.664 pazienti (età media 62 anni; 58% maschi, 42% femmine; asmatici 42%,
BPCO 52%), di cui 843 e 1.113 rispettivamente stavano usando inalatori pressurizzati e polveri inalatorie.
Errori sono stati rilevati con tutti gli inalatori in entrambi gli studi. Nella prima e nella seconda indagine errori
critici erano presenti a seconda dell’inalatore considerato, dal 17% al 24% e tra il 12% e il 43%, rispettivamente
sul totale delle osservazioni. Aver ricevuto educazione da parte di sanitari era il singolo fattore modificabile
associato a ridotta frequenza di errori di tecnica inalatoria per ogni inalatore considerato in entrambi
gli studi; sfortunatamente, molti soggetti riferivano di non aver mai ricevuto alcuna istruzione sul corretto uso
degli inalatori prescritti.
Conclusioni. Una scorretta tecnica inalatoria rimane comune in Italia nonostante la recente introduzione di
erogatori apparentemente semplici da usare. L’educazione sul corretto uso da parte di sanitari può migliorare
la tecnica inalatoria, ma è scarsamente applicata.
Summary
Introduction. Poor inhaler technique is common in real life and often cause of uneffective drug delivery in the
lungs. To the aim of solving this problem, the pharmaceutical industry has recently introduced some newer
user-friendly inhalers. However, it is not clear whether proper inhaler use is effectively improving in real life.
Materials and methods. Comparison of two multicenter, cross-sectional, observational surveys performed
on 2001 and 2008. Both studies included a large population of Italian patients, mostly suffering from asthma
or COPD and experienced in the use of the most commonly inhalers. All enrolled subjects were assessed during
scheduled pulmonary visits in an outpatient setting. They gave information about their inhalation treatment
at home by a standardised questionnaire and showed their inhalation technique with the used devices to the
investigator who completed a standardised step-by-step checklist.
Results. The 1st study included 1.404 subjects (mean age 57 years; males 45%, females 55%; asthmatics
48%, COPD 39%); 1.056 and 721 patients were respectively using Metered Dose Inhalers (MDIs) and Dry
Powder Inhalers (DPIs). The 2nd study enrolled 1.664 patients (mean age 62 years; males 58%, females 42%;
asthmatics 42%, COPD 52%); 843 and 1.113 were respectively using MDIs and DPIs.
We found high rates of misuse for all evaluated inhalers in both studies. Critical mishandlings for the different
devices ranged from 17% to 24% for the 1st study and from 12% to 43% for the 2nd study. Education by
health care givers was the only modifiable factor associated with reduced misuse for all the studied inhalers
in both studies. Importantly, most subjects were not trained in inhaler technique by health care givers and this
problem seems to be increasing.
Conclusions. Poor inhaler use remains common in Italian real life despite the introduction of newer userfriendly
devices. Education by health care givers may improve inhaler technique, but it is not ubiquitously
performed.
Despite significant advances in the technology associated with the administration of all forms of inhalation therapy, patient adherence in the management of chronic conditions such as asthma and chronic obstructive pulmonary disease (COPD) is poor. The focus of laboratory testing of orally inhaled products (OIPs) has largely ignored the way in which the patient interacts with the device, paying attention instead to requirements for data obtained by methods that are simplified to achieve the necessary degree of robustness. Although such testing is clearly essential in the context of asserting product quality, regulatory agencies are beginning to recognize the need for additional information about performance that relates to the intended user experience. In this context, the drug product and delivery device, including add-ons such as spacers and valved holding chambers (VHCs) used with pressurized metered dose inhalers (pMDIs) have to be treated as a single entity. Laboratory methods simulating age-appropriate breathing patterns, poor coordination of inhaler actuation and inhalation, and the possibility that the patient interface may be a facemask rather than a mouthpiece are therefore needed. It is hoped that such approaches will eventually become incorporated into the suite of compendial methods, once validated satisfactorily. Evaluations of inhalers simulating patient use can be very useful in product design and development phases, where increasing emphasis is being placed on a risk management approach. In this way, the patient adherence problem can be better addressed with the next generation of 'patient-friendly' inhalers.
Objectives:
The study aimed to assess usage of inhalation devices in asthma and chronic obstructive pulmonary disease (COPD).
Methods:
In this two-round Delphi survey, 50 experts in asthma and COPD completed a 13-item, Internet-based, self-administered questionnaire about choice of inhalation device, training and monitoring of inhalation techniques, the interchangeability and the role of costs in the selection of inhalation devices. For each item, the median (central tendency) and interquartile ranges (degree of consensus) were calculated.
Results:
Experts considered that the choice of inhalation device was as important as that of active substance (very good consensus) and should be driven by ease of use (good to very good consensus) and teaching (very good consensus). Experts recommended giving oral and visual instructions (good consensus) and systematic monitoring inhalation techniques. Pulmonologists and paramedics have predominantly educational roles (very good consensus). Experts discouraged inhalation device interchangeability (good consensus) and switching for cost reasons (good to very good consensus) without medical consultation (good consensus).
