Inhaler educational resources

Welcome to this series of four educational modules aimed at supporting the use of the Easyhaler® range of inhalers.

These medical education online learning resources are funded by Orion Pharma (UK) Ltd as part of a commitment towards supporting the appropriate use of inhaled medicines. Orion Pharma (UK) Ltd has had input into the module title and reviewed the educational content for quality and factual accuracy.

Module 1

Module 2

Module 3

Module 4

Click on the images above to head directly to each module

Module 1: Introduction to Easyhaler®

Easyhaler® is a breath-actuated, dry powder inhaler (DPI) device used to deliver a range of medicines for patients with asthma or chronic obstructive pulmonary disease (COPD).¹

The aim of this series of modules is to familiarise pharmacists with the function and features of the Easyhaler range so as to support patients either at the point of supply or during structured reviews.

There are an increasing number of observational studies showing that pharmacists can improve disease management for respiratory patients.² A 2016 review looked at nine studies (including observational) involving community pharmacists and COPD patients.³ The analysis showed that educational interventions by pharmacists do have a positive impact on both inhaler technique and adherence.³ Two of the studies, including one in the UK, also showed cost savings per patient in terms of hospitalisation and severe exacerbation rates.³ A systematic review and meta-analysis in 2020 identified 13 randomised, controlled trials (RCT) including both asthma and COPD patients.² They concluded that significant improvements in inhaler technique and adherence can be achieved through pharmacist-led interventions.²

There is a range of resources, including instructional videos on how to use Easyhaler®, available for patients and healthcare professionals on the manufacturer’s website.

The Easyhaler® range

The Easyhaler® device, available since 1993, was designed to be a reliable alternative to pressurised metered dose inhalers (pMDI).⁴ The device resembles a pMDI in appearance and has a similar delivery system, but without the need for co-ordination between breathing and actuation.⁴

Easyhaler® is plastic and consists of a bulk powder chamber with a spring-loaded overcap and a metering cylinder with dosing cup.¹ Clicking down the overcap once rotates the cylinder and prepares a metered dose in the dosing cup.

During inspiration, air is drawn into the device (1) with medium to high resistance due to the small size of the air vents.⁵ This resistance creates turbulent airflow over the dosing cup (2) which ensures the de-aggregation of drug particles and a high ‘fine particle dose’ (FPD)(3).⁵

A full description of how to use Easyhaler® will be given in module 4 and can be found in the manufacturer’s patient information.

But for now, three simple steps describe the overall process;

1. Shake the inhaler vertically 3-5 times⁶
2. Click down and release the cap once⁶
3. Inhale and hold breath.⁶

The Easyhaler® range includes a number of different medicines and combinations allowing for prescribing in line with best practice guidelines.¹

Easyhaler® Salbutamol 100mcg and 200mcg

Easyhaler® Salbutamol 100mcg and 200mcg is indicated for symptomatic relief of asthma attacks in adults and children over 4 years, and prevention of exercise-induced asthma.^7,8 Salbutamol is a short-acting beta agonist (SABA) that is used as required.^7,8 BTS/SIGN guidelines for asthma in adults recommend that a patient needing three or more doses per week should move to the next step of treatment.⁹

Easyhaler® Beclometasone 200mcg

Easyhaler® Beclometasone 200mcg is indicated for prophylactic management of asthma in adults.¹⁰ Beclometasone is an inhaled corticosteroid (ICS) to be taken regularly, initially at a dose of 200mcg twice each day.¹⁰ Regular prevention with low-dose ICS is the second step in the BTS/SIGN guidelines for asthma in adults.⁹ Higher daily doses in line with step 4 can be divided into two, three or four times daily administration.¹⁰

Easyhaler® Budesonide 100mcg, 200mcg and 400mcg

Easyhaler® Budesonide 100mcg, 200mcg and 400mcg indicated for treatment of persistent asthma in adults and children over 6 years.^11,12,13 Budesonide is an ICS used once or twice daily¹¹ in line with steps 2 and 4 of BTS/SIGN guidelines.⁹

