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

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Research in the Exercise Physiology Lab

Research in the Exercise Physiology Lab

AtmosphericPressure

IntrapulmonaryPressure(Ppul ,Palv)

IntrapleuralPressure

(Pip , PPL, PL)

TranspulmonaryPressure

= Ppul - Pip

Chest wall

Pleurae Air

flo

w (

L/s

ec)

-6-4-20246

Pm

(cm

H2O

)

-3-2-10123

Pes

(cm

H2O

)-30-20-10

01020

Pp

tp (

cmH

2O

)

-30

-20

-10

0

10

20

Pressure = R(V) x E(V’)

Lung function is variable in the asthmatic

Airway function

Normal

Impaired

JAN 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 loops Airflow(L/sec)

Volume (L)

10

8

5

4

Altered pre-exercise lung function

Asthma Group

Control BD SHAM BC

Fo

rced

exp

irat

ory

vo

lum

e 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 5F

low

(L

/sec

)

0

1

2

3

4

5

6

7

8

9ControlAlbuterolSHAMHyperpnea 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

20

40

60

80

100

120

140

VE/VCO2

Minute ventilation

L/m

in

20

25

30

35

40

45

50

VE

/VC

O2

20

25

30

35

40

45

50 A

0

20

40

60

80

100

120

140

Asthma Group

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Exercise

Rest WU 1 3 End Rec10

20

30

40

50

Min

ute

ven

tila

tio

n (

L/m

in)

0

20

40

60

80

100

120

140

ControlBronchodilationSHAMBronchoconstriction

Tid

al v

olu

me

(L/b

reat

h)

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Exercise

Rest WU 1 3 End Rec

Bre

ath

ing

fre

qu

ency

(b

pm

)

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

Pu

lmo

nar

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

Flo

w (

L/s

ec)

0

1

2

3

4

5

6

7

8

9ControlAlbuterolHyperpnea

0 1 2 3 4 50

1

2

3

4

5

6

7

8

9

Volume (L)

Pre-exercise Post-exercise

Exercise-induced bronchodilation allows for adequate ventilation during exercise

Volume (L)

0 1 2 3 4 5

Air

flo

w (

L/s

ec)

0

2

4

6

8

10

12

Volume (L)

0 1 2 3 4 5

Air

flo

w (

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)40

70

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

V

enti

lati

on

(L

/min

)

405060708090

100 Spontaneous ventilation

Tid

al V

olu

me

(L)

2.0

2.4

2.8

3.2

Bre

ath

ing

Fre

qu

ency

(B

PM

)

16

24

32

40

FE

V1.

0 (L

)

2.8

3.2

3.6

4.0

4.4

FE

V1.

0 (L

)

2.8

3.2

3.6

4.0

4.4

Pu

lmo

nar

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

V

enti

lati

on

(L

/min

)

40

60

80

100Spontaneous ventilationControlled ventilation

Tid

al V

olu

me

(L)

2.0

2.4

2.8

3.2

Bre

ath

ing

Fre

qu

ency

(B

PM

)

24

32

40

FE

V1.

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

FE

V1.

0 (L

)

2.6

2.8

3.0

3.2

3.4

3.6

3.8

4.0

4.2

4.4 Spontaneous ventilationControlled ventilation

Workload

(% m

ax)40

70

v v

Stationary isocapnic replication of exercise ventilation

Stationary isocapnic hyperpnea causes bronchodilation but not fluctuating airway diameter

FE

V1.

0 (L

)

1.5

2.0

2.5

3.0

3.5

4.0

Spontaneous ventilation

Isocapnic replication

FE

V1.

0 (p

erce

nt

chan

ge)

-5

0

5

10

15

20

25

30

35

Min

ute

V

enti

lati

on

(L

/min

)

20

40

60

80

100 Spontaneous ventilationStationary hyperpnea

Tid

al V

olu

me

(L)

1.0

1.5

2.0

2.5

3.0

Bre

ath

ing

Fre

qu

en

cy (

BP

M)

5

10

15

20

25

30

FE

V1.

0 (L

)

2.0

2.5

3.0

3.5

4.0

4.5

5.0

Workload

(% m

ax)40

70

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

INBRE, NIGMS, NCRR