Lung Mechanical Control of Airway Function During Exercise

in the Asthmatic Adult

Vermont Genetics NetworkAnnual RetreatAugust 7, 2013

Hans Christian Haverkamp, Ph.D.Johnson State College

Search Google for “Biomedical Research”

Research in the Exercise Physiology Lab

Research in the Exercise Physiology LabAtmospheric

Pressure

IntrapulmonaryPressure(Ppul ,Palv)

IntrapleuralPressure

(Pip , PPL, PL)

TranspulmonaryPressure

= Ppul - Pip

Chest wall

Pleurae Airf

low

(L/s

ec)

-6-4-20246

Pm (c

mH

2O)

-3-2-10123

Pes

(cm

H2O

)-30-20-10

01020

Pptp

(cm

H2O

)

-30-20-10

01020

Pressure = R(V) x E(V’)

Lung function is variable in the asthmatic

Airway function

Normal

ImpairedJAN JUN DECMAR SEP

Seasonal Variation

Daily Variation

12:00am 12:00pm 11:00pm6:00am 6:00pm

Airway function

Normal

Impaired

Circumstantial Variation

Visit friend w/cat Bronchodilator

Airway function

Normal

Impaired

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

FourExperimental

Studies

Albuterol (BD)

Hyperpnea (BC)

SHAM (hyperpnea)

Control

Exercise

Outcome data• Exercise ventilation

– Tidal volume• Liters/breath

– Breathing frequency• Breaths/minute

– Minute ventilation• Liters/min

– Flow-volume loopsAirflow(L/sec)

Volume (L)

10

8

5

4

Altered pre-exercise lung function

Asthma Group

Control BD SHAM BC

Forc

ed e

xpira

tory

vol

ume

1.0

(L)

2.5

3.0

3.5

4.0

4.5

5.0

Baseline Post-Intervention

Δ = 1.4 L

*

Relativeairway diameter

Volume (L)0 1 2 3 4 5

Flow

(L/s

ec)

01

23456

789

ControlAlbuterolSHAMHyperpnea Challenge

No effect of variable pre-exercise airway function on exercise ventilation

Rest WU 1 3 End Rec20

25

30

35

40

45

50A

Rest WU 1 3 End Rec0

20406080

100120140

VE/VCO2

Minute ventilation

L/m

in

20

25

30

35

40

45

50

VE/V

CO

2

20

25

30

35

40

45

50 A

020406080

100120140

Asthma Group

0.5

1.0

1.5

2.0

2.5

3.0

3.5

ExerciseRest WU 1 3 End Rec

10

20

30

40

50

Min

ute

vent

ilatio

n (L

/min

)0

20406080

100120140

ControlBronchodilationSHAMBronchoconstriction

Tida

l vol

ume

(L/b

reat

h)

0.5

1.0

1.5

2.0

2.5

3.0

3.5

ExerciseRest WU 1 3 End Rec

Bre

athi

ng fr

eque

ncy

(bpm

)

10

20

30

40

50

Control Group

B

DC

E

G

ControlBronchodilationSHAMBronchoconstriction

L/br

eath

BPM

Tidal volume

Breathing frequencyRest WU 1 min 3 min End Rec

Pulm

onar

y re

sist

ance

(cm

H2O

/L/s

ec)

1

2

3

4

5

6

ControlAlbuterolHyperpneaSHAM

Exercise-induced bronchodilation

Volume (L)0 1 2 3 4 5

Flow

(L/s

ec)

0123456789

ControlAlbuterolHyperpnea

0 1 2 3 4 50123456789

Volume (L)

Pre-exercise Post-exercise

Exercise-induced bronchodilation allows for adequate ventilation during exercise

Volume (L)0 1 2 3 4 5

Airf

low

(L/s

ec)

0

2

4

6

8

10

12

Volume (L)0 1 2 3 4 5

Airf

low

(L/s

ec)

0

2

4

6

8

10

12

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

Weibel, Am J Respir Crit Care Med, vol 187, 2013

Airways tethered open by lung parenchyma

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

4 minute exercise stages

Workload

(% m

ax)4070

Tida

l vo

lum

eBr

eath

ing

freq

uenc

yM

inut

eve

ntila

tion

Rest

Spontaneous VE

Spontaneous fb

Spontaneous VT

Iso VE

Iso fb

Iso VT

Experimental Design

• Forced exhalations• Pulmonary resistance

Airway diameter fluctuates during variable intensity exercise in asthma

Min

ute

Vent

ilatio

n (L

/min

)

405060708090

100 Spontaneous ventilation

Tida

l Vol

ume

(L)

2.0

2.4

2.8

3.2

Bre

athi

ngFr

eque

ncy

(BPM

)

16

24

32

40

FEV1

.0 (L

)

2.8

3.2

3.6

4.0

4.4

FEV1

.0 (L

)

2.8

3.2

3.6

4.0

4.4

Pulm

onar

y re

sist

ance

(c

mH

2O/L

/sec

)1.5

2.0

2.5

3.0

3.5

4.0

Workload

(% m

ax)40

70BL Exercise

Min

ute

Vent

ilatio

n (L

/min

)

40

60

80

100Spontaneous ventilationControlled ventilation

Tida

l Vol

ume

(L)

2.0

2.4

2.8

3.2

Bre

athi

ngFr

eque

ncy

(BPM

)

24

32

40

FEV1

.0 (L

)

2.8

3.2

3.6

4.0

4.4

Airway diameter fluctuates despite maintained tidal volume and minute ventilation

VE Δ, 23 L/min

VT Δ, 0.25 L

FEV1

.0 (L

)

2.62.83.03.23.43.63.84.04.24.4 Spontaneous ventilation

Controlled ventilationW

orkload(%

max)40

70

v v

Stationary isocapnic replication of exercise ventilation

Stationary isocapnic hyperpnea causes bronchodilation but not fluctuating airway diameter

FEV1

.0 (L

)

1.5

2.0

2.5

3.0

3.5

4.0

Spontaneous ventilation

Isocapnic replication

FEV1

.0 (p

erce

nt c

hang

e)-505

10152025

3035

Min

ute

Vent

ilatio

n (L

/min

)

20

40

60

80

100 Spontaneous ventilationStationary hyperpnea

Tida

l Vol

ume

(L)

1.0

1.5

2.0

2.5

3.0

Bre

athi

ngFr

eque

ncy

(BPM

)

5

10

15

20

25

30

FEV1

.0 (L

)

2.02.53.03.54.04.55.0

Workload

(% m

ax)40

70

RestRest

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*– Jeni Demar*– Andrew Klansky*– Adam Lacayo*– Matthew Rossman– Susan Nader– Francesca Orsini– Dustin Berry

INBRE, NIGMS, NCRR