The depth and effectiveness of an inhaled drug depend on many factors, such as the size and physical characteristics of the aerosol particles, the amount of aerosol produced, the geometry of the airways, and the control of ventilation. Therapeutic aerosols are generally composed of a wide range of particle sizes and shapes. In those studies reviewed by Foral et al assessing mainly COPD patients, in which particle size was indicated to be 2.3 to 3 μm, a solution of morphine was more likely to deposit in the peripheral airways during tidal breathing than in those studies in which particle size was 4.9 μm, which tends to cause impaction in the central airways.1
Indeed, only in the study in which the particle size was 2.3 μm was there a statistically significant increase in exercise endurance time. This suggests that opioid receptors are present mainly in the peripheral airways, or that systemic absorption of the narcotic was enhanced. Furthermore, the underlying disease for which the aerosol is delivered may influence the deposition of particles. Secretions, bronchoconstriction, or dynamic collapse may trap aerosolized drugs in the major airways. By contrast, the airways of patients with ILD may permit peripheral penetration of drugs since their caliber is large in relation to the lung volume because of increased elastic recoil and they are generally devoid of secretions. At the same time, this feature may be counteracted by an increased respiratory rate that promotes deposition of the aerosol in the upper airway. In the small study with ILD patients, the use of morphine in two different doses (ie, 2.5 and 5 mg) did not result in a significant relief of dyspnea, perhaps because of upper airway deposition, or because the dose of morphine was too small.