Formoterol Easyhaler® 12mcg

Formoterol Easyhaler® 12mcg is indicated for long-term bronchodilation in COPD patients and the treatment of asthma in adults and children over 6 years in line with current guidelines.14 Formoterol is a long-acting beta-agonist (LABA) taken twice daily¹⁴ in addition to a low-dose ICS, in line with the third step of BTS/SIGN guidelines.⁹

Fobumix Easyhaler® 80mcg/4.5mcg, 160mcg/4.5 mcg and 320mcg/9mcg

Fobumix Easyhaler® 80mcg/4.5mcg, 160mcg/4.5 mcg and 320mcg/9mcg contain a combination of formoterol (LABA) and budesonide (ICS). Fobumix Easyhalers® 160/4.5 and 320/9 are indicated for the symptomatic treatment of asthma and COPD (where FEV1 is <70%) in adults over 18 years where use of a combination inhaler is appropriate.^15,16,17 Fobumix 80/4.5 is indicated in asthma but not in COPD.¹⁵ When adding a LABA to ICS, BTS/SIGN guidelines recommend the use of combination inhalers to improve inhaler adherence and to guarantee that a LABA is not taken without an ICS.⁹

Fobumix 80/4.5 and 160/4.5 are also indicated for maintenance and reliever therapy (MART) in asthmatic patients.^15,16 This is where a daily maintenance dose is taken regularly either once or twice daily, but additional doses can be taken as required to relieve symptoms.15,16 Patients needing a total daily dose of more than 8 inhalations should be referred onward to have their maintenance dose re- assessed.^15,16 Fobumix Easyhaler 320/9 is indicated for maintenance therapy only in asthma, not MART.¹⁷

It’s worth explaining here that unlike the other Easyhalers where the labelled strength describes the measured or metered dose of medication,^{7,8,10-14,18,19} the labelled strength of Fobumix Easyhaler® describes the delivered dose (DD).^15,16,17 The delivered dose is the amount of medication that actually leaves the mouthpiece, which will usually be less than the metered dose.¹⁵ We’ll see later how this translates to a respirable dose, the amount that reaches the lungs. Note that there is actually very little difference between the metered dose and the delivered dose of Fobumix Easyhaler®.^15,16,17

The DD of Fobumix Easyhaler® corresponds to the DD of other budesonide/formoterol inhalers even where their labelled strengths describe a larger, metered dose.¹⁵ To illustrate the point, a Fobumix Easyhaler® with a delivered dose of 160mcg/4.5mcg corresponds to other inhalers that have a metered dose of 200mcg/6mcg.¹⁶ If you are unsure as to whether an inhaler’s labelled strength is describing the metered dose or the delivered dose, check the manufacturer’s SPC before dispensing.

Fusacomb Easyhaler® 50mcg/250mcg and 50mcg/500mcg

Fusacomb Easyhaler® 50mcg/250mcg and 50mcg/500mcg contain a combination of salmeterol (LABA) and fluticasone (ICS). Fusacomb Easyhalers are indicated for maintenance therapy in asthma in adults and children over 12 and patients with COPD (FEV1 is <60%), when a combination inhaler is appropriate.^18,19 This combination of LABA and ICS provides an alternative treatment option in line with step 3 of BTS/SIGN guidelines.⁹ Fusacomb Easyhalers are not licensed for MART in asthma.^18,19

Module 2: Problems with inhaling medicines

After non-drug measures have been implemented, inhaled medicines are first-line treatments in the management of chronic asthma²⁰ and COPD.²¹ The difficulties encountered by patients using inhalers are well documented, but it is worth reminding ourselves.

Firstly, in in vitro trials and when used correctly in line with the manufacturer’s instructions, the pMDIs and various DPIs are all as effective as each other, given the same medications.^1,22 But there are many studies which show that errors in use are very common for both pMDIs and DPIs and that this can impair delivery of drug to the lungs.²³ Consequently there can be poor symptom control and more frequent exacerbations and hospitalisation.²³

Pressurised metered dose inhalers (pMDI)

pMDIs deliver a fixed dose as an aerosol from a pressurised canister containing a mixture of liquid medicine and propellant.²³ When the aerosol is inhaled the propellant evaporates and the drug is deposited in the respiratory tract.²³

