title: Reprint of "Non-invasive measure of respiratory mechanics and conventional respiratory parameters in conscious large animals by high frequency Airwave Oscillometry".
abstract: BACKGROUND
  A number of drugs in clinical trials are discontinued due to potentially life-threatening airway obstruction. As some drugs may not cause changes in core battery parameters such as tidal volume (Vt), respiratory rate (RR) or minute ventilation (MV), including measurements of respiratory mechanics in safety pharmacology studies represents an opportunity for design refinement. The present study aimed to test a novel non-invasive methodology to concomitantly measure respiratory system resistance (Rrs) and conventional respiratory parameters (Vt, RR, MV) in conscious Beagle dogs and cynomolgus monkeys.
  
  
  METHODS
  An Airwave Oscillometry system (tremoFlo; THORASYS Inc., Montreal, Canada) was used to concomitantly assess Rrs and conventional respiratory parameters before and after intravenous treatment with a bronchoactive agent. Respiratory mechanics measurements were performed by applying a short (i.e. 16s) single high frequency (19Hz) waveform at the subject's airway opening via a face mask. During measurements, pressure and flow signals were recorded. After collection of baseline measurements, methacholine was administered intravenously to Beagle dogs (n=6) and cynomolgus monkeys (n=4) at 8 and 68μg/kg, respectively.
  
  
  RESULTS
  In dogs, methacholine induced significant increases in Vt, RR and MV while in monkeys, it only augmented RR. A significant increase in Rrs was observed after methacholine administration in both species with mean percentage peak increases from baseline of 88 (53)% for dogs and 28 (16)% for cynomolgus monkeys.
  
  
  CONCLUSIONS
  Airwave Oscillometry appears to be a promising non-invasive methodology to enable respiratory mechanics measurements in conscious large animals, a valuable refinement in respiratory safety pharmacology.
authors.affiliation: CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3.
authors.forename: Leanne
authors.initials: L
authors.lastname: Bassett
authors.affiliation: Faculty of Veterinary Medicine, University of Montreal, P.O. Box 5000, St-Hyacinthe, QC, Canada, J2S 7C6.
authors.forename: Eric
authors.initials: E
authors.lastname: Troncy
authors.affiliation: SCIREQ Scientific Respiratory Equipment Inc., 6600 St-Urbain, Montreal, QC, Canada, H2S 3G8.
authors.forename: Annette
authors.initials: A
authors.lastname: Robichaud
authors.affiliation: SCIREQ Scientific Respiratory Equipment Inc., 6600 St-Urbain, Montreal, QC, Canada, H2S 3G8; THORASYS Thoracic Medical Systems Inc., 6600 rue St-Urbain, Montreal, QC, Canada, H2S 3G8.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schuessler
authors.affiliation: CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3.
authors.forename: Mylène
authors.initials: M
authors.lastname: Pouliot
authors.affiliation: CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3.
authors.forename: Alexis
authors.initials: A
authors.lastname: Ascah
authors.affiliation: CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3; Faculty of Veterinary Medicine, University of Montreal, P.O. Box 5000, St-Hyacinthe, QC, Canada, J2S 7C6. Electronic address: authiers@ca.citoxlab.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Authier
keywords: Airwave Oscillometry; Airway resistance; Dog; Methacholine; Monkey; Respiratory; Safety pharmacology