title: Comparison of realistic and idealized breathing patterns in computational models of airflow and vapor dosimetry in the rodent upper respiratory tract.
abstract: BACKGROUND
  Computational fluid dynamics (CFD) simulations of airflows coupled with physiologically based pharmacokinetic (PBPK) modeling of respiratory tissue doses of airborne materials have traditionally used either steady-state inhalation or a sinusoidal approximation of the breathing cycle for airflow simulations despite their differences from normal breathing patterns.
  
  
  OBJECTIVE
  Evaluate the impact of realistic breathing patterns, including sniffing, on predicted nasal tissue concentrations of a reactive vapor that targets the nose in rats as a case study.
  
  
  METHODS
  Whole-body plethysmography measurements from a free-breathing rat were used to produce profiles of normal breathing, sniffing and combinations of both as flow inputs to CFD/PBPK simulations of acetaldehyde exposure.
  
  
  RESULTS
  For the normal measured ventilation profile, modest reductions in time- and tissue depth-dependent areas under the curve (AUC) acetaldehyde concentrations were predicted in the wet squamous, respiratory and transitional epithelium along the main airflow path, while corresponding increases were predicted in the olfactory epithelium, especially the most distal regions of the ethmoid turbinates, versus the idealized profile. The higher amplitude/frequency sniffing profile produced greater AUC increases over the idealized profile in the olfactory epithelium, especially in the posterior region.
  
  
  CONCLUSIONS
  The differences in tissue AUCs at known lesion-forming regions for acetaldehyde between normal and idealized profiles were minimal, suggesting that sinusoidal profiles may be used for this chemical and exposure concentration. However, depending upon the chemical, exposure system and concentration and the time spent sniffing, the use of realistic breathing profiles, including sniffing, could become an important modulator for local tissue dose predictions.
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Colby
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors.forename: Senthil
authors.initials: S
authors.lastname: Kabilan
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Jacob
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Kuprat
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Einstein
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Corley
mesh_terms: D000079:Acetaldehyde / Q000493:pharmacokinetics; D000818:Animals; D005260:Female; D057446:Hydrodynamics; D008954:Models, Biological; D010993:Plethysmography, Whole Body; D017207:Rats, Sprague-Dawley; D012119:Respiration; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000378:metabolism*
chemical_list: D000079:Acetaldehyde
keywords: Acetaldehyde; CFD; PBPK; olfaction; realistic breathing; sniffing; tissue dose