title: What Causes Uneven Aerosol Deposition in the Bronchoconstricted Lung? A Quantitative Imaging Study.
abstract: BACKGROUND
  A previous PET-CT imaging study of 14 bronchoconstricted asthmatic subjects showed that peripheral aerosol deposition was highly variable among subjects and lobes. The aim of this work was to identify and quantify factors responsible for this variability.
  
  
  METHODS
  A theoretical framework was formulated to integrate four factors affecting aerosol deposition: differences in ventilation, in how air vs. aerosol distribute at each bifurcation, in the fraction of aerosol escaping feeding airways, and in the fraction of aerosol reaching the periphery that is exhaled. These factors were quantified in 12 of the subjects using PET-CT measurements of relative specific deposition sD*, relative specific ventilation sV* (measured with dynamic PET or estimated as change in expansion between two static HRCTs), average lobar expansion FVOL, and breathing frequency measured during aerosol inhalation fN.
  
  
  RESULTS
  The fraction of the variance of sD* explained by sV* (0.38), by bifurcation effects (0.38), and by differences in deposition along feeding airways (0.31) were similar in magnitude. We could not directly estimate the contribution of aerosol that was exhaled. Differences in expansion did not explain any fraction of the variability in sD* among lobes. The dependence of sD* on sV* was high in subjects breathing with low fN, but weakened among those breathing faster. Finally, sD*/sV* showed positive dependence on FVOLamong low fNsubjects, while the dependence was negative among high fNsubjects.
  
  
  CONCLUSIONS
  The theoretical framework allowed us to analyze experimentally measured aerosol deposition imaging data. When considering bronchoconstricted asthmatic subjects, a dynamic measurement of ventilation is required to evaluate its effect on aerosol transport. The mechanisms behind the identified effects of fNand FVOLon aerosol deposition need further study and may have important implications for aerosol therapy in subjects with heterogeneous ventilation.
authors.affiliation: 1 Department of Mechanical Engineering, Massachusetts Institute of Technology , Boston, Massachusetts.|2 Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Elliot Eliyahu
authors.initials: EE
authors.lastname: Greenblatt
authors.affiliation: 2 Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Tilo
authors.initials: T
authors.lastname: Winkler
authors.affiliation: 2 Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Robert Scott
authors.initials: RS
authors.lastname: Harris
authors.affiliation: 2 Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Vanessa Jane
authors.initials: VJ
authors.lastname: Kelly
authors.affiliation: 2 Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Mamary
authors.initials: M
authors.lastname: Kone
authors.affiliation: 3 R&D Medical , Air Liquide Santé International, Les-Loges-en-Josas, France .|4 Department of Mechanical Engineering, Lafayette College , Easton, Pennsylvania.
authors.forename: Ira
authors.initials: I
authors.lastname: Katz
authors.affiliation: 5 Department of Mechanical Engineering, University of Alberta , Edmonton, Alberta, Canada .
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Martin
authors.affiliation: 3 R&D Medical , Air Liquide Santé International, Les-Loges-en-Josas, France .
authors.forename: George
authors.initials: G
authors.lastname: Caillibotte
authors.affiliation: 2 Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Jose
authors.initials: J
authors.lastname: Venegas
keywords: aerosol deposition; asthma; bronchoconstriction; escape fractions; sedimentation; ventilation