title: Pulmonary function tests fail to predict exercise intolerance in sheep with emphysema.
abstract: OBJECTIVE
  The purpose of this study was to examine ventilatory parameters, gas exchange, and exercise tolerance in sheep undergoing cardiopulmonary exercise testing and pulmonary function testing at baseline and after induction of emphysema using nebulized papain, to improve our understanding of the contributions of parenchymal emphysema with minimal airway disease to exertional dysfunction in mild-to-moderate emphysema.
  
  
  METHODS
  Static lung physiology (total lung capacity, residual volume, static elastance, and diffusing capacity of carbon monoxide) and lung (ZL) input impedance were measured, and cardiopulmonary exercise testing (CPET) was performed in 12 sheep before and after induction of emphysema. Papain treatment was delivered over a 12-wk period, as a single dose per week, to induce mild-to-moderate emphysema without airway disease. Static and dynamic lung physiology, as well as CPET, were then repeated.
  
  
  RESULTS
  At the emphysema time point (EMPH), all animals were asymptomatic for emphysema at rest. There was a 60% increase in residual volume and a 57% decrease in static elastance, accompanied by a 36% reduction in diffusing capacity. Airway resistance was consistently, mildly increased, resulting in an increased expiratory time constant for all sheep at EMPH. There were no significant differences at EMPH versus baseline for any measured physiological variables during CPET (VO2peak, VCO2peak, RER, anaerobic threshold, O2 pulse, tidal volume, peak flow, peak VE/VO2, or peak VE).
  
  
  CONCLUSIONS
  There is notable conservation of exercise capacity in sheep with mild-to-moderate parenchymal emphysema; this is not predicted by pulmonary function tests. In the absence of significant airway narrowing, mild-to-moderate emphysema is unlikely to result in airflow limitation.
authors.affiliation: Department of Clinical Sciences, Tufts University School of Veterinary Medicine, North Grafton, MA 01536, USA. melissa.mazan@tufts.edu
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Mazan
authors.forename: Edward P
authors.initials: EP
authors.lastname: Ingenito
authors.forename: Larry
authors.initials: L
authors.lastname: Tsai
authors.forename: Andrew
authors.initials: A
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D004646:Emphysema / Q000139:chemically induced / Q000503:physiopathology*; D005080:Exercise Test / Q000379:methods; D005260:Female; D016014:Linear Models; D008168:Lung / Q000502:physiology / Q000503:physiopathology*; D010206:Papain; D012756:Sheep; D014109:Total Lung Capacity / Q000502:physiology*
chemical_list: D010206:Papain