Disclosures. Learning Objectives 3/25/2017. Novel Inhalers for COPD and Asthma

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1 This activity is supported by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. Novel Inhalers for COPD and Asthma Dennis Williams, PharmD., BCPS. AE-C Associate Professor and Vice Chair UNC Eshelman School of Pharmacy Chapel Hill, NC Michael J. Cawley, PharmD., RRT, CPFT, FCCM Professor of Clinical Pharmacy Vice-Chair Department of Pharmacy Practice and Administration Philadelphia College of Pharmacy University of the Sciences Philadelphia, PA Disclosures Michael J. Cawley declares no conflict of interest Dennis Williams reports that his spouse is an employee and owner of stock for GSK The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Target Audience: Pharmacists ACPE#: L04-P Activity Type: Application-based Learning Objectives 1. Identify novel inhalers available for the treatment of asthma and chronic obstructive pulmonary disease (COPD) 2. Discuss patient related factors to consider when selecting among inhaler devices 3. Evaluate common errors with inhaler techniques and identify strategies to correct them 4. Recommend strategies to support patient access to novel inhalers 5. Demonstrate how to use devices for the management of asthma and COPD and how to educate patients on their proper use 1

2 Which of the following errors is common using the Respimat Delivery System? The FIRST step for the pharmacist educating a patient with a new inhaler device would be: Not shaking the device to disperse medication Not piercing the dry powder capsule Not holding the device upright Not priming the device correctly Demonstrate assembly and correct use of the device with a checklist Provide patient written instructions on how to use the device Demonstrate proper maintenance and cleaning of the device Review device instructions and practice with placebo prior to teaching Hydrofluoroalkanes (HFAs) are contained in A forceful inhalation effort is generally required when using a: Metered dose inhalers (MDI) Dry powder inhalers (DPI) Jet nebulizers All inhalation delivery systems Metered dose inhaler Dry powder inhaler Jet nebulizer Peak flow meter A significant barrier to obtaining inhalational products for treating asthma and COPD is that : Formularies only include generic equivalents on the available list Coverage is provided for rescue medications only Co pays tend to be high for the chronic medications Effectiveness is not established for most products Managing Lung Disease with Inhalational Therapies Preferred strategy for managing common lung diseases Major advantage is delivery of medication directly to site of action Companies now use device as platform for multiple products Incorrect use of all inhalational delivery systems is common, resulting in suboptimal outcomes 2

3 Inhalational Delivery Systems Inhalational Delivery Systems Metered dose inhaler (MDI pressurized) Dry Powder inhaler Inhalation Spray Nebulizer (Jet or Ultrasonic) Inhalation delivery systems have undergone significant technological advances during the last 50 years The device used to deliver the dose is as important as the medication itself Patient s ability to use inhalation device is an important and modifiable limitation Inhalational Devices Many companies have adopted a specific delivery system that is used as a platform for their product line Examples Aerosphere (MDI) Diskus (DPI) Ellipta (DPI) Neohaler (DPI) Pressair (DPI) Respimat (Multidose Liquid, Soft mist) Combinations of ICS/LABA or LABA/LAMA are available The optimal inhalation device is the one that is best for an individual patient in a specific situation and setting Quick History pmdi 1959 First pmdi patented in 1959 A few cosmetic changes over the next 20 years 1975 study proved that most of dose was swallowed 1984 Waxman Hatch Act to develop strategies for bioequivalence 1986 Signing of the Montreal Protocol to eliminate CFC propellants New 30 years significant advances in MDI technologies and exploration for alternative devices Reproduced with permission from Allergy and Asthma Network Respiratory Inhaler Poster. AllergyAsthmaNetwork.org Dalby R et al. Advanced Drug Delivery Reviews 2003; 55:

4 Key Components of a pmdi pmdi Formulations Canister Metering valve Actuator Mouthpiece Solutions or suspensions Can contain excipients such as ethanol or surfactants as solubilizers or to stabilize suspensions Propellants that are nontoxic, nonflammable, and compatible with drug formulation Propellant should maintain consistent vapor pressure for life of product Ibrahim M et al. Med Devices: Evidence and Research 2015;8: pmdi Technical Performance When not in use, an inner valve is open and allows metering chamber to fill with propellant drug mixture When actuated (pressed) by patient, outer valve opens, inner valve closes, and metered dose of medication is released Newer actuators include dose counter Ibrahim M et al. Med Devices: Evidence and Research 2015;8: pmdis 2 nd Decade of 21 st Century Significant advances in technology have occurred during last 20 years Dose counters becoming standard Auxillary devices (e.g., spacers, valved holding chambers VHC) important to allow evaporation, deceleration, and filtering of large particles Spacers and VHC can modestly improve lung deposition and reduce risks VHCs may include features to facilitate teaching and improve technique Dalby R et al. Advanced Drug Delivery Reviews 2003; 55: Quick History of DPI Spinhaler and Rotahaler early devices in 60s and 70s Relied on patient s inspiratory force to disperse dose from capsule and carry to airways Progressed to a variety of single dose, multi dose, blister, and reservoir systems Active, breath assisted devices still in development (e.g., Spiros) Dry Powder Inhalers Emerged as option during CFC transition Challenges include internal resistance (e.g., inspiratory force required to aerosolize powder) Risk of hygroscopicity 4

5 Current Dry Powder Inhaler Classification Single unit dose Multi unit dose Multi dose reservoir Dry Powder Inhalers (DPI) Where We Are Today Significant advances in technology and ease of use Each device has specific instructions Efforts to simply use by open inhale close instructions Products include dose counter or indicator Multi dose liquid inhalers Considerations in Designing an Inhaler Example: Respimat Aerosolizes a propellant free drug solution as a soft mist Tension spring forces metered volume of drug through a capillary tube into a micropump When dose release button is pressed, the dose enters a uniblock (e.g., a combination of filters and nozzles made of silicon and glass) Two converging jets of solution collide to produce an aerosol Dalby RN et al. Medical Devices: Evidence and Research 2011;4: Aerosol Properties Mass median aerodynamic diameter (MMAD) Geometric standard deviation (GSD) Fine particle fraction (FPF) Air/Particle velocity Physicochemical Properties Solubility Hygroscopicity Ibrahim M et al. Med Devices: Evidence and Research 2015;8: Particle Properties Volume diameter Bulk density Tap density Shape Charge Lung Properties Geometry of respiratory tree Influence of disease Breathing pattern Desirable Features of Aerosol and Particles Particle sizes of 0.5 to 5 microns are generally considered respirable, depositing by sedimentation in the terminal bronchioles and alveoli GSDs of < 2 optimize the monodisperse characteristics Factors Influencing Effective Administration of Aerosolized Medications Patient s age Physical and cognitive ability Delivery system Patient device interface Arzu A et al. Respir Care 2012; 57(4):

6 Multiple Factors Impact Delivery to Airways Problems with Inhalation Delivery Systems Hand lung coordination with pmdi Electrostatic forces with VHC Poor inspiratory force with DPI Inefficient dose delivery with nebulizer Optimal Delivery of Aerosol Drug Molecule Characteristics Suboptimal technique with all devices Lack of knowledge and instruction among clinicians with all devices Created from Ibrahim M et al. Med Devices: Evidence and Research 2015;8: Factors Influencing Effective Administration of Aerosolized Medications Nebulizers and pmdis with VHC suggested for children <4 years of age DPIs reserved for >4 years of age upon sufficient demonstration of adequate inspiratory flow If mouthpiece is a problem, use mask Blow by technique not recommended Use relaxed and nondistressed breathing pattern Aerosol Product Recipe Drug Molecular Characteristics and Properties Equal Parts?? Delivery Device Characteristics and Properties Arzu A et al. Respir Care 2012; 57(4): What a patient wants from a pulmonary delivery device No need for external power Convenient and unobtrusive to carry Quiet and unobtrusive to use in public Robust enough to survive routine transport, use, and cleaning No extraordinary respiratory maneuvers required for correct use Dose counter What a clinician wants from a pulmonary delivery device Intuitive and easy to use Technique that can be easily taught Mastery of technique can be visually confirmed Familiar instructions for use Dalby R et al. Advanced Drug Delivery Reviews 2003; 55: Dalby R et al. Advanced Drug Delivery Reviews 2003; 55:

7 Case Scenario Case Scenario Jessie Z. is a 68 year old male with longstanding diabetes and COPD who was recently hospitalized with a COPD exacerbation. His COPD is attributed to a 60 pack year smoking history, although he stopped smoking 2 years ago. Prior to admission, he was treated with a tiotropium handihaler, 18 mcg daily, and used albuterol by nebulization as needed. Upon discharge from the hospital, he is prescribed a budesonide/formoterol inhaler (160/4.5) 2 puffs twice daily, and an albuterol MDI for PRN use. He expresses a concern about using a MDI as he feels that he has developed some arthritis in his hands; however, he feels the spray works for him even when he is very short of breath. He notes some difficulty in loading the capsule in his handihaler in the past. He prefers to continue to have his nebulizer for use at home when symptoms are severe. Considerations in Device Selection for this Patient Recognize that he is using multiple devices with different techniques required Periodic monitoring and education is essential to ensure that he gets the optimal benefit from the therapies Consider other options (both medication and device related) based on his specific situation Common Mistakes Not shaking Not priming Not exhaling prior to dose Not holding breath Multiple actuations with single inhalation Holding incorrectly Poor coordination of spray and inhalation Wrong inhalation rate Using empty inhaler Inadequate cleaning Considerations When Counseling Patients Regarding Inhalation Devices Inhalation technique vary pmdi slow, deep inhalation DPI rapid, forceful inhalation MDI is often 2 puffs, DPI is usually 1 puff Mouth rinsing recommended for ICS Periodic cleaning of devices is required, but differs according to product To teach, one must know and understand 7

8 Patient Case Helen is a 65 year old female with COPD who presents to your pharmacy with a new prescription for olodaterol/tiotropium (Respimat delivery system) Medical problems include COPD x 5 years and rheumatoid arthritis (RA) x 5 years Smoker (32 pack year history) Occupational history retired grade school teacher Presently the patient is prescribed an albuterol inhaler PRN and sulfasalazine 2 g/day and naproxen 1000mg/day Patient Case (cont.) Over the past few weeks, her SOB has increased, requiring use of her albuterol inhaler up to 4x per day, with some relief In addition her RA has been flaring up and she has been applying topical capsaicin 0.1% at bedtime to her hands which has been helping You begin the process of counseling Helen with her new olodaterol/tiotropium (Respimat delivery system) Which of the following strategies would be the MOST beneficial to assist Helen with her new inhaler device? Explain technical operation of the device and steps for proper maintenance Providing written information on the device Calling the manufacturer of the device help line on proper use Explain the steps in drug delivery and observe patient using the device Which of the following strategies would be the MOST beneficial to assist Helen with her new inhaler device? A. Explain technical operation of the device and steps for proper maintenance B. Providing written information on the device C. Calling the manufacturer of the device help line on proper use D. Explain the steps in drug delivery and observe patient using the device Respiratory Inhalers Alarming Inhaler Facts.. HandiHaler Respimat Neohaler 40% of COPD demonstrate at least one error in technique In a review of 20 studies, only 28% of doctors and 22% of nurses were able to describe or perform all critical steps in inhaler use Poor training coupled with complex procedures for use, mean that 50 90% of asthma patients show incorrect technique for use Critical inhaler errors lead to increase risk of hospitalization, ED visits, antibiotic prescribing and oral corticosteroids Even with optimal use of any aerosol delivery system, lung deposition may range from 10 15% of the total medication dose Minnesota Department of Health. Accessed November 21, 2016 Rootmensen GN et al. J Aerosol Med Pulm Drug Deliv 2010;23: Self TH et al. J Asthma 2007;44:593 8 Toumas Shehata M et al. NPJ Prim Care Respir Med 2014;24: Virchow JC et al. J Market Access and Health Policy 2015;3:

9 Common Errors with Inhalers Unfamiliar with device Failure to hold breath for sufficient time after drug delivery Multiple actuations without waiting or shaking in between doses (pmdis) Incorrect position of device Failure to breathe deeply and with enough force to deliver medication (dry power inhalers) Exhaling into device American Association for Respiratory Care Guide to Aerosol Delivery Devices. Accessed November, 2016 Common Errors with pmdi Not shaking the canister before each use Inhaling at the wrong time (not in sync with activating inhaler) Aiming the mouthpiece at the roof of the mouth or tongue Inhaling an unnoticed foreign body that has entered the inhaler Damaged or sticky spacer valve that limits the delivery of the medicine Institute for Safe Medication Practices. Accessed November 14, 2016 Common Errors with Dry Powder (Breath Activated) Failing to load dose before inhaling Loss of some medication by holding the inhaler mouthpiece upside down during or after loading a dose Failure to inhale strongly enough to draw medication out of the device Common Errors with Dry Powder (Capsule Loading) Not piercing the capsule Forgetting to remove the spent capsule and not using a new capsule for each dose Failing to take a second breath (if indicated) to receive the full dose Swallowing the capsule instead of inhaling its contents Placing capsule into the inhaler mouthpiece instead of holding chamber Institute for Safe Medication Practices. Accessed November 14, 2016 Institute for Safe Medication Practices. Accessed November 14, 2016 Common Errors with Respimat Delivery System Not priming the inhaler (twist base x 3) Shaking the device Breathing into device Covering air vent holes Device not used more than 3 days needs to be primed once Device not used more than 21 days needs to be primed three times Steps for Clinicians to Ensure Correct Use Review device instructions and practice with placebo prior to teaching Demonstrate assembly and correct use with a checklist Provide patient written instruction on how to use device and written plan for medication frequency Have patient practice use while being observed by clinician Review use of device at each return visit Review patients understanding of the inhaled medication at each return visit (when to use, purpose of drug, prescribed frequency) Have high index of suspicion for incorrect or non adherence if poor management of airway disease occurs. 9

10 Pharmacists and Inhaler Assessment and Education Plethora of data available PubMed approximately 100 randomized controlled trials within past 10 years (MeSH terms include: pharmacists, inhalers, nebulizers/vaporizers) Google Scholar greater than 16,000 results (pharmacists and inhaler) Large international authorship Targeting Technique accuracy Patients and healthcare providers Knowledge and attitudes Outcomes on disease Assessment of Inhaler Device Objective: To compare use and handling of various respiratory devices in primary care setting Methods: Observational study of 3811 French patients treated for 1 month with device (Aerolizer, Autohaler, Diskus. pmdi or Turbohaler). Results: 76% of patients made at least 1 error with pmdi compared to 49 55% with breath actuated inhalers. Errors compromising treatment efficacy were made by 11 12% with Aerolizer, Autohaler or Diskus compared to 28% and 32% treated with pmdi and Turbohaler. Conclusion: Continued education of prescribers and users are needed to improve treatment efficacy Molimard M et al. Journal of Aerosol Medicine 2004;16(3): Assessment of Inhaler Device Objective: To evaluate the inhalation technique of a large sample of outpatient attending respiratory clinics in Italy Methods: Cross sectional observational study 24 clinics encompassing 1664 adult subjects treated with device (Aerolizer, Diskus, HandiHaler, Turbohaler and pmdi). Results: Of 2288 records of inhaler technique, critical mistakes ranged from 12% pmdis, 35% Diskus and HandiHaler and 44% Turbohaler. Strongest association of error was older age (p=0.008), lower schooling (p=0.001) and lack of instruction from healthcare provider (p<0.001) Conclusion: Instruction by healthcare providers was the only modifiable factor useful for reducing inhaler mishandling. Melani AS et al. Respiratory Medicine 2011;105: Educational Interventions on Inhaler Device Use Objective: To assess the effectiveness of a single educational intervention on inhaler technique skills Methods: 31 pharmacists were trained to assess and teach correct Turbuhaler and Diskus inhaler technique during a 6 month study. Pharmacists were reassessed 2 years after initial training Results: Initial assessment few pharmacists demonstrated correct technique (Turbuhaler 13%, Diskus 6%). Two years later pharmacists in active group demonstrated significant inhaler technique than control group (p<0.05) for Turbuhaler and Diskus (83% vs 11%; 75% vs 11%) Conclusion: Providing patient education and encouraging involvement in educating patients contribute to pharmacists competence in correct inhaler technique Basheti IA et al. Amer J Pharmaceutical Educ 2009;73(2): Article 32. Educational Interventions on Inhaler Device Use Objective: To evaluate the feasibility, acceptability and effectiveness of education about inhaler technique and use of inhaler technique labels by community pharmacists to asthma patients Methods: 31 pharmacists received training to teach dry powder inhaler technique to patients at 4 visits over 6 months Results: At 6 months inhaler technique score was significantly better in active vs control patients (2.8 +/ 1.6 vs 0.9 +/ 1.4, p<0.001) and asthma severity was significantly improved (p=0.015) Patient Case Back to Helen(cont.) During your counseling to assist Helen with her new olodaterol/tiotropium (Respimat delivery system) she is concerned that she will not use the device correctly and her COPD will get worse Conclusion: Pharmacists educators and use of simple inhaler technique labels on inhalers can lead to improvement in inhaler technique and asthma outcomes Basheti IA et al. Patient Education and Counseling 2008;72:

11 However, as you continue counseling Helen, which of the following reasons would concern you that the Respimat delivery system would not be a good choice? Diagnosis of COPD is only 5 years ago Diagnosis of RA Olodaterol/tiotropium would not be an optimum choice for COPD None of the above However, as you continue counseling Helen, which of the following reasons would concern you that the Respimat delivery system would not be a good choice? A. Diagnosis of COPD is only 5 years ago B. Diagnosis of RA C. Olodaterol/tiotropium would not be an optimum choice for COPD D. None of the above Cognitive/Physical Limitations and Device Selection Based upon her physical limitations which of the following device(s) would be a better choice for Helen at this time? Rheumatoid Arthritis Stroke Alzheimer s Disease Multiple Sclerosis Parkinson s Disease Diabetic neuropathy Guillain Barre Syndrome Myasthenia gravis Idiopathic pulmonary fibrosis Arm Amputee Blindness (color) Deafness Handihaler Tudorza/Pressair Ellipta B and C Based upon her physical limitations which of the following device(s) would be a better choice for Helen at this time? A. HandiHaler B. Tudorza/Pressair C. Ellipta D. B and C Cognitive/Physical Limitations and Device Selection Cognitive Limitations Rheumatoid Arthritis Stroke Alzheimer s Disease Arm Amputee Multiple Sclerosis Parkinson s Disease Diabetic neuropathy Blindness (color) Deafness HandiHaler Tudorza / Pressair Respimat B Ellipta D Which device would be the best choice for each limitation? 11

12 Cognitive/Physical Limitations and Device Selection HandiHaler B Rheumatoid Arthritis (C,D) Stroke (C,D) Alzheimer s Disease (D) Arm Amputee (C,D) Multiple Sclerosis (C,D) Tudorza / Pressair Parkinson s Disease (C,D) Diabetic neuropathy (C,D) Blindness (color) (D) Deafness (A,D) Respimat D Ellipta Inhaler Training Devices Measure key factors for proper inhaler use: Activation of the device Inhalation flow Timing of actuation Breath hold time Lavorini F et al. Primary Care Resp Journal 2010;19(4): Inhaler Training Devices Inhaler Trainer Devices: 2Tone Trainer Turbutest In CheckDial Mag Flo inhaler flow indicator Inhalation manager SmartMist Turbuhaler Usage Trainer (TUT) Turbuhaler Aerosol Inhalation Monitor (AIM) MDI, MDI + Spacer, DPI T Haler MDI Lavorini F et al. Primary Care Resp Journal 2010;19(4): Vitalograph. AIM Accessed November 30, 2016 Cambridge Consultants. T Haler haler inhaler training device. Accessed November 30, 2016 Do Inhaler Trainers Work. Objective: To assess the ability to use pmdi using the Aerosol Inhalation Monitor. Methods: 100 clinical practices encompassing 8843 asthma patients in the UK were invited to participate. All patients underwent inhaler technique assessment by a trained nurse. Patients underwent two assessments using the Aerosol Inhalation Monitor. Results: 2123 patients were reviewed (85.6%) using pmdi failed the first training device assessment. However, 78.4% and 65.7% of those tested twice and three times, respectively, failed the trainer assessment despite instruction. Conclusion: A majority of symptomatic asthma patients were unable to use pmdi correctly. Hardwell A, et al. Primary Care Resp Journal 2011;20(1): Choice of inhaler.. Inhaler Use House MD What are the problems. Cost of device(s) Inhaler complexity Confidence in efficacy Complex dosing Multiple devices What the patient wants.patient preference and satisfaction leads to improved outcomes.. Low cost Small in size Easy to use dose preparation mechanism Enough medicine for at least one month of treatment All medications to be delivered in one device 12

