Optimizing aerosol therapy in mechanically ventilated acute respiratory distress syndrome: a delivery-fidelity framework.

Aerosol therapy is frequently used in adults with acute respiratory distress syndrome (ARDS) receiving invasive mechanical ventilation, yet its clinical effects remain difficult to interpret because prescribed dose is not equivalent to lung exposure. This Mini Review examines aerosol therapy as a drug-device-circuit-patient intervention by integrating ARDS guideline context, delivery evidence, drug-class literature, and implementation data. Exposure is shaped by generator and formulation, fill and residual volume, position, humidification, ventilator flow, artificial airway, filters, inline components, and interruptions. Most technical evidence is bench-derived and does not establish ARDS-specific clinical benefit. We retain gaseous inhaled nitric oxide only as a non-aerosol physiological comparator. Nebulized prostacyclins may improve oxygenation, but patient-centered benefit remains uncertain; aerosolized antibiotics should be interpreted within infection-defined ventilator-associated pneumonia; and bronchodilators or mucoactive therapies should not be used routinely on the basis of the ARDS label alone. Optimization should seek reproducible, target-appropriate exposure while preserving lung-protective ventilation, circuit integrity, treatment continuity, filtration surveillance, and staff and environmental safety. We propose a candidate minimum delivery-reporting dataset, while emphasizing that it is not a validated exposure surrogate or clinical score. Future studies should align mechanism, delivery, phenotype, response window, safety, and patient-centered endpoints to distinguish biological failure from inadequate or interrupted exposure.