Conclusions:
The results of this survey thus suggested that inhalation devices are as important as active substances and training and monitoring are essential in ensuring effective treatment of asthma and COPD. Inhalation device switching without medical consultation should be avoided.
This review integrates pharmaceutical science with routine clinical practice to explain why inhalation manoeuvres through a dry powder inhaler (DPI) should start with a gentle exhalation, away from the inhaler. Place the inhaler in the mouth and ensure the lips form a tight seal. This should be followed by an immediate forceful inhalation that is as fast as possible and continued for as long as the patient can comfortably achieve. Although this is universally accepted, there has been a lot of attention on inhalation flow as an indicator of adequate inspiratory effort. This has led to the wrong assumption that inhalation flows through each DPI should be the same, and that low flows through some DPIs suggest that dose delivery is impaired. Most miss the concept that inhalation flow together with the resistance of the DPI combine to create a turbulent energy which de-aggregates the formulation and provides an effective emitted dose. A low flow through a DPI with high resistance generates the same turbulent energy as fast flow with low resistance. Therefore, depending on the device, different inhalation flows are compatible with potentially effective use. Flow measurements should be a guide to train patients to inhale faster. The focus of inhaler technique training should be the use of the above generic inhalation manoeuvre.
Asthma and chronic obstructive pulmonary disease are both common conditions with an increasing prevalence worldwide. Inhaled therapy for these conditions has a number of advantages over systemic therapy, including reduced side effects and quicker onset of action. The effective use of inhaled therapy is critically dependent upon the nature of the drug-delivery system and the ability of the patient to use the system correctly. There are a wide number of inhaler devices on the market, each with positive and negative aspects. A crucial part of patient care is to ensure that the choice of inhaler device for the individual is an effective therapy. There are a number of interventions that can help with the choice of inhaler device and also improve the ability of the patient to use inhaled therapy. Inhaler technique training needs to be a cornerstone of the care of patients with asthma or chronic obstructive pulmonary disease to ensure optimal therapy.
Current treatment strategies for asthma and chronic obstructive pulmonary disease (COPD) emphasize the inhalation route, yet patients often misuse metered-dose inhalers (MDI). To address this problem, patient education by medical personnel has been recommended and a variety of alternate inhaler devices have been developed.
We surveyed medical personnel to assess their knowledge of and ability to use three widely used inhaler devices; MDI, MDI with a spacing chamber (Aerochamber, Trudell Medical, Canada), and a breath-actuated multidose dry powder inhaler (Turbuhaler, Astra Pharmacy, Inc., Conada). Thirty respiratory therapists (RT), 30 registered nurses (RN), and 30 medical house staff physicians (MD) were asked to demonstrate the use of each device using placebo inhalers and to answer 11 clinically relevant questions related to the use and maintenance of the tested devices.
The RT's percent mean knowledge score (67 +/- 5 percent) was significantly higher than those achieved by either the RNs (39 +/- 7 percent) or the MDs (48 +/- 7 percent) (for all p < 0.0001). Similarly, percent mean demonstration scores for each device were significantly higher for RTs than either RN or MD groups; for MDI, 97 +/- 3 percent versus 82 +/- 13 percent and 69 +/- 24 percent, respectively (p < 0.0001); for the Aerochamber, 98 +/- 2 percent versus 78 +/- 20 percent and 57 +/- 31 percent (p < 0.0001); and for the Turbuhaler, 60 +/- 30 percent versus 12 +/- 23 percent and 21 +/- 30 percent (p < 0.0001). Knowledge of and practical skills with the devices were roughly proportional to the length of time the device had been in clinical use, Turbuhaler demonstration scores being lower than either MDI or Aerochamber scores (p = 0.05 and p = 0.09, respectively). More RTs (77 percent) had received formal instruction on the use of devices at school than either RNs (30 percent) or MDS (43 percent) (p < 0.05).
We conclude that (1) many medical personnel responsible for monitoring and instructing patients in optimal inhaler use lack rudimentary skills with these devices, (2) nurses and physicians seldom receive formal training in the use of inhaling devices, and (3) newer inhaling devices designed to obviate problems of technique are at present less likely to be used well by medical personnel soon after their introduction.
This study assessed whether the improper use of pressurized metered-dose inhalers (pMDIs) is associated with decreased asthma control in asthmatics treated by inhaled corticosteroids (ICS). General practitioners (GPs) included consecutive asthmatic outpatients treated by pMDI-administered ICS and on-demand, short-acting beta2-agonists. They measured an asthma instability score (AIS) based on daytime and nocturnal symptoms, exercise-induced dyspnoea, beta2-agonist usage, emergency-care visits and global perception of asthma control within the preceding month; the inhalation technique of the patient also was assessed. GPs (n=915) included 4,078 adult asthmatics; 3,955 questionnaires were evaluable. pMDI was misused by 71% of patients, of which 47% was due to poor coordination. Asthma was less stable in pMDI misusers than in good users (AIS: 3.93 versus 2.86, p<0.001). Among misusers, asthma was less stable in poor coordinators (AIS: 4.38 versus 3.56 in good coordinators, p<0.001). To conclude, misuse of pressurized metered-dose inhalers, which is mainly due to poor coordination, is frequent and associated with poorer asthma control in inhaled corticosteroid-treated asthmatics. This study highlights the importance of evaluating inhalation technique and providing appropriate education in all patients, especially before increasing inhaled corticosteroid dosage or adding other agents. The use of devices which alleviate coordination problems should be reinforced in pressurized metered-dose inhaler misusers.