13 Key Points of Inhaler Devices Low cost Small size Simple ergonomic design Dosing mechanism easy to operate Once a day dosing Medication to last at least 30 days Optimally all medications delivered with one device Patient education and videos can be found: Access to Medications A Relevant Issue for Inhalation Devices Inhaled medications and technologies are expensive Few generic alternatives exist Patients may face numerous co pays at higher tier levels Barriers to Access Cost of medication is a problem for patients with inadequate insurance coverage Risk of nonadherence higher when out of pocket costs >$20/month Nonadherence associated with higher frequency of ED visits and hospitalizations Barriers to Access One Center s Strategy Medications at no charge for patients at or below 200% of federal poverty level and uninsured or underinsured Sources of medications Bulk replenishment programs Drug repository Charitable distributor Purchase (Charitable pharmacy budget) Singrey AM, et al. Innovations in Pharmacy 2016;7(2): Singrey AM, et al. Innovations in Pharmacy 2016;7(2): Barriers to Access One Center s Strategy and Experiences Evaluated services for 3 month period Services provided for asthma and COPD Sources of medications Bulk replenishment programs 38% Drug repository 11% Charitable distributor 10% Purchase (Charitable pharmacy budget)41% Nearly 25% of patients reported using other sources for medications as well Collected opinions from patients which revealed that their medication needs were only partially addressed by this program Singrey AM, et al. Innovations in Pharmacy 2016;7(2): Alliance For Patient Access Video produced in July 2016 Highlighted problems of Covering only low potency steroids Not covering ancillary devices Limiting coverage to specific devices Recommended eliminating plan designs and cost sharing structures which limit access for patient access releases new video access toasthma medications/ 13

14 CDC s 6/18 Initiative CDC s 6/18 Initiative Focuses on 6 common, preventable health conditions and 18 evidence based prevention and control interventions that can improve health and control costs Evidence is provided to health care purchasers, payers, and providers to inform their decisions when considering coverage, access, utilization and quality Asthma is one of the six conditions Payers are encouraged to: Promote evidence based medical management consistent with EPR 3 Promote strategies that improve access and adherence to medications and devices Expand access to self management education Expand access to home visits to improve self management education and reduce triggers at home Access to Medications On the Ground, Front Line Solutions Bulk replenishment programs Manufacturer Assistance Programs Co Pay foundations and Discount Cards Investigate subsidies Federal, state, local and institutional Apply for grant support (e.g., foundations, commercial) Barriers to Access Summary For inhaled medications used to treat asthma and COPD, an economic barrier exists for many patients Pharmacists can be an important resource in assisting patients in obtaining needed inhalational medication Several options are available to defray economic costs of inhalational therapies Which of the following errors is common using the Respimat Delivery System? The FIRST step for the pharmacist educating a patient with a new inhaler device would be: Not shaking the device to disperse medication Not piercing the dry powder capsule Not holding the device upright Not priming the device correctly Demonstrate assembly and correct use of the device with a checklist Provide patient written instructions on how to use the device Demonstrate proper maintenance and cleaning of the device Review device instructions and practice with placebo prior to teaching 14

15 Hydrofluoroalkanes (HFAs) are contained in A forceful inhalation effort is generally required when using a: Metered dose inhalers (MDI) Dry powder inhalers (DPI) Jet nebulizers All inhalation delivery systems Metered dose inhaler Dry powder inhaler Jet nebulizer Peak flow meter A significant barrier to obtaining inhalational products for treating asthma and COPD is that : Formularies only include generic equivalents on the available list Coverage is provided for rescue medications only Co pays tend to be high for the chronic medications Effectiveness is not established for most products References Minnesota Department of Health. Rootmensen GN et al. J Aerosol Med Pulm Drug Deliv 2010;23: Self TH et al. J Asthma 2007;44:593 8 Toumas Shehata M et al. NPJ Prim Care Respir Med 2014;24: Virchow JC et al. J Market Access and Health Policy 2015;3: American Association for Respiratory Care Guide to Aerosol Delivery Devices. Institute for Safe Medication Practices. American Association for Respiratory Care Guide to Aerosol Delivery Devices. Molimard M et al. Journal of Aerosol Medicine 2004;16(3): Melani AS et al. Respiratory Medicine 2011;105: Basheti IA et al. Amer J Pharmaceutical Educ 2009;73(2): Article 32. Basheti IA et al. Patient Education and Counseling 2008;72: Lavorini F et al. Primary Care Resp Journal 2010;19(4): haler inhaler training device. inhalers.com/ 15