NebNeb Doctor’sDoctor’s AerosolAerosol TrainingTraining ProgramProgram

PartPart 22 SpecificsSpecifics

1 JetJet NebulizersNebulizers DrivenDriven byby CompressorsCompressors

Home setting: Jet nebulizers driven by compressed air created by compressor

Hospital & Clinic use: Jet nebulizers are driven by “wall” air” which is usually higher pressure and flow

22 HowHow JetJet NebulizersNebulizers WorkWork

z Nebulizers utilize the Bernoulli Principle: P when a pressurized P flow of air is directed through a constricted orifice, the velocity (not the pressure) of P the airflow is P increased to create a jet stream.

33 HowHow JetJet NebulizersNebulizers WorkWork

z The jet stream creates a Sub-atmospheric pressure zone

Aerosol sub-atmospheric Particles pressure zone (vacuum) Jet Stream which draws the fluid up the capillary tube. Capillary Atmospheric Pressure Tube z The impact of a jet stream with liquid

Nebulizer Solution produces aerosol particles.

44 HowHow JetJet NebulizersNebulizers WorkWork

z The aerosol stream flows to the baffle; particles collide with baffle and either: Î fall back into reservoir, Î break into smaller particles that continue on inspiratory flow path, or Î follow inspiratory flow path around baffle.

55 TwoTwo BasicBasic NebulizerNebulizer TypesTypes

Small Volume Nebulizer (SVN) “Hand-held Neb” or “Small- volume Nebulizer” or “Handset” Primarily used to administer drugs Large Volume Nebulizer Mouthpiece or mask May be heated or cool Primarily used to administer “bland” solutions to hydrate airways and/or reduce inflammation Face or trach mask

66 ConventionalConventional “T”“T” TraditionalTraditional SmallSmall VolumeVolume NebulizersNebulizers

z Continuous gas flow

z Approx. 50% of solution is wasted

z Approx. 25-30% of particles are in respirable range, depending on liter flow ClosedClosed System:System: Patient’s inspiratory flow does NOT contribute to aerosol output.

77 ConventionalConventional “T”“T” TraditionalTraditional SmallSmall VolumeVolume NebulizersNebulizers Advantages Disadvantages z Inexpensive for short- z Low respirable dose term use (14 days max.) compared to PARI reusable nebulizers Expensive for z Higher doses than MDI are possible long term use z Long treatment times z “T” design can be used with ventilator circuits z High pressure/flow required and tracheotomy masks z Inspiratory flow dilutes aerosol z Performance deteriorates in days z Not dishwasher safe, cannot 88 be boiled PARIPARI BreathBreath--EnhancedEnhanced JetJet NebulizersNebulizers

z Continuous gas flow to neb chamber combined with patient’s inspired air

z Exhaled air does not mix with aerosol, amount of solution wasted is minimized

z Approx. 63-87% of particles OpenOpen System:System: are in respirable range, Patient’s inspiratory flow DOES depending on liter flow and contribute to aerosol output. nebulizer model

99 PARIPARI BreathBreath--EnhancedEnhanced JetJet NebulizersNebulizers

1010 PARIPARI BreathBreath--EnhancedEnhanced JetJet NebulizersNebulizers Advantages Disadvantages z High output, short treatments z Not cost-effective for z Higher dose than T-Neb or short-term use MDI is possible z Cannot be used in z Multiple “one-way” valves ventilator circuits reduce waste z Not readily adaptable z Dishwasher safe, may be to tracheotomy masks boiled, or autoclaved z 6 Month Warranty z Cost-effective for long-term use z Reimbursed by Medicare,

1111 Medicaid, Private Payors PARIPARI LCLC®® PlusPlus JetJet ReusableReusable NebulizerNebulizer

The most clinically tested Reusable Nebulizer in the world The only Reusable Nebulizer approved for use with TOBI® Breath-enhanced delivery Balance of fast treatment time and optimal treatment efficiency