Most of the drugs that are currently used to treat airway diseases interact with receptors expressed by cells in the airways. This makes inhaled delivery efficient because it reaches the key target cells and has a low risk of systemic side effects. Both beta(2)-agonists and anticholinergics target autonomic receptors on airway smooth muscle of large and small airways. Inhaled beta(2)-agonists also interact with beta(2)-receptors expressed on other important target cells, including mast cells and postcapillary venules. Anticholinergic bronchodilators target M(3) muscarinic receptors on airway smooth muscle, which in small airways may be activated by extraneuronal acetylcholine. Corticosteroids target glucocorticoid receptors (GR), which are widely distributed so that they are best given by inhalation to interact with intracellular GR in the respiratory tract and to avoid side effects from activation of GR in extrapulmonary tissues such as bone. By contrast, cysteinyl-leukotriene 1 receptors are mainly expresses in airway smooth muscle so that antileukotrienes are less effective clinically than beta(2)-agonists and corticosteroids, but oral delivery is possible as there are minimal side effects. There are many other receptor targets in lung and for several of these receptors, such as receptors for chemotactic agonists, selective antagonists are in clinical development. For drugs that inhibit chemotactic receptors, systemic delivery is more appropriate to prevent the inflammatory cells that bear these receptors from being recruited into the airways by locally released chemotactic factors. Many novel receptors, including orphan receptors, have now been identified as these may be future targets for developing novel therapies for asthma and chronic obstructive pulmonary disease.
Although the principles of asthma management are well established in Europe, the available data indicate that asthma in patients is not well controlled. Many patients derive incomplete benefit from their inhaled medication because they do not use inhaler devices correctly and this may compromise asthma control. The Aerosol Drug Management Improvement Team (ADMIT), incorporating clinicians from the UK, Germany, France, Italy, Spain and The Netherlands, reviewed published evidence to examine ways to improve the treatment of reversible airways disease in Europe. Data indicate that there is a clear need for specific training of patients in correct inhalation technique for the various devices currently available, and this should be repeated frequently to maintain correct inhalation technique. Devices which provide reassurance to patients and their physicians that inhalation is performed correctly should help to improve patient compliance and asthma control. Educational efforts should also focus on primary prescribers of inhaler devices. ADMIT recommends dissemination of information on the correct inhalation technique for each model of device by the use of an accessible dedicated literature base or website which would enable to match the appropriate inhaler to the individual patient. There is also a need for standardisation of prescribing practices throughout Europe. Regular checking of inhalation technique by prescribers is crucial as correct inhalation is one of the keystones of successful asthma management.
Many different inhalers are available for delivering aerosol therapy in respiratory medicine. As a consequence, the prescribing physicians may have some difficulty tailoring the most suitable inhaler to each patient. This multicenter, observational study using a self-administered questionnaire analyzed the characteristics of a large sample of patients (n = 1,305; 55% females; mean age 57.4, with a range of 15-88 years; most suffering from asthma or chronic obstructive pulmonary disease [COPD]) familiar with several different types of inhalers in relation to their most commonly used delivery device. Data on the inhalation technique for 2,057 observations of 1,126 patients using device-specific checklists and factors associated to misuse were also evaluated. Prevalent usage of newer dry powder inhalers (DPIs) was significantly associated with male sex, higher education, better respiratory function, and prescription from a respiratory physician. Patients using DPIs had received less instruction by health caregivers and were more likely to have read the instruction leaflet than users of metered dose inhalers (MDIs). Under these conditions, inhaler misuse was common and similar for both pressurized metered dose inhalers (pMDIs) and DPIs. For both types of inhalers, misuse was significantly and equally associated to increased age, less education, and less instruction by health care personnel. We conclude that many doctors are not familiar with the relevant characteristics of currently available inhalers. The prescription of newer DPIs may be subjected to gender, socio-economic, and instruction bias. The simple change of device from the pMDI to the newer DPIs is not associated with improved inhalation technique.
Long-acting beta-agonists and inhaled corticosteroids are used to treat chronic obstructive pulmonary disease (COPD), but their effect on survival is unknown.
We conducted a randomized, double-blind trial comparing salmeterol at a dose of 50 microg plus fluticasone propionate at a dose of 500 microg twice daily (combination regimen), administered with a single inhaler, with placebo, salmeterol alone, or fluticasone propionate alone for a period of 3 years. The primary outcome was death from any cause for the comparison between the combination regimen and placebo; the frequency of exacerbations, health status, and spirometric values were also assessed.
