Exercise physiology in COPD

Chris Burtin
 Cardiac output
and circulation Muscle
Ventilation
O2 O2 O2

O2

CO2

CO2 CO2 CO2

Diffusion Diffusion
 Cardiac output
Muscle
Ventilation and circulation

O2 O2 O2

O2

CO2

CO2 CO2 CO2

Diffusion Diffusion
 Ventilation during exercise
• Increased ventilatory requirements compared to
healthy people
– Increased dead space ventilation
– Impaired gas exchange VENTILATION-PERFUSION MISMATCH
 Ventilation during exercise
• Increased ventilatory requirements compared to
healthy people
– Increased dead space ventilation (1)
– Impaired gas exchange (2)
– Increased ventilatory demand as a consequence of
deconditioning and peripheral muscle dysfunction (3)
 Ventilation during exercise
• Maximal ventilation is lower than normal
– Expiratory airflow obstruction
– Dynamic hyperinflation (COPD specific)

180
Maximal Voluntary Ventilation = FEV1(L) x 37.5
160
140
VE (L/min)

120
100
80
60
40
20
0
0 1 2 3 4
VO2 (L/min)
 Ventilation during exercise
• Maximal ventilation is lower than normal
– Expiratory airflow obstruction
– Dynamic hyperinflation (COPD specific)

180
160
140
VE (L/min)

120
100
80 Maximal Voluntary Ventilation = FEV1(L) x 37.5
60
40
20
0
0 1 2 3 4
VO2 (L/min)
 Ventilation during exercise
• Maximal ventilation is lower than normal
– Expiratory airflow obstruction
– Dynamic hyperinflation (COPD specific)

O’Donnell, AJRCCM 2001

 Ventilation during exercise
• Maximal ventilation is lower than normal
– Expiratory airflow obstruction
– Dynamic hyperinflation (COPD specific)

CAL = chronic airflow limitation

O’Donnell, AJRCCM 1997
 Cardiac output
Muscle
and circulation
Ventilation
O2 O2 O2

O2

CO2

CO2 CO2 CO2

Diffusion Diffusion
 Gas exchange during exercise
• Hypoxemia/Hypoxia can occur and leads to
augmented ventilation due to:
– Increase of peripheral chemoreceptor output
– Increase of lactic acid production

Oxygen dissociation curve

Haldane effect

Influence of:
• Temperature
• 2-3 DPG
• pH
 Cardiac output
Muscle
and circulation
Ventilation
O2 O2 O2

O2

CO2

CO2 CO2 CO2

Diffusion Diffusion
 Cardiovascular function during exercise
• Can be normal, but complications might arise

Reddit.com
 Cardiovascular function during exercise
• Can be normal, but complications might arise
• Main problem: increase in right ventricular afterload due to
elevated pulmonary vasculary resistance
» Hypoxic vasoconstriction
• Right ventricular hypertrophy
» Vascular injury and remodelling • Right heart failure
» Erythrocytosis • ↓ left ventricular filling due
to septal shift

• Tachyarrythmias
 Cardiac output
Muscle
and circulation
Ventilation
O2 O2 O2

O2

CO2

CO2 CO2 CO2

Diffusion Diffusion
Deconditioning?? Myopathy??
 Reason for this muscle dysfunction?
Systemic
Smoking? Physical activity?
inflammation?

Renin-angiotensin
Oxidative stress?
system?

Vitamin D
Hypoxia?
deficiency?

Corticosteroids? Hypercapnia?

Anabolic
Impaired energy
hormones and
balance?
growth factors?
 COPD, more than a lung disease

Lying
% of 12h-measurement

Sitting
COPD Standing
Walking
Others

Healthy

0 20 40 60 80 100

!
43% ↓ in time spent active
Decrease in physical activity already starts
24%↓ in intensity of in patients with GOLD I, when patients are
performed activities typically still asymptomatic

Pitta, AJRCCM 2005; Vorrink, Resp Res 2011

 COPD, more than a lung disease

Lying
% of 12h-measurement

Sitting
COPD Standing
Walking
Others

Healthy

0 20 40 60 80 100

!
Inactive patients have a higher risk to be
43% ↓ in time spent active admitted to hospital for an exacerbation, a
24%↓ in intensity of higher mortality risk and possibly a higher
performed activities risk for an accelerated disease progression

Pitta, AJRCCM 2005; Vorrink, Resp Res 2011, Garcia-Aymerich Thorax 2007 and AJRCCM 2006
 Muscle function and exercise tolerance

Hamilton AL, Am J Resp Crit Care Med 1995

Impact on physical activity in daily life
 Deterioration during exacerbations
• A change in the patient’s baseline dyspnoea, cough and/or sputum, which is
beyond normal day-to-day variations, is acute in onset and may warrant a
change in regular medication (0)

• “An acute worsening of respiratory symptoms that results in additional

therapy“ – GOLD update 2017

• Mild (short-acting bronchodilators only)

• Moderate (SABD + antibiotics and/or oral corticosteroids)
• Severe (requires hospitalization or emergency room visit)

Wedzicha JA, Lancet 2007 GOLD summary 2017 update

 Deterioration during exacerbations

400
75 patients without exacerbations
6MWD (m)

350

130 patients with exacerbations

300

250

0 10 20 30
Time (months)

Cote, Chest 2007

Deterioration during exacerbations
80
Daily walking time

60
(min)

40
Hospital
20

0
 Respiratory muscle function during exercise

Alison McConnell, Respiratory Muscle Training; Theory and Practice, Elsevier, Oxford, 2013
Respiratory muscle function during exercise
• Diaphragm of patients with COPD adapts to chronic overload
and has greater resistance to fatigue
At identical absolute lung volumes, inspiratory muscles
can generate more pressure

• Problem: mechanical disadvantage due to static and dynamic

hyperinflation

Siafakas NM, Thorax 1999

Respiratory muscle function during exercise
• Diaphragm of patients with COPD adapts to chronic overload and
has greater resistance to fatigue
At identical absolute lung volumes, inspiratory muscles can
generate more pressure

• Problem: mechanical disadvantage due to static and dynamic

hyperinflation

Functional inspiratory muscle strength and endurance goes

down

Contributes to hypercapnia, dyspnea, nocturnal oxygen

desaturation and reduced exercise performance
 PImax in COPD patients VS. healthy subjects
200
PImax (% predicted)
150

100

50

0
0 20 40 60 80 100

FEV1 (%predicted)

Revalis database, UZ Leuven

Capacity of respiratory muscles is frequently reduced in patients
Slide courtesy of Troosters T.with

chronic cardiorespiratory disease

 Development of respiratory muscle fatigue

1.0

0.8
Critical zone

FATIGUE
0.6
COPD
TI/TTOT (during
exercise)
0.4 
 NORMAL

0.2
NO FATIGUE

0.2 0.4 0.6 0.8 1.0

PI/PImax

Adapted from: Bellemare F and Grassino A, J. Appl. Physiol. 1982

 Acute disturbances in load-capacity balance of the
respiratory muscles are related to breathlessness

Caroline J. Jolley; John Moxham; Am J Respir Crit Care Med 2016.

 Effect of respiratory muscle work on exercise
performance: mechanisms

Dempsey et al, Respir Physiol Neurobiol, 2002