1212 PARIPARI BreathBreath EnhancedEnhanced NebulizerNebulizer ComparedCompared toto ConventionalConventional “T”“T” NebulizerNebulizer InspiratoryInspiratory PhasePhase

1313 PARIPARI BreathBreath EnhancedEnhanced NebulizerNebulizer ComparedCompared toto ConventionalConventional “T”“T” NebulizerNebulizer ExpiratoryExpiratory PhasePhase

1414 ParticleParticle SizeSize ComparisonComparison

PARI LC Plus Reusable Nebulizer vs. Conventional “T” Nebulizer

80%

PARI LC Plus 60%

Conventional

40% % of Total Particles Total of %

20%

0% < 5 microns 1-2 Microns 15 15 Particle Size Data on file, REV 7/98 FS-22-819 PARIPARI LCLC ®® PLUSPLUS AssemblyAssembly

Inspiratory Valve Cap

Baffle Insert Mouthpiece w/Exhalation Valve

Medication Chamber

Source Gas Tubing (air, O2, 1616 He/O2 10-20% Faster treatment times than PARI LC PLUS

Effective drug delivery comparable to the PARI LC Plus

Simple, ergonomic design improves Ease of Use for Patient

“No-spill” top

“Connected” inspiratory valve cap

1717 Easy view medication level KeyKey SellingSelling FeaturesFeatures –– PARIPARI LCLC®® SprintSprint ReusableReusable NebulizerNebulizer

Higher aerosol output at similar MMD particle size Simple, ergonomic, compact design Inspiratory valve cap can’t be lost Design prevents medication from spilling Fits together only one way Easy viewTM medication level indicator Robust, flexible nozzle construction Medication cup self-drains when upside down.

1818 Inspiratory Flow valve cap is attached

Spill Resistant Top

Ergonomic design for easy handling / dissassembly One-Way Twist-On Assembly 1919 Only Four Simple Parts Nebulizer Top

Nebulizer Insert/Baffle

Mouthpiece

2020 Nebulizer Cup Transparent Medication Window

2121 Self-Draining Nebulizer Cup The top is designed to remain attached throughout the 6 month expected life under normal usage The PARI LC® Sprint is compatible with the PARI BABY™ conversion kits and Adult aerosol mask The PARI LC® Sprint will not work with the current PARI PEP™ adaptor

2222 PARIPARI LCLC Star®Star®

n Specialty product; produces higher percentage of particles in 1-2 micron range than PARI LC PLUS o Targets peripheral airways and lung parenchyma (tissue) p Treatment time slightly longer than PARI LC PLUS (~ 1-2 minutes)

2323 PARIPARI LCLC STARSTAR NebulizerNebulizer PerformancePerformance

Nebulization of Dornase Alfa (Pulmozyme)

0.5 8

0.45 7 0.4 6 0.35 0.3 5 0.25 4 (mg) 0.2 3 0.15 2 Time Delivery

Fine Particle Dose 0.1 0.05 1 0 0 LC® Star LC® Plus Hudson Updraft® Sidestream® Nebulizer Data from Geller et al, Ped Pulm 2001:S22:310-311 „Choice of Nebulizer and Compressor Affects Small Particle Delivery of Dornase Alfa“ – Tested with PARI PRONEB Ultra Compressor, 2.5mg dose of Dornase Alfa (1mg/ml). 2424 Measured with laser diffraction using simulated breathing 18 l/min. PARIPARI LCLC®® DisposableDisposable ((akaaka LCLC D)D) What makes the LC D different?

