Chapter_5-_Aerosol_Therapy__1_

AEROSOL THERAPY

Introduction

• Aerosol: solid or liquid particles suspended in a gas.

• Common practice in respiratory and critical care: delivery of drugs in aerosolized form.

• Benefits of aerosolized therapy:

  • Directly targets the airway, minimizing systemic side effects.

  • Bypasses first-pass metabolism in the gastrointestinal tract and liver.

Indications for Aerosol Therapy

Diagnostic Uses

• Airway responsiveness and bronchodilator reversibility tests

• Ventilation scans

• Dosimetry

Therapeutic Uses

• Treatment of lung diseases:

  • Airway and lung parenchymal diseases

  • Systemic diseases like diabetes mellitus

  • Infections

Classification of Aerosols

A) Bland Aerosols

• Types: heated or cooled sterile water, saline

• Uses: treatment of upper airway diseases, humidification of bypassed airways, sputum induction.

B) Medicated Aerosols

• Contains: bronchodilators, steroids, mucokinetic agents, local anesthetics, antimicrobials, etc.

• Uses:

  • Upper airway conditions (inflammation, nasal allergy, infections)

  • Lower airway diseases: obstructive airway disease, cystic fibrosis, ARDS, and infections.

  • Nasal spray applications: insulin for diabetes and vasopressin for diabetes insipidus.

Aerosol Physics

• Factors affecting depth of aerosol delivery:

  1. Size and characteristics of aerosol

  2. Amount of aerosol

  3. Airway anatomy and geometry

  4. Breathing patterns

• Aerosols get deposited by 3 mechanisms, namely:

  • Diffusion

  • Inertial impaction

  • Sedimentation

Mechanisms of Aerosol Deposition and Particle Sizes

• Major mechanisms:

  • Inertial impaction occurs with larger (>3 µm), fast-moving particles

  • Gravitational sedimentation (function of mass and time)

  • Diffusion (Brownian motion ) occurs with particles smaller than 1 µm

• Particle filter effects:

  • 10 µm: filtered in the nose/oropharynx

  • 5–10 µm: reach proximal lower respiratory tract

  • 1–5 µm: reach lung periphery

Mass Median Aerodynamic Diameter (MMAD)

• Clinical aerosols are heterodisperse (varied sizes).

• MMAD: measures particle size in µm above and below which 50% of the mass is contained.

• Higher MMAD indicates more larger particle sizes.

Size and Particle Deposition

• Particle size deposition:

  • <0.5 µm: no deposition

  • 0.5–2 µm: alveoli

  • 2–5 µm: bronchi and bronchioles

  • 5–100 µm: mouth, nose, and upper airway

  • 100 µm: filtered by the upper respiratory tract

Size and Physical Characteristics

• Important characteristics: volume/surface area ratio, MMAD, geometric standard deviation; MMAD is the most crucial.

• Therapeutic aerosols: MMAD typically ranges from 0.5 to 5 microns.

• Influences on aerosol size and site of impaction: density, temperature, humidity, and more.

Effect of Ventilatory Pattern on Deposition

• Normal breathing flow rate: 0.5 L/s promotes aerosol delivery to bronchi/bronchioles (laminar flow).

• Higher flow rates cause turbulence, aerosol fragmentation.

• Optimal technique: slow, deep breathing with a 5-10 seconds breath-hold.

Airway Geometry and Aerosol Delivery

• Inhalation method influences deposition: mouth inhalation improves delivery compared to nose inhalation.

• Intervals (2-10 minutes) between inhaler actuation can aid in better drug delivery during subsequent doses.

Advantages and Disadvantages of Aerosol Therapy

Advantages

• Smaller doses compared to systemic therapies.

• Faster onset of action than oral dosing.

• Direct lung delivery minimizes systemic exposure.

• Less painful than injections, relatively comfortable.

Disadvantages

• Low lung deposition fraction: many variables can impact delivery efficacy.

• Coordination issues in using devices can hinder effectiveness.

• Variability in device types can confuse users.

Hazards of Aerosol Therapy

• Adverse reactions: headaches, insomnia, and potential bronchospasm from cold/high-density aerosols.

• Increased drug concentration in nebulizers due to evaporation or heating.

• Risk of infection from contaminated aerosol devices.

• Eye irritation from medication delivered via face masks.

Methods of Aerosol Generation

1. Nebulizers:

   • Types include pneumatic, ultrasonic, and vibrating mesh nebulizers.

2. Metered Dose Inhalers (MDI):

   • Pressurized devices featuring a canister and holding chamber.

3. Dry Powder Inhalers:

   • Such as Rotahaler and Turbuhaler.

Nebulizers

Pneumatic/Jets Nebulizers

• Function based on Bernoulli Principle.

• Types: Small Volume Nebulizers (SVNs) and Large Volume Nebulizers.

Small Volume Nebulizers (SVN)

• Hand-held or used in ventilation circuits.

• Gas flow rates: 6-8 L/m, optimal solution volume: 4-5 ml, particle size: 1-5 µm.

Large Volume Nebulizers

• Suitable for prolonged aerosol delivery, effective in upper airway edema treatment.

Ultrasonic Nebulizers

• Use a piezoelectric crystal to create ultrasonic vibrations, generating aerosol.

Vibrating Mesh Nebulizers

• Use mesh deformation to push liquid drug through mesh, creating inhalable droplets.

Metered Dose Inhalers (MDIs)

• Portable, multi-dose devices.

• Contains medication, surfactant, and propellant (HFA).

Advantages and Disadvantages of pMDI

Advantages

• Compact and portable

• Multiple doses with reduced infection risk

• Short treatment time with reproducible doses

Disadvantages

• Requires coordination between hand and breath

• Challenges in determining remaining doses.

Optimal Technique for MDI Use

• Important factors: coordination, breath-holding, and proper storage at 37 °C to maintain pressure and aerosol size.

Dry Powder Inhalers

• Advantages: portable, no CFC hazards, no synchronization required.

• Limitations: Some need assembly, affected by humidity, and high inspiratory flow rates required for efficacy.

Summary of Hazards of Aerosol Therapy

Risks for Patients

• Include bronchospasm, infection, airway obstruction, and device malfunction.

Risks for Caregivers

• Exposure to asthma and infections.

Environmental Risks

• CFCs contribute to ozone layer depletion; HFA is less harmful.