Using a pMDI effectively requires the patient to co-ordinate the actuation of the device with breathing in; first start breathing in slowly but deeply, then actuate the inhaler while continuing to breathe in, and then hold the breath for around 10 seconds.²³ It is important to breathe in slowly to minimise deposition of drug in the mouth and throat.²³

Many patients, including children and the elderly, therefore find the overall process difficult.²³

To illustrate the problem, The CRITIKAL study of 2017 analysed data from 3660 patients involved in an asthma review service, looking for inhaler errors and any associated asthma outcomes.²⁴ They found that 24.9% of patients using a pMDI actuated the device before inhaling and that this was associated with uncontrolled asthma.²⁴

In a 2016 systematic review of errors in inhaler use, the authors searched for articles describing direct observation of inhaler technique by healthcare professionals over a 40 year period.²⁵ The review found 144 articles reporting on 59,584 observed tests of technique.²⁵ The most common errors found for pMDIs were in coordination (45%; 95% CI, 41%-49%), speed and/or depth of inspiration (44%; 40%-47%), and no post-inhalation breath-hold (46%; 42%-49%).²⁵

Spacer devices can be used to help patients mitigate the problems of pMDIs, allowing more of the drug to reach the lungs, although spacers can also bring their own challenges.²³

Dry powder, breath-actuated inhalers (DPI)

Breath-actuated DPIs were designed to avoid the problem of co-ordinating actuation with breathing. However, DPIs are not without their own problems, which can differ according to the device used.²³

For example, exhaling into the device prior to inhaling can disperse the powder, affecting the dose and potentially clogging the device.²³

Environmental conditions such as humidity and temperature can affect the de-aggregation of drug and carrier particles (see below).²³ And a few patients may not be able to generate a sufficient inspiratory flow rate for their device to work effectively.^1,23,24

In contrast to pMDI, with most DPI the patient is advised to breathe in as forcibly as possible.²³ The reason for this is twofold.

Firstly, in the absence of a propellant, there must be a sufficient force for the full dose to leave the device. Secondly, the airflow must be sufficiently turbulent to de-aggregate the drug from the carrier particle²³ – a problem arising from particle size.

Particle size, flow and de-aggregation

During inhalation, an even distribution of drug within the lungs is only achieved for drug particle sizes between 1 and 5 microns.²⁶ The proportion of drug particles emitted from the inhaler (the delivered dose [DD]) that are within this range is termed the respirable, or fine particle dose (FPD).²⁶

Now, in order for a dose to be accurately measured out by a DPI (the metered dose) the powder has to flow smoothly and consistently.²⁶ Unfortunately, particles smaller than 5 microns do not exhibit these flow properties.²⁶ This can be overcome by mixing the drug particles with larger, inert carrier particles, the most commonly used being lactose.²⁶ The drug and carrier bind weakly to each other but this bond has to be broken during inhalation to obtain the fine particle dose – the process of de-aggregation.²⁶

De-aggregation is achieved through the force generated by the patient’s inspiratory flow combined with the airflow resistance inherent in the particular device.²⁶ Each DPI is therefore designed to create an optimum fine particle dose based on the formulation of the powder, leading to differences in airflow resistance between devices.²⁶

Some DPI have a relatively low internal resistance requiring the patient to breathe in faster and harder to achieve de-aggregation. Other DPI have a higher internal resistance, allowing for consistent fine particle doses at lower inspiration rates.²³

Evidence of DPI errors

In the 2017 CRITIKAL study, not breathing in sufficiently strongly was a common error in DPI users, made by 32%-38% of patients.²⁴ This error was associated with uncontrolled asthma and increased rates of exacerbation.²⁴

In the 2016 systematic review of inhaler use described above, the most common errors identified in DPI users were:

• incorrect preparation in 29% of patients (95% CI: 26%-33%)²⁵
• no full expiration before inhalation in 46% of patients (42%-50%)²⁵
• and no post-inhalation breath-hold in 37% of patients (33%-40%).²⁵

When considering both pMDI and DPI users, the systematic review found the overall prevalence of correct technique was 31% (28%-35%), acceptable technique was 41% (36%-47%) and poor technique 31% (27%-36%).²⁵

Conclusions

The authors of the 2016 systematic review concluded that incorrect inhaler technique was unacceptably frequent and that it hadn’t improved in the 40 years prior to 2015.²⁵

