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ERS Annual Congress Milan
09–13 September 2017
Postgraduate Course
PG18 Targeting the locomotor and respiratory
muscles in chronic obstructive pulmonary disease:
novel interventional tools and rehabilitation
strategies
Saturday, 9 September 2017

14:00-17:30
Space 1 + 2 (South) MICO
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Postgraduate Course : PG18
Targeting the locomotor and respiratory muscles in chronic obstructive
pulmonary disease: novel interventional tools and rehabilitation
strategies
Aims : To update on the benefits of exercise training and other multimodal therapeutic strategies that
aim to combat skeletal muscle wasting in COPD patients; to instruct on the currently available non-
pharmacological therapeutic strategies that optimise the benefits of lower limb and respiratory muscle
training and nutritional support when they are selectively applied to COPD patients with specific
phenotypes; to learn about new advances in the diagnosis of COPD locomotor and respiratory muscle
dysfunction; to familiarise participants with novel devices available that are used to mitigate dynamic
lung hyperinflation and dyspnoea sensations during rehabilitation exercise training.
Tracks: Exercise, rehabilitation and physiology

Tags: Basic translational science
Target audience: Allied health professional - Clinician - Educationalist - Engineer - Fellow - General
practitioner - Junior member - Lung function technician - Nurse - Patient - Physiologist - Physiotherapist
- Pulmonologist - Researcher - Resident - Respiratory physician - Respiratory therapist - Scientist -
Student - Trainee
Chairs : Alda Sofia Pires De Dias Marques (Aveiro, Portugal), Esther Barreiro Portela (BARCELONA,
Spain)
14:00 Muscular and functional effects of partitioning exercising muscle mass in COPD
Andre Nyberg (Umeå, Sweden)
14:30 The relevance of respiratory muscle dysfunction and novel treatment options in
COPD
Daniel Langer (Leuven, Belgium)
15:00 Group assignment
15:30 Break
16:00 Targeted pulmonary rehabilitation and nutritional support in patients with COPD:
do phenotypic differences matter?
Frits M.E. Franssen (Horn, Netherlands)
16:30 Novel diagnostic tools and interventions for COPD locomotor and respiratory
muscle dysfunction
Ioannis Vogiatzis (ATHENS, Greece)
17:00 Group assignment

ERS monograph
Controversies in COPD
Edited by Antonio Anzueto, Yvonne Heijdra and John R. Hurst
ISBN 978-1-84984-063-7
“…contains a vast amount of information on the disease, its prevalence, signs and symptoms,
diagnostic tests and treatment options. The book’s format makes it quick and simple to find out what
you need to know, and its size would make it easy to take to work for use in practice […] invaluable
for anyone working with patients with the disease.”
Emma Vincent, Nursing Standard
To buy printed copies, visit the ERS Bookshop in the World Village at the ERS International
Congress 2017 or go to ersbookshop.com
If you’re an ERS member, you automatically have full online access to the ERS Monographs.
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authors.
 2017 by the authors

MUSCULAR AND FUNCTIONAL EFFECTS OF
PARTITIONING EXERCISING MUSCLE MASS IN COPD
PG18:Targeting the locomotor and respiratory muscles in chronic

obstructive pulmonary disease: novel interventional tools and
rehabilitation strategies
André Nyberg, RPT, PhD

MSc Sport Medicine, MSc Physiotherapy, Bsc Sport Science
Department of Community Medicine and Rehabilitation, Physiotherapy
Umeå University, SE-90187 Umeå, Sweden
Conflict of interest disclosure
 I have no real or perceived conflicts of interest that relate to this presentation.
 I have the following real or perceived conflicts of interest that relate to this presentation:
Affiliation / Financial interest Commercial Company

Grants/research support:
Honoraria or consultation fees:
Participation in a company sponsored bureau:
Stock shareholder:
Spouse / partner:
Other support / potential conflict of interest:
This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest. The intent of this disclosure
is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products
or services relevant to the talk) from making a presentation, but rather to provide listeners with information on which they can make their own judgments. It remains
for audience members to determine whether the speaker’s interests, or relationships may influence the presentation. The ERS does not view the existence of these
interests or commitments as necessarily implying bias or decreasing the value of the speaker’s presentation. Drug or device advertisement is forbidden.
Introduction
AIMS
Partitioning exercising muscle mass in COPD

• What?
• Why?
• When?
• Who?
Principles of exercise training
• Effect of exercise training = intensity * duration

– Aerobic exercises
– Resistance exercises
• The principle of specificity

– Exercise training adaptations are “specific” to the stimulus applied.
ACSM 2009, MSSE.

Exercise intolerance in COPD
• Exercise limitation in COPD
– Ventilatory limitation
– Gas exchange limitation
– Cardiac limitation
– Limb muscle dysfunction
– Respiratory muscle dysfunction
Spruit 2013, AJRCCM, O'Donnell 2001, MSSE, Maltais 2014, AJRCCM


How can we reduce the impact of exercise limiting factors

in COPD, thus improving the benefits of exercise training?

“By reducing the amount of active muscle mass during an exercise, the
demand on the cardiorespiratory system will decrease, thus resulting in a
shift from a central to a peripheral limb muscle limitation to exercise”
Richardsson, 1999 AJRCCM; Richardsson 2004, AJRCCM;

• Exercise modalities
– Aerobic exercises
• continuous, interval,
• effects and feasibility
– Resistance exercises
• resistance training (limb muscle strength/endurance),
• effects and feasibility
Richardsson, 1999 AJRCCM; Richardsson 2004, AJRCCM; Bjorgen 2009, Eur J Appl Physiol; Brostad 2012, Eur Respir J; Dolmage 2006, Chest, Dolmge
2008, Chest; Nyberg 2014, Novel Physiotherapies; Nyberg 2014, Clin Respir J; Evans 2015, Ann Am Thorac Soc; Nyberg 2016, MSSE.
Dolmage 2006, Chest

Two-legged
Dolmage 2006, Chest

One-leg
Dolmage 2006, Chest

Dolmage 2008, Evans 2015

• 30 min continuous cycling (15min/leg) at the highest tolerable power
Bjorgen 2009
• 4 x 4 min interval cycling at 85-95% of peak heart rate with 3 min
rest periods between exercise intervals
Bjorgen 2009, Eur J Appl Physiol; Dolmge 2008, Chest; Evans 2015, Ann Am Thorac Soc;
25
20
Workload - Watts
15
10
0
TL SL diff
Dolmage 2008, Chest; Bjorgen 2009, Eur J Appl Physiol

25
20
Workload - Watts
15
10
0
TL SL diff


Additional improvements from partitioning exercising muscle

mass during aerobic exercises
6MWD + 72 meters
Self-paced walk time, min + 23 min
CRQ dyspnea + 1.6 units Larger than the
MCID and than
CRQ fatigue + 1.9 units
effects of PR
CRQ emotional function + 1.4 units
CRQ mastery + 1.6 units
Evans 2015 Ann Am Thor Soc

Feasibility
• Compliance 69 to 89% across studies
• Use fixed wheel system, if not available the cycle ergometer may
require removal of the free-wheel sprocket mechanism by the
manufacturer (or use a counterweight).
• All physiotherapists considered one-legged cycling safe and easy
• Continue to describe it “some of the time”, excluding patients with

orthopedic conditions or poor balance.
Evans 2015 Ann Am Thor Soc; Dolmage 2008, Chest; Bjorgen 2009, Eur J Appl Physiol
Increasing the effects of partitioning exercise in COPD
• Breathing supplemental oxygen or inspiring a helium-hyperoxia

mixture does not increase exercise endurance
Dolmage 2014, JCRP, Bjorgen Int J Sports Med 2009.