No one-way valves Specialty product for doctor’s offices, clinics, hospitals, etc. Disposable, designed for short term use (plastic not as durable) Very fast treatment time: 5.5 - 7 minutes but with higher wastage

2525 NebulizerNebulizer PerformancePerformance

PRONEB Ultra II with LC® Sprint LC® Plus LC® Star

MMD (um) 3.5 3.8 3.1

Total Output 500 440 400 Rate % < 5um 65-68 % 65 % 78 %

6.5 – 8 Treatment Time 5 min 5-7 min min

1Measured with Malvern MasterSizer X at 50% RH, 0.9% NaCl solution, inspiratory flow 20 l/min continuous nebulization 23OC, fill volume 2.5 ml

2626 ParticleParticle SizeSize ComparisonComparison

Nebulizer Particles Below 5μ Particles in 1-2μ Range

Traditional 25 - 30% Variable “T” nebs LC PLUS 63 - 74% 20 - 33%

LC Star 78 - 87% 34 - 45%

LCD 78 - 87% 34 - 45%

LC Sprint 68% 20 - 33% 2727 AerosolAerosol MasksMasks

PARI Mask Traditional Mask Front Load Design Bottom Load Design

2828 BottomBottom LoadLoad AerosolAerosol MaskMask Does not directs aerosol toward the mouth

Inefficient because of impaction of aerosol onto bridge of mask

2929 PARIPARI AerosolAerosol MasksMasks Adult and Pediatric Masks z Polyvinylchloride (PVC) Soft Plastic z Efficient and effective z Directs aerosol to mouth z Prevents impaction of aerosol z Minimizes eye and face deposition

3030 BUBBLESBUBBLES THETHE FISHFISH™™ IIII AerosolAerosol MaskMask

Unique mask design minimizes ocular and facial deposition. Recommended Fits children aged 3+ years. Elongated mask “snout” creates a “reservoir” where the aerosol velocity slows down and congregates before inhalation by the patient which; increases “respirable” dose.

3131 BUBBLESBUBBLES THETHE FISHFISH IIII AerosolAerosol MaskMask

The vented underside of the mask allows for efficient evacuation of aerosol from the mask upon inspiration. This results in increased “respirable” dose available for inhalation compared to other mask designs

3232 InhaledInhaled Mass,Mass, FacialFacial andand OcularOcular AerosolAerosol DepositionDeposition

3333 Sangwan, G et al. Facemasks and Facial Depositions of Aerosols. Pediatric Pulmonlogy,37 :447-452. 2004 FacialFacial andand OcularOcular DepositionDeposition ofof AerosolAerosol

Facial and ocular deposition of nebulized budesonide. Effect of face mask design. G. Smaldone. AM J Respir Crit Care Med 169:7; A150. 2004 3434 PARIPARI BABYBABY

Efficient, closed-circuit delivery system for infants and small children Soft, silicon masks with elbow- adapter that can be rotated 180° - enables caregivers to administer treatments to children in a variety of positions Dishwasher safe

Size 0: Newborn-1 Month Size 1: 1 Month-1 Year Size 2: 1–3 Years Size 3: 3+Years

3535 NebulizerNebulizer andand CompressorCompressor InteractionInteraction The interaction between the air source (compressor, wall) and the nebulizer determine the % of particles in the respirable range. The air source is just as important to aerosol output as is the nebulizer cup.

3636 NebulizerNebulizer andand CompressorCompressor InteractionInteraction

PARI LC Plus with Ultra MMAD 3.5 um, TOR .50 ml/min, PARI LC Plus @ 6 lpm MMAD 3.2 um, TOR .54 ml/min

PARI LC-D with Ultra MMAD 3.1 um, TOR .44 ml/min PARI LC-D @ 6 lpm MMAD 2.5 um, TOR .52 ml/min PARI LC-D @ 8lpm MMAD 2.0 um, TOR .58 ml/min

3737 PARIPARI CompressorCompressor FiltersFilters

Solid, white micropore air filter:

Up to 500 hrs. of use Changed when filter is soiled, clogged, or wet Checked regularly Other materials cannot be substituted

Best Practice: Change when nebulizer is replaced!

