Systematic Review

Isolated Resistance Training Programs to Improve Peripheral

Muscle Function in Outpatients with Chronic Obstructive
Pulmonary Diseases: A Systematic Review
Simone Pancera 1,*, Nicola F. Lopomo 2, Luca N. C. Bianchi 1, Paolo Pedersini 1 and Jorge H. Villafañe 1

1 IRCCS Fondazione Don Carlo Gnocchi, 20148 Milan, Italy; [email protected] (L.N.C.B.);
[email protected] (P.P.); [email protected] (J.H.V.)
2 Department of Information Engineering, University of Brescia, Via Branze 38, 25123 Brescia, Italy;

[email protected]
* Correspondence: [email protected]

Abstract: This systematic review aims to establish which isolated resistance training (RT) programs
have been used in outpatients with chronic obstructive pulmonary disease (COPD) and their impact
on all aspects of peripheral skeletal muscle function. Electronic databases were systematically
searched up to June 2021. The eligibility criteria were: (1) randomized controlled trials investigating
the effects of supervised and isolated RT programs in outpatients with COPD and (2) RT programs
Citation: Pancera, S.; Lopomo, N.F.;
lasting 8–12 weeks, (3) including at least one outcome measure related to trainable muscle
Bianchi, L.N.C.; Pedersini, P.;
characteristics. Initially, 6576 studies were identified, whereas 15 trials met the inclusion criteria.
Villafañe, J.H. Isolated Resistance
All the included trials reported that isolated RT improved both upper and lower limbs’ maximal
Training Programs to Improve
Peripheral Muscle Function in
strength. Muscle endurance and power also increased after RT but received less attention in the
Outpatients with Chronic analysis. Furthermore, few studies assessed the effect of RT on muscle mass and cross‐sectional
Obstructive Pulmonary Diseases: area, reporting only limited improvement. Isolated RT programs carried out 2–3 days a week for 8–
A Systematic Review. 12 weeks improved skeletal muscle function in individuals with COPD. The RT program should be
Healthcare 2021, 9, 1397. specifically focused to the trainable muscle characteristic to be improved. For this reason, we further
https://doi.org/10.3390/ encourage the introduction of a detailed assessment of muscle function and structure during the
healthcare9101397 pulmonary rehabilitation practice.

Academic Editors: Clement Keywords: chronic obstructive pulmonary disease; pulmonary rehabilitation; resistance training;
Medrinal, Marius Lebret
muscle strength; systematic review
and Michelle Chatwin

Received: 7 September 2021

Accepted: 16 October 2021
Published: 19 October 2021
1. Introduction
Peripheral muscle dysfunction in patients with chronic obstructive pulmonary
Publisher’s Note: MDPI stays disease (COPD) results in a combination of intrinsic modifications—including muscle
neutral with regard to jurisdictional fiber shift, changes in capillarization, mitochondrial disorder, and oxidative damage—
claims in published maps and and functional limitations [1]. The most clinically relevant consequences of these
institutional affiliations. alterations are loss of muscle mass, muscle weakness, and an inability to sustain or even
perform exercise [2]. Furthermore, all these factors could lead individuals with COPD to
an increased use of healthcare and a deterioration in their quality of life, thus aggravating
the overall socio‐economic burden of this disease [3,4].
Copyright: © 2021 by the authors.
Resistance training (RT) refers to the exercise performed by local muscle groups
Licensee MDPI, Basel, Switzerland.
against body weight or external resistance and represents a key component in the
This article is an open access article
comprehensive pulmonary rehabilitation (PR) program addressing patients with COPD
distributed under the terms and
conditions of the Creative Commons
[5]. Moreover, RT is not limited to muscle strength exercises but refers to further trainable
Attribution (CC BY) license
muscle characteristics, such as muscle power and local muscle endurance [6]. Indeed,
(https://creativecommons.org/license there is evidence that all these muscle characteristics contribute to enhancing the overall
s/by/4.0/).

Healthcare 2021, 9, 1397. https://doi.org/10.3390/healthcare9101397 www.mdpi.com/journal/healthcare

