What are the mechanisms of aerosol deposition in the lungs of a mechanically ventilated patient with Chronic Obstructive Pulmonary Disease (COPD) or asthma?

Mechanisms of Aerosol Deposition in Mechanically Ventilated COPD/Asthma Patients

Aerosol deposition in mechanically ventilated patients with COPD or asthma occurs through three primary mechanisms: inertial impaction in the oropharynx and large airways, gravitational sedimentation in small airways and alveoli, and Brownian diffusion for ultrafine particles, though deposition efficiency is markedly reduced (1.2-6% reaching the lungs) compared to spontaneous breathing due to altered flow dynamics and circuit losses. 1, 2

The Three Deposition Mechanisms

Inertial Impaction

• Inertial impaction occurs when aerosol particles with sufficient momentum cannot follow the airstream around bends and curves, causing them to collide with airway walls in the oropharynx, endotracheal tube, and large conducting airways 2, 3, 4
• This mechanism is most efficient for larger particles (>6 μm) and becomes dominant in areas of high airflow velocity and sharp directional changes 3
• In mechanically ventilated patients, significant impaction losses occur in the ventilator circuit itself and the artificial airway, substantially reducing the drug mass reaching the lungs 5

Gravitational Sedimentation

• Gravitational sedimentation is the primary deposition mechanism for particles in the 0.5-5 μm range during resting breathing conditions, occurring predominantly in small conducting airways and alveoli where airflow velocity is low 2, 6, 4
• Particles settle under gravity's influence when they have sufficient residence time in the airways, making this mechanism most effective in the distal lung regions 6, 3
• For mechanically ventilated COPD/asthma patients, sedimentation is enhanced by breath-holding maneuvers (though often not feasible) and reduced by rapid respiratory rates that limit particle residence time 2

Brownian Diffusion

• Brownian diffusion becomes the dominant mechanism for ultrafine particles (<0.5 μm), where random molecular motion causes particles to contact airway walls 4
• This mechanism is most efficient in the smallest airways and alveoli where distances are short and surface area is large 3, 4
• A theoretical minimum deposition exists near 0.3 μm particle size where neither sedimentation nor diffusion is particularly efficient 4

Critical Factors Reducing Deposition Efficiency in Mechanical Ventilation

Aerosol deposition from nebulizers and metered dose inhalers is substantially reduced during mechanical ventilation compared with spontaneous breathing, with only 1.2-3.0% of the dose depositing in adult lungs from jet nebulizers and 4-6% from metered dose inhalers with spacers. 1

• The reduction occurs because ventilated patients have more severe underlying lung disease with increased airway obstruction, altered ventilation-perfusion relationships, and dynamic hyperinflation 1
• Circuit-related losses are substantial, with aerosol depositing on tubing walls, humidification systems, and the endotracheal tube before reaching the lungs 5
• Particle size distribution shifts unfavorably due to hygroscopic growth in humidified circuits, increasing impaction losses 5