Inhaler errors can be categorised as device-related, patient-related and healthcare professional- related (for example insufficient knowledge or failure to educate patients).²⁷ There are many different types of inhaler device, each requiring a certain level of skill, manual dexterity and lung capacity or coordination to ensure optimum use.²⁷

Research has shown that written and verbal instructions can help patients with inhaler technique, but that a physical demonstration by a pharmacist leads to better retention of skills.²⁷ Even a simple few minutes spent with a trained community pharmacist has been shown to improve inhaler technique and asthma outcomes for patients.²⁷

Module 3: Why has Easyhaler® been prescribed?

Given the range of medicines and combinations available for respiratory conditions, the prescriber will select the most appropriate treatment for their patient in line with national best practice and licensed indications. The choice of device, however, can be a shared decision between prescriber and patient²³, taking into account the patient’s breathing capacity and their preferences in terms of ease of use and convenience.²⁷

This module will look at the factors which might lead to a prescriber or patient choosing Easyhaler® as their preferred device.

Inspiratory flow rate

In in vitro trials, Easyhaler® has been shown to deliver consistent fine particle doses at a range of inspiratory flow rates from 30-90 L/minute, whilst showing less variability than the comparison DPIs.²⁸ This demonstrates a low dependence of the device on any specific inspiration rate for successful dosing.²⁸

In addition, consistent therapeutic doses have been achieved at flow rates as low as 28 L/minute which is usually achievable even for young children with asthma and elderly patients with COPD.²⁸ Patients are more likely to receive the same dose of medication each time, even at low or varying flow rates.²⁸

The graphs below show the results of in vitro studies into the consistency of dosing of Easyhaler® at varying flow rates.¹

Patient satisfaction (efficacy and ease of use)

A number of clinical trials have been conducted to measure the efficacy, safety and acceptability of Easyhaler® when delivering salbutamol and beclometasone.³⁰ Easyhaler® was compared to a pMDI with and without spacer and two alternative DPIs.³⁰ A meta-analysis in 2000 identified nine such trials, involving over 800 patients, and in all cases the safety and efficacy of Easyhaler® was comparable to the reference products.³⁰

In terms of patient acceptability, the meta-analysis selected 5 factors from patient questionnaires: ease of use, ease of learning technique, ease of dose loading, ease of inhaling and patient’s overall choice.³⁰ The analysis identified a clear difference in favour of Easyhaler® with an overall preference of 87% v 7% when compared to a pMDI and 60% v 35% when compared to an alternative DPI.³⁰

More recently, a number of real-world studies have looked at patient-reported outcomes with Easyhaler® devices. In a 2018 study looking at budesonide/formoterol Easyhaler®, nearly 1500 patients with asthma and COPD were treated for 12 weeks and assessed for efficacy and patient satisfaction.³¹ Roughly 30% of patients were newly diagnosed and 70% were switching from other types of inhaler.³¹ Efficacy was assessed using spirometry, asthma control tests and quality of life questionnaires.³¹

Importantly, this real-world study showed that after 12 weeks of treatment with budesonide/formoterol Easyhaler® patients showed improved lung function and all patient groups showed significant improvement in quality of life scores.³¹

Of those patients switched from other inhalers, 72.4% rated Easyhaler® as very good (the top rating) and a further 24.8% rated it as good, a total of 97.2%.³¹ This compares to 50% or less of patients rating their previous pMDI or DPI as good or very good.³¹ Overall patients considered Easyhaler® to be portable, easy to use and easy to keep clean.³¹

Patient satisfaction by inhaler type (visit 3, following 12 weeks’ treatment with the Bufomix Easyhaler; visit 1 for other devices) (n = 1043).

