Aerosol Delivery Devices and Peak Flowmeters Fritz Merkel, BS, RCP Community Healthworker Training February 2008

Hang in there! Getting near the end. Hopefully we’ll have a little fun, and Learn something. NAEPP says….blah, blah, blah But you HAVE TO KNOW HOW TO USE THESE AEROSOL DEVICES.

Delivery Devices - Choices- Choice of aerosol delivery system depends on: - Effective dose - Drug deposition - Patient ability - Patient acceptance - Cost (immediate vs. cost effective) 1 Incorrect use of aerosol devices is a major factor in sub-optimal therapy. Patient ability: age, understanding, willingness, physical ability. Refer to handout for Advantages and Disadvantages. Cost: Immediate cost vs. cost effectiveness (refer to Marcia’s outcomes talk)

Poor Technique = Poor Medication Delivery Majority of health professionals teaching MDI use do not perform procedure perfectly. 2-3 Allow 10-30 minutes for instruction. (Few patients ever get this) Explain > Demonstrate > Practice > Return demonstration. Repeated demonstration improves performance. (Up to 3 sessions required). Up to 2/3 of users and health professionals do not use correctly. -No reason to believe you are any more capable than your patients. Demonstration works well for the kinesthetic learner. There are > 22 branches in the tracheobronchial tree. Surface area of 80-100 sq. meters.

MDI Output range is 30-100 ml. 4 Velocity 15 m/s > falls rapidly (0.2 second) 4 80% deposition in oropharynx. 10-15% deposited in in lungs. Optimal deposition size is < 6 mm (1-5 mm) 5 Propellant chlorofluorocarbon – banned 1987 (exempted under “essential use” ruling) -lose permanent exemption end 2008. 96 percent of the short-acting beta-agonist inhalers sold in 2004 contained chlorofluorocarbon (CFC) propellants, according to IMS Health information

Distribution of Aerosol-MDI Radiolabeled aerosol delivered with no add-on spacer device. 16

MDI Problems - Common Hard to do right for anyone: esp. very young, very old, handicapped, mentally compromised. Cough (medication lost ). Rapid inhalation. Short breath hold. Cold MDI (poor aerosolization). Plugged orifice-Keep capped when not in use. Multiple actuations/breath. Poor timing - too soon, too late, blow out… Oral deposition Shake canister. Excessively rapid inhalation. Poor timing with inhalation > too soon > too late > blow out. Cold freon effect-abrupt cessation at actuation from cooling of CFC plume. Oral/Vocal cord deposition, esp. w/steroids. Determining when canister is empty. Best method is to count puffs or estimate date used up>mark your calendar based on usage. Some newer devices have built in counters: Discus Turbuhaler

Oral & Vocal Cord Deposition **Candida (thrush)/hoarseness, mouth sore** (for inhaled steroids only) Use a VHC or Spacer Tilt head back and “open” the throat shaping it as though making a deep “O”. Inhale slowly…slower…..even slower. Immediately rinse, gargle and spit. Use mouthwash instead of water. Tilt does not work with DPI’s. DPI’s > inhale faster to break up particle aggregates.

Lose Track of Doses Check package insert for number of doses. Mark off on calendar. Put tape on MDI and check off doses. Dose counter-(30 day calendar) Water floatation not recommended (inaccurate + may plug nozzle)17

Spacers Add-on tube; no valve. Needs sufficient volume (100-700cc) for propellant to evaporate. Reduces oral/vocal cord deposition but does NOT help with hand-breath coordination problems. Reduces (bad) “taste”. (users may need to be re-educated that this is OK.) To over come some of the MDI problems devices have been developed. Bring toilet tube. Plastic bottle spacer.

Valved Holding Chamber One-way inspiratory valve protecting the patient from poor hand-breath coordination Traps large particles: > reduce pharyngeal deposition > 10-15x less than MDI alone. 4-5 Slows down & “matures” droplets. Better lung distribution. One way valve acts as baffle that impacts larger particles. Two types: 1. Manufacturer’s dispenser 2. Integrated canister actuator Some evidence indicates that integrated dispensers may not be as effective as manufacturer’s, especially with alternative formulations. Masks can be used to overcome size, age, coordination or mental status problems, BUT, only if assistant knows how to use it. Other Problems: Rapid Inhalation. Slow 3-5 count while inhaling. Listen…avoid the spacer “whistle”. Practice in front of a mirror. Poor Timing- Spacer will lose more (or all) medication if blown into. Demonstrate…return demonstration. Use a “coach”.

VHC & Infants No difference between Mouthpiece and close fitting mask. No published data of efficacy of blow-by. Crying=long exhalation with short inhalation. This almost totally prevents lower airway deposition. Do not give to crying babies. Infants/children (0~5/6) – May use multiple breaths to empty the aerosol from the VHC. Minimal mask dead space > Good mask fit.

VHC & Infants No benefit to VHC volume > 150cc. Need to be able to evacuate chamber. Do not give to crying babies! - Poor deposition (same with nebs) - - Crying is an exhalation maneuver.

Young/Elderly/Handicapped Young > add mask+VHC (<5-6 years) - “Parent” must know how to use. Elderly > VHC Explain > Demonstrate > Practice > Return demonstration Analyze failure > Nebulizer if appropriate. Add Leukotreine Modifiers ? (~ 50% effective) For compromised individuals appropriate teaching must be provided for the support individuals.

Hydrofluroalkane (HFA) Replaces chlorofluorocarbon (CFC). Lower Jet velocity (slower med plume) Quieter, softer sound. Less affected by ambient temperature. Less cold freon effect. As effective as CFC MDI >>possibly more effective<< QVAR (ICS), Proventil & Xopenex HFA Cold freon not a problem if VHC is used. 1. Proventil HFA 2. Qvar (beclamethasone)

Gamma scan: Beclomethasone (BDP)-healthy subject Right: BDP with HFA propellant = greater lung deposition & less oropharygeal deposition than CFC propellant. 9 (no spacer)

Beclomethasone with HFA (¨ ) vs CFC (. ). HFA dose (200 µg) vs Beclomethasone with HFA (¨ ) vs CFC (*). HFA dose (200 µg) vs. half CFC (400 µg) Single dose 14 Days

Don’t Use with HFA Built in canister actuator Medispacer E Z Spacer EZ Spacer is a poor product.

Spacer/VHC Variations One device can increase lung drug delivery and decrease delivery with another drug. 2-6 fold variation in respirable dose emitted with various devices. Due to variations it may be best to use same combinations that were studied. But-no specific combinations have been specifically approved by FDA.14

Spacer/VHC Cleaning & Prep Rinse plastic Spacer/VHC when new and once a month with dilute liquid household detergent. 1-2 drops/cup of water. Let drip dry, do not rinse. Defeats static cling (so does normal use)

DPI-Requirements Rapid, deep inhalation critical: 30-120 lpm required. 5 Inadequate flow = inadequate delivery. Unsuited to the very young, very ill, weak patients, elderly, or altered mental status. (But so are MDI’s) Conflicts with breathing pattern for MDI. (Slow vs. Fast) May appear more expensive than MDI. Need to look at effectiveness and # of doses/container. Retraining may be necessary.

Fast vs. Slow Inhalation Higher flow picks up more medication.

DPI-Problems Particulate irritation may cause cough (rare). High humidity may cause clumping of powder, esp. when leaving the cap off or moving from very cold to warm environment (non-blister pack). Blowing into DPI may blow drug out and will introduce internal humidity. Different inhalation pattern from MDI. Units using a blister pack type of device may be more protected from humidity (Discus in blister packs)

Manufacturer flow rates

DPI – Internal Resistance Turbuhaler greater resistance than Discus (easier for kids). Aerosolizer = low

Lung deposition; % of the emitted dose, Different DPIs 2 different inspiratory flow rates. Dolovich.9 Most DPIs deliver lower amounts of aerosol to the lungs at less than the optimal flow rates.

DPI-Instruction Health care provider MUST know technique appropriate to the device to teach effectively. New devices and techniques being developed requiring providers to stay abreast of developments. Different devices = different techniques.

DPI - Models and Instruction DISKUS - 60 doses (blister pack tape) Pulmicort Turbuhaler – 200 dose (single container) Floradil Aerosolizer – single doses (blister pack - pill) Asmanex Twisthaler - 30, 60, 120 dose (single cont.)

Discus Internal View

Nebulizer Newer designs provide enhanced performance. Breath Actuated Nebs > BAN - one-way valves; Pari AeroEclipse. Various reservoir types. Thumb valves. Should deliver 50% of total dose at 1-5 microns MMAD in <_10 minutes. Higher flows tend to decrease particle size. As little as 10% of the dose is inhaled by the patient. Reservoir = length of tubing on T-pc > improves by 20% Pari-breathes through the valve during inspiration and out through a one-way valve on expiration > improves 2—50% Less waste with these models.

Nebulizer Cups Many different kinds. Little attention often paid to matching compressor to cups. Some models are proprietary and MUST be matched. Inexpensive models are usually disposable but may be used (regularly) for > 1 month if cleaned regularly. Non-disposable (Pari) may have superior output and may be used for 6-12 months. PARI and Medic-Aid are manufacturers that have provided validated systems for the US market.

Neb - Medication Problem Unit-dose bronchodilator usual Rx. Mixing medication problems > Children: Unit-dose bronchodilator + Unit-dose Intal = excessive dilution > (longer treatment). Get “concentrate” bronchodilator solution. Less of a problem than it used to be. “Blow by” has not been found to be effective in children-use a mask. 14

Neb Cleaning After each treatment, rinse the nebulizer cup with warm water, shake off excess water and let it air dry. At the end of each day, the nebulizer cup, mask or mouthpiece should be washed in warm, soapy water using a mild detergent, rinsed thoroughly and allowed to air dry. The Pari reusable nebulizer is dishwasher safe, run through cycle on top rack only in a small parts basket.