Healthcare 2021, 9, 1397 2 of 17

function of peripheral muscles in individuals with COPD, inducing structural and

metabolic adaptations and improving the patient’s functional exercise capacity [7,8].
However, the RT programs available for treating patients diagnosed with COPD are
characterized by a great variability; hence, it is difficult to properly assess their short‐ and
long‐term effectiveness [9]. In fact, even though these protocols are usually adapted
according to the patients’ existing condition and clinical status, the recommendations for
the assessment and treatment of muscle dysfunction in individuals with COPD are
frequently poor of proper indications for clinical practice. In addition, there is increasing
evidence that specific aspects of muscle function have currently received less attention
with respect to muscle strength [10]. Therefore, specific RT programs and methods
targeting these emerging perspectives on muscle function should be preferred to a
generalized approach that may be unable to improve the compromised function of the
patients [11,12]. In this perspective, practical aspects of RT regarding the trainable muscle
characteristics to be improved, the target muscle groups, and the choice of appropriate
load and volume should be further elucidated in order to increase the rehabilitation tools
available to therapists during PR programs for individuals with COPD [13].
Moreover, though RT is an established component of PR and has been included in
almost 70% of PR programs in Europe, with a minimum recommended length of 24
sessions, strength outcomes are not yet considered as one of the most important measures
in the clinical evaluation of patients with COPD [1,14]. For this reason, the assessment of
peripheral muscles function is poorly integrated in the clinical routine in most cases
[13,15]. Therefore, there is an increasing need to identify appropriate standard and
complementary evaluations of peripheral muscles function in order to better define the
progression and effects of RT programs in patients with COPD [16].
Some earlier reviews have explored the effects of RT on respiratory function and
exercise capacity in individuals with COPD [17–19], whereas other reviews focused on the
effects of exercise training on muscle strength [20–22]. However, these reviews often
included studies on combined RT and endurance training (ET) programs, reviewed
multiple design studies, or even reported outcomes that are limited to a single aspect of
peripheral muscle function. Therefore, considering the heterogeneity of the interventions
currently adopted to improve peripheral muscle function and the need for addressing
important clinical issues concerning present and emerging RT methods used in patients
diagnosed with COPD, a systematic review was conducted in order to clarify these aspects
directly related to the PR practice.
More specifically, this systematic review aimed to establish which isolated RT
programs have been used in outpatients with COPD and their impact on peripheral
muscle strength, local muscle endurance, and muscle power. Additionally, the effects of
these treatments on the cross‐sectional area (CSA) and fat‐free mass (FFM) of the muscles
are presented. An overview of the methods used to assess these muscle characteristics is
also provided.

2. Methods
In accordance with guidelines [23], the protocol for this systematic review was
registered in the International Prospective Register of Systematic Reviews (PROSPERO)
on 14 February 2020, under identification number CRD42020168650.

2.1. Search Strategy

The primary search was conducted for English, French‐, Spanish‐, or Portuguese‐
language studies published up to June 2020 in the following electronic databases:
MEDLINE (PubMed), The Cochrane Central Register of Controlled Trials (CENTRAL),
Web of Science, Embase, and Scopus. The secondary search was carried out for reference
lists, focusing on all the included papers and reviews performed on the same topic. The
search was re‐run in June 2021 to retrieve new studies suitable for inclusion in this
Healthcare 2021, 9, 1397 3 of 17

systematic review. The complete search strategy used in the main databases is provided
in the Table S1 (Supplementary Materials).
The literature search and sifting process were conducted by two separate reviewers
(SP, JHV), applying previously determined inclusion criteria. A third neutral investigator
(NFL) was questioned when conflicts arose between the reviewers.

2.2. Eligibility Criteria

This systematic review included randomized controlled trials investigating the
effects of supervised and isolated (i.e., performed as the main and only intervention) RT
programs on any trainable muscle characteristic (i.e., muscle strength, muscle power, and
local muscular endurance) in outpatients diagnosed with COPD (Global Initiative for
Obstructive Lung Disease, GOLD stage I–IV) [24]. Primary outcomes included any
objective measure of muscle strength endurance or power with no restrictions regarding
the assessment method used (e.g., one repetition maximum, dynamometry, force plates).
Secondary outcomes included measures of muscle CSA and FFM. The duration of the RT
program could vary between 8 and 12 weeks (≥24 sessions), and the exercises could be
carried out using external resistance (free weights, weight machines, or elastic bands) or
body weight training. Intervention in the control group could involve ET, combined RT
and ET, breathing exercises, education, or usual care. Studies were excluded if they used
home‐based RT programs, passive training methods, nutritional, or pharmacological
supplementation as the main intervention. Studies that enrolled healthy subjects as sole
controls were also excluded.

2.3. Data Extraction

The percentage of change from baseline for each outcome measure of the included
studies related to muscle strength, endurance, and power was extracted and reported in
the results section. If not available, these percentages were calculated by the reviewers
using pre‐ and post‐training values for each outcome measure. Information about number
and size of groups, duration, type of intervention, and protocol of RT (i.e., frequency,
volume, intensity, load, and progression) were also extracted from each included study

2.4. Quality Assessment

The methodological quality of the included studies was assessed using the
Physiotherapy Evidence Base Database (PEDro) scale that was reported to be a valid
measure of the methodological quality for clinical trials [25]. Included studies were rated
with a minimum score of 0 and a maximum score of 10 points [26] and were considered
to be of “good” to “excellent” quality when scoring ≥ 6 points, while studies scoring ≤ 5
points were defined as “low” to “fair” quality [27].