3838 EstimatingEstimating FilterFilter DurationDuration

Filter duration is on average 1-3 years. 2.5 ml of nebulizer solution Average treatment time is 7 minutes Assume the patient takes treatments 4 times/day Estimation: 500 hours x 60 minutes = 30,000 minutes 30,000 minutes ÷ 7 minutes = 4,285 treatments 4,285 treatments ÷ 4 treatments per day = 1,071 days 1,071 days ÷ 365 days per year = 2.9 years

3939 OurOur CompetitorsCompetitors

Breath-Enhanced Nebulizer z Non-valve, open vent design z High efficiency aerosol production z Reusable and disposable versions

Sidestream® • Manufactured by MEDIC-AID (UK) • Sold by Allegiance and Invacare Invacare Passport

4040 OurOur CompetitorsCompetitors

Breath-Actuated Nebulizer z “On-demand” therapy z Spring-valve stops air flow to jet nozzle during exhalation z “Biofeedback” feature encourages optimum patient effort L/M AeroEclipse™ z Requires high flows ~ 8 • Manufactured by Trudell (CA) z Disposable; no warranty • Sold by Monaghan z Does not fit standard masks

4141 OurOur CompetitorsCompetitors

Breath-Enhanced Nebulizer z Reusable, w/one-way valves

z 7 ml med chamber

z Operating Liter Flow = 2L/M

z AC, 12V DC, and optional rechargeable battery CompAir Elite by Omron z .7 lbs

z 5 Yr. Warranty

z Does not fit standard masks

4242 OurOur CompetitorsCompetitors

Breath-Enhanced Nebulizer z Reusable, w/one-way valves

z Anti-drool feature

z Requires high flows ~ 7L/M

z 3cc in 7 min @ 7L/M

z PEP device available

z Dishwasher safe, autoclavable NebuTech™ HDN™ by Salter z Does not fit standard masks

4343 OurOur CompetitorsCompetitors

Breath-Enhanced Nebulizer z Reusable, w/one-way valves z Minimum driving gas flow - 5L/M z MMAD 3.6 - 4.0 Microns (μ) z Spill-proof design z Dishwasher safe, not autoclavable Model 800 z by DeVilbiss / Sunrise Does not fit standard masks

4444 OurOur CompetitorsCompetitors

PARI “Bubbles” Mask

Nic the Dragon Pediatric Mask Sold by Allegiance Traditional T-Neb Mask 4545 UltrasonicUltrasonic NebulizersNebulizers

 High frequency sound waves applied to piezoelectric transducer to create vibrations. The vibrations pass through the solution that breaks the surface of the liquid into particles

 Sound wave frequency determines particle size

 Amplitude influences aerosol output

4646 UltrasonicUltrasonic NebulizersNebulizers Advantages Disadvantages z Portable, lightweight z Expensive z Small residual volume z Not reimbursed by z Quiet Medicare, Medicaid z Minimal waste z Ultrasonic waves may inactivate some drugs z MMAD ~ 3.5 μ z Not durable, requires careful handling, prone to breakdown MicroAir by Omron Mystique by AirSep

4747 MeteredMetered--DoseDose InhalersInhalers

z A drug-filled canister fitted to a mouthpiece Canister Drug/Propellant z Compression of canister Liquid Mixture opens a valve to release a precise (“metered”) dose of medication under the force Metering Valve of a pressurized propellant Actuator Nozzle Actuator Seat z New drug formulations are being offered with HFA instead of CFC propellants

4848 CorrectCorrect MDIMDI UseUse

c Warm MDI to body temperature, and shake vigorously. d Open mouth wide, keep tongue from obstructing mouthpiece. e Place MDI between lips or ~ 4 cm (2 fingers’ width) from mouth. f Breathe out normally. g Breathe in slowly (<0.5 L/sec) and actuate MDI at beginning of inspiration. h Continue to inhale to Total Lung Capacity. i Hold breath for 4-10 seconds. j Wait at least 30 seconds between inhalations. 4949 MeteredMetered--DoseDose InhalersInhalers Advantages z Portable z No residual volume z Quiet z Fast Disadvantages z Expensive z Not reimbursed by Medicare, Medicaid z Technique dependent z Higher risk of over use or under use