Neb Disinfecting Every third day, after washing your equipment, disinfect using a vinegar/water solution or the disinfectant solution your supplier suggests. Vinegar solution-mix 1/2 cup white vinegar with 1-1/2 cups of water. Soak for 30 minutes and rinse well under a steady stream of water. Shake off the excess water and allow to air dry on a paper towel. Always allow the equipment to completely dry before storing in a plastic, zipper storage bag.

Nebulizer vs. MDI+VHC Several studies done with acutely ill infants and children in the ER. With PROPER instruction and administration of MDI+VHC: > No difference shown in rate of improvement or clinical score over conventional nebulizer treatment. 6-7 Patients randomized to receive either bronchodilator with nebulizer or MDI+VHC.

Drug Deposition Deposition from major types of early (pre-1990) aerosol delivery devices: MDI, MDI-spacer, SVN, DPI 15

Approx. % of drug dose deposited DPI’s vs. pMDI Dolovich Approx. % of drug dose deposited DPI’s vs. pMDI Dolovich.11 (Turbuhaler, Diskus, Spiros, and Clickhaler)

Traditional vs. Newer Devices Lung Deposition (various studies) between traditional and newer devices. hydrofluroalkane-beclomethasone, small volume neb, dry powder inhaler. 40-50% possible now vs. 10-15% 16

Dosage Differences for Various Devices Deposition of devices to the lungs (**has been**) similar. Starting (nominal) dose is not the same. Nebulizer starting dose is 11-12x larger than the MDI dose. MDI’s can have similar clinical effect but may need increased # of puffs. 14

Ultrasonic Nebulizer More Expensive Special batteries Fragile No insurance coverage Silent Fast > Dense output Possibly less waste Many different types.

Developing Aerosol Technologies

Respimat Soft Mist Inhaler (propellant free, spring driven “MDI” - Boehringer Ingelheim) Mouthpiece Uniblock Dosing Chamber Dose-release button Upper housing Capillary tube Transparent base Spring Cartridge

Spiros DPI Breath-actuated, multi-dose cassette, battery-powered inhalation assist 12

AERx Pulmonary Device Aradigm Corporation Pre-packaged, single-use disposable blister packet and disposable nozzle. Utilize a piston mechanism to expel formulation from the AERx Strip

Mystic Inhaler Ventaira Pharmaceuticals Pharmaceuticals Pharmaceuticals Electronic nebulization process. Electrical field is applied to a conductive liquid leading to the formation of a soft mist droplet aerosol. Soft mist, breath-activated, robust, easy to use, programmable hand-held device.

Aria Chrysalis Technologies >Altria >Phillip Morris (that’s right!) Looking for a cigarette that would appeal to health-conscious smokers ( speaker’s note - ????) Device that allowed smokers to inhale a mist laced with nicotine rather than inhale smoke – Didn’t take off. Aerosol device could be used to deliver drugs to the lungs.

Current Aerosol Delivery Systems - Problems Lack of uniformity: 3 major device categories: metered dose inhaler (MDI-2 kinds) small-volume nebulizer (SVN-many) dry powder inhaler (DPI-several) More devices coming Confusing – To patients and healthcare professionals alike.

Aerosol Delivery Systems -Problems- Need for ancillary equipment (e.g. holding chamber or spacer) depending on age, coordination, or drug used. -Frequently not provided, understood, or used. Ability to use the different device categories differs by age and disease.

Aerosol Delivery Systems -Problems- Each category of device requires a different breathing maneuver. Continuing low efficiency of lung deposition in all devices (though improving). Contamination of ambient air (provider/family exposure - trivial). Drug loss in all devices (waste/expense).

Peak Flow Meters Most useful for moderate-to severe persistent asthma. Designed for monitoring. Not a diagnostic tool. Dependent on effort and technique. Good instruction and frequent review is needed. Same PFM should be used at all times. It should be checked periodically for proper function. Different PFM’s may read differently.

PFM-Reliability Most units provide highly repeatable est. of PF. Recommended > + 10% over full range: 100-400 L/min-children; 100-700 L/min-adults. Reproducibility of + 10% or 5% of reading. Different PFM’s will give different readings. Astech met all criteria. 13 Most units provide highly repeatable ESTIMATES of peak flows. Recommendation of + 10% over the full range: 100-400 L/min children; 100-700 L/min adults. - reproducibility of + 10 L/m or 5% or the reading, - whichever is larger. - Only unit to meet ALL criteria was Astech. Assess had the most problems but seemed to be a batch issue.

PFM - Real World Use Most useful with an ACTION PLAN. The patient must know WHAT to do with the PFM information. Instruction is often inadequate due to time constraints. (So-what’s new?) Action plans may take multiple visits and considerable time to set up. Follow-ups necessary for maintenance. Instruction in ALL aspects of asthma care is the niche this audience can utilize.

When you can’t breathe, Nothing else matters. Some thing are not meant to be inhaled.