3. Results
3.1. Study Selection
A total of 6576 studies were initially identified through database searching, of which
136 full‐text articles were assessed for eligibility. Overall, 121 studies were excluded
because they did not meet the inclusion criteria, as shown in Figure 1, whereas 15 trials
published between February 1992 and May 2021 were finally included in the systematic
review.
Healthcare 2021, 9, 1397 4 of 17

Identification
Records identified through Additional records identified
database searching through other sources
(n = 6565) (n = 72)

Records after duplicates removed

(n = 6576)
Screening

Records excluded after Abstract screening

(n = 6443)

Full‐text articles assessed Full‐text articles excluded,

Eligibility

for eligibility (n = 121)

(n = 136) Not RCTs: 17
Different topic: 24
Unstable patients: 7
Training volume: 21
Studies included in Training type: 44
Included

qualitative synthesis Not valid outcomes: 8

(n = 15)

Figure 1. Flow diagram of the study selection. RCTs, randomized controlled trials.

3.2. Quality Rating

The quality of included studies was rated ≤ 5 points in seven trials [28–34] and ≥6
points in eight other studies [35–42]. The sample size of the included studies varied
between 12 and 48 subjects and was calculated a priori in 7 out of 15 trials
[29,33,34,36,37,41,42]. The attrition rate was ≤ 10% in four studies [28,35,36,40], between
11% and 30% in eight studies [29–31,33,34,37,38,41], and ≥30% in three studies [32,39,42].
The quality assessment of the included studies is detailed in Table 1.
Healthcare 2021, 9, 1397 5 of 17

Table 1. Quality assessment of the included studies.

Concealed Baseline Blind Blind Blind Between‐Group Point Estimates Attrition

Study Randomization FU ITT PEDro Score
Allocation Comparability Subjects Therapists Assessor Comparison and Variability Rate (%)
Clark [28] 1 0 1 0 0 0 1 0 1 1 5/10 0
Dourado [29] 1 0 1 0 0 0 0 0 1 1 4/10 28
Freire [41] 1 1 1 0 0 1 0 1 1 1 7/10 27
Hoff [35] 1 0 1 0 0 0 1 1 1 1 6/10 0
Kongsgaard [30] 1 0 1 0 0 0 0 0 1 1 4/10 28
Nyberg [36] 1 1 1 0 0 1 1 1 1 1 8/10 9
Nyberg [42] 1 1 1 0 0 1 0 1 1 1 7/10 30
Ortega [31] 1 0 1 0 0 0 1 0 1 1 5/10 13
Ramos [37] 1 1 1 1 0 0 0 0 1 1 6/10 24
Silva [32] 1 0 1 0 0 1 0 0 1 1 5/10 32
Silva [33] 1 1 1 0 0 0 0 0 1 1 5/10 27
Simpson [38] 1 0 1 0 0 1 1 0 1 1 6/10 18
Spruit [39] 1 1 1 0 0 1 0 0 1 1 6/10 38
Vonbank [34] 1 0 1 0 0 0 0 0 0 1 3/10 16
Zambom‐Ferraresi [40] 1 1 1 0 0 1 1 0 1 1 7/10 10
FU, follow‐up; ITT, intention‐to‐treat analysis.
Healthcare 2021, 9, 1397 6 of 17

3.3. Study Characteristics

The total number of patients with COPD in the 15 included studies was 493 (mean
age, 63 years; mean percentage of predicted forced expiratory volume in 1 second, 48%),
with a percentage of female subjects of 25%. The length of the training programs ranged
from 24 and 36 sessions, with a training frequency of two or three times weekly, and each
session lasted between 60 and 90 min (Table 2).
The initial training load prescribed was between 50% and 85% of the one‐repetition
maximum or based on the maximal load that could be lifted between 15 and 30 times. The
subsequent training load was established by repeating the maximal test [28–33,38], by
using the Borg scale [36], or with increases of predetermined loads [35], or percentages of
the maximal load achieved by patients [37,39,42]. The number of days before the
recalculation of the workload, if specified, varied between 2 and 50 days. The included
trials prescribed two to seven sets for each exercise, with 5–30 repetitions and 1–3 min of
rest. The gym equipment used in the studies was represented by free weights, weight
machines, pulleys, and elastic tubing or bands.
There were 13 studies that adopted RT programs for both the upper and lower limbs
[28,29,31–34,36–42], while two studies exercised only the lower limbs [30,35]. In two trials,
the training program was designed to enhance the peripheral muscle endurance [36,42],
imposing a moderate‐fast velocity of contraction, whereas two studies focused on the
muscle power, giving emphasis to the explosive movement performed during the
concentric phase of the exercise [30,35]. Most of the remaining trials did not report a
specific velocity of contraction or adopted a 1:1 velocity of contraction in the concentric
and eccentric phases.
The control groups performed no intervention, education, or breathing exercise in 6
out of 15 studies [28,30,35,36,38,40]. Three studies compared RT with ET [31,34,39],
whereas one trial made a comparison between RT and light‐intensity training or a
combination of both [29]. The remaining five studies compared RT carried out with
weights by using different elastic resistances [32,33,37,41] or even involving one or two
limbs at a time [42].