5050 HoldingHolding ChambersChambers Sometimes referred to as “spacers” Designed to overcome patient technique problems

When MDI is actuated, Aerochamber aerosol is temporarily By Monaghan suspended within chamber

5151 HoldingHolding ChambersChambers Advantages Disadvantages z Minimizes importance z Can be expensive of timing coordination z Not reimbursed by z Ensures sufficient Medicare, Medicaid distance z Bulky, extra item to carry z Reduces incidence of z Electrostatic charge may side effects reduce delivered dose z Improve MDI dose delivery significantly; approx. 18-22% vs. 9- 11% with MDI alone

5252 AerosolAerosol CharacteristicsCharacteristics

- + + Electrostatic charge + - - + z Inherent to all plastic devices because of the nonconductive properties of plastic

z Particles develop a charge when they are produced, by nebulizer or MDI, with random variation (+ or -).

z In the airways, deposition is enhanced by the effect of electrical charge. Particles that carry an opposite charge than bronchial walls are attracted to the airway wall (opposite charges attract); particles with the same charge as airway walls are repelled, enhancing deposition by inertial impaction. 5353 DoseDose VariationVariation FactorsFactors

z Delay of Inhalation z Chamber Size

z Multiple Actuations z Chamber Shape

z Electrostatic Charge z Valve Resistance

z Ventilatory Pattern z Dead Volume

5454 ConsistentConsistent DeliveryDelivery PARI VORTEX™ Valved Holding Chamber

z Static-Free, Anodized Aluminum z Latex-Free z Universal MDI Receptacle z Clear Mouthpiece z 3 Mask Sizes z Dishwasher Safe

5555 TheThe VORTEXVORTEX™™ DifferenceDifference

z PARI's VORTEX™ holding chamber is made of anodized aluminum, a non electrostatic or "static-free“ material

z By eliminating static, the VORTEX ™ enables the patient to receive more of their medication and CONSISTENTLY get an OPTIMAL DOSE.

z VORTEX ™ cyclonic flow design may improve dose delivery to patients with low tidal volumes

z VORTEX ™ is more economical than conventional devices to improve prescription-fill compliance.

5656 TheThe VORTEXVORTEX™™ DifferenceDifference

5757 TheThe VORTEXVORTEX™™ DifferenceDifference

5858 TheThe VORTEXVORTEX™™ DifferenceDifference

5959 DryDry PowderPowder AerosolizationAerosolization

carrier/drug static powder bed carrier/drug dilated powder carrier and stripped drug aerosol dispersion

6060 DryDry PowderPowder InhalersInhalers Spinhaler, Rotohaler, Diskhaler 5 Steps to Use a DPI c Load medicine into device d Breathe out normally e Place DPI in mouth and close lips tightly around it f Breathe in slowly and deeply g Hold breath for 5-10 sec and exhale normally

6161 DryDry PowderPowder InhalersInhalers Advantages Disadvantages z Portable z Expensive z Minimal technique z Not reimbursed by coordination needed Medicare, Medicaid z Quiet z Requires fast z Fast inspiratory flow z No propellant required z Single dose unit z Limited drug formulations available

6262 PeakPeak FlowFlow MetersMeters

z Peak Expiratory Flow Rate (PEFR)

z Measures how fast you can move air out of your lungs

z PEFR are highest when large airways are clear and lower when they are narrowed or blocked

z Used by patients to monitor asthma severity

6363 PeakPeak FlowFlow MetersMeters

Green Zone = All Clear (80-100% of personal best) No asthma symptoms are present, patient is instructed to follow their Self Management Plan as usual, by taking their prevention (“Controller”) medicine(s).

6464 PeakPeak FlowFlow MetersMeters

Yellow Zone = Warning! (50-80% of personal best) The patient may be having an episode of asthma that requires an increase in their medicines. Or, the patient’s overall asthma may not be under control. Patient is instructed to increase prevention medicines.

6565 PeakPeak FlowFlow MetersMeters

Red Zone = Danger! (below 50% of personal best) The patient must take an inhaled bronchodilator (rescue medicine) right away and seek medical attention immediately if their peak flow number does not return to and stay in their Yellow or Green Zone.

6666 CorrectCorrect UseUse ofof PFMPFM c Place the indicator at base of numbered scale d Stand up e Take a slow deep breath f Place PFM in mouth and close lips around mouth piece g Blow out as hard and fast as possible– a short, sharp blast h Record peak flow number; repeat steps 1-5 two more times. The highest of three measurements is patient’s 6767 personal best. PEPPEP TherapyTherapy

z Positive Expiratory Pressure

z Adjunct to Chest Physical Therapy

z Self-administered

z Used to facilitate the mobilization and removal of tenacious pulmonary secretions.

6868 AirwayAirway ClearanceClearance

z Mucociliary transport is responsible for normal clearance of secretions from the lower respiratory tract.

z Cough is responsible for secretion clearance in cases of acute and chronic respiratory disease.

6969 MucociliaryMucociliary TransportTransport

7070 CoughCough MechanismMechanism

7171 ChestChest PhysicalPhysical TherapyTherapy

7272 PEPPEP TherapyTherapy

z Pressure manometer is used to set a therapeutic pressure range: 10-20 cmH20

z Patient uses diaphragm to breathe in a volume of air larger than normal, but not to total lung capacity, and exhales through the PEP valve

z Sets of 10-20 breaths, followed by controlled coughing moves secretions up and out of the

7373 airways RespiratoryRespiratory MedicationsMedications

Beta-2 Adrenergic Drugs Anti-Cholinergic Drugs

SYMPATHETIC PARASYMPATHETIC Agonists Antagonists stimulate production block production of cAMP of cGMP

bronchial relaxation bronchial constriction normal tone

7474 BronchodilatorsBronchodilators

z Category 1 - Referred to as rescue or reliever drugs z Beta-agonists z Fast acting: 2-10 minutes z Prevents and treats bronchospasm

Brand Name Generic Name Proventil Albuterol Ventolin Albuterol Alupent Metaproternol Xoepenex Levalbuterol

7575 BronchodilatorsBronchodilators

z Category 2 – “maintenance reliever” drugs z Anti-cholinergic z Fast acting: 15-30 minutes z Prevents and treats bronchospasm

Brand Name Generic Name

Atrovent Ipratropium bromide

DuoNeb Ipratropium and Albuterol

7676 AntiAnti--inflammatoryinflammatory AgentsAgents

z Category 1: “controllers” or “maintenance” drugs z Slow acting: 20-30 minutes z Prevents / treats airway swelling by decreasing response to histamine release

Brand Name Generic Name Pulmicort Respules Budesonide Flovent Fluticasone propionate Azmacort Triamcinolone acetonide Vanceril Beclomethasone dipropionate

7777 AntiAnti--inflammatoryinflammatory AgentsAgents

z Category 2: nonsteroidal drugs - “maintenance” or “stabilizer” medications z Slow acting: require 1-2 wks to become effective z Prevent airway swelling by inhibiting release of histamine

Brand Name Generic Name

Intal Cromolyn sodium Tilade Nedocromil sodium

7878 MucolyticsMucolytics

z Liquefies secretions to facilitate mobilization z Indicated for pulmonary patients with thick, tenacious secretions: cystic fibrosis, chronic bronchitis, etc.

Brand Name Generic Name Mucosil Acetylcysteine Pulmozyme Dornase alfa

7979 AntimicrobialsAntimicrobials

z Research for the delivery of antimicrobials by aerosol therapy an expanding field z Currently accepted clinical applications include: œ anti-pseudomonal antibiotic: TOBI CF œ Pentamidine prophylaxis HIV+ œ Ribavirin RSV

8080 ClinicalClinical TrialsTrials

8181