1. Optimising the use of Inhalers in COPD
Dr Toby Capstick
Lead Respiratory Pharmacist at Leeds Teaching Hospitals NHS Trust & Chair at UKCPA Respiratory Group
@tcapper78
@UKCPAResp

2. Declarations of Interest
Payment received for educational events and conference sponsorship from:
Almirall
AstraZeneca
Boehringer Ingelheim
Chiesi
GSK (travel only)
Novartis
Pfizer
Teva
I have not been paid to speak at this GSK sponsored symposium

3. My Inhaler Technique Obsessions…
Photo of older man = “The inhaler should be placed 3 finger-breadths from the mouth and activated while you are starting an inhalation” (from Pulmonary-Critical Care Associates of East Texas)

4. What do Guidelines Recommend?
BTS/SIGN Asthma Guidelines 2016
Prescribe inhalers only after patients have:
Received training in the use of the device, and
Have demonstrated satisfactory technique
Before initiating a new drug therapy practitioners should check:
Adherence with existing therapies
Inhaler technique, and
Eliminate trigger factors
NICE COPD Guidelines 2010
Inhalers should be prescribed only after patients have
received training in the use of the device, and
have demonstrated satisfactory technique
Patients should have their ability to use an inhaler device regularly assessed by a competent healthcare professional and, if necessary, should be re-taught the correct technique
BTS/SIGN Asthma Guidelines 2016
NICE clinical guideline 101: Chronic obstructive pulmonary disease. 2010

5. Choosing Inhaled Drugs: Getting more complicated!

6. Asthma & COPD: Inhalers in 2010
Bronchodilators
SABAs
Salbutamol (7+ devices)
Terbutaline (1 device)
SAMAs
Ipratropium (2 devices)
LABAs
Formoterol (2 devices)
Salmeterol (2 devices)
LAMAs
Tiotropium (2 devices)
Corticosteroids
ICS
Beclometasone (4 devices)
Beclometasone extra-fine (3 devices)
Budesonide (3 devices)
Ciclesonide (1 device)
Fluticasone propionate (2 devices)
Mometasone (1 device)
ICS/LABA
Fostair (1 device)
Seretide (2 devices)
Symbicort (1 device)

7. Asthma & COPD: Increasing Complexity
Bronchodilators
SABAs
Salbutamol (7 devices)
Terbutaline (1 device)
SAMAs
Ipratropium (1 devices)
LABAs
Formoterol (4 devices)
Salmeterol (2 devices)
Indacaterol (1 device)
Olodaterol (1 device)
† Vilanterol
LAMAs
Aclidinium (1 device)
Glycopyrronium (1 device)
Tiotropium (3 devices)
Umeclidinium  (1 device)
LAMA/LABAs
Anoro (umeclidinium/vilanterol) (1 device)
Duaklir (aclidinium/formoterol) (1 device)
Ultibro (glycopyrronium/indacaterol) (1 device)
Spiolto (tiotropium/oldaterol) (1 device)
Corticosteroids
ICS
Beclometasone (3 devices)
Beclometasone extra-fine (3 devices)
Budesonide (3 devices)
Ciclesonide (1 device)
Fluticasone propionate (2 devices)
† Fluticasone furoate
Mometasone (1 device)
ICS/LABA
Aerivio (fluticasone propionate/salmeterol) (1 device)
AirFluSal (fluticasone propionate/salmeterol) (2 devices)
DuoResp (budesonide/formoterol) (1 device)
Flutiform (fluticasone propionate/formoterol) (1 device)
* Fobumix (budesonide/formoterol) (1 device)
Fostair (beclometasone/formoterol) (2 devices)
Relvar  (fluticasone furoate/vilanterol) (1 device)
Sereflo (fluticasone propionate/salmeterol) (1 device)
Seretide (fluticasone propionate/salmeterol) (2 devices)
Sirdupla (fluticasone propionate/salmeterol) (1 device)
Symbicort (budesonide/formoterol) (2 devices)
†Not available as monotherapy *Awaiting UK launch date

8. Currently/Commonly Used Devices Less Commonly Used Devices
How Many?
Currently/Commonly Used Devices
Newer Devices
Less Commonly Used Devices
…introducing
Discontinued Devices

9. Which is the best inhaler device?
The one the patient can & will use!
Features:
Roche et al. EMJ Respir. 2013;1:64-71

10. Which Device do Patients Want?

11. New Devices Claimed easier / simpler devices. But…
Often industry sponsored studies
“Of the 29 studies, 23 were sponsored by the pharmaceutical industry, and 83% of the sponsored trials favoured the device manufactured by the sponsoring company.”
Increased patient choice
Education required
Healthcare professionals
Patients

12. Generic Prescribing Budesonide/formoterol ● Beclometasone/formoterol
Fluticasone/salmeterol
Formoterol
Salbutamol Breath-actuated
Symbicort
Turbohaler
DuoResp
Spiromax
Symbicort
MDI
pMDI
NEXThaler
Seretide Accuhaler
AirFluSal
Forspiro
Aerivio Spiromax
Atimos Modulite pMDI
Formoterol Easyhaler
Foradil Aeroliser
Oxis Turbohaler
BTS/SIGN 2016
Accuhaler
Easyhaler
Easi-Breathe
Clickhaler
Autohaler
Pulvinal
Novolizer

13. Switching Inhaler Devices: Effect of unconsented switch (Asthma)
A 2 year retrospective matched cohort study of 824 patients from 55 practices identified that asthma control deteriorated when inhaled corticosteroid (ICS) inhalers were switched without a consultation. 53% of switches were from drug powder inhalers (DPI) to metered dose inhaler (MDI), 13% from DPI to an alternative DPI, 18% from DPI to breath-actuated inhaler and 13% from breath-actuated inhaler to MDI. Asthma control was defined by the mean short-acting β2-agonist dose, number of oral corticosteroid courses per year, required change in controller therapy and requirement for hospitalisation. Two years after a switch in ICS, fewer patients were successfully controlled than in the matched cohort (19.7% vs. 34.3%), and more had unsuccessful treatment (50.7% vs. 37.9%). After adjusting for confounding factors, the odds ratio for treatment success in the switched cohort compared with controls was 0.29 (95% confidence interval [CI], 0.19 to 0.44; p < 0.001) and for unsuccessful treatment was 1.92 (95% CI, 1.47 to 2.56; p < 0.001).
Treatment Success OR:
0.29 [95% CI: 0.19, 0.44; p<0.001)
Thomas et al. BMC Pulmonary Medicine 2009;9:1-10

14. “We should only use inhalers that we’re familiar with”

15. How Frequently do Patients make Errors Using Inhaler Devices?
Accuhaler
(n = 894), %
pMDI
(n = 552),
Turbohaler
(n = 868),
At least one error 49 76 54
At least one critical error 11 28 32
GPs opinion that the patient inhaled the correct dose 75 50 70
Overestimation of good inhalation by GPs 9 6 24
A CRITICAL error is an error that would substantially affect dose delivery to the lung.
575 GPs recruited to assess inhaler technique on at least 4 patients, using a specific checklist.
3,811 inhalation questionnaires were returned (769 Aerolizer®, 728 Autohaler®, 894 Diskus®, 552 pMDI, 868 Turbuhaler®).
The two most common errors were failure to breathe out before actuation (28.9%) and not holding breath a few seconds (28.3%).
Molimard M et al. Journal of Aerosol Medicine 2003;16:249-54

16. Inhaler Technique: Has it Improved Over 40 Years. Systematic review
Inhaler Technique: Has it Improved Over 40 Years? Systematic review. 144 studies, 54,354 patients
Sanchis et al. Chest 2016; 150(2):

17. Can Healthcare Professionals use pMDIs?
150 Hospital doctors, hospital nurses, general practitioners, practice nurses, hospital and community pharmacy staff
Baverstock M et al. Thorax 2010;65(Suppl 4): A117-A118

18. Misuse of Inhalers is Associated with Decreased Asthma Stability
AIS = Asthma Instability Score
0: best asthma stability
9: worst asthma stability
Frequency distribution of the number of errors in inhalation technique (left axis)
Asthma Instability Score (right axis)
Instability = Increased symptoms, increased beta2-agonist use, nocturnal waking, exercise induced dyspnoea, ER visits, increased global perception of asthma.
The MDI is renowned for incorrect use.
In this study (915 GPs, 4,078 adult asthmatics) it was reported that only 30% of patients were able to perform the correct inhaler technique when using their MDI. It was found that the more mistakes that were made decreased their asthma control. It is important, therefore that patients are trained how to use their MDI and that they are able to perform the necessary inhalation manoeuvres for the MDI product.
The common problems associated with MDI use were:
Not breath-holding
Inhaling too fast
Co-ordination
Stopping inhaling when the dose hits the back of the throat
Giraud V. Eur Respir J 2002;19:

19. Association Between Inhaler Technique and COPD exacerbations
OR 1.47; p=0.001
OR 1.62; p<0.001
OR 1.50; p<0.001
OR 1.54; p<0.001
Melani et al. Resp Med 2011;105:930-8
864 COPD patients
Diskus users 302
HandiHaler users 421
MDIs users 356
Aerolizer users 42
Turbohaler users 159
There was always a statistical significance (p < 0.05) even considering separately asthmatics and COPD patients.
Melani et al. Resp Med 2011;105:930-8

20. Potential Cost Savings

21. Prescription Cost Analysis - England, 2015
Drug
Quantity Supplied
Expenditure 1
Tiotropium 18mcg refills
3,815,821
£150,452,307 2
Seretide 250 MDI
1,683,731
£123,539,695 3
Symbicort 200/6 Turbohaler
1,936,368
£95,985,727 4
Seretide 500 Accuhaler
1,812,558
£87,383,991 5
Sitagliptan 100mg tablets
1,995,456
£75,825,739
Total approx £8.5billion
Total for top 5 approx £542million (~6%)
Inhaled medicines account for 6 of the top 10 drugs in terms of overall expenditure in primary care
(includes Symbicort 400/12 Turbohaler & Fostair 100/6 MDI)
accounting for £583 million in England
BUT, are we getting value for money?
Health & Social Centre Information Centre
accessed 1st December 2016

22. COPD Inhaler Costs (May 2017)
LAMA
LAMA/LABA
ICS/LABA
Prices from eMIMs May 2017

23. Switching Inhaler Devices: Practical Considerations
Patients who may be suitable for inhaler device switch:
Poor inhaler technique with current device
Poor control of asthma / COPD
Poor adherence
Prescribed expensive inhalers
When and how?
Face-to-face consultations
Check inhaler technique
Patient consent essential

24. How should we teach inhaler technique?

25. Inhaler Standards and Competency
Sets standards for HCPs to work with patients to optimise their inhaler technique and maximise benefits of medication.
All HCPs should ensure that patients know how to use their inhaler device
Before initiation & regularly thereafter
Use placebos (single-patient use only) or patient’s own
Before changing inhaler Rx: check technique & adherence
Do not switch to an alternative device until inhaler technique checked & patient consents
Give advice on care, maintenance and storage of the device
Advise against regularly testing the device and wasting doses
Regular audit of the quantity of inhalers prescribed and collected
UK Inhaler Group. Inhaler Standards and Competency Document. January

26. Example Competency Statements for HCPs

27. Example Competency Statements for Patients

28. Resources for teaching Inhaler Technique
Placebos
Videos e.g.:
London Medicines Evaluation Network
Placebo Inhaler Ordering Guide

29. How Should We Teach Inhaler Technique?
Verbal – Instructions on TH technique following the text of PIL from the manufacturer
Augmented Verbal – As verbal, but extra info reinforcing the essential steps (remove cap, keep TH upright, rotate until click etc, inhale forcefully and deeply)
Augmented Verbal and Physical – as Augmented Verbal, but with a show and tell technique by the researcher.
Proportion of patients with optimal and satisfactory technique, before (pre) and 2 weeks after (post) counseling.
Optimal technique score 9/9, all Turbuhaler steps correct.
Satisfactory technique steps 1, 2, 3, and 7 correct (essential steps).
Augmented Verbal
Augmented Verbal + Physical
Verbal
Basheti IA et al. Respir Care 2005;50:

30. Impact of “Show and Tell” Inhaler Technique Counselling Service
Assess Technique using Placebos
“Show and Tell” training method
Re-assess technique
Complete Inhaler Technique Labels
Repeat at frequent intervals
31 pharmacists received brief workshop education
Active = 16; control =15
Active group received training on how to assess and teach DPI technique.
Patients were recruited when they presented with prescriptions for TH or Accs.
97 patients were recruited (A53; C44)
Basheti IA et al. Patient Education and counseling 2008;72:26-33

31. Impact of “Show and Tell” Inhaler Technique Counselling Service
Active group in black
Control group in grey

32. Impact of “Show and Tell” Inhaler Technique Counselling Service
Change in asthma severity. Figure shows Active group (upper panel) and Control group (lower panel), with both inhaler types combined. Asthma severity was significantly better in the Active group at 2 months ( p = 0.001), 3 months ( p < 0.001) and 6 months ( p = 0.015). Asthma severity was assessed by a modification of the criteria in the Australian Asthma Management Handbook.

33. Choosing Inhaler Devices

34. Categorising Inhaler Devices
Aerosol
Dry Powder Inhaler (DPI)
Metered Dose Inhaler (MDI)
Soft Mist Inhaler
Breath-actuated pMDI
Single dose DPI –
Blister
Capsule
Reservoir Multidose DPI
pMDI
Respimat
Autohaler
Accuhaler
Aeroliser
Clickhaler
Easi-Breathe
Ellipta
Breezhaler
Easyhaler
Forspiro
HandiHaler
Genuair
Zonda
NEXThaler
Novolizer
Spiromax
Turbohaler
Twisthaler

35. Choosing an Inhaler
Usmani, Capstick, Chowhan & Scullion. Choosing an appropriate inhaler device for the treatment of adults with asthma or COPD. Dec 2016.

36. Inhaler Technique: 7 Steps to Success
Preparation
Check dose counter
Shake inhaler (where applicable)
Priming
Before first use (where applicable)
Open inhaler / remove cap
Exhaling
Fully and away from mouthpiece
Mouth
Place mouthpiece in mouth & close lips for tight seal
Inhalation
DPI: quick and deep inhalation (within 2–3 seconds)
pMDI/SMI: slow and steady inhalation (over 4–5 seconds)
Breath holding
Remove from mouth, hold breath for 5 seconds
Closing and repeating
Close inhaler / replace cap
Repeat as necessary
Usmani, Capstick, Chowhan & Scullion. Choosing an appropriate inhaler device for the treatment of adults with asthma or COPD. Guidelines.co.uk . In Press.
(adapted from Anna Murphy (simplestepseducation) Seven Step approach)

37. Comparison of Inspiratory Resistance & Inspiratory Flow
Kruger P et al. on behalf of Almirall. ERS Poster 2014

38. Measuring Inspiratory Flow: In-Check DIAL

39. Aerosol Inhalers MDI SMI BA-MDI Respimat Autohaler/Easi-Breathe
Range of Drugs
Wide range of drugs/classes
Compatibility with Spacer (needed for many)
Long-acting bronchodilators
ICS and SABA only
Dose Delivery
Low IFR needed
Many inhale too fast
Efficient dose delivery
Ease of Use
Moderate dexterity
Coordination required
Many use incorrectly
Haleraid available
High dexterity
Complex loading/priming
Locks when empty
Low dexterity
Dose Counter
Dose counter: ICS/LABA (not SABA or ICS)
Dose indicator
None
Feedback
Taste / sound
Taste / click

40. Single Dose DPI - Blisters
Accuhaler
Ellipta
Forspiro
Range of Drugs
SABA
LABA
ICS; ICS/LABA
ICS/LABA
LAMA
LAMA/LABA
FP/Salm only (1 strength)
Dose Delivery
Medium-low airflow resistance
Relatively consistent across IFR 30-90L/min
Do not invert
Consistent across IFR L/min
Ease of Use
Low-moderate dexterity
Gritty if not used correctly
Low dexterity
Simple device
Moderate-high dexterity
Dose Counter
Small dose counter
Large dose counter
Dose counter
Feedback
Taste
Visual: loading of doses & used blisters

41. Ellipta 2-item Feedback: Dose Counter Taste
Dose counter counts as cover open (clicks).
Lose dose if cover closed before inhalation
Six-week expiry
Image from
Relvar Ellipta .Summary of Product Characteristics. Glaxo Group Ltd Dec 2014

42. Ellipta Low resistance device: 0.0286 kPa1/2 l/min.1
Asthma patients and COPD (moderate to v. severe) could all achieve PIFR >43 L/min. 1
Consistent dosing with IFRs 43.5 – 130 L/min.2
Correct technique assessed in 2 Anoro Ellipta crossover exercise studies:3
After initial instruction: 98% (n=632).
At 6-weeks 99% (n=587).
Prime D. et al. Am J Respir Crit Care Med. 2012;185:A2941
Hamilton M et al. Am J Respir Crit Care Med. 2012;185:A2940
Riley JH et al. European Respiratory Society (ERS) Congress Poster No. P4145

43. ForSpiro License: COPD only (500/50) Single dose DPI Feedback:
No comparative data vs. Seretide in COPD
Asthma: equivalent efficacy for 100/50 & 500/50 (no data for 250/50).
EMA submission withdrawn for 250/50 & 500/50
Single dose DPI
Doses in separate blisters in a foil strip
Feedback:
Dose counter
Taste (contains lactose)
Used foil blisters will appear in the side chamber (although used blisters will not appear until 2 days after each one is used)
Kuna. Allergy Asthma Proc 2015;36:352-64

44. Forspiro
Medium-low airflow resistance kPa0.5min/L (identical to Accuhaler).1
Equivalent efficacy to Seretide.2
Relatively consistent dosing across range of inspiratory flow rates (30-90 L/min).1
Similar preference to Accuhaler.1,2 2
Virchow. Expert Opin Drug Deliv 2014;
Kuna. Allergy Asthma Proc 2015;36:352-64

45. Single Dose DPI - Capsule
Breezhaler
HandiHaler
Zonda
Range of Drugs
LABA
LAMA
LAMA/LABA
Dose Delivery
Low airflow resistance
Relatively consistent across IFR L/min
Do not invert
Risk of inhaling capsule fragments
High airflow resistance
Relatively consistent across IFR 28-60L/min
No data on drug delivery?
? Risk of inhaling capsule fragments ?
Ease of Use
High dexterity
Significant manipulation
Redesigned blisters easier to open
Blisters difficult to open
Capsules in bottle
Dose Counter
Capsule count (in blister)
Feedback
Taste
Whirring/vibration
Visual: transparent caps
Visual: open caps

46. Zonda Inhaler High airflow resistance
cmH2O0.5min/L (higher than HandiHaler cmH2O0.5min/L)1
Licence
Hybrid licence
Bio-equivalent to Spiriva HandiHaler1
4-item feedback
Capsule count (in bottle)
Taste (contains lactose)
Sound (vibration of capsule)
Visual (transparent capsule)
60-day expiry of capsules in bottle 1
Algorta J. Clinical Drug Investigation 2016;39:

47. Reservoir Multidose DPI (1)
Easyhaler
Spiromax
Turbohaler
Range of Drugs
SABA
LABA
ICS
ICS/LABA (due 2017)
ICS/LABA
Dose Delivery
High airflow resistance
Consistent across IFR 30-60L/min
Do not invert
Medium airflow resistance
Higher dose delivery at faster IFRs (90 vs 40 L/min)
Medium-high airflow resistance
Ease of Use
Low dexterity
Prime in vertical position
Simple device
Prime in vertical-horizontal position
Moderate dexterity
Turn aid available
Dose Counter
Dose counter (steps of 10)
Dose counter (steps of 2)
Dose counter (Symbicort – steps of 20) or indicator
Feedback
Taste
Window shows unused doses
Generally no taste

48. Spiromax No Phase 3 clinical efficacy or safety studies (not required)
MA is based on pharmacokinetic equivalence to Symbicort.
Lack of PK study for low strength (80/4.5) – application withdrawn
2-item Feedback:
Dose Counter
Taste
No multi-dosing
Dose counter counts as cover open (clicks).
6-month expiry out of foil.
Drug Reservoir
Mouthpiece
Dose Counter
Cyclone
Bellows
Dose Cup
Adapted from TEVA Slideset, data on file

49. Spiromax vs. Turbohaler
Medium resistance:
Spiromax: kPa1/2 l/min vs. Turbohaler: kPa1/2 l/min.2
After PIL training, mean PIF:
Spiromax: 57.5 L/min vs.
Turbohaler 50.0 L/min (p<0.0001)
CHMP Assessment Report
Azouz W. et al. BMC Pulmonary Medicine 2015;15:47

50. Reservoir Multidose DPI (2)
Genuair
NEXThaler
Range of Drugs
LAMA
LAMA/LABA
ICS/LABA
Dose Delivery
Medium airflow resistance
Consistent
No delivery <35L/min
Do not invert
Medium-high airflow resistance
Relatively consistent across IFR 30-90L/min
No delivery <30L/min
Ease of Use
Low dexterity
Prime in vertical position
Locks when empty
Simple device
Dose Counter
Dose counter (steps of 10)
Dose counter (steps of 1)
Feedback
Taste
Click
Window Green -> Red

51. Genuair Cyclone dispersion system Feedback: Dose counter
Colour Indicator window
‘Click’ during inhalation
Triggers at 40L/min1
Dose emitted at ≥ 25 L/min (reduced FPP)1
Dose counter
No multi-dosing
Locks when empty
Expiry after opening the pouch:
90 days (Eklira)
60 days (Duaklir) 2
Van der Palen J. Ther. Deliv. 2014;5:795–806
Duaklir▼ SmPC (accessed July 2015)

52. Genuair Medium airflow resistance 0.0305–0.0308 kPa1/2 l/min.1
Moderate – severe COPD could all achieve minimum PIFR >45L/min2
Consistent dosing with IFRs L/min2
Chrystyn H et Niederlaender C. Int J Clin Pract 2012;66:309-17
Magnussen H et al. Respir Med 2009;1832-7

53. NEXThaler 3-item Feedback:
Click on inhalation (activation of BAM –Breath-actuated mechanism)
Dose Counter
Taste
Dose counter does not count down if dose is not inhaled
6-month expiry out of foil.
Fostair NEXThaler Summary of Product Characteristics. Chiesi Limited. October 2014
Corradi M et al. Expert Opin Drug Deliv.

54. NEXThaler
Medium-High resistance device: kPa1/2 l/min corresponding to a flow rate of 55 l/min at 4 kPa.1
Consistent emitted FPF Dose released only when IFR >35L/min1
Fewer errors vs. Acc / TH2
Corradi M et al. Expert Opin Drug Deliv. In Press
Voshaar T et al. J aerosol Med 2014;27:1-8

55. Summary
Sup-optimal prescribing and use of respiratory medicines is widespread amongst patients and healthcare professionals.
New inhaled drugs & devices provide opportunities for greater patient choice & may assist in medicines optimisation.
Education is a key intervention.