3.4. Outcome Measures

The main outcome measures of muscle function are summarized in Table S2
(Supplementary Materials) and Figure 2. The maximal isometric strength of the knee
extensors was evaluated in six studies, where an increase between 15% and 34% was
found after RT [30,32,33,37–39]. Five trials assessed the maximal isotonic strength of the
knee extensors, reporting improvements from 18% to 53% [28,29,31,38,41]. The maximal
isokinetic strength of the knee extensors was measured in four trials and changed between
5% and 18% from baseline [28,30,36,42]. In addition, three studies assessed the muscle
endurance of the knee extensors, and two of them reported an 11% increase after a RT
program focused on muscle endurance [36,42]. Five trials measured the maximal strength
of the knee flexors, finding an improvement between 18% and 35% and between 27% and
107% from baseline in isometric [32,37,39] and isotonic [31,41] conditions, respectively.
The combined leg press exercise was tested in six studies that reported an increase
between 16% and 58% [29,30,34,35,38,40]. In addition, the overall muscle power of the
lower limbs was assessed in three studies: one of these found an improvement of 83% in
the rate of force development [35], whereas two studies measured the power output and
found a 19% increase and no change, respectively [30,40].
The maximal isometric strength of the elbow flexors was measured in four studies
that reported an improvement between 21% and 36% [32,33,37,39]. Two studies
investigated the maximal isotonic strength of the elbow flexors, but only two of them
reported an increase between 23% and 33% after the RT program [38,41]. The maximal
isometric strength of the shoulder flexors showed an improvement between 19% and 43%
in two studies [32,37], while the maximal isokinetic strength of the shoulder flexors was
Healthcare 2021, 9, 1397 7 of 17

measured in other two studies, showing an increase between 8% and 15% from baseline
[36,42]. The same trials assessed the muscle endurance of the shoulder flexors, finding a
16% or a 21% improvement [36,42], respectively. The maximal strength during combined
exercises for chest muscles (i.e., chest press and butterfly) were evaluated in four studies
that reported an increase between 20% and 75% from baseline, respectively [29,31,34,40],
whereas three trials reported an improvement between 20% and 27% in the combined
exercises for back muscles (i.e., lat pull) [29,31,34]. The handgrip strength was found to
have increased by 18% [38] in one study and did not change in two other studies that
measured it [29,39].
Concerning secondary outcomes, one trial showed a 4% increase of the CSA of the
quadriceps after RT, measured via magnetic resonance imaging [30]. Two studies assessed
the FFM using bioimpedance analysis (BIA) and one study using dual‐energy X‐ray
absorptiometry (DEXA). These trials found no change or 4% of increase after RT in the
first case [29,41] and a 2% of increase in the second [37].
Healthcare 2021, 9, 1397 8 of 17

Table 2. Characteristics of the included studies.

Study Study Groups Study Intervention Study Duration Training Protocol

Frequency: 2 d/w
CO: 8 exercises (chest press, body squat, squat calf, Reps: 3 × 10
Conventional resistance
lat machine, arm curls, leg press, knee extension, Phase velocity: NA
Clark [28] training (CO): 26; Control 12 weeks
knee flexion) with weights. Rest: NA
(CG): 17
CG: No intervention. Load: 70% of 1RM
Progression: Every 6 weeks (repeating 1RM test)
CO: 7 exercises (leg press, leg extension, lat pull
Frequency: 3 d/w
Conventional resistance down, chest press, seated rowing, triceps pulley, and
Reps: 3 × 12 (CO); 2 × 8 (CT)
training (CO): 11; Low‐ biceps curl) with weight machines.
Phase velocity: NA
Dourado [29] intensity training (LIT): 13; LIT: 30 min of walking and 30 min of low‐intensity 12 weeks
Rest: 2 min
Combined training (CT): CO with free weights, on exercise mats and on
Load: 50–80% of 1RM
11 parallel bars.
Progression: Every 3 weeks (repeating 1RM test)
CT: 30 min of CO group and 30 min as LIT group.
Frequency: 3 d/w
Conventional resistance CO: 5 exercises (shoulder abduction, elbow flexion, Reps: 2 × 15 (weeks 1–2); 3 × 15 (weeks 3–6); 3 × 10
training (CO): 16; Elastic shoulder flexion; knee extension and knee flexion) (weeks 7–9); 3 × 15 (weeks 10–12)
Freire [41] tubing resistance (ER): 18; with weight machines. 12 weeks Phase velocity: 2 s
Elastic bands resistance ER and EB: The same exercise program of CO was Rest: 2 min
(EB): 14 carried out with elastic tubing or bands. Load: established with nRM
Progression: Each session with the nRM test
Frequency: 3 d/w
Reps: 4 × 5
Conventional resistance Phase velocity: Explosive concentric, slow eccentric
CO: 1 exercise (leg press).
Hoff [35] training (CO): 6; Control 8 weeks Rest: 2 min
CG: No intervention.
(CG): 6 Load: 85–90% of 1RM
Progression: 2.5 kg increment when 5 reps were
exceeded
Frequency: 2 d/w
Reps: 4 × 8
Conventional resistance CO: 3 exercises (leg press, knee extension, knee
Phase velocity: Explosive concentric
Kongsgaard [30] training (CO): 6; Control flexion) with weight machines. 12 weeks
Rest: 2–3 min
(CG): 7 CG: Breathing exercise.
Load: 80% of 1RM
Progression: Every week
Healthcare 2021, 9, 1397 9 of 17