Of 6112 patients in the efficacy population, 875 died within 3 years after the start of the study treatment. All-cause mortality rates were 12.6% in the combination-therapy group, 15.2% in the placebo group, 13.5% in the salmeterol group, and 16.0% in the fluticasone group. The hazard ratio for death in the combination-therapy group, as compared with the placebo group, was 0.825 (95% confidence interval [CI], 0.681 to 1.002; P=0.052, adjusted for the interim analyses), corresponding to a difference of 2.6 percentage points or a reduction in the risk of death of 17.5%. The mortality rate for salmeterol alone or fluticasone propionate alone did not differ significantly from that for placebo. As compared with placebo, the combination regimen reduced the annual rate of exacerbations from 1.13 to 0.85 and improved health status and spirometric values (P<0.001 for all comparisons with placebo). There was no difference in the incidence of ocular or bone side effects. The probability of having pneumonia reported as an adverse event was higher among patients receiving medications containing fluticasone propionate (19.6% in the combination-therapy group and 18.3% in the fluticasone group) than in the placebo group (12.3%, P<0.001 for comparisons between these treatments and placebo).
The reduction in death from all causes among patients with COPD in the combination-therapy group did not reach the predetermined level of statistical significance. There were significant benefits in all other outcomes among these patients. (ClinicalTrials.gov number, NCT00268216 [ClinicalTrials.gov].).
Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.
Controlled studies evaluating patient inhaler preferences may not tell us about important factors influencing patient inhaler usage outside clinical trials. For instance, in such studies, treatment and efficacy characteristics are held constant between the different inhalers being compared. This is unlikely in real life. Inhaler preference studies almost never proceed to evaluate actual usage, so we do not know if expressed preference translates into greater adherence to an inhaler. There may be important inhaler characteristics which encourage regular use, but which are not consciously recognised by patients. Real-life inhaler use will be influenced by personal styles of medication adherence, patient perceptions of the benefits and costs of inhaler use for them, characteristics of therapeutic regimen and device characteristics. This paper considers some key questions about inhaler use by patients with chronic obstructive pulmonary disease (COPD).
Objective - To determine the prevalence of an incorrect inhalation technique and to examine its determinants among primary care patients with asthma or chronic obstructive pulmonary disease (COPD). Design - Cross-sectional study. Setting - 28 general practitioners in The Netherlands. Subjects - 558 asthma and COPD patients, aged 16-75 years. Main outcome measures - Inhalation technique was assessed using a standardised inhaler-specific checklist. Pulmonary function assessment and questionnaires were used to collect data about inhaler, patient and disease characteristics. Results - Overall, 24.2% of the patients made at least one essential mistake in their inhalation technique. The type of inhaler appeared to be the strongest independent determinant of an incorrect inhalation technique. Compared to patients using the Diskhaler, patients using the Rotahaler/Spinhaler, Turbuhaler, Metered Dose Inhaler (MDI) or Cyclohaler/Inhaler-Ingelheim were at significantly higher risk of making inhalation mistakes (odds ...
Synopsis: Treatment with amoxicillin-clavulanic acid was effective in treating exacerbations of mild to moderate chronic obstructive pulmonary disease and delayed the time to recurrence. Source: Llor C, Moragas A, Hernandez S, et al. Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:716–723.
Objective:
To compare the effect of bronchodilator delivery by use of a metered-dose inhaler (MDI) or wet nebulizer on objective measurements of acute airflow obstruction in adult patients.
Methods:
Published and unpublished research was identified by MEDLINE searches for articles published from 1966 to 1994, review of scientific citations, review of article bibliographies, communication with experts in the area of asthma therapy and aerosol delivery, primary investigators, and a manufacturer of spacer devices. Eighteen studies were selected from 159 potentially relevant articles by independent review in triplicate. Selection criteria included randomized trials that compared bronchodilator delivery by use of an MDI and wet nebulizer in adults with acute exacerbations of asthma or chronic obstructive pulmonary disease who were treated in an emergency department or a hospital. Data for patient characteristics, study setting, bronchodilator doses, outcomes, and methodological quality were independently extracted.
Results:
Twelve studies with a total of 507 patients had sufficient data to calculate an effect size (in SD units) for improvement in airflow obstruction after bronchodilator delivery. All but 2 studies used spacer devices with the MDI. The overall treatment effect size was -0.02 (95% confidence interval [CI], -0.20 to 0.16) that favored the MDI, but the magnitude of the effect size was not clinically or statistically significant. No significant effect was observed in the subgroup analyses that compared the diagnosis: asthma, -0.17 (CI, -0.41 to 0.07) compared with chronic obstructive pulmonary disease, 0.23 (CI, -0.35 to 0.81); bronchodilator dose; or methodological quality. The results of a sensitivity analysis that included 5 of 6 excluded studies supported the findings from the primary analysis: 0.05 (CI, -0.11 to 0.20).
