Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size

Am J Respir Crit Care Med. 2005 Dec 15;172(12):1497-504. doi: 10.1164/rccm.200410-1414OC. Epub 2005 Sep 28.


Rationale: Aerosol particle size influences the extent, distribution, and site of inhaled drug deposition within the airways.

Objectives: We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery.

Methods: In a randomized, double-blind, placebo-controlled study, 12 subjects with asthma (FEV1, 76.8 +/- 11.4% predicted) inhaled technetium-99m-labeled monodisperse albuterol aerosols (30-microg dose) of 1.5-, 3-, and 6-microm mass median aerodynamic diameter, at slow (30-60 L/min) and fast (> 60 L/min) inspiratory flows. Lung and extrathoracic radioaerosol deposition were quantified using planar gamma-scintigraphy. Pulmonary function and tolerability measurements were simultaneously assessed. Clinical efficacy was also compared with unlabeled monodisperse albuterol (15-microg dose) and 200 microg metered-dose inhaler (MDI) albuterol.

Results: Smaller particles achieved greater total lung deposition (1.5 microm [56%], 3 microm [50%], and 6 microm [46%]), farther distal airways penetration (0.79, 0.60, and 0.36, respective penetration index), and more peripheral lung deposition (25, 17, and 10%, respectively). However, larger particles (30-microg dose) were more efficacious and achieved greater bronchodilation than 200 microg MDI albuterol (deltaFEV1 [ml]: 6 microm [551], 3 microm [457], 1.5 microm [347], MDI [494]). Small particles were exhaled more (1.5 microm [22%], 3 microm [8%], 6 microm [2%]), whereas greater oropharyngeal deposition occurred with large particles (15, 31, and 43%, respectively). Faster inspiratory flows decreased total lung deposition and increased oropharyngeal deposition for the larger particles, with less bronchodilation. A shift in aerosol distribution to the proximal airways was observed for all particles.

Conclusions: Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation. Altering intrapulmonary deposition through aerosol particle size can appreciably enhance inhaled drug therapy and may have implications for developing future inhaled treatments.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Albuterol / administration & dosage
  • Albuterol / chemistry*
  • Albuterol / pharmacokinetics*
  • Asthma / diagnostic imaging
  • Asthma / drug therapy
  • Asthma / metabolism*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / chemistry*
  • Bronchodilator Agents / pharmacokinetics*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Metered Dose Inhalers
  • Particle Size
  • Radionuclide Imaging
  • Respiratory System / diagnostic imaging
  • Respiratory System / metabolism*
  • Treatment Outcome


  • Bronchodilator Agents
  • Albuterol