Frequency: 3 d/w
EB: 8 exercises (latissimus row, chest press, leg Reps: 2 × 25
Elastic bands resistance extension, straight arm shoulder flex, leg curl, elbow Phase velocity: 1 s
Nyberg [36] 8 weeks
(EB): 22; Control (CG): 22 flexion, leg heel raise, leg step‐up). Rest: 1 min
CG: 4 days of education. Load: Established nRM
Progression: Every 2 sessions (if Borg scale < 4)
Frequency: 3 d/w
Reps: 3 × 25–30
Elastic band single‐limb SEB: 7 exercises (knee extension, leg curl, latissimus
Phase velocity: 1 s
resistance (SEB): 16; Elastic row, chest press, elbow flexion, shoulder flexion,
Nyberg [42] 8 weeks Rest: 1 min
band two‐limb resistance calf) with a single limb at a time.
Load: Established nRM
(TEB):17 TEB: As SEB but using both limbs at a time.
Progression: Increased every two sessions by 10% if
patients exceeded 30 reps
Frequency: 3 d/w
Conventional resistance
CO: 5 exercises (lat pull, butterfly, neck press, leg Reps: 4 × 6–8 (CO); 2 × 6–8 (CT)
training (CO): 17;
flexion, leg extension) with gymnastic apparatus. Phase velocity: NA
Ortega [31] Endurance training (ET): 12 weeks
ET: 40 min of cycling at 70% of peak work capacity. Rest: NA
16; Combined training
CT: 20 min of cycling plus CO. Load: 70–85% of 1RM
(CT): 14
Progression: Every 2 weeks (repeating 1RM test)
Frequency: 3 d/w
CO: 5 exercises (knee extension, knee flexion, Reps: 3 × 10 (CO); 2–7 × maximum in 20 s (ER)
Conventional resistance shoulder abduction, shoulder flexion, elbow flexion) Phase velocity: NA
Ramos [37] training (CO): 17; Elastic with weight machines. 8 weeks Rest: 2 min
tubing resistance (ER): 17 ER: Same exercises as CO group, performed with Load: 60% (week 1) to 80% (week 8) of 1RM
elastic tubing. Progression: Increased by 4% every four sessions
(CO); increased by one set every two sessions (ER)
Frequency: 3 d/w
Reps: 2 × 15 (weeks 1–3); 3 × 15 (weeks 4–6); 3 × 10
CO: 5 exercises (knee flexion, knee extension,
(weeks 7–9); 4 × 6 (weeks 10–12)
Conventional resistance shoulder flexion, shoulder abduction, elbow flexion)
Phase velocity: 1.8 s
Silva [32] training (CO): 10; Elastic with weight machines. 12 weeks
Rest: 2 min
tubing resistance (ER): 9 ER: Same exercises as CO group, performed with
Load: 15RM
elastic tubing.
Progression: Increased when patients exceeded the
nRM
Frequency: 3 d/w
Conventional resistance CO: 5 exercises (knee flexion, knee extension,
Reps: 2 × 15 (weeks 1–3); 3 × 15 (weeks 4–6); 3 × 10
Silva [33] training (CO): 11; Elastic shoulder flexion, shoulder abduction, elbow flexion) 12 weeks
(weeks 7–9); 3 × 15 (weeks 10–12)
resistance (ER): 24 with weight machines.
Phase velocity: NA
Healthcare 2021, 9, 1397 10 of 17