Conclusions:
Bronchodilator delivery by means of an MDI or wet nebulizer is equivalent in the acute treatment of adults with airflow obstruction. Spacer devices were used for bronchodilator delivery with an MDI in most studies and are recommended for the treatment of acute airflow obstruction. The choice of the delivery method will depend on the need for expedient treatment, availability of staff, consideration of costs, and findings from studies designed to evaluate treatment effects from larger than standard doses of bronchodilators delivered by use of an MDI.Arch Intern Med. 1997;157:1736-1744
Studies involving the direct measurement of clinical response to inhaled asthma drugs, especially inhaled corticosteroids, may be very difficult to conduct. However, the deposition of drug in the lungs may be considered as a measure of local bioavailability, and may be quantified by radionuclide imaging techniques, or for some drugs by pharmacokinetic methods. This paper reviews evidence for considering lung deposition data as a surrogate for the clinical response to inhaled asthma drugs, based mainly upon a series of case histories. The appropriate use of lung deposition data in regulatory packages, especially to document the equivalence or comparability of two products, offers the possibility of significant time saving in the drug development process, and hence a faster drug development programme for inhaled asthma products.
Inhaled medications are the preferred therapies for patients with asthma and COPD, but their effectiveness is limited by the patient's ability to use the device properly, an issue often neglected when these medications are prescribed. Correct inhaler technique must be taught and learnt, and requires educational and motivational programs aimed at patients and healthcare providers alike. Written instructions alone are manifestly insufficient: education must include practical demonstration and periodic re-assessment and reeducation, since correct technique and motivation usually deteriorate with time. Several devices are available on the market, the purpose of which is to train patients to use inhalers correctly. They are often directed at particular devices or groups of devices and/or particular critical aspects of technique. This paper reviews the devices currently available for training patients in the correct use of both pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs).
For patients with COPD, inhalation is the preferred route of administration of respiratory drugs for both maintenance and acute treatment. Numerous inhaler types and devices have been developed, each with their own particularities, advantages and disadvantages. Nevertheless, published COPD management guidelines pay little attention to the optimal choice of inhaler devices for COPD patients. Although efficacy and safety are the primary factors determining the choice of an inhaler device, randomised controlled trials (RCTs) directly comparing the efficacy and safety of different inhalers in COPD patients are scarce. Systematic reviews on this subject failed to find significant differences between devices for any of the clinical outcomes studied. When selecting a device for the delivery of inhaled drugs in 'real life' patients with COPD, other factors should be considered. These include availability and affordability of the inhaled drugs and inhaler devices, the uniformity of inhaler devices when several drugs are to be inhaled, the ability of patients to handle correctly the selected device - in particular taking into account the advanced age of the average COPD patient, and finally the patient's preference. The prescribing clinician's task is to provide comprehensive instructions for correct handling of the device and to review regularly the patient's inhalation technique.
Aerosol inhalation is considered the optimal route for administering the majority of drugs for the treatment of obstructive airways diseases. A number of Pressurised Metered-Dose and Dry Powder Inhalers are available for this purpose. However, inhalation of therapeutic aerosols is not without difficulty; it requires precise instructions on the inhalation manoeuvre, which is different from spontaneous normal breathing. Also, the characteristics of the inhaler device have to be suitable for the user. Available data indicate a frequent lack of knowledge demonstrated by health professionals and patients on the inhalation manoeuvre and handling of inhalers, resulting in a reduction of therapeutic benefit. This paper reviews the literature concerning the fundamental aspects of inhaler devices, inhalation manoeuvre and device selection, in an attempt to increase the knowledge of, and to optimise the clinical use of, therapeutic inhalers.
Previous studies showing that tiotropium improves multiple end points in patients with chronic obstructive pulmonary disease (COPD) led us to examine the long-term effects of tiotropium therapy.
In this randomized, double-blind trial, we compared 4 years of therapy with either tiotropium or placebo in patients with COPD who were permitted to use all respiratory medications except inhaled anticholinergic drugs. The patients were at least 40 years of age, with a forced expiratory volume in 1 second (FEV(1)) of 70% or less after bronchodilation and a ratio of FEV(1) to forced vital capacity (FVC) of 70% or less. Coprimary end points were the rate of decline in the mean FEV(1) before and after bronchodilation beginning on day 30. Secondary end points included measures of FVC, changes in response on St. George's Respiratory Questionnaire (SGRQ), exacerbations of COPD, and mortality.
Of a total of 5993 patients (mean age, 65+/-8 years) with a mean FEV(1) of 1.32+/-0.44 liters after bronchodilation (48% of predicted value), we randomly assigned 2987 to the tiotropium group and 3006 to the placebo group. Mean absolute improvements in FEV(1) in the tiotropium group were maintained throughout the trial (ranging from 87 to 103 ml before bronchodilation and from 47 to 65 ml after bronchodilation), as compared with the placebo group (P<0.001). After day 30, the differences between the two groups in the rate of decline in the mean FEV(1) before and after bronchodilation were not significant. The mean absolute total score on the SGRQ was improved (lower) in the tiotropium group, as compared with the placebo group, at each time point throughout the 4-year period (ranging from 2.3 to 3.3 units, P<0.001). At 4 years and 30 days, tiotropium was associated with a reduction in the risks of exacerbations, related hospitalizations, and respiratory failure.
In patients with COPD, therapy with tiotropium was associated with improvements in lung function, quality of life, and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV(1). (ClinicalTrials.gov number, NCT00144339.)