31. Adv Ther (2018) 35:1140–1152 https://doi.org/10.1007/s12325-018- 0753-6

Clinical Effectiveness of Budesonide/Formoterol Fumarate Easyhaler for Patients with Poorly Controlled Obstructive Airway Disease: a Real-World Study of Patient-Reported Outcomes

The study also gathered the opinions of the prescribers involved.³¹ Over 90% of the physicians described Easyhaler® as easy to teach, with around 73% of patients learning the technique within 5 minutes and 98.9% by 10 minutes.³¹

To put this in context, a small study in 2016, involving 25 patients with asthma, investigated their attitudes, perceptions and preferences regarding their inhalers.³² Irrespective of the device, ease of use was considered the most important feature of their inhaler and patients associated ease of use with effectiveness in symptom control and satisfaction and fulfilment with their therapy.³²

Real-world reliability

One of the requirements of the Committee for Medicinal Products for Human Use (CHMP) guidelines is that the performance of a product be tested under conditions that mimic real-life patient use.⁵

A 2018 study into the budesonide Easyhaler® investigated some of the environmental stress conditions that might impact on device performance.³³ Three in vitro studies assessed dose uniformity by measuring the delivered dose under different conditions.³³ Acceptable dose uniformity was declared to be between 80% and 120% of the expected dose, in line with the limits set by the European Pharmacopeia.³³

The conditions tested include:

DD of budesonide using Easyhaler® before and after: (a) dropping tests and (b) vibration tests. Data presented as mean + standard deviation. DD: delivered dose.

33. J. Haikarainen, P. Rytila, S. Roos, S. Metsarinne, A. Haponnen. Dose uniformity of budesonide

Easyhaler® under simulated real-life conditions and with low inspiration flow rates. Chronic Respiratory Disease 2018, Vol. 15(3) 265–271; DOI:10.1177/1479972317745733;https://journals.sagepub.com/doi/10.1177/ 1479972317745733

A further pharmacokinetic study in 2020 extended the investigations with additional environmental stress conditions, this time with the fluticasone/salmeterol Easyhaler®.⁵ Three inhalers of each strength were assessed under separate conditions and over the lifetime of the inhaler (30 days at twice daily dosing).⁵ In addition to the same dropping and vibration tests described above, inhalers were also tested at a temperature of 30⁰C and 75% humidity for 48 hours and after a freeze-thawing process (-20⁰C to +25⁰C).⁵

The delivered dose remained stable throughout the lifetime of the inhaler, ranging from 95% to 104% of the labelled strengths.⁵ Similar delivered doses and fine particle doses were found both before and after each of the tests with very little variation, and no breakages occurred during testing.⁵

Whilst we cannot infer reliability under more severe conditions, such as a higher temperature or dropping from a greater height, or from a combination of differing conditions, the results of these studies suggest that reliable dosing can be achieved under real-life stress conditions.⁵ Pharmacists can reassure their patients as to the durability and reliability of their Easyhaler® device.

Module 4: How to use the Easyhaler® device.

As we have seen, patients find Easyhaler® easy to use,³¹ prescribers find it easy to teach,³¹ and it delivers consistent dosing even at low inspiratory flow rates^1,28,29 and under simulated stress conditions.^5,33

This module will explain how to use Easyhaler®, providing hints and tips to help you advise and train your patients in correct use.

Wehale.Life is a manufacturer-led website providing a range of online resources for healthcare professionals wanting to learn more about respiratory management and the Easyhaler® portfolio.

An instructional video is available from the manufacturer which patients can access via a link in the PIL or via the Wehale.life website.

Storage, hygiene and replacement

Easyhalers are packaged in laminate foil pouches to protect the powdered medication from moisture during storage and transit. The foil bag should not be opened until the patient is ready to start using the inhaler.⁶ It is a good idea to note the date it was opened on a calendar. Depending on the specific product, Easyhalers should be disposed of between one and six months after opening the foil bag.^7,8,10-19

Easyhaler® has a dose counter to let the patient know when the doses are running low and a new prescription is required. The dose counter shows increments of 10 and the counter moves once every 5 clicks. Once the dose counter reaches the red zone there are 20 doses left. The inhaler should be replaced once the dose counter reaches zero, even if the powder is still visible in the device.⁶

The mouthpiece of Easyhaler® is protected by a dust cap which, when in place, also prevents the accidental loading of a dose.⁶ The dust cap should remain in place when the inhaler is not in use to keep the mouthpiece clean and free from foreign objects.

