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Lung Mechanical Control of Airway Function During Exercise in the Asthmatic Adult. Vermont Genetics Network Annual Retreat August 7, 2013 Hans Christian Haverkamp , Ph.D. Johnson State College. Search Google for “Biomedical Research”. Research in the Exercise Physiology Lab.
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Lung Mechanical Control of Airway Function During Exercise in the Asthmatic Adult Vermont Genetics Network Annual Retreat August 7, 2013 Hans Christian Haverkamp, Ph.D. Johnson State College
Research in the Exercise Physiology Lab Atmospheric Pressure Chest wall Intrapleural Pressure (Pip , PPL, PL) Intrapulmonary Pressure (Ppul ,Palv) Pleurae Transpulmonary Pressure Ppul - Pip = Pressure = R(V) x E(V’)
Normal Seasonal Variation Airway function Impaired SEP JAN MAR JUN DEC Normal Daily Variation Airway function Impaired 11:00pm 12:00am 6:00am 12:00pm 6:00pm Normal Circumstantial Variation Airway function Impaired Visit friend w/cat Bronchodilator Lung function is variable in the asthmatic
Study 1: Question & Purpose • What is the effect of variable pre-exercise airway function on the responses to whole-body exercise in asthmatic humans? • Pulmonary system • Ventilation • Airway mechanics • Determine effects of improved and worsened pre-exercise airway function on the pulmonary system responses to whole-body exercise in asthmatic humans
Experimental design Control Albuterol (BD) Four Experimental Studies Exercise SHAM (hyperpnea) Hyperpnea (BC)
Outcome data • Exercise ventilation • Tidal volume • Liters/breath • Breathing frequency • Breaths/minute • Minute ventilation • Liters/min • Flow-volume loops 10 5 Airflow (L/sec) 4 8 Volume (L)
Altered pre-exercise lung function Δ = 1.4 L * Relative airway diameter
No effect of variable pre-exercise airway function on exercise ventilation VE/VCO2 Tidal volume L/breath Minute ventilation Breathing frequency L/min BPM
Exercise-induced bronchodilation Pre-exercise Post-exercise
Exercise-induced bronchodilation allows for adequate ventilation during exercise Pre-exercise Post-exercise
Study 1: Summary & Conclusions • Despite highly variable pre-exercise airway function: • Exercise ventilation similar • Significant exercise-induced bronchodilation • Allows for adequate exercise ventilatory response • In mild-to-moderate asthma, the pulmonary system is robustly responsive to increased demand for airflow during whole-body exercise • Mechanisms for exercise bronchodilation??? • Lung mechanical mechanisms • Current studies
The airways are embedded within the lung parenchyma Airways tethered open by lung parenchyma Weibel, Am J RespirCrit Care Med, vol 187, 2013
Study 2: Purpose & Hypothesis • Purpose: Determine effects of lung inflation on airway diameter during whole-body exercise in asthmatic adults • Hypothesis: Increased ventilation and tidal volume – and thus lung inflation – provides the principle physiological stimulus for changes in airway diameter during exercise in asthmatic adults
Experimental Design Spontaneous VE Iso VE Minute ventilation Isofb Spontaneous fb Breathing frequency • Forced exhalations • Pulmonary resistance Spontaneous VT Iso VT 70 Workload (% max) Tidal volume 40 Rest 4 minute exercise stages
Airway diameter fluctuates during variable intensity exercise in asthma 70 Workload (% max) 40 Exercise BL
Airway diameter fluctuates despite maintained tidal volume and minute ventilation v v VE Δ, 23 L/min VT Δ, 0.25 L 70 Workload (% max) 40
Stationary isocapnic hyperpnea causes bronchodilation but not fluctuating airway diameter 70 Workload (% max) 40 Rest Rest
Summary • Bronchodilation occurs during whole-body exercise in the asthmatic adult • Allows for adequate exercise ventilation despite variable baseline lung function • Airway function is dynamic during variable workrate exercise in the asthmatic • ↑ exercise intensity = bronchodilation • ↓ exercise intensity = bronchoconstriction • Changing lung volume during exercise does not account for the variable airway function • Neural mechanisms • Chemical mediator mechanisms • Lung and airway mechanical mechanisms
Undergraduate Research Assistants • Undergraduate students • Adriane Morrison-Taylor* • JeniDemar* • Andrew Klansky* • Adam Lacayo* • Matthew Rossman • Susan Nader • Francesca Orsini • Dustin Berry INBRE, NIGMS, NCRR