This double-blind crossover study compared the efficacy of two methods of delivery (MDI-spacer and nebulizer) of inhaled albuterol to patients hospitalized for an acute exacerbation of COPD. Within 24 h of admission, 20 subjects (mean age, 69 years) with severe airflow obstruction (mean FEV, 0.69 L) were subjected to a treatment with an MDI-spacer (0.36 mg of albuterol or placebo) followed by treatment with a nebulizer (2.5 mg of albuterol or placebo). Active drug was given by only one device (randomly assigned in a double-blind manner), and the entire sequence was repeated in 4 h, with active drug given in the alternate device. Spirometric data and the Borg dyspnea score were obtained before and 1 h after each sequence of treatments. Treatment resulted in significant improvements in the FEV1, FVC, and Borg score. The percent improvement in the FEV1 was slightly larger after treatment with the nebulizer (16.7 percent vs 13.4 percent). Improvements in the Borg score were slightly larger after treatment with the MDI-spacer (-1.08 vs -0.73). However, these differences were not statistically significant. This study suggests that the MDI-spacer system is an effective method of sympathomimetic delivery in this setting, provided patients are able to master the technique.
The use of pressurized aerosol inhalers was assessed in a total of 1173 out-patients attending hospital during a three month period. One hundred and thirty-five patients already being treated with drugs by inhalation were found to have a poor inhaler technique, even though most had received instruction on how to use a pressurized aerosol and were considered to be able to use one of these devices correctly. Eighty patients who had not used an inhaler before were found to be unable to use a pressurized aerosol efficiently after reading an instruction pamphlet or having the correct use of an aerosol demonstrated to them. Fifty-one percent of patients studied were observed to have difficulty in co-ordinating aerosol release with inspiration. In 24% the release of aerosol into the mouth caused a halt of inspiration and in a further 12% the aerosol was actuated into the mouth, but inspiration was achieved through the nose with no air being drawn in through the mouth. Twelve percent of patients already being treated with inhalers actuated the aerosol on two or more occasions during one inspiration.
Metered dose inhalers (MDIs) are widely used in clinical practice for administering pharmaceuticals targeted to the lung. It is well known that the inhalation technique used with MDIs can substantially influence the clinical response to inhaled medications. To determine the acceptability of MDI maneuvers, we studied 59 subjects (26 females and 33 males; age, 20 to 81 yr; mean age, 38 yr) to determine whether the MDI technique used by these individuals complied with published recommendations for acceptable inhalation technique. Measurements were made with an MDI adapter that contained an unobtrusive, lightweight, miniature sensing system. Inspiratory flow at the moment of MDI actuation (Va), the volume (integrated from airflow) at actuation as a fraction of total inspiratory volume (Va/VI), breath-holding time (tBH), and inspiratory volume as a fraction of FVC (VI/FVC) were determined from 59 uncoached inhalations. We defined an acceptable maneuver, based on published data, by four components: (1) inspiratory flow at actuation (Va) between 25 and 90 L/min; (2) actuation during early inspiration (0 < Va/VI < or = 0.20); (3) adequate breath-holding time (tBH > 4 s), and (4) a deep inhalation (VI/FVC > 0.50). For all subjects, only 25% of inhalation maneuvers met all four criteria for acceptability. We found that a significantly higher proportion of male than female subjects performed an acceptable MDI maneuver (43% versus 4%, p < 0.001). There were no significant differences in technique between younger and older subjects or between patients with a diagnosis of asthma or chronic obstructive pulmonary disease (COPD). We conclude that most patients use their MDIs incorrectly; females of all ages are much more likely to have improper MDI technique than are males.
To compare the effect of bronchodilator delivery by use of a metered-dose inhaler (MDI) or wet nebulizer on objective measurements of acute airflow obstruction in adult patients.
Published and unpublished research was identified by MEDLINE searches for articles published from 1966 to 1994, review of scientific citations, review of article bibliographies, communication with experts in the area of asthma therapy and aerosol delivery, primary investigators, and a manufacturer of spacer devices. Eighteen studies were selected from 159 potentially relevant articles by independent review in triplicate. Selection criteria included randomized trials that compared bronchodilator delivery by use of an MDI and wet nebulizer in adults with acute exacerbations of asthma or chronic obstructive pulmonary disease who were treated in an emergency department or a hospital. Data for patient characteristics, study setting, bronchodilator doses, outcomes, and methodological quality were independently extracted.
Twelve studies with a total of 507 patients had sufficient data to calculate an effect size (in SD units) for improvement in airflow obstruction after bronchodilator delivery. All but 2 studies used spacer devices with the MDI. The overall treatment effect size was -0.02 (95% confidence interval [CI], -0.20 to 0.16) that favored the MDI, but the magnitude of the effect size was not clinically or statistically significant. No significant effect was observed in the subgroup analyses that compared the diagnosis: asthma, -0.17 (CI, -0.41 to 0.07) compared with chronic obstructive pulmonary disease, 0.23 (CI, -0.35 to 0.81); bronchodilator dose; or methodological quality. The results of a sensitivity analysis that included 5 of 6 excluded studies supported the findings from the primary analysis: 0.05 (CI, -0.11 to 0.20).