Resistance training (low-load/high-repetition)

• 2-3 sets, > 20-30 repetitions, lower and upper limb exercises
Nyberg 2014, Novel Physiotherapies; Nyberg 2014, Clin Respir J; Nyberg 2016, MSSE.
Exercise workloads
• Rowing + 17%
• Elbow flexion + 19%
• Chest press + 14%
• Shoulder flexion + 33%
• Leg curl + 23%
• Leg extension + 24%
Mean + 22%
Nyberg 2016, MSSE.

Exercise workloads
• Rowing + 17%
• Leg curl + 23%
Mean + 22%
Nyberg 2016, MSSE.

Exercise workloads
• Rowing + 17%
• Leg curl + 23%
Mean + 22%
Exercise workloads
• Rowing + 17%
• Leg curl + 23%
• Leg extension + 24% > 15% difference in
Mean + 22% pre-post Qtw pot
More patients considered ”fatiguers”

after SL than TL: 83% vs 50%
Exercise workloads
• Rowing + 17%
• Leg curl + 23%
• Leg extension + 24% > 15% difference in
Mean + 22% pre-post Qtw pot
Larger effects in people who develop

contractile fatigue
Nyberg 2016, MSSE, Burtin 2012, ERJ
Exercise workloads
• Rowing + 17%
What about exercise
induced symptoms?
• Leg curl + 23%
Mean + 22%
Exercise workloads
• Rowing + 17%
What about exercise
induced symptoms?
• Leg curl + 23%
Mean + 22%
Exercise workloads
• Rowing + 17%
No difference in dyspnea ratings
during SL compared to TL despite
larger exercise workloads
• no difference in dyspnea
• no difference in dyspnea
Mean + 22%
Exercise workloads
• Rowing + 17%
• Leg curl + 23%
Mean + 22%
Exercise workloads
• Dyspnea lower during SL
Dyspnea ratings
0.5 to 0.8 points lower
during SL than TL
• Leg curl + 23%
Dyspnea lower during SL
Additional improvements from partitioning exercising muscle

mass during resistance exercises
6MWD + 34 meters
6 minute pegboard and ring test + 10%
Unsupported upper limb exercise test + 18%
Shoulder flexion endurance + 15%
Knee extension endurance + 11%
No effect on endurance cycling capacity or quality of life.
Nyberg 2015, Clin Respir J

Feasibility
• 94% attendance rate, mean exercise intensity: 79% of predicted
maximum intensity
• Compliance to exercise protocol

• 96% among people with COPD
• 100% among physiotherapists
• Adverse events
• Reported in 3.6% of attended exercise sessions, all minor.
• More time consuming

• Takes twice the time than bilateral resistance training
Nyberg 2014, Novel Physiotherapies
Cardiorespiratory requirements during low/load high-repetition
knee extension compared to CPET
Outcome Single-limb Two-limb
%VO2 achieved 58% 68%
%HR achieved 89% 97% †
%VE achieved 73% 88% †
VE/MVV ratio* 77% 93% †
*VE/MVV ratio > 80% indicates a ventilatory limitation
† p < 0.05
3 sets until failure at about 50-55% of 1 RM
Nyberg 2017 (unpublished)

%HR achieved 89% 97% †
%VE achieved 73% 88% †
† p < 0.05

%HR achieved 89% 97% † Lower peak cardiorespiratory
demands despite larger (22%)
%VE achieved 73% 88% † exercise workloads
† p < 0.05

%HR achieved 89% 97% † Lower peak cardiorespiratory
demands despite larger (22%)
%VE achieved 73% 88% † exercise workloads
† p < 0.05

Cardiorespiratory requirements during high-load/low repetition
Outcome Single-limb Two-limb Single-limb Two-limb
%VO2 achieved 58% 68% 40% 39%
%HR achieved 89% 97% † 81% 86%
%VE achieved 73% 88% † 65% 60%
VE/MVV ratio* 77% 93% † - -
† p < 0.05
1 set, 10 repetitions at 80% of 1 RM

Robles 2017, Respirology
Cardiorespiratory requirements during high-load/low repetition
Outcome Single-limb Two-limb Single-limb Two-limb
%VO2 achieved 58% 68% 40% 39%
%HR achieved 89% 97% † 81% 86%
%VE achieved 73% 88% † 65% 60%
VE/MVV ratio* 77% 93% † - -
† p < 0.05
3 sets until failure at about 50-55% of 1 RM 1 set, 10 repetitions at 80% of 1 RM

Nyberg 2017 (unpublished), Robles 2017, Respirology
Bronstad 2012, ERJ

Work performance
Peak work (watts) + 37%
Femoral blood flow at peak work + 24%
Muscle VO2 at peak work + 24%
Pulmonary VO2 at isotime -26%

VE at isotime -20%
Restores work performance and oxidatative capacity of the

quadriceps muscle in COPD
Bronstad 2012, ERJ

For whom?
- Studies have mainly been performed in patients with more severe airway obstruction
(GOLD III-IV)
- Studies have included close to a similar amount of men/women (53/47%)

- Lack of studies separating effects based on sex
Evans 2015 Ann Am Thor Soc; Nyberg 2016, MSSE; Dolmage 2008, Chest, Brostad 2012, ERJ, Bjorgen 2009, Eur Appl Physiol, Nyberg 2014, Clin Resp J.
Conclusions
• One-legged cycling can increase exercise workloads, exercise capacity and quality of
life more than traditional bilateral cycling.
• Single limb execution of high-repetitive resistance exercises can increase exercise

workloads, decreases exercise induced dyspnea and increase quadriceps muscle
fatigue in comparison to bilateral resistance exercises
• Partitioning exercises are feasible in patients with COPD and seem to be sutiable for
implementation in pulmonary rehabilitation.
Inspiratory Muscle Training in COPD
DANIEL LANGER PT, PhD

LEUVEN, BELGIUM
 I have no real or perceived conflicts of interest that relate to this
presentation.
 I have the following real or perceived conflicts of interest that relate to this
presentation:
Honoraria or consultation fees:
Participation in a company
sponsored bureau:
Stock shareholder:
Spouse / partner:
Other support / potential conflict of

interest:
This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest. The intent of
this disclosure is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers
of any commercial products or services relevant to the talk) from making a presentation, but rather to provide listeners with information on which they
can make their own judgments. It remains for audience members to determine whether the speaker’s interests, or relationships may influence the
presentation. The ERS does not view the existence of these interests or commitments as necessarily implying bias or decreasing the value of the
speaker’s presentation. Drug or device advertisement is forbidden.
Content
● Physiological Principles
● Evidence IMT
● Modalities IMT
● Recent Developments
Exercise limitation in Cardiorespiratory Disease
LUNGS and AIRWAYS
MOTIVATION
CARDIOCIRCULATORY
RESPIRATORY MUSCLES
PERIPHERAL MUSCLES
Killian KJ, et al. Clin Chest Med 1988

Hamilton N, et al. Am J Respir Crit Care Med 1995
Gosselink R, et al. Am J Respir Crit Care Med 1996 Adapted from Gosselink R
Published in: Caroline J. Jolley; John Moxham; Am J Respir Crit Care Med 2016: 193, 236-238.
Guidelines of the Spanish Society of Pneumology and Thoracic Surgery
(SEPAR)for the Evaluation and Treatment of Muscle Dysfunction in Patients
With Chronic Obstructive Pulmonary Disease
Barreiro E., Gea J., Puente-Maestu, Roca, et al. Arch Bronconeumol 2015;51:384-95
Respiratory Muscle Weakness in COPD
200
(% pred)
100
PI MAX
0
Normals COPD
Dysfunction or Adaptation?
150 Normal
Emphysema
PdiMax (cmH 2O)
100 FRC FRC

RV
RV
50
TLC
TLC
0
25 50 75 100 125 150

Lung volume (% pred. TLC)
Bellemare F, et al. Chest 2002;121:1898-1910
HEALTHY
COPD
Levine S et al. J Appl Physiol 2002;92:1205-1213

Expiratory flow limitation
Flow
6
-2
-4
-6 0 1 2 3 4
Volume
Modified from O’Donnell DE. AJRCCM 2006;3:180-184
Slide adapted from Troosters T.
Campbell Diagram
Inspiratory WOB
Loring et al. J Appl Physiol 107: 309-314. 2009

Pressure-volume relationship
Expiratory flow limitation
Flow
6
PIF -2
(faster contraction)
-4
-6 0 1 2 3 4
Volume
Modified from O’Donnell DE. AJRCCM 2006;3:180-184
Slide adapted from Troosters T.
Pressure-flow relationship
Inspiratory muscle weakness and exertional dyspnea
10
Borg Dyspnea (0-10)
8 1 = Pi,max < 40 cm H 2 O
2 = Pi,max 40-80 cm H 2 O
6
3 = Pi,max > 80 cm H 2 O
4
FEV1 >80% pred
2 FEV1 40-80% pred
FEV1 <40% pred
0
1
2
3
1
2
3
1
2
3
50 % PREDICTED EXERCISE CAPACITY
Killian KJ and Jones NL. Respiratory Muscles and Dyspnea. Clinics

• Improvement in inspiratory muscle1988;9(2):237-47.
in Chest Medicine. strength (PImax ↑) should
reduce perceived effort (PI/PImax) and dyspnea during exercise.
Killian KJ, et al. Clin Chest Med 1988
Content
● Evidence IMT
● Modalities IMT
 Studies had to satisfy the following criteria to be
included for further analysis:
 1) true experimentation (i.e. randomised or quasi-
randomised controlled trial);
 2) Diagnosis COPD confirmed with pulmonary
function tests;
 3) IMT at an intensity of ≥30%PI,max or respiratory
muscle endurance training in a controlled manner
Meta-analysis (Intervention n=430, Control n=409)
Outcome measures Natural units P-value

PImax +13 cmH2O 0.001
What
6MWD
about effects of IMT as add-on
+32 m
therapy
0.001
to general
Dyspnea-Borg CR-10 exercise
-0.9 training?
0.001
CRQ-Dyspnea +1.1 0.068
Gosselink et al., ERJ 2011

General exercise
training (GET)
Resistance exercises
Arm Ergometry
Treadmill walking Cycling exercise
Stair climbing / Step
Spruit MA, et al. Am J Respir Crit Care Med 2013

Targets of Exercise Training as Part of a Pulmonary Rehabilitation
Program for Patients with COPD
Casaburi R, ZuWallack R. N Engl J Med 2009;360:1329-1335.

Introduction Chapter 2 Chapter 3 Chapter 4.1 Chapter 4.2 Conclusion
Meta-analysis (treatment n=277, control n=242)
1.2 100
Δ CRDQ (points)
Δ 6 MWD (m)
1.0
75
0.8
0.6 50
0.4
25
0.2
0.0 0
DYS FAT EMO MAS 6MWD
Lacasse Y, et al. Cochrane Database Syst Rev, 2002

McCarthy B, et al. Cochrane Database Syst Rev, 2015
Effects of IMT added to a general exercise training program:
Inspiratory muscle strength

Effects of IMT added to a general exercise training program:
Functional exercise capacity

Content
● Evidence IMT
● Modalities IMT
● Voluntary isocapnic hyperpnea
● Inspiratory flow resistive loading (IFRL)
● Mechanical threshold loading (MTL)
● Tapered flow resistive loading (TFRL)
Voluntary Isocapnic Hyperpnea
● Endurance Training (30 min/day)

● Deep and fast breathing (% MVV)
● Rebreathing prevents hypocapnia
● High Flow (velocity) / Low Pressure (tension)
Voluntary isocapnic hyperpnea
+ Home training possible

 Spirotiger
- Technically difficult
- Comfort in COPD
- No improvement pressure generating
capacity, only velocity of contraction
- 1400€
Inspiratory Flow Resistive Loading
● Diameter  = resistance 
+ Improvement strength and
velocity
+ Hometraining possible
● Respifit-S
- Resistance flow-dependent
- 1000 €
Mechanical Threshold Loading
● Known resistance
+ Resistance flow-independent
+ Improvement strength and velocity
+ Short high intensity protocols effective 1,2
+ 30-40€
● Threshold IMT
- Supervision necessary
1 Hill K, et al., ERJ 2006; 27: 1119-28
2 Sturdy G, et al., Chest 2003; 123: 142-50
Tapered Flow Resistive Loading
● Known resistance
+ Resistance flow-independent
+ Improves strength and velocity
+ Less supervision needed
● PowerBreathe K-series
● 600€
Mechanical threshold loading device Tapered flow resistive loading device
(MTL) (TFRL)
Work = Pressure x Volume

Work (cmH 2 O*L)
60 Pressure 4 60 4
Work (cmH 2 O*L)
Volume Pressure
50 60%PImax 50
Pressure (cmH2O)
Pressure (cmH 2 O)
3 3
 Constant threshold loading  Dynamically adjusted flow resistive loading Volume
Volume (L)
Volume (L)
40 40
30 2 30 2
20 20
1 1
10 10
AUC = 88
AUC = 58
0 0 0 0
0 25 50 75 100 125 150 175 0 25 50 75 100 125 150 175
Time (1/100 sec) Time (1/100 sec)
Pressure and lung volume
100 TLC
80
Lung volume ( % TLC )
60
FRC
40
Pmus
20 RV
Pmus PRS
PImax
-100 -50 0 50 100
Pressure ( cm H2O )
J. T. Sharp et al. Clin Chest Med 1983, 4: 421- 432.

Vergelijking Apparatuur
Content
● Evidence IMT
● Modalities IMT
● Voluntary isocapnic hyperpnea
● Inspiratory flow resistive loading (IFRL)
● Mechanical threshold loading (MTL)
● Tapered flow resistive loading (TFRL)
Novel method for IMT
Background
● Most IMT interventions in patients with COPD have been
implemented as supervised daily training for 30 minutes
with controlled training loads using mechanical
threshold loading (MTL) devices.
Aims of the study

● To assess the efficacy of a short and largely home-based
IMT program
● To find out whether performing and monitoring this
program with a TFRL device would enable patients to
reach higher training intensities and achieve larger
improvements in inspiratory muscle function than after
training with a MTL device
Evidence Athletes
2
Comparison MTL- vs. TFRL-IMT
MTL-IMT (n=10)
Stable COPD patients 8 week

Baseline
(PImax 50-100% of pred value) RANDOM
assessment
assessment
(n=20)
TFRL-IMT (n=10)
Both groups:
● Followed the pulmonary rehabilitation program 3 times/week

● Performed daily sessions of IMT at equal duration
Training
- 2 sessions/week with supervision (14%)

- 8 weeks 2*30 breaths/day (~8 minutes/day)
***Short program with minimal supervision***
- Intermediate PImax measurement (once weekly)

- Modified Borg CR10 Scale (4-6/10)
***Highest tolerable resistance (aim: ≥ 50% PImax)***

Results: Progression of training load
Borg: 3.0±1.6
TFRL
MTL
Borg: 3.6±1.1
* = p<0.05
Two-Way ANOVA analysis with Bonferroni corections
Results: Inspiratory muscle function
TFRL MTL p-value

(n=10) (n=9)
∆ PImax (cmH2O) +31 ± 4 * +18 ± 6 * 0.02#
* indicates a statistically significant increase within groups (p<0.05). ANCOVA

# indicates a statistically significant difference between groups (p<0.05)
Effects of this IMT protocol in comparison with
previous protocols
Hill K, et al., ERJ 2006; 27: 1119-28

Sturdy G, et al., Chest 2003; 123: 142-50
(MTL-IMT: short, fully supervised)
(MTL-IMT: short, less supervision )
(TFRL-IMT: short, less supervision)

Results: Inspiratory muscle function
TFRL-IMT (n=10) MTL-IMT (n=9) p-value

∆ PImax (cmH2O) +31 ± 4 * +18 ± 6 * 0.02#
∆ Duration (sec) +532 ± 204* +187 ± 233* 0.02#
∆ Avg. Peak Vt/Ti (L/sec) +1.4 ± 0.6* +0.1 ± 0.3 0.001#
∆ Avg. Mean power per breath (Watt) +2.3 ± 1.0* +0.5 ± 1.2 0.004#
∆ Avg. Inspiratory time; Ti (sec) -1.1 ± 0.8* +0.2 ± 0.3 0.02#
∆ Ti/Ttot; duty cycle (%) -16 ± 6* -5 ± 5* 0.02#
Breathing pattern changes during exercise ?
* indicates a statistically significant increase within groups (p<0.05).

Results
Baseline Characteristics
Variables IMT Group (n=25) Control Group (n=25)
Age (years) 66±6 66±7

BMI (kg/m2) 26±6 24±6
FEV1
50%pred FEV1 (%pred) 51±17 48±21
PImax (cmH2O) 65±13 65±13
PImax
65%pred
PImax (%pred) 65±12 65±15
Peak work rate (%pred) 50±24 55±21
6MWD
65%pred 6MWD (% pred) 65±19 66±22
Results
Changes in inspiratory muscle function, exercise capacity and dyspnea
Variables IMT Group (n=25) Control Group (n=25) p-value

∆ PImax (cmH2O) +29±15# +1±12 < 0.001
∆ PImax (%pred) +30±18# +1±12 0.000
∆ Peak work rate (Watts) +13±14# +2±12 0.004
∆ Peak VE (L/min) +3±6# -2±7 0.013
∆ Dyspneoa score after cycle test +0.0±2.4 -0.0±1.5 0.201
Results: Breathing pattern

Published in: Caroline J. Jolley; John Moxham; Am J Respir Crit Care Med 2016: 193, 236-238.
Endurance Cycling Task
Flow Measurements:
• Operating lung volumes
6
• Ventilation
• Breathing pattern
4 • Gas exchange
1 minute
2 Every (2) minute(s)
-2
-4
-6 0 1 2 3 4
Volume
Methods
Raw EMGdi
Pes
Pdi EMGdi
Pga
Pes = Esophageal Pressure

Pga = Gastric Pressure
Pdi = Transdiaphragmatic Pressure Luo, Y.M. et al. Clin Sci 2008;115(8):233-44
EMGdi = Diaphragmatic Electromyogram
30 30 *
***
Pes,tid
Pes,ti
20 20
Effects
10 of IMT on neural drive
10
0
to diaphragm Baseline
0 8weeks
st '2 '4 t'6 '8 0 2 4 6 st '2 '4 ' 6 ar t ' 8 0 2

'1 8w 4 6
Re a r 8w '1 '1 '1 '1 Re St '1 '1 '1
t lt im
tli
mSham
S lim
t Intervention
tli
m
0.8 0.8 Baseline
EMGdi / EMGdi,max
0.7
EMGdi / EMGdi,max
0.7 8weeks
0.6 0.6
*
0.5 0.5
**
0.4 0.4
*
0.3 0.3
0.2 Baseline 0.2
0.1 8weeks 0.1
'2 '4 '6 '8 0 2 4 6 '2 '4 '6 art '8 0 '1
2 4 6
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Daniel Langer et al. Eur Respir J 2014;44:1912

Effects of IMT on dyspnea in COPD
Sham Intervention
10 10 Baseline
9 9
Borg Dyspnea (0-10)

Borg Dyspnea (0-10)
8 8 8weeks
7 7
6 6
5 5
4 4
3 3
2 2 * *
1 Baseline 1
0 8weeks 0
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Daniel Langer et al. Eur Respir J 2014;44:1912
A multicentre, randomised, double-blind,
controlled trial of adjunctive inspiratory muscle
training for patients with chronic obstructive
pulmonary disease (IMTCO)
Charususin N, Gosselink R, Decramer M, Demeyer H, McConnell A,

Saey D, Maltais F, Derom E, Vermeersch S, Helvoort H, Heijdra Y,
Garms L, Schneeberger T, Kenn K, Gloeckl R, Langer D
Manuscript in preparation
Baseline and 12 week measurements
Primary outcome : 6 minutes walking distance
Secondary outcomes : Inspiratory muscle function,
maximal and endurance exercise capacity,
Chronic Respiratory Disease Questionnaire (CRDQ)
IMTCO Investigators
Study Design
Intervention group
(≥50%PImax)
Stable COPD patients 12 week
Baseline
(PImax < 60 cmH2O or RANDOM assessment
assessment
< 50% of pred value)
Control group
(10%PImax)
Both groups:
● Followed general exercise training program 3 times/week

● Performed daily sessions of IMT at equal duration
COPD patients in pulmonary
rehabilitation program assessed for
Enrollment
eligibility in five centers (n=998)
- 2/2012 – 9/2016 (Leuven)
- 2/2012 – 9/2016 (Gent)
- 4/2013 – 6/2016 (Quebec) Excluded (n=790)
- 11/2012 – 9/2016 (Nijmegen)  Not meeting inclusion criteria
- 4/2013 – 10/2016 (Germany) - PImax > 60 cmH2O (n=580)
 Exclusion criteria (n=119)
- Cognitive or psychiatric problems (n=39)
21% - Musculoskeletal problem (n=57)
- Previous rehabilitation program inclusion <1yr (n=23)
 Other reasons (n=40)
 Declined to participate (n=51)
Randomized (n=208)
Allocation
Allocated to intervention group (n=105) Allocated to control group (n=103)
Follow-Up
Lost to follow-up Lost to follow-up
(dropout from rehabilitation program) (n=16) (dropout from rehabilitation program) (n=18)
Discontinued intervention Discontinued intervention
(lack of motivation to continue IMT) (n=4) (lack of motivation to continue IMT) (n=5)
Analysis
Analysed (n=89): Analysed (n=85):
Excluded from analysis (no post-training Excluded from analysis (no post-training evaluation
evaluation data) (n=16) data) (n=18)
Baseline and 12 week measurements
Primary outcome : 6 minutes walking distance
Secondary outcomes : Inspiratory muscle function,
maximal and endurance exercise capacity,
Chronic Respiratory Disease Questionnaire (CRDQ)
IMTCO Investigators
Baseline characteristics
Intervention (n=105) Control (n=103)

FEV1
~ 41%pred
FEV1 (%pred) 40 ± 15 43 ± 17
FRC (%pred) 181 ± 48 180 ± 45
PImax (cmH2O) 52 ± 14 52 ± 12
PImax
~ 51%pred PImax (%pred) 51 ± 15 52 ± 15
Peak work rate (%pred) 45 ± 25 45 ± 23
6MWD (%pred) 56 ± 20 57 ± 18
IMT
training progression
Intervention group
Avg compliance (%) 79 ± 4
Avg inspiratory effort score 3.5 ± 0.3
Control group
Avg compliances (%) 81 ± 4
Avg inspiratory effort score 2.6 ± 0.3
Total work performed progression
Available data
Intervention group: 85 %
Control group: 83 %
Results: inspiratory muscle function
Variables Intervention (n=89) Control (n=80) p-value

∆ PImax (cmH2O) +22±14* +9±10* ˂0.001#
∆ Endurance breathing time (sec) +353±260* +162±221* ˂0.001#
* indicates a statistically significant difference within groups (p<0.05).

General exercise training progression
Results: exercise capacity
Variables Intervention (n=89) Control (n=80) p-value

∆ 6MWD (m) +35±44* +33±46* 0.967
∆ Constant work rate cycling time (sec) +225±252* +163±199* 0.048#
∆ Dyspnoea scores at iso time -2.4±2.6* -1.5±1.7* 0.049#
∆ Leg effort scores at iso time -1.9±2.5* -0.4±1.7 0.052#
∆ Peak work rate (W) +10±15* +5±12* 0.069
∆ CRQ_dyspnea +4.4±5.4* +4.1±4.4* 0.601
* indicates a statistically significant difference within groups (p<0.05).

Conclusions
 IMT can improve respiratory muscle function,
symptoms of dyspnea and exercise capacity in patients
with COPD
 Threshold loading most used form of IMT
 Resistive loading (IFRL of TFRL) interesting alternatives
 Training regimens used in athletes (short duration/

high intensity) are effective and seem to be suitable
for implementation in pulmonary rehab
THANK YOU FOR YOUR ATTENTION!
QUESTIONS?
Targeted pulmonary rehabilitation and
nutritional support in patients with COPD:
do phenotypic differences matter?
Frits M.E. Franssen, MD, PhD

The Netherlands
I have no, real or perceived, conflicts of interest that

relate to this presentation
This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest.
The intent of this disclosure is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with
manufacturers or providers of any commercial products or services relevant to the talk) from making a presentation, but rather to provide listeners
with information on which they can make their own judgments. It remains for audience members to determine whether the speaker’s interests, or
relationships may influence the presentation. The ERS does not view the existence of these interests or commitments as necessarily implying bias
or decreasing the value of the speaker’s presentation.
Drug or device advertisement is forbidden.
Agenda:
1) Rationale for a targeted approach in pulmonary rehabilitation
2) Respiratory and systemic targets
3) Targeted approach for phenotypes based on body composition
4) Towards precision rehabilitation
5) Summary and discussion

Definition
‘Pulmonary rehabilitation is a comprehensive intervention based on a thorough
patient assessment followed by patient tailored therapies that include, but are not
limited to, exercise training, education, and behavior change, designed to improve
the physical and psychological condition of people with chronic respiratory disease
and to promote the long-term adherence to health-enhancing behavior’
Spruit et al., Am J Respir Crit Care Med 2013

Updated meta-analysis: ‘Pulmonary rehabilitation for COPD’
Aim: to compare the effects of pulmonary rehabilitation versus usual care on health-
related quality of life and functional and maximal exercise capacity in patients
with COPD
65 randomized controlled trials; 3822 participants (FEV1 39%, age 62y)
‘Pulmonary rehabilitation’
* Exercise training > 4 weeks
* +/- Education
* +/- Psychological support
‘Usual care’
* Conventional care
* No education
* No additional interventions
McCarthy et al., Cochrane Database Syst Rev. 2015

Updated meta-analysis: ‘Pulmonary rehabilitation for COPD’
Pulmonary rehabilitation results in statistically significant improvements in:
 Dyspnoea, fatigue, emotional function and mastery score of CRQ

(MD > +0.5)
 Symptoms, activity, impact and total score of SGRQ

(MD -6.89)
 Maximal exercise capacity, indicated by Wmax

(MD +6.77 W)
 Six-minute walk distance

(MD +44 m)
McCarthy et al., Cochrane Database Syst Rev. 2015

Differential response to pulmonary rehabilitation in COPD
2068 COPD patients,

classified as:
Very good responsers
Good responsers
Moderate responsers
Poor responsers
Need for a more targeted approach
Spruit et al., Eur Respir J 2015

Treatable traits that may require a targeted approach during PR
Respiratory traits Targeted treatments
✤ Airflow limitation ✤ Individualized pharmacotherapy

✤ Emphysema ✤ Lung volume reduction therapies
✤ Hyperinflation ✤ (High-flow) oxygen therapy
✤ Exacerbations ✤ Noninvasive ventilatory support
✤ Dyspnea ✤ Lung transplantation
✤ Chronic bronchitis
✤ Hypoxemia
✤ Hypercapnia
✤ Bacterial colonisation
✤ Bronchiectasis
Adapted from: Agusti et al., Eur Respir J 2016

Treatable traits that may require a targeted approach during PR
Systemic traits Targeted treatments
✤ Smoking ✤ Lifestyle intervention

✤ Cachexia ✤ Nutritional supplements
✤ Obesity ✤ Anabolic agents
✤ Deconditioning ✤ Diet & meal replacements
✤ Muscle weakness ✤ Exercise training
✤ Depression ✤ NMES
✤ Anxiety ✤ Psychological support
✤ Coping ✤ Education
✤ Compliance ✤ Social environment
✤ Comorbidities ✤ Specific comorbidity treatment
Adapted from: Agusti et al., Eur Respir J 2016

Clustering of comorbidities in COPD patients
Obesity Atherosclerosis Hypertension
Diabetes
Metabolic Cardiovascular
Dyslipidemia
Underweight
Less
comorbidity Low FFM
Cachectic
Osteoporosis
Psychological Renal dysfunction
Anxiety Depression
Myocardial infarction
Vanfleteren et al., Am J Respir Crit Care Med 2013

The impact of comorbidity clusters on outcomes of PR in COPD
Comorbidity clusters do not affect the outcomes of pulmonary rehabilitation
6MWD SGRQ
But… they need a targeted approach!
Mesquita, Vanfleteren et al., Eur Respir J 2015

COPD is a heterogenous and multi-component disease
Emphysema Atherosclerosis
Underweight Overweight
Osteoporosis
Low muscle
mass Bronchial
wall
thickening
Fibre type
shift I > II Low fat mass
High fat mass
Cachectic phenotype Metabolic phenotype
ERS Taskforce ‘Nutrition in COPD’, Eur Respir J 2014

Impact of abnormal body weight and composition in COPD
Low body weight/muscle mass High fat mass
Decreased muscle strength Increased dyspnea
Reduced exercise performance Reduced functional capacity
Reduced health status Reduced health status
Poor prognosis Poor prognosis (mild/moderate disease)
Cachexia Precachexia Sarcopenia Sarcopenic obesity Obesity
Schols et al., Eur Respir J 2014; Lambert et al., CHEST 2017

Nutritional risk stratification in COPD
Schols et al., Eur Respir J 2014

The impact of static hyperinflation and outcomes of PR
RV RV RV RV RV
N=1981 100 - 149.9% 150 - 199.9% 200 - 249.9% 250 - 299.9% 300 - 349.9% p
N=691 N=685 N=332 N=85 N=20
Age, years 68 ± 9 66 ± 9 64 ± 8 62 ± 7 60 ± 9 < 0.01

Female, n (%) 292 (42%) 323 (47%) 178 (54%) 54 (64%) 10 (50%) < 0.01
BMI, kg/m2 27 ± 5 25 ± 5 23 ± 4 21 ± 3 22 ± 6 < 0.01
FFMI, kg/m2 17 ± 2 16 ± 2 16 ± 2 15 ± 1 15 ± 2 < 0.01
FEV1, % predicted 61 ± 7 46 ± 14 34 ± 10 26 ± 8 24 ± 11 < 0.01
FEV1/FVC 0.5 ± 0.1 0.4 ± 0.1 0.3 ± 0.1 0.3 ± 0.1 0.3 ± 0.1 < 0.01
FRC, % predicted 123 ± 17 155 ± 16 185 ± 15 214 ± 13 233 ± 20 < 0.01
RV, % predicted 127 ± 13 173 ± 14 219 ± 13 269 ± 14 316 ± 12 < 0.01
TLC, % predicted 107 ± 13 121 ± 11 124 ± 10 143 ± 10 149 ± 18 < 0.01
DLCO SB, % predicted 58 ± 20 51 ± 17 46 ± 16 39 ± 12 34 ± 11 < 0.01
LTOT, n (%) 80 (13%) 119 (19%) 103 (33%) 33 (41%) 11 (55%) < 0.01
274 232 206 165 154
CWRT, s < 0.01
(198; 387) (176; 342) (158; 276) (122; 248) (107; 184)
475 450 417 335 246
6MWD, m < 0.01
(395; 541) (365; 518) (337; 485) (245; 433) (197; 396)
47 52 57 59 66
SGRQ-t, points < 0.01
(32; 60) (36; 63) (43; 67) (48; 67) (53; 74)
Vanfleteren et al., submitted

The impact of static hyperinflation and outcomes of PR
> MCID CWRT

% of patients improving ≥100s on CWRT % of patients>improving
MCID 6MWD
≥30m on 6MWD
70% 70%
60% 60%
50% 50%
40% 40%
30% 30%
20% 20%
10% 10%
0% 0%
<100 100-149,9 150-199,9 200-249,9 250-299,9 300-349,9 <100 100-149,9 150-199,9 200-249,9 250-299,9 300-349,9
(n=140) (n=640) (n=673) (n=351) (n=82) (n=23) (n=155) (n=682) (n=727) (n=386) (n=109) (n=32)
RESIDUAL VOLUME CATEGORIES (% pred) RESIDUAL VOLUME CATEGORIES (% pred)
RV categories RV categories
Vanfleteren et al., submitted

Nutritional supplementation for stable COPD
Change in body weight
Ferreira et al., Cochrane Database Syst Rev 2012

Change in fat-free mass

Change in functional exercise capacity
Low-quality evidence of NO significant difference in: maximal

inspiratory pressure, health status or FEV1
Nutritional supplementation should be considered in the
management of undernourished COPD patients

Multimodal targeted nutritional intervention in severe COPD
122 COPD patients, chronic respiratory failure, BMI < 21 kg/m2 or FFMI < 25th percentile
INTERVENTION: education + endurance exercise + nutrition (600 kcal/d) + oral testosterone (12 w)
CONTROLS: education
Function Body composition Survival

30 2.0 **
** **
1.5
Change in kg
20
1.0
Change
10 0.5
0.0
0
-0.5
Controls Intervention Controls Intervention
-10 -1.0
t
s
,m
gh
as
h,
ei
m
D
W
gt
W
e
re
n
6M
re
t-f
St
Fa
Pison et al., Thorax 2011
Multidimensional treatment of adult obesity
Intitial goal: loss of 10% of baseline weight after six months at a rate of 0.5 - 1.0 kg per week
Pharmacotherapy Dietary therapy Surgery
Behavioral
Physical activity
modification
(including smoking
cessation)
Expert Panel on the Identification, Evaluation, and Treatment of

Overweight and Obesity in Adults, National Institute of Health, 1998
Targeting the obese phenotype of COPD
Inclusion: COPD, BMI > 30 kg/m2, FEV1 < 80%, clinically stable
Exclusion: Current smoking, cardiac disease, insulin

users, significant orthopaedic problems
Program: - Low-energy diet, 2 meal replacements, high-

protein intake
- Home-based strength training 3 days/week
- Two weekly treatment visit, two weekly phone call
- 12 weeks
McDonald et al., Respirology 2016

-6.4 kg


Sarcopenia in COPD
Sarcopenia, defined as loss of muscle mass and reduced muscle function, is present in 15% of COPD patients
Age GOLD stage iBODE
Jones et al., Thorax 2015

The effects of pulmonary rehabilitation in sarcopenic COPD
Sarcopenia does not impact on the response to rehabilitation and is reversible
Gait speed Hand grip strength Muscle mass
Jones et al., Thorax 2015

Targeted nutrition during PR in COPD patients with low fat-free mass
81 COPD patients, BMI 22.7 kg/m2, FFMI < 25th percentile
NUTRITION: 4 months outpatient PR + 187 kCal, enriched with leucine, n-3 PUFA and vitamin D
PLACEBO: 4 months outpatient PR + non-caloric solution
Inspiratory
Muscle strength Cycle endurance Physical activity
muscle strength
Van de Bool et al., J Cachexia Sarcopenia Muscle 2017

Profiling the sarcopenic COPD phenotype:
understanding the impact of abdominal obesity
The prevalence of sarcopenia and abdominal obesity differs by BMI class
Van de Bool et al., Eur Respir J 2015

Antagonistic implications of sarcopenia and abdominal
obesity on physical performance in COPD
Abdominal obesity seems to have protective effects on physical functioning.
ASMI is a better predictor for physical functioning than FFMI.

Van de Bool et al., Eur Respir J 2015
Personalised management of stable COPD
Lifestyle intervention Comorbidity management
Pharmacotherapy Oxygen therapy
Education Non-invasive ventilation
Exercise training ELVR
Nutritional support Surgical treatments
Psychological intervention Lung transplantation
ADL training Palliative care
Medication adherence
GOLD Strategy for COPD 2017 Report

Summary and discussion:
1) Pulmonary rehabilitation is an essential component of COPD management
2) Not all patients benefit from pulmonary rehabilitation, highlighting the need for
more personalised, targeted interventions
3) Body composition is an important discriminating factor in clinical phenotyping of COPD
4) For underweight patients, nutritional supplementation is beneficial; for other

phenotypes a differential treatment is required
5) Better understanding of the pathophysiology of COPD phenotypes is essential

in order to further advance in PR
@fritsfranssen
Novel diagnostic tools and interventions for COPD
locomotor and respiratory muscle dysfunction
Ioannis Vogiatzis, Ph.D.

Professor of Rehabilitation Sciences
Chair Group 1.02: Rehabilitation and Chronic Care
 I have no real or perceived conflicts of interest that relate to this presentation.
 I have the following real or perceived conflicts of interest that relate to this presentation:

Honoraria or consultation fees: NOVARTIS, CHIESI
Participation in a company sponsored bureau:
Stock shareholder:
Spouse / partner:
Other support / potential conflict of interest:
This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest. The intent of this disclosure
is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products
or services relevant to the talk) from making a presentation, but rather to provide listeners with information on which they can make their own judgments. It remains
for audience members to determine whether the speaker’s interests, or relationships may influence the presentation. The ERS does not view the existence of these
interests or commitments as necessarily implying bias or decreasing the value of the speaker’s presentation. Drug or device advertisement is forbidden.
Aims
• Describe innovative methodology to assess respiratory muscle

blood flow by Near Infrared Spectroscopy (NIRS) during exercise
• Introduce the concept of locomotor muscle heterogeneity for blood

flow and metabolism assessed by NIRS during exercise
• Discuss potential interventions to improve locomotor and respiratory

muscle blood flow and oxygen availability during exercise
First Aim
Describe innovative methodology to assess respiratory muscle blood

flow by Near Infrared Spectroscopy (NIRS) during exercise
Respiratory (intercostal and abdominal) muscle blood flow
Measured by Near-Infrared Spectroscopy and the light absorbing tracer

Indocyanine Green (ICG) Dye
Healthy COPD
Habazettl H. et al, J Appl Physiol 108:962-967, 2010.

JAP 2014;117(3):267-76
Abdominal
Β)
Intercostal muscles
C)
Quadriceps muscle
Α)
muscles
blood flow blood flow
blood flow
(ml/min/100g) (ml/min/100g)
(ml/min/100g)
2
4
6
8
10
12
5
7
9
11
13
15
0
8
16
24
32
40
Rest
†
†
*
*
†
*
Iso-Time
†
†
‡
†
‡
‡
Exhaustion
Abdominal muscles Intercostal muscles Quadriceps
F)
E)
D)
O2 delivery O2 delivery muscle O2

(ml/min/100g) (ml/min/100g) delivery
(ml/min/100g)
0.8
1.9
3.0
4.1
5.2
6.3
0.9
1.1
1.3
1.5
1.7
1.9
0.9
1.2
1.5
1.8
2.1
2.4
Rest
*
*
*
*†
*
*
Iso-Time
‡
‡
‡
‡†
Exhaustion
Intercostal muscles Abdominal muscles
(Borg) 0.0 0.0
(Borg)
Change in Dyspnea
Change in Dyspnea
-1.0 Oxygen, r= -0.64 -1.0 Oxygen, r= -0.71

-2.0 p=0.039 -2.0 p=0.011
-3.0 -3.0
-4.0 -4.0
score
score
-5.0 -5.0
0.00 0.20 0.40 0.60 0.80 1.00 0.00 0.20 0.40 0.60 0.80 1.00
Change in O2 delivery (ml/min/100g) Change in O2 delivery (ml/min/100g)
Arterial Lactate
Arterial Lactate
0.0 0.0
Change in
Change in
Oxygen, r= -0.82 Oxygen, r= -0.81
(mmol/l)
(mmol/l)
-1.0 -1.0
p<0.001 p<0.001
-2.0 -2.0
-3.0 -3.0
-4.0 -4.0
-5.0 -5.0
0.00 0.20 0.40 0.60 0.80 1.00 0.00 0.20 0.40 0.60 0.80 1.00
Change in O2 delivery (mlO2/min/100g) Change in O2 delivery (mlO2/min/100g)

Louvaris et al. Clinical Respiratory J 2017; in press
Second Aim
Introduce the concept of locomotor muscle heterogeneity for blood flow

and metabolism during exercise
• In the lungs, the concept of matching of blood perfusion to
alveolar ventilation (VA) is well-established
 In the lungs, it is how VA is distributed in relation to blood flow (Q)
that is important
 VA/Q ratio is 0.8
West JB, Respir Physiol, 1974

• In the muscle, it is how blood flow (Q) is distributed in relation
to regional metabolic rate (VO2 ): VO2 /Q
 If muscle regions are substantially underperfused in relation to
metabolic demand, then muscle function is impaired
 If muscle regions are overperfused, perfusion is wasted
 While in the lung many methods exist to quantifyVA/Q
heterogeneity, in muscle there is no method to quantify VO2 /Q
heterogeneity during exercise
Using near-infrared spectroscopy with 6 optodes over the quadriceps
A1 KNEE
HIP B1 C1
• Measure perfusion (Q) with iv indocyanine green

• Estimate VO2/Q by measuring StO2
• Calculate VO2 from Q and VO2/Q
Vogiatzis et al, J. Applied Physiol, 118:783-793, 2015
NORMAL
SUBJECT
Flow measurement
distal, lateral,
Probe 1 vastus lateralis
distal, medial,
vastus lateralis
Probe 2
0.07
0.06
Probe 1, Q = 55 ml/min/100g; StO2 = 47%
ICG Concentration [µmol/L]
0.05
0.04 ICG ICG Injection

injection
0.03
V Probe 2, Q = 21 ml/min/100g; StO2 = 51%

0.02
Optode 1, Q=55 mL/min/100g; StO2=47 %

0.01
Optode 2, Q=21 mL/min/100g, StO2=51 %
1500 1510 1520 1530 1540
TIme [s]
NORMAL
SUBJECT
Flow measurement
distal, lateral,
distal, medial,
vastus lateralis
Probe 2
0.07
0.06
0.05

injection
0.03

0.02

0.01
1500 1510 1520 1530 1540
TIme [s]
NORMAL
SUBJECT
Flow measurement
distal, lateral,
distal, medial,
vastus lateralis
Probe 2
0.07
0.06
0.05

injection
0.03

0.02

0.01
1500 1510 1520 1530 1540
TIme [s]
1 normal subject, normoxia & hypoxia, rest & exercise
80
Femoral vein O2 saturation (%)
70 Fick principle:
60
VO2 = Q x [CaO2 – CvO2]
50
Or
40
30 VO2/Q = [CaO2 – CvO2]

20
10
10 20 30 40 50 60 70 80
NIRS Blood flow-weighted StO2 (%)
This relationship is used to estimate venous O2 saturation

beneath each optode from the corresponding StO2 values
All normal subjects: Each point = 1 subject, 1 exercise
level, 1 FIO2
1,2
StO2
VO2/Q
RD: StO2, VO2/Q, VO2

1,0
VO2
0,8
0,6
0,4
0,2
0,0
0,0 0,2 0,4 0,6 0,8 1,0 1,2
RD: BLOOD FLOW
0,6
0,5
GRAND MEAN RD
0,4
0,3
0,2
0,1
0,0
BLOOD FLOW VO2 StO2 VO2/Q
All normal subjects: Each point = 1 subject, 1 exercise
level, 1 FIO2
1,2
StO2
VO2/Q
RD: StO2, VO2/Q, VO2

1,0
VO2
0,8
0,6
0,4
0,2
0,0
0,0 0,2 0,4 0,6 0,8 1,0 1,2
RD: BLOOD FLOW
0,6
0,5
GRAND MEAN RD
0,4
0,3
0,2
0,1
0,0
BLOOD FLOW VO2 StO2 VO2/Q
Q 1.0 VO2
RELATIVE DISPRESSION
1.0
0.8 0.8
Normal 0.6 0.6
subjects
0.4 0.4
0.2 AIR 0.2 AIR

HYPOXIA HYPOXIA
0.0 0.0
R UN 20 50 80 R UN 20 50 80
L. EXERCISE INTENSITY, % PEAK L. EXERCISE INTENSITY, % PEAK
0.20 StO2 0.20 VO2/Q

0.15 0.15
0.10 0.10
0.05 0.05
AIR AIR
0.00 HYPOXIA 0.00 HYPOXIA
R UN 20 50 80 R UN 20 50 80
L. L. EXERCISE INTENSITY, % PEAK
EXERCISE INTENSITY, % PEAK
Q 1.0 VO2
1.0
0.8 0.8
Healthy 0.6 0.6
subjects
0.4 0.4
0.2 AIR 0.2 AIR

HYPOXIA HYPOXIA
0.0 0.0
R UN 20 50 80 R UN 20 50 80
0.20 StO2 0.20 VO2/Q

0.15 0.15
0.10 0.10
0.05 0.05
AIR AIR
R UN 20 50 80 R UN 20 50 80
Q 1.0 VO2
1.0
0.8 0.8
Healthy 0.6 0.6
subjects
0.4 0.4
0.2 AIR 0.2 AIR

HYPOXIA HYPOXIA
0.0 0.0
R UN 20 50 80 R UN 20 50 80
0.20 StO2 0.20 VO2/Q

0.15 0.15
0.10 0.10
0.05 0.05
AIR AIR
R UN 20 50 80 R UN 20 50 80
Q 1.0 VO2
1.0
0.8 0.8
Healthy 0.6 0.6
subjects
0.4 0.4
0.2 AIR 0.2 AIR

HYPOXIA HYPOXIA
0.0 0.0
R UN 20 50 80 R UN 20 50 80
0.20 StO2 0.20 VO2/Q

0.15 0.15
0.10 0.10
0.05 0.05
AIR AIR
R UN 20 50 80 R UN 20 50 80
Q VO2
1.0 1.0
RELATIVE DISPERSION
RELATIVE DISPERSION
Air * Air
0.8 100% O2 0.8 100% O2
*
0.6 0.6
COPD
0.4 0.4
*
0.2 0.2
0.0 0.0
rest unl. 20 50 80 rest unl. 20 50 80
EXERCISE INTENSITY, % PEAK EXERCISE INTENSITY, % PEAK
StO22
StiO VO2/Q
0.20 0.20
RELATIVE DISPERSION
RELATIVE DISPERSION
Air Air
0.15 0.15 100% O2
100% O2
0.10 0.10
0.05 0.05
0.00 0.00
rest unl. 20 50 80 rest unl. 20 50 80
EXERCISE INTENSITY, % PEAK EXERCISE INTENSITY, % PEAK
Louvaris et al Resp. Physiol. Neurobiol 237:42-50, 2017.

Relative dispersion (RD) values,
All FIO2 & exercise levels
0.6
*
* ATHLETES
0.5
GRAND MEAN RD
0.4 COPD
0.3
0.2
*
0.1
0.0
Q VO2 StiO2 VO2/Q

• Heterogeneity of VO2 /Q in each of the six optodes was minimal
(only about 0.15 relative dispersion)
 Indicates a strong capacity to regulate blood flow relative to
regional metabolic demand, during exercise as metabolic &
environmental conditions change profoundly
 Minimal impact of heterogeneity on muscle oxygen availability
 Possible assessment of local muscle StO2 as index of heterogeneity

in patients before and after exercise training
Third Aim
Discuss potential interventions to improve locomotor and respiratory

muscle blood flow and oxygen availability during exercise such as:
1. Inspiratory muscle training

2. Intermittent positive airway pressure (PAP) support
3. Interval Exercise Training
Inspiratory muscle training
Intermitent Positive Airway Pressure (PAP) support
PAP provides 10 cmH2O pressure support to reduce the work of breathing for
patients and keep their airways open during exhalation.
Interval Exercise Training
Vogiatzis et al. ERJ 2004

Interval Exercise Training
○ Interval: mean 130% PWR
● Continuous: mean 65% PWR
Vogiatzis et al. ERJ 2002

Conclusions
1. Measurement of respiratory and locomotor muscle blood flow index (BFI)

by Near Infrared Spectroscopy (NIRS) during exercise may inform on
effectiveness of interventions on muscle blood flow regulation
1. Assessment of local muscle tissue oxygenation (StO2) by NIRS can be

used as index of heterogeneity for local muscle blood flow and
metabolism in patients before and after exercise training
1. Inspiratory muscle training, application of intermittent positive airway

pressure and high-intensity interval exercise training may maximize the
benefit of pulmonary rehabilitation

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ERS Annual Congress Milan

09–13 September 2017

Saturday, 9 September 2017

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Tracks: Exercise, rehabilitation and physiology

17:00 Group assignment

Find out more ERSPUBLICATIONS.COM

 2017 by the authors

PG18:Targeting the locomotor and respiratory muscles in chronic

André Nyberg, RPT, PhD

Affiliation / Financial interest Commercial Company

Honoraria or consultation fees:

Participation in a company sponsored bureau:

Other support / potential conflict of interest:

Partitioning exercising muscle mass in COPD

• Effect of exercise training = intensity * duration

• The principle of specificity

ACSM 2009, MSSE.

Spruit 2013, AJRCCM, O'Donnell 2001, MSSE, Maltais 2014, AJRCCM

Spruit 2013, AJRCCM, O'Donnell 2001, MSSE, Maltais 2014, AJRCCM

How can we reduce the impact of exercise limiting factors

Spruit 2013, AJRCCM, O'Donnell 2001, MSSE, Maltais 2014, AJRCCM

Richardsson, 1999 AJRCCM; Richardsson 2004, AJRCCM;

Dolmage 2006, Chest

Dolmage 2006, Chest

Dolmage 2006, Chest

Dolmage 2008, Evans 2015

Dolmage 2008, Chest; Bjorgen 2009, Eur J Appl Physiol

Dolmage 2008, Chest; Bjorgen 2009, Eur J Appl Physiol

Dolmage 2008, Chest; Bjorgen 2009, Eur J Appl Physiol

Additional improvements from partitioning exercising muscle

Evans 2015 Ann Am Thor Soc

• All physiotherapists considered one-legged cycling safe and easy

• Continue to describe it “some of the time”, excluding patients with

Increasing the effects of partitioning exercise in COPD

• Breathing supplemental oxygen or inspiring a helium-hyperoxia

Dolmage 2014, JCRP, Bjorgen Int J Sports Med 2009.

Resistance training (low-load/high-repetition)

Nyberg 2016, MSSE.

Nyberg 2016, MSSE.

More patients considered ”fatiguers”

Larger effects in people who develop

Additional improvements from partitioning exercising muscle

No effect on endurance cycling capacity or quality of life.

Nyberg 2015, Clin Respir J

• Compliance to exercise protocol

• More time consuming

3 sets until failure at about 50-55% of 1 RM

Nyberg 2017 (unpublished)

3 sets until failure at about 50-55% of 1 RM

Nyberg 2017 (unpublished)

3 sets until failure at about 50-55% of 1 RM

Nyberg 2017 (unpublished)

3 sets until failure at about 50-55% of 1 RM

Nyberg 2017 (unpublished)

1 set, 10 repetitions at 80% of 1 RM

3 sets until failure at about 50-55% of 1 RM 1 set, 10 repetitions at 80% of 1 RM

Bronstad 2012, ERJ

Pulmonary VO2 at isotime -26%

Short program with minimal supervision

Highest tolerable resistance (aim: ≥ 50% PImax)