Improving Medication Adherence in COPD with an Effective Device Orapan Poachanukoon, MD.

เนื้อหา ปััจจัยที่มีผลต่อการตกสะสมของยา อุปกรณ์พ่นยาชนิดต่างๆ วิธีการเลือกอุปกรณ์พ่นยาที่เหมาะสมกับผู้ป่วย

Particle deposition in the respiratory tract

Relationship between aerodynamic chamber and lung deposition Laube et al Eur Respir J 2011; 37: 1308–1331. Total Oropharynx Bronchial/ Conducting airways Alveolar

Factor affecting deposition of aerosols in lung PhysicalVentilatoryAnatomic Particle size Particle shape Particle density Humidity Temperature Tidal volume Inspiratory flow Breath-hold time Breathing frequency Nose vs mouth breathing Airway diameter Age Disease Rubin BK, Fink JB. Respir Care Clin N Am 2001;7:

Patient-related variables impacting correct device use Pulmonary function and disease stage Smoking status, age, sex, being overweight Comorbidities Manual dexterity Ability to understand and follow instructions Eyesight Psychosocial issues Fink JB et al. COPD 2013;10: 1-13.

Patient’s inhaler device preference in COPD Increased patient satisfaction and preference with a device can help optimize patient adherence to treatment 1,2. Factors affecting patient preferences: Perceived efficacy of device by patients Ability to use a given inhaler easily Psychological or physical issues o Such as comorbidities (neuromuscular disorders and arthritis) can impact inhaler technique. Inhaler features considered “very important” by COPD patients (Data from Moore and Stone 2004) Restrepo et al. Int J COPD 2008:3(3) Anderson et al. ERR Jones et al. PCRJ 2004

Aerosol devices Nebulizers DPI pMDI

MDI vs MDI with Spacer

Spacer devices

B E Valved holding chamber Nebuchamber Aerochamber BabyhalerACE spacer

Volumatric

DIY Spacer

Petty patent of Thailand No DIY

2013. Gold Prize in International Exhibition of Inventions of Geneva.Swiss Confederation April Special Award from Taiwan Invention Association Silver Prize in SII: Korea Excellence Award “Thai-ASEAN” Thaksin University National Conference. AWARDS

DIY SPACER on THAMMASAT DIY SPACER อุปกรณ์ช่วยพ่นยา TU Asthma Club

Clinical efficacy of spacer therapy with/without electrostatic charge Arch. Dis. Child. 2001;84; This study showed no negative influence of ESC on plastic spacers in children with asthma.

Dry Powder Inhaler (DPI)

MDI and DPI: advantages and disadvantages AdvantagesDisadvantages Portable and compactCoordination of actuation and inhalation needed Short treatment timeMost patients inhale too fast No contamination riskImportant to prime before first use High reproducibility between dosesOften difficult to determine remaining doses Spacers available for some devicesSpacers more expensive and less portable Chrystyn & Price. Prim Care Resp J 2009; Laube et al. Eur Respir J 2011 No coordination requiredForceful inhalation needed to aerosolize particles Not to be used with spacerMore expensive than MDIs Portable and compact; multi-dose devices available Only used with drug that is dispensed with the device Single-dose devices with doses kept separately in sealed packs Must be kept upright or horizontal during inhalation Breath actuatedPatients not to exhale into device once prepared Short treatment timeSingle devices require repeat loading DPI MDI

MDI and DPI: advantages and disadvantages AdvantagesDisadvantages Portable and compactCoordination of actuation and inhalation needed Short treatment timeMost patients inhale too fast No contamination riskImportant to prime before first use High reproducibility between dosesOften difficult to determine remaining doses Spacers available for some devicesSpacers more expensive and less portable Chrystyn & Price. Prim Care Resp J 2009; Laube et al. Eur Respir J 2011 No coordination requiredForceful inhalation needed to aerosolize particles Not to be used with spacerMore expensive than MDIs Portable and compact; multi-dose devices available Only used with drug that is dispensed with the device Single-dose devices with doses kept separately in sealed packs Must be kept upright or horizontal during inhalation Breath actuatedPatients not to exhale into device once prepared Short treatment timeSingle devices require repeat loading DPI MDI

