Use of functional respiratory imaging to characterize the effect of inhalation profile and particle size on lung deposition of inhaled corticosteroid/long-acting β2-agonists delivered via a pressurized metered-dose inhaler

Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618760948. doi: 10.1177/1753466618760948.


Background: Functional respiratory imaging (FRI) uses three-dimensional models of human lungs and computational fluid dynamics to simulate functional changes within airways and predict the deposition of inhaled drugs. This study used FRI to model the effects of different patient inhalation and drug formulation factors on lung deposition of an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combination, administered by a pressurized metered-dose inhaler.

Methods: Three-dimensional models of the lungs of six patients with asthma (mean forced expiratory volume in 1 s, 83%), treated with an ICS/LABA, were included. FRI modelling was used to simulate (1) the effects on lung deposition of inhalation duration and particle size [fine particle fraction (FPF), proportion of particles <5 µm; and mass median aerodynamic diameter (MMAD), average size of inhalable particles]; (2) deposition of fluticasone propionate/formoterol (FP/FORM) 125/5 µg; and (3) how inhalation profiles and flow rates affected FP/FORM deposition.

Results: Total lung depositions (TLDs) following 1-, 3- and 5-s inhalations were 22.8%, 36.1% and 41.6% (metered dose), respectively, and central-to-peripheral deposition (C:P) ratios were 1.81, 0.86 and 0.61, respectively. TLD increased with increasing FPF, from ~8% at 10% FPF to ~36% at 40% FPF (metered dose); by contrast, MMAD had little effect on TLD, which was similar across MMADs (1.5-4.5 µm) at each FPF. FP/FORM deposited throughout central and peripheral airways with gradual (sinusoidal) and sharp (rapid) inhalations. TLD ranged from 35.8 to 44.0% (metered dose) for gradual and sharp inhalations at 30 and 60 L/min mean flow rates.

Conclusions: These data provide important insights into the potential effects of inhalation characteristics (inhalation profile and duration) and aerosol formulation (FPF) on lung deposition of inhaled therapies. FRI thus represents a useful alternative to scintigraphy techniques. Future FRI studies will further our understanding of the deposition of inhaled drugs and help improve the management of asthma.

Keywords: fine particle fraction; functional respiratory imaging; inhalation; inhaled corticosteroid/long-acting β2-agonist combination; lung deposition; pressurized metered-dose inhaler.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Adult
  • Aerosols
  • Aged
  • Asthma / diagnostic imaging*
  • Asthma / drug therapy
  • Asthma / metabolism
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Drug Combinations
  • Female
  • Fluticasone / administration & dosage*
  • Fluticasone / metabolism
  • Forced Expiratory Volume
  • Formoterol Fumarate / administration & dosage*
  • Formoterol Fumarate / metabolism
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / adverse effects
  • Humans
  • Hydrodynamics
  • Imaging, Three-Dimensional / methods
  • Lung / diagnostic imaging*
  • Lung / drug effects
  • Lung / metabolism
  • Lung / physiopathology
  • Male
  • Metered Dose Inhalers*
  • Middle Aged
  • Particle Size
  • Patient-Specific Modeling*
  • Predictive Value of Tests
  • Pressure
  • Radiographic Image Interpretation, Computer-Assisted / methods
  • Tomography, X-Ray Computed / methods*
  • Young Adult


  • Adrenergic beta-2 Receptor Agonists
  • Aerosols
  • Bronchodilator Agents
  • Drug Combinations
  • Glucocorticoids
  • fluticasone-formoterol
  • Fluticasone
  • Formoterol Fumarate