Bronchodilator delivery by means of an MDI or wet nebulizer is equivalent in the acute treatment of adults with airflow obstruction. Spacer devices were used for bronchodilator delivery with an MDI in most studies and are recommended for the treatment of acute airflow obstruction. The choice of the delivery method will depend on the need for expedient treatment, availability of staff, consideration of costs, and findings from studies designed to evaluate treatment effects from larger than standard doses of bronchodilators delivered by use of an MDI.
Many different metered-dose inhalation devices are becoming available for the treatment of airway diseases. Each of these inhalers differs in its delivery characteristics. An assessment of the efficacy of drug delivery by these inhalers is essential, in view of their therapeutic use. A review of the literature on the relationship between airway deposition and airway effects of drugs delivered from metered-dose inhalers is presented. Nebulizers or spacers are not discussed. The effect of an inhaler depends on the characteristics of the inhaler and the inhalation manoeuvre performed by the patient. This review focuses on the influence of inhaler characteristics on the airway deposition and airway effects. Data from several studies show that there is a significant relationship between the amount of drug deposited in the airways and the airway effects of the drug. Studies on the relationship between airway deposition and airway effect have been troubled by methodological problems, such as the absence of multiple dose comparisons and the difficulty in obtaining steep dose-response curves. The techniques for measuring airway deposition of inhaled drugs, namely the scintigraphic and the pharmacokinetic method, are discussed and compared. The appropriate use of these techniques can help to define and compare the drug delivery characteristics of different devices, thus enabling inhaled therapy to be optimized.
Inhaled medication is important in the treatment of chronic obstructive pulmonary disease (COPD). In this paper a comparison of the long-term efficacy of three instruction-models is presented. A total of 152 COPD-patients were randomized into one of four groups: Personal-, video-, group-instruction and a control group. Inhalation technique was assessed by means of checklists, on which essential inhalation manoeuvres were identified. Up to 9 months later, 148 patients returned for follow-up assessment. Prior to instruction 61% of patients in the control group had a perfect score on essential actions, compared to 62, 65 and 53% for those receiving group-, personal- and video-instruction respectively. At follow-up these percentages were 49, 97, 75 and 76%. For group-(35%) and video-instruction (24%) the increase from baseline was significant. Examining the different inhalers under investigation, it is striking, that only 24% of all patients with a Metered Dose Inhaler (MDI) performed all essential checklist items correctly, versus 96% for those using a Diskhaler. The fact that for the MDI this percentage improved to 90% post-instruction, shows that time spent on instruction, is time well spent. We conclude that group instruction seems superior to personal counselling, and equally effective or even better than video instruction. Personal instruction should not be dismissed and a combination with video instruction might prove to be effective as well.
Inefficient inhaler technique is a common problem resulting in poor drug delivery, decreased disease control and increased inhaler use. The aim of this study was to assess patients' use of different inhaler devices and to ascertain whether patient preference is indicative of ease of use and whether current inhaler use has any influence on either technique or preference. We also wished to define the most appropriate method of selecting an inhaler for a patient, taking into account observed technique and device cost. One hundred patients received instruction, in randomized order, in the use of seven different inhaler devices. After instruction they were graded (using predetermined criteria) in their inhaler technique. After assessment patients were asked which three inhalers they most preferred and which, if any, they currently used. Technique was best using the breath-actuated inhalers; the Easi-Breathe and Autohaler, with 91% seen to have good technique. The pressurized metered dose inhaler (pMDI) fared poorly, in last position with only 79% of patients showing good technique, despite being the most commonly prescribed. The Easi-Breathe was by far the most popular device with the patients. The Autohaler came in second position closely followed by the Clickhaler and Accuhaler. The majority of patients (55%) currently used the pMDI but the pMDI did not score highly for preference or achieve better grades than the other devices. Only 79% of patients tested could use the pMDI effectively even after expert instruction yet it continues to be commonly prescribed. This has important repercussions for drug delivery and hence disease control. Prescribing a patient's preferred device increases cost but can improve efficiency and therefore be cost effective in the long term. Using an inexpensive device (pMDI) when technique is good and the patient's preferred inhaler device when not is one way to optimize delivery and may even reduce cost.
Clinical observations have shown that some older patients are unable to learn to use a metered dose inhaler (MDI) despite having a normal abbreviated mental test (AMT) score, possibly because of dyspraxia or unrecognised cognitive impairment. Thirty inhaler-naive inpatients (age 76–94) with an AMT score of 8–10 (normal) were studied. Standard MDI training was given and the level of competence reached was scored (inhalation score). A separate observer performed the minimental test (MMT), Barthel index, geriatric depression score (GDS), ideational dyspraxia test (IDT), and ideomotor dyspraxia test (IMD). No correlative or threshold relationship was found between inhalation score and Barthel index, GDS, or IDT. However, a significant correlation was found between inhalation score and IMD (r = 0.45, p = 0.039) and MMT (r = 0.48, p = 0.032) and threshold effects emerged in that no subject with a MMT score of less than 23/30 had an inhalation score of 5/10 or more (adequate technique requires 6/10 or more), and all 17/18 with an inhalation score of 6/10 or more had an IMD of 14/20 or more.
The three patients with a MMT >22 and inhalation score <6 had abnormal IMD scores. Inability to learn an adequate inhaler technique in subjects with a normal AMT score appears to be due to unrecognised cognitive impairment or dyspraxia. The MMT is probably a more useful screening test than the AMT score in this context.
To determine the prevalence of an incorrect inhalation technique and to examine its determinants among primary care patients with asthma or chronic obstructive pulmonary disease (COPD).
Cross-sectional study.
28 general practitioners in The Netherlands.
558 asthma and COPD patients, aged 16-75 years.
Inhalation technique was assessed using a standardised inhaler-specific checklist. Pulmonary function assessment and questionnaires were used to collect data about inhaler, patient and disease characteristics.
Overall, 24.2% of the patients made at least one essential mistake in their inhalation technique. The type of inhaler appeared to be the strongest independent determinant of an incorrect inhalation technique. Compared to patients using the Diskhaler, patients using the Rotahaler/Spinhaler, Turbuhaler, Metered Dose Inhaler (MDI) or Cyclohaler/Inhaler-Ingelheim were at significantly higher risk of making inhalation mistakes (odds ratios (OR) were 16.08, 13.17, 11.60 and 3.27, respectively). Other significant determinants of an incorrect inhalation technique were low emotional quality of life (OR = 1.73) and being treated in a group practice (OR = 2.26).
An incorrect inhalation technique is common among pulmonary disease patients in primary care. Our study suggests that especially patients using the Rotahaler/Spinhaler, Turbuhaler or MDI, patients with emotional problems and patients in a group practice are at increased risk for an incorrect inhalation technique.
Ageing is associated with important anatomical, physiological and psychosocial changes that may have an impact on the management of obstructive airway diseases (asthma and chronic obstructive pulmonary disease (COPD)) and on their optimal therapy. Ageing-related modifications might be responsible for a different effectiveness of bronchodilators in the elderly patients as compared to younger subjects. Furthermore, the physiological involution of organs and the frequent comorbidity, often interfere with pharmacokinetics of bronchodilator drugs used in asthma and COPD. This review will focus on the use of bronchodilators in the elderly, with particular attention to the achievable goals and to rationale, utility and pitfalls in using the inhalation therapy in this age group. beta(2)-agonists, anticholinergics and methylxanthines will be discussed and their side effects in the elderly will be considered.
Incorrect usage of inhaler devices might have a major influence on the clinical effectiveness of the delivered drug. This issue is poorly addressed in management guidelines.
This article presents the results of a systematic literature review of studies evaluating incorrect use of established dry powder inhalers (DPIs) by patients with asthma or chronic obstructive pulmonary disease (COPD).
Overall, we found that between 4% and 94% of patients, depending on the type of inhaler and method of assessment, do not use their inhalers correctly. The most common errors made included failure to exhale before actuation, failure to breath-hold after inhalation, incorrect positioning of the inhaler, incorrect rotation sequence, and failure to execute a forceful and deep inhalation. Inefficient DPI technique may lead to insufficient drug delivery and hence to insufficient lung deposition. As many as 25% of patients have never received verbal inhaler technique instruction, and for those that do, the quality and duration of instruction is not adequate and not reinforced by follow-up checks.
This review demonstrates that incorrect DPI technique with established DPIs is common among patients with asthma and COPD, and suggests that poor inhalation technique has detrimental consequences for clinical efficacy. Regular assessment and reinforcement of correct inhalation technique are considered by health professionals and caregivers to be an essential component of successful asthma management. Improvement of asthma and COPD management could be achieved by new DPIs that are easy to use correctly and are forgiving of poor inhalation technique, thus ensuring more successful drug delivery.
on behalf of the Task Force. Optimal assessment and management of COPD. A consensus statement of the European Respiratory Society
- Nm Siafakas
- P Vermeire
- Pride
- Nb
Siafakas NM, Vermeire P, Pride NB, et al. on behalf of the Task Force. Optimal assessment and management of COPD. A consensus statement of the European Respiratory Society. Eur Respir J 10.1183/09031936.95.0808139
Associazione Italiana Pneumologi Ospedalieri Educational Group. Prescription bias and factors associated with improper use of inhalers
- P Sestini
- V Cappiello
- M Aliani
Sestini P, Cappiello V, Aliani M, et al. Associazione Italiana Pneumologi Ospedalieri
Educational Group. Prescription bias and factors associated with improper use of
inhalers. J Aerosol Med 2006;19(2):127-36. http://dx.doi.org/10.1089/
jam.2006.19.127
Antibiotic therapy in exacerbations of COPD
- N R Anthonisen
- J Manfreda
- Cpw Warren
- E S Hershfield
- Gkm Harding
- N A Nelson
Anthonisen NR, Manfreda J, Warren CPW, Hershfield ES, Harding GKM, Nelson
NA. Antibiotic therapy in exacerbations of COPD. Ann Intern Med 1987;106:196-204.
Antibiotic therapy in exacerbations of COPD.
- Anthonisen
Problems patients have using pressurised aerosol inhalers.
- Crompton