ER: Same exercises as CO group, performed with Rest: NA

elastics. Load: Established nRM
Progression: Increased when patients exceeded the
nRM
Frequency: 3 d/w
Reps: 3 × 10
Conventional resistance CO: 3 exercises with weights using a single limb at a
Phase velocity: Slow concentric
Simpson [38] training (CO): 14; Control time (arm curl, leg extension, leg press). 8 weeks
Rest: NA
(CG): 14 CG: No intervention.
Load: 50% (week 1) to 85% (week 8) of 1RM
Progression: Every 6 sessions (repeating 1RM test)
CO: 6 exercises (quadriceps, pectorals, triceps Frequency: 3 d/w
Conventional resistance brachia, deltoids, biceps brachia, hamstrings) with Reps: 3 × 8
training (CO): 14; weight machines. Phase velocity: NA
Spruit [39] 12 weeks
Endurance training (ET): ET: Cycling or walking for 25 min at 75% of peak Rest: NA
16 work or 60% of 6‐min walk speed) plus arm Load: 70% of 1RM
cranking (4–9 min). Progression: Increased by 5% of 1RM every week
Frequency: 2 d/w
CO: 8 exercises (chest press, chest cross, shoulder Reps: 2 × 8–15 (weeks 1–4); 3 × 8‐15 (weeks 5–9); 4 ×
Conventional resistance
press, pull downs, biceps curl, triceps extensions, sit‐ 8–15 (weeks 10–12)
training (CO): 12;
ups, leg press). Phase velocity: NA
Vonbank [34] Endurance training (ET): 12 weeks
ET: Cycling for 20 min (increased by 5 min every 4 Rest: NA
12; Combined training
weeks) at 60% of estimated VO2peak. Load: Established nRM
(CT): 12
CT: CO plus ET Progression: Increased when patients exceeded the
nRM
CO: 6 exercises (leg press, knee extension, knee
Frequency: 2 d/w
flexion, chest press, seated row, shoulder press) with
Conventional resistance Reps: 3–4 × 6–12
weight machines.
Zambom‐ training (CO): 14; Phase velocity: NA
CT: one d/w of CO and 1 d/w of cycling for 20–35 12 weeks
Ferraresi [40] Combined training (CT): Rest: NA
min at 65–90% of peak heaCO rate (increased each
14; Control (CG): 8 Load: 50–70% of 1RM
session).
Progression: Every 6 weeks (repeating 1RM test)
CG: No intervention.
1RM, one repetition maximum; 15RM, fifteen maximal repetitions; CG, control group; CO, conventional resistance training; CT, combined training; EB, resistance training
with elastic bands; ER, resistance training with elastic tubing; ET, endurance training; LIT, low‐intensity training; NA, not applicable; nRM, maximum number of
repetitions; SEB, single‐limb resistance training; TEB, two‐limb resistance training.
Healthcare 2021, 9, 1397 11 of 17

60 60 5 60 80
Knee extension Knee extension Knee flexion Leg press
50 50 4 6 50 4
60
40 6 40 40 5
6 3
6 4
30 5 30 30 40 4
%

6 5 7 6 6
20 4 20 20 6
20
10 10 10
0 0 0 0
Isometric strength Isotonic strength Isometric strength Isotonic strength

60 60 120 5 100
Knee extension Knee extension Knee flexion 6 Leg press
50 50 100 80
40 40 80
60
30 30
%

60
4 40
20 20 8 7 40 7 4
8 7 20
10 10 20
0 0 0 0
Isokinetic strength Muscle endurance Isotonic strength Muscle power

60 60 60 60 60
Shoulder flexion Shoulder flexion Shoulder abduction Elbow flexion Back
50 50 5 50 50 50 5
40 40 40 40 5 40
5
30 7 5 4
30 30 30 6 30
%

6 6 3
20 20 7 20 20 20
10 10 10 10 10
0 0 0 0 0
Isometric strength Isotonic strength Isotonic strength Isometric strength Isotonic strength

60 60 60 60 80 5
Shoulder flexion Shoulder flexion Shoulder abduction Elbow flexion Chest
50 50 50 5 50 70
60
40 40 40 40 6 50
7 7 7
30 30 30 6 30 40 4
%

8 6
20 8 20 20 20 30 3
7 20
10 10 10 10
10
0 0 0 0 0
Isokinetic strength Muscle endurance Isometric strength Isotonic strength Isotonic strength

Figure 2. Harvest plots of the effect of isolated RT on peripheral muscle function in outpatients with COPD. Changes for the various outcome measures are expressed as
percentage of baseline. For studies that adopted more than one modality of RT (e.g., conventional RT or RT with elastic bands), the highest increase was reported. Numbers
above the bars refer to the quality score of the studies (from 0 to 10). The length of the training program is indicated by black bars (36 sessions) or white bars (24 sessions).
Combined exercises for chest muscles (i.e., chest press and butterfly) and back muscles (i.e., lat pull) are grouped in the “chest” and “back” graphs, respectively.
Healthcare 2021, 9, 1397 12 of 17