A protective cover is also available for patients to use which encloses the entire inhaler. The protective cover should be used with the dust cap in place to prevent accidental loading of a dose. The inhaler can be used without removing the protective cover.⁶ The protective cover can be ordered by contacting the manufacturer’s medical information team.

Encourage patients to use the protective cover and dust cap to keep the inhaler clean and improve the durability of the product.⁶ The MHRA has previously issued safety warnings to patients using pMDIs due to a risk of accidental inspiration of foreign objects.³⁴ They advise that if inhalers are stored without a dust cap in place, loose objects can become trapped within the mouthpiece and inhaled into the back of the throat.³⁴ A fully protected Easyhaler® can minimise this problem.

Patients should be advised not to use water to clean the Easyhaler® device as the powder will be sensitive to moisture.⁶ The mouthpiece can be wiped with a dry cloth or tissue to keep clean.⁶

Instructions for correct use of Easyhaler®^6,7,8,10-19

1. Open the protective cover (if in use) and remove the dust cap (the inhaler will not click with the dust cap on).
2. Hold the top and bottom of the inhaler between the forefinger and thumb.
3. Shake the inhaler vertically three to five times.

4. Keeping the inhaler upright, click down once on the inhaler and release to prepare a dose. Do not tip the inhaler forwards as some powder may be lost.

5. Exhale normally and then place the mouthpiece between your teeth and form a tight seal with your lips. Do not exhale into the mouthpiece as this could affect the dose.

6. Inhale as strongly and as deeply as you can. Pharmacists, remember that Easyhaler® works independently of inspiratory flow rate, so even young or breathless patients can use it.²⁸

7. Remove the inhaler from your mouth and hold your breath for at least 5 seconds before exhaling normally.

8. Repeat the process for a second dose if necessary.

9. Replace the dust cap and close the protective cover.

Patients using inhaled corticosteroids should be advised to rinse their mouth and spit out and/or brush their teeth after using their inhaler to prevent oral irritation or infection.⁶

The powder in the Easyhaler® device may need to be emptied without inhaling if:⁶

• The inhaler is clicked by accident when not required
• The inhaler is clicked more than once during use
• The patient exhales into the mouthpiece

If this happens tap the mouthpiece onto a hard surface or the palm of your hand to remove the powder.⁶ Re-start the process if a dose is still required.⁶

Supporting patients with their Easyhaler®

As we’ve seen, a few minutes of inhaler education with a trained community pharmacist can significantly improve inhaler technique and disease outcomes.²⁷ The most effective inhaler training technique is verbal instruction combined with physical demonstration.²⁷ And repeating this training over time increases the proportion of patients who maintain correct technique.²⁷

Just by working through these modules, learning about the problems patients can encounter with inhaled medicines, and by learning how to use different inhaler types you are already helping your patients.

Next time you dispense an inhaler, ask your patient if they’ve been shown how to use it. Ask if they would like any help or a demonstration, or if they would like to demonstrate it to you.

Signpost your patients to the Wehale.life website for videos and guides about dealing with respiratory conditions and using their Easyhaler®.

If a patient tells you about any side-effects after using an Easyhaler® please remember to submit a report via the Yellow Card Scheme www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Cases can also be reported directly to Orion Pharma (UK) Ltd on 01635 520300.

Disclaimer

This medical education online learning module is funded by Orion Pharma (UK) Ltd as part of a commitment towards supporting the appropriate use of inhaled therapy. Orion Pharma (UK) Ltd has had input into the module title and reviewed the educational content for quality and factual accuracy.

References and Further Reading

1. Lavorini F. Easyhaler®: an overview of an inhaler device for day-to-day use in patients with asthma and chronic obstructive pulmonary disease. Drugs in Context 2019; 8: 212596. DOI: 10.7573/dic.212596; https://www.drugsincontext.com/easyhaler-an-overview-of-an-inhaler-device-for-day-to-day-use-in-patients-with-asthma-and-chronic-obstructive-pulmonary-disease/

2. Jia. X, Zhou. S, Luo. D, Zhao. X, Zhou. Y, Cui. Y‐M. Effect of pharmacist‐led interventions on medication adherence and inhalation technique in adult patients with asthma or COPD: A systematic review and meta‐ analysis. J Clin Pharm Ther. 2020; 45: 904– 917; https://doi.org/10.1111/jcpt.13126

3. Hesso I, Gebara SN, Kayyali R. Impact of community pharmacists in COPD management: Inhalation technique and medication adherence. Respir Med. 2016 Sep;118:22-30. doi: 10.1016/j.rmed.2016.07.010. Epub 2016 Jul 15. PMID: 27578467; https://www.resmedjournal.com/article/S0954-6111(16)30157-3/fulltext.

4. M. Vidgren , M. Silvasti, P. Vidgren, H. Sormunen, K. Laurikainen, P. Korhonen (1995) Easyhaler® Multiple Dose Powder Inhaler—Practical and Effective Alternative to the Pressurized MDI, Aerosol Science and Technology, 22:4, 335-345, DOI:10.1080/02786829408959751; https://www.tandfonline.com/doi/abs/10.1080/02786829408959751.

5. Anni Turpeinen, Patrik Eriksson, Anita Happonen, Johanna Husman-Piirainen, Jussi Haikarainen. Consistent Dosing Through the Salmeterol–Fluticasone Propionate Easyhaler for the Management of Asthma and Chronic Obstructive Pulmonary Disease: Robustness Analysis Across the Easyhaler Lifetime. Journal of Aerosol Medicine and Pulmonary Drug Delivery, Volume 33, Number 0, 2020 Pp1-8. Mary Ann Liebert, Inc. (Publishers); Published Online:22 Sep 2020 https://doi.org/10.1089/jamp.2020.1592.

6. Patient Information Leaflet (PIL), Fusacomb Easyhaler 50/250 & 50/500 inhalation powder: Package leaflet. Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated March 2018; https://www.medicines.org.uk/emc/product/9224/pil.

7. Easyhaler® Salbutamol 100mcg – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated June 2018; https://www.medicines.org.uk/emc/product/6339/smpc.

8. Easyhaler® Salbutamol 200mcg – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated June 2018; https://www.medicines.org.uk/emc/product/6340/smpc.

9. Scottish Intercollegiate Guidelines Network (SIGN) and British Thoracic Society (BTS); SIGN 158, British guideline on the management of asthma: Quick reference guide; Revised edition published July 2019; https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma/.

10. Easyhaler® Beclometasone 200 micrograms/dose inhalation powder – Summary of Product Characteristics (SmPC); Orion Pharma (UK( Ltd, The electronic Medicines Compendium, dated January 2017; https://www.medicines.org.uk/emc/product/239/smpc.

11. Easyhaler® Budesonide 100 mcg – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated April 2017; https://www.medicines.org.uk/emc/product/241/smpc.

12. Easyhaler® Budesonide 200 mcg – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated April 2017; https://www.medicines.org.uk/emc/product/242/smpc.

13. Easyhaler® Budesonide 400 mcg – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated April 2017; https://www.medicines.org.uk/emc/product/243/smpc.

14. Formoterol Easyhaler® 12 micrograms per dose inhalation powder – Summary of Product Characteristics (SmPC) ); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated April 2015; https://www.medicines.org.uk/emc/product/312/smpc.

15. Fobumix Easyhaler 80/4.5 inhalation powder – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated January 2017; https://www.medicines.org.uk/emc/product/8707/smpc.

16. Fobumix Easyhaler 160/4.5 inhalation powder – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated January 2017; https://www.medicines.org.uk/emc/product/8706/smpc.

17. Fobumix Easyhaler 320/9 inhalation powder – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated January 2017; https://www.medicines.org.uk/emc/product/8438/smpc.

18. Fusacomb Easyhaler 50/250 inhalation powder – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated January 2019; https://www.medicines.org.uk/emc/product/9224/smpc.

19. Fusacomb Easyhaler 50/500 inhalation powder – Summary of Product Characteristics (SmPC); Orion Pharma (UK) Ltd, The electronic Medicines Compendium, dated January 2019; https://www.medicines.org.uk/emc/product/9226/smpc.

20. Medicines Complete, British National Formulary (BNF), Treatment summary: Asthma, chronic; last updated 6th May 2020; BNF © BMJ Group and the Royal Pharmaceutical Society 2020; https://doi.org/10.18578/BNF.806509645.

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