Patients’ perspectives and preferences in the choice of inhalers: the case for Respimat^® or HandiHaler^®

Figures & data

Figure 1 Association between asthma and COPD disease control and at least one critical inhaler error.

Notes: (A) Describes the relationship between risk of at least one critical inhaler error and Asthma Control Test questionnaire score. (B) Describes the relationship between risk of at least one critical inhaler error and self-reporting of some unscheduled health-care resources use in the last year. Data from Melani et al.⁵⁷
Abbreviation: COPD, chronic obstructive pulmonary disease.

Figure 2 ADMIT asthma therapy adjustment flow chart.

Note: Adapted from from Respir Med, 100/9, Crompton GK, Barnes PJ, Broeders M, et al, The need to improve inhalation technique in Europe: a report from the Aerosol Drug Management Improvement Team, 1479–1494, Copyright 2006, with permission from Elsevier.¹⁵
Abbreviation: ADMIT, Aerosol Drug Management Improvement Team.

Table 1 Major components, advantages, and disadvantages of inhaler devices

Inhaler	Formulation	Metering system	Advantages	Disadvantages
pMDI	Drug suspended or dissolved in propellant (with surfactant and cosolvent)	Metering valve and reservoir	Portable and compact Multidose device Relatively inexpensive Cannot contaminate contents Available for most inhaled medications Dose indicator (new-generation devices)	Contains propellants Not breath actuated Many patients cannot use it correctly High oropharyngeal deposition
pMDI + spacer			Low dependence on inspiratory flow rate Easier to coordinate Large drug doses delivered more conveniently Less oropharyngeal deposition Low dependence on inspiratory flow rate Higher lung deposition than a pMDI	Less portable than a pMDI Plastic spacers may acquire static charge Additional cost to a pMDI
BA-MDI	Drug suspended in propellant	Metering valve and reservoir	Portable and compact Multidose device Breath actuated (no coordination needed) Cannot contaminate contents	Contains propellants “Cold Freon” effect Requires moderate inspiratory flow to be triggered
DPI	Drug blend in lactose, drug alone, drug/excipient particles	Capsules, blisters, multidose blister packs, reservoirs	Portable and compact Breath actuated (no coordination needed) Does not contain propellants Dose indicator (new generation devices) Locking mechanism when empty (new generation devices)	Requires a minimum inspiratory flow May not be appropriate for emergency situations Many patients cannot use it correctly Most types are moisture sensitive
SMI (Respimat^®)	Aqueous solution or suspension	A spring-loaded system provides the energy required to force aqueous solution from a reservoir through the “uniblock” to produce the soft mist	Portable and compact Multidose device Low dependence on inspiratory flow rate (slow moving aerosol) High fine particle fraction High lung deposition Does not contain propellants Dose indicator Locking mechanism when empty	Not breath actuated
Nebulizers	Aqueous solution or suspension	Nebule dispensed into reservoir chamber of nebulizer	May be used at any age No specific inhalation technique required Vibrating mesh is portable and does not require an outside energy source May dispense drugs not available with pMDIs or DPIs	Jet and ultrasonic nebulizers require an outside energy source Treatment times can be long Performance varies between nebulizers Jet nebulizers cannot aerosolize a certain volume of solution Risk of bacterial contamination Newer nebulizers are expensive

Note: Data from Lavorini²² and Lavorini et al.⁵

Abbreviations: BA-MDI, breath-actuated metered dose inhaler; DPI, dry powder inhaler; pMDI, pressurized metered dose inhaler; SMI, Soft Mist™ Inhaler.

Figure 3 Typical scintigraphic images for Respimat^®, Turbuhaler^® DPI at slow and fast inhaled flow rates, and pMDI.

Notes: (A) Respimat^® SMI; (B) Turbuhaler^® DPI – slow; (C) Turbuhaler^® DPI – fast; (D) pMDI. Reproduced from Pitcairn G, Reader S, Pavia D, Newman S. Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry powder inhaler. J Aerosol Med. 2005;18(3):264–272.³³ The publisher for this copyrighted material is Mary Ann Liebert, Inc. publishers.
Abbreviations: DPI, dry powder inhaler; pMDI, pressurized metered dose inhaler; SMI, Soft Mist™ Inhaler.

Table 2 Correct techniques for using pMDI, DPI (specifically HandiHaler^®), and SMI (Respimat^®) devices

Inhaler type	Correct technique	Errors in technique
pMDIa	1. Shake the inhaler well before use (three or four shakes) 2. Remove the cap 3. Breathe out, away from inhaler 4. Place inhaler between teeth and close mouth around it 5. Start to breathe in slowly. Press the top of inhaler once and keep breathing in slowly until a full breath has been taken 6. Remove the inhaler and hold breath for about 10 seconds, then breathe out 7. If a second puff is needed, wait 30 seconds, shake inhaler again, and repeat above steps 8. Rinse mouth (after ICS) and record the number of doses taken	Inhaler not primed Inhaler not shaken No exhalation Holding mouthpiece away from mouth/poor seal around mouthpiece Firing device before start of inhalation Firing device at or after end of inhalation Inhaling through nose Stopping inhalation as device is fired Fast inhalation No breath-hold/short breath-hold
HandiHaler^® (DPI)b,c	1. Open the HandiHaler^® device. Separate only one of the blisters from the blister card; then open the blister 2. Insert the Spiriva^® (Boehringer Ingelheim) capsule and close the mouthpiece firmly against the gray base until a click is heard 3. Press the green piercing button once until it is flat (flush) against the base, then release 4. Breathe out completely. Then, with the HandiHaler^® in the mouth, breathe in deeply until lungs are full. Patient should hear or feel the Spiriva^® capsule vibrate (rattle) 5. Patient must inhale twice from the same Spiriva^® capsule in order to take full daily dose	Incorrect dose loading Failure to pierce capsule or release piercing button Breathing out into device Inhalation vents blocked Poor seal around mouthpiece Patients inhaling too forcefully (>40–50 L/min)d Insufficient flow “acceleration” Inhaling through nose No breath-hold/short breath-hold Inappropriate storage
Respimat^® (SMI)e,f	1. Keep cap closed. Turn base in direction of the arrows on label until a click is heard 2. Flip cap open until it clicks into open position 3. Close lips around the mouthpiece end. While taking in a slow, deep breath, press dose release button; keep breathing in slowly. Close cap 4. Repeat for a total of two puffs	Failure to prime device/load dose Failure to open mouthpiece cap No exhalation Mouthpiece vents blocked Firing device before start of inhalation Firing device at or after end of inhalation Inhaling through nose Stopping inhalation as device is fired Fast inhalation No breath-hold/short breath-hold

Notes:

a Instruction manual (Canada);

b Instruction manual (USA);

c HandiHaler^® SmPC;⁵⁸

d Crucial error for some DPIs;

e Instruction manual (USA);

f Respimat^® SmPC.⁵⁹ Data from Newman.^60,61

Abbreviations: DPI, dry powder inhaler; ICS, inhaled corticosteroids; pMDI, pressurized metered dose inhaler; SMI, Soft Mist™ Inhaler; SmPC, summary of product characteristics.

Figure 4 Algorithm for choosing inhaler device according to the patient’s inspiratory flow and ability to coordinate inhaler actuation and inspiration.

Note: Reprinted from Respir Med, 107/12, Dekhuijzen PN, Vincken W, Virchow JC, et al, Prescription of inhalers in asthma and COPD: towards a rational, rapid and effective approach, 1817–1821, Copyright 2013, with permission from Elsevier.¹²
Abbreviations: BA-pMDI, breath-actuated pressurized metered dose inhaler; DPI, dry powder inhaler; pMDI, pressurized metered dose inhaler; SMI, Soft Mist™ Inhaler.

Figure 5 Proportions of patients indicating preference for Respimat^® SMI versus alternative inhaler devices in three studies using the Patient Satisfaction and Preference Questionnaire.