4. Discussion
The main objective of this systematic review was to explore the literature about the
available isolated RT programs used for the treatment of outpatients with COPD and their
impact on the patient’s peripheral muscle function. All 15 included trials reported a
positive effect of isolated RT programs on maximal isometric, isotonic, and isokinetic
muscle strength of both the upper and lower limbs and, to a limited extent, also on local
muscle endurance and muscle power after 8 to 12 weeks of training. A small number of
studies also showed a positive impact of RT on muscle CSA and FFM in patients with
COPD. In general, exercise interventions showed a large variability with regard to the
program design, the prescription and progression of the training load, and the volume of
training recommended. The reported outcome measures were also heterogeneous for both
the choice of the muscle group and the muscle function being assessed. The included
studies reported an overall quality ranging from “fair” to “good”.

4.1. RT Program Design

This systematic review found that RT programs for outpatients with COPD are
usually of 24 or 36 sessions, 2–3 days a week. However, since individuals with COPD
suffer from early fatigability, their level of conditioning and recovery ability should be
taken into account when prescribing the optimal RT frequency [43]. In any case, a certain
degree of muscle fatigue is suggested in order to induce a functional adaptation to training
in patients with COPD [44].
The training intensity should also be target specific; starting, for example, with initial
lighter loads (45–50% of one repetition maximum) or higher number of repetitions (15–
30) may represent a suitable strategy for deconditioned or frail individuals, such as
individuals with COPD [12]. Then, the initial load should be progressively increased up
to 80%—or more—in order to focus the training effect on maximal muscle strength or
maintained to a lower extent in order to improve, for example, local muscle endurance
[36,42]. In fact, most of the studies included in this systematic review chose an initial load
within this wide range, and with few exceptions, all the trials adopted a load‐increasing
strategy to intensify the exercise over time. However, highly variable progression
strategies were found with regards to the timing and magnitude of the increase; therefore,
it is difficult to speculate on the proper progression strategy for patients with COPD so
far.

4.2. Impact of RT on Trainable Muscle Characteristics

Despite the large variability among the interventions, all the studies included in this
systematic review reported an improvement in maximal muscle strength testing after RT,
with more limited and lower‐quality evidences for the upper compared to the lower
limbs. Handgrip strength was the only exception to this trend, probably because it
represents the strength of the forearm muscles rather than the overall muscle strength of
the upper limbs; thus, specific training is required to improve it [45]. Moreover, in contrast
with the findings of this systematic review, the maximal strength of the knee extensors
did not change in 17% of the studies included in a previous review, thus suggesting that
patients with COPD may respond in a different manner to similar RT programs [22].
Nevertheless, contrary to this systematic review, those authors reviewed an elevated
number of studies with multiple design and different RT modalities.
The local muscle endurance—usually reduced in individuals with COPD [46]—
improved in both the upper and lower limbs in particular when a high number of
repetitions and a minimum recovery were used [36,42]. Furthermore, as found in two
studies included in the systematic review, there is a strong correlation between change in
isokinetic muscle endurance and change in treadmill endurance [28] or change in the
number of capillaries per muscle fiber [42] after RT. Therefore, these results empower the
Healthcare 2021, 9, 1397 13 of 17

previously suggested idea that RT may induce similar benefits on physical and metabolic
function compared with aerobic training [7,47]. Moreover, considering the lower
cardiopulmonary stress induced by RT [48], a training regime focused on the
improvement of the local muscle endurance might be suitable for individuals with COPD.
In particular, performing exercises using a single limb at a time could increase the
participation of those patients who are severely limited by dyspnea or are unable to
sustain prolonged or high‐intensity ET [42].
This systematic review also highlighted the improvement of lower‐limb muscle
power after RT in patients with COPD, particularly when the emphasis was on the
explosivity of the exercise (i.e., explosive concentric phase and slow eccentric phase), and
high loads (80 to 90% of 1RM) were adopted [30,35]. However, using relatively low loads
(50 to 70% of 1RM) produced slighter effects on muscle power, unless RT was combined
with ET, as shown in one study included in this systematic review [40]. In contrast, no
data were available for muscle power of the upper limbs, probably due to the difficulty in
measuring it. Since muscle power has been reported to be reduced by 30% in patients with
COPD, there is increasing support for its inclusion in RT programs during PR [49]. In
addition, this muscle characteristic may be associated with light‐intensity activities and
functional performance (e.g., gait speed), as seen in previous studies and confirmed by
the findings of this systematic review [30,50].