Why dry powder inhalers? Automatic co-ordination of inhalation and drug release 1,2 : –reduces patient errors associated with need to co-ordinate inhalation and drug release Dose counting or low warning (multi-dose DPIs) –also a feature of newer pMDIs Lack of propellant is environmentally friendly 3 –although plastics content, electronics (with some devices) and fewer doses per device may contribute to a less environmentally friendly profile 1. Ashurst, et al. Pharm Sci Technol Today 2000; 2. Newman, Busse. Respir Med Byron. PATS 2004

Lung deposition of devices Respir Care Clin N Am 2001

How to choose right aerosol delivery device Inspiratory flow > 30 L/min Inspiratory flow < 30 L/min Inspiratory flow > 30 L/min Inspiratory flow < 30 L/min pMDI DPI Nebulizer pMDI Nebulizer pMDI+spacer DPI Nebulizer pMDI+spacer Nebulizer Good coordination Poor coordination Laube et al Eur Respir J 2011; 37: 1308–1331.

Evaluating Drug Delivery of DPI Fine Particle Mass Inspiratory Flow Device Resistance

Airflow resistance in DPIs sis Inspiratory effort (kPa) Flow rate (L/min) Breezhaler2.2  kPa 1/2 L -1 min Diskus2.7  kPa 1/2 L -1 min Turbuhaler3.4  kPa 1/2 L -1 min Handihaler5.1  kPa 1/2 L -1 min Increasing tan re ce Singh D et al. ATS 2010 (poster)

Patients with mild to very severe COPD achieved a flow rate of ≥60 L/min (>18.9 cmH 2 O pressure drop) using Breezhaler ® MildModerateModerate/SevereVerysevere PIFR (L/min) COPD severity Peak inspiratory flow rate (PIFR) Breezhaler was not affected by COPD severity Peak inspiratory flow rates via the device were determined in patients with COPD using an Inhalation Profile Recorder. Each bar represents one patient Pavkov et al. CMRO 2010; 26 (11): N=26 COPD patients

Particle size & Dose Regional Deposition in Lung Delivered dose are usually in range of 75%-90% of metered dose. FPD/FPM are very much dependent from formulation and delivery system but never 100% of delivered dose.

Consistent results for fine particle mass Indacaterol 150 µg Indacaterol 300 µg ** Fine particle mass = drug particles <4.7 μm in diameter Pavkov et al. CMRO 2010; 26 (11):

Estimated drug deposition in Breezhaler ® and HandiHaler ® Intrathoracic deposition (% of delivered dose) BreezhalerHandihaler Patient Mean Mean ±SD±SD Laube et al. Eur Respir J 2011; 2. Chapman et al. Int J COPD 2011 Particles <5 μm have greatest potential for lung deposition 1 FPF (proportion of particles <5 μm) was higher with Breezhaler (27%) vs HandiHaler (10%) 2 Mean estimated intrathoracic drug deposition: 31% Breezhaler; 22% HandiHaler 2 Mean estimated extrathoracic drug deposition: 57% Breezhaler; 71% HandiHaler 2

Breezhaler-new capsule based DPI Taste, Transparent Easy to use, Feedback on correct use Low airflow resistance

The Breezhaler ® device: suitable for use by COPD patients Compact size Low airflow resistance – suitable for all COPD patients, even those with severe obstruction 1 Confidence that full dose taken – hear – taste – see empty capsule 1. Pavkov et al. Curr Med Res Opin 2010

Reasons for Non-adherence Impact on adherence Pt/HCW partnership patients features cost/reimbursement difficult to access patient education complexity of treatment, S/E Possible avoidance chronicity

Technique to improve adherence to aerosol medications Written explanation and demonstration Have patient bring medication to every appointment and check technique at each visit Ask the patient specifically about adherence Follow up on unfilled and refilled Minimized medications, keep it simple Parents need to take responsibility (> 13 years take medicine independently) Respiratory care 2011.

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