Notes: Respimat^® SMI versus (A) pMDI, (B) Turbuhaler^®, (C) Diskus^®. Republished with permission of Dove Medical Press, from Patient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat Soft Mist inhaler, Hodder R, Price D, Int J Chron Obstruct Pulmon Dis, 4, copyright 2012;³⁵ permission conveyed through Copyright Clearance Center, Inc.
Abbreviations: pMDI, pressurized metered dose inhaler; SMI, Soft Mist™ Inhaler.

Table 3 Proposed psychosocioeconomic questions to ask patients with COPD to estimate compliance and to assess adherence phenotype and status

Questions for a treatment naïve patient prior to prescribing inhaled therapy	Questions for patients already under treatment to confirm adherence to inhaled therapy
How many different medications do you take every day? Who do you live with? Are you worried?a Would you stop taking a medication if it gave you side effects or if it was too complicated to take? What do you think about inhaled medications? Do you see any pulmonologists for check-up examinations?	How often did you forget to take your inhaled therapy in the past month? Are you more likely to forget taking your medicines in the morning or the evening? Do you find your therapy dangerous? Do you prefer inhaled drugs to oral tablets? Do you think your prescription is appropriate for your disease?

Notes: Each question has a defined set of four responses. Responses are scored using the Morisky scale to give a general indicator of risk.¹¹ See Sanduzzi et al¹¹ for the complete questionnaires.

a Question relates to the patient’s health condition, and economic and family situations. Data from Sanduzzi et al.¹¹

Abbreviation: COPD, chronic obstructive pulmonary disease.

MelaniASBonaviaMCilentiVInhaler mishandling remains common in real life and is associated with reduced disease controlRespir Med2011105693093821367593

 PubMed Web of Science ®Google Scholar

CromptonGKBarnesPJBroedersMThe need to improve inhalation technique in Europe: a report from the Aerosol Drug Management Improvement TeamRespir Med200610091479149416495040

 PubMed Web of Science ®Google Scholar

LavoriniFThe challenge of delivering therapeutic aerosols to asthma patientsISRN Allergy2013201310241823984095

 PubMedGoogle Scholar

LavoriniFFontanaGAUsmaniOSNew inhaler devices – the good, the bad and the uglyRespiration201488131524902629

 PubMed Web of Science ®Google Scholar

PitcairnGReaderSPaviaDNewmanSDeposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry powder inhalerJ Aerosol Med200518326427216181001

 PubMedGoogle Scholar

Boehringer Ingelheim LtdSPIRIVA^® HandiHaler® Summary of Product CharacteristicsBoehringer Ingelheim Ltd Available from: http://www.medicines.org.uk/emc/medicine/10039/SPC/Accessed 2012

 Google Scholar

Boehringer Ingelheim Pharma GmbH & Co. KGSummary of Product Characteristics – SPIRIVA^® Respimat^® 2.5 Microgram, Inhalation SolutionIngelheim, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG2013 Available from: http://products.boehringer-ingelheim.com/products/prescription_medicines/respiratory/copd/spiolto/public/assets/spiriva_respimat_spc_published.pdfAccessed 2014

 Google Scholar

NewmanSImproving inhaler technique, adherence to therapy and the precision of dosing: major challenges for pulmonary drug deliveryExpert Opin Drug Deliv201411336537824386924

 PubMed Web of Science ®Google Scholar

NewmanSPInhaler treatment options in COPDEur Respir Rev200514102108

 Google Scholar

DekhuijzenPNVinckenWVirchowJCPrescription of inhalers in asthma and COPD: towards a rational, rapid and effective approachRespir Med2013107121817182124120398

 PubMed Web of Science ®Google Scholar

HodderRPriceDPatient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat Soft Mist inhalerInt J Chron Obstruct Pulmon Dis2009438139019888356

 PubMedGoogle Scholar

SanduzziABalboPCandoliPCOPD: adherence to therapyMultidiscip Respir Med2014916025485108

 PubMedGoogle Scholar