4.3. Training Modes

Consistent with previous work [20,21], the studies included in this systematic review
reported improvements in maximal muscle strength of the upper and lower limbs when
RT was compared to no or light intervention. In addition, although limited to the lower
limbs, a greater enhancement in local muscle endurance and power was also observed for
patients with COPD undergoing RT compared to non‐exercising controls [28,30,36]. The
comparison between isolated RT and ET programs, on the other hand, gave contrasting
results, as reported in a previous review on this topic [47]. However, the findings of this
systematic review suggest that the reason for such conflicting results may lie in the
difference of intensity prescribed in these studies [31,39]. Surprisingly, in one study, RT
failed to produce further gains in the isometric maximal strength of the upper limbs when
compared to ET [39]. Nevertheless, these authors additionally exercised the endurance
group with arm cranking, which might have produced improvements in the maximal
strength of the upper limbs. Furthermore, this systematic review reported a similar
increase in maximal muscle strength when RT was isolated or combined with ET [29,31].
However, one of these studies suggests that enhancing peripheral muscle strength with
an appropriate RT program may optimize the performance of tasks related to functional
exercise capacity in patients with COPD [29].
Finally, the studies included in this systematic review reported similar gains in
maximal muscle strength after RT with weight machines or elastic bands; thus, the
superiority of one modality over the other was not established [32,33,37,41]. In addition,
with evidence limited to one study [42], training with one rather than two limbs at a time
did not appear to have a different impact on maximal muscle strength and endurance of
the upper and lower limbs but only induced less exertional dyspnea in the former case, as
previously mentioned.

4.4. Methods to Assess Muscle Function in Clinical Practice

The quadriceps were the reference muscle group for assessing muscle function using
isometric strength testing, particularly with the hand‐held dynamometer or, in a few
studies, with the computerized dynamometer. The hand‐held dynamometer is obviously
well suited for the clinical setting; nevertheless, it involves a risk of over or
underestimation of muscle gains [51]. On the other hand, the isokinetic evaluation showed
good reliability and accuracy in patients with COPD, but it is costly and time consuming
for clinical practice [45]. Moreover, the isokinetic dynamometer may be useful for the
Healthcare 2021, 9, 1397 14 of 17

evaluation of local muscle endurance despite the differences in measurement protocols

between the included studies [28,36,42].
When the maximal muscle strength was assessed dynamically, the preferred method
was to test the isotonic one‐repetition maximum using the same equipment as during the
training. In line with a previous review, the isotonic strength was found to be more
responsive to RT compared with the other maximal strength outcomes, probably due to
the “familiarization” with the testing device [22].
In this systematic review, as in the current literature, the evaluation of muscle power
received less attention among individuals with COPD although it may provide important
clinical value [50]. In addition, even when muscle power was evaluated, different devices
and protocols were used between the included studies, which does not allow the
comparison of results [30,35,40].

4.5. Structural and Systemic Effects of RT

This systematic review found weak evidence that RT was suitable for improving the
CSA of the quadriceps; nevertheless, this characteristic would require further attention.
Since the CSA of the quadriceps represents an independent predictor of survival,
simplified and reliable methods should be widely introduced to assess this muscle
characteristic in clinical practice [52].
FFM has also been shown to decline with COPD disease severity [2], and this was
evaluated in this systematic review using two different methods, with conflicting results:
(1) BIA represents a non‐invasive, inexpensive, and rapid methodology; (2) DEXA
provides more accurate results but involves logistical difficulties and costs [53]. Therefore,
in PR practice, the choice of measurement method is likely to be determined by the
availability of resources and equipment [54].

4.6. Study Limitations

This review presents potential limitations. (1) A limited number of randomized
controlled trials were found that investigated RT in isolation for patients with COPD
despite a methodologically accurate research. (2) Many of the included studies had a risk
of bias due, for example, to an inadequate sample size or the absence of a power
calculation as well as variation in measured outcomes and treatments carried out by the
control group. (3) The risk of publication bias is an inherent limitation of any systematic
review; the authors tried to limit this risk by searching for unpublished studies or non‐
English‐language studies, but nevertheless, the impact of the publication bias was not
calculated.

5. Conclusions
This systematic review provides an overview of the isolated RT programs that have
been used so far in outpatients with COPD and identifies gaps in the current literature,
producing recommendations for future research on this topic. Relying only on high‐
quality studies, supervised, isolated RT was found to be effective in improving maximal
muscle strength of both the upper and lower limbs in outpatients with COPD when
carried out 2 to 3 days a week for 8 to 12 weeks, performing three series of 8 to 15
repetitions with loads between 70 and 90% of 1RM. When the objective is instead to
improve local muscle endurance, a lower load and a higher number of repetitions (25–30)
should be preferred. Conversely, to enhance muscle power, which represents an
interesting but poorly explored perspective in clinical practice, emphasis should be placed
on the explosivity of the exercise when a high‐load (85–90% of 1RM) regime is applied.
However, designing a RT program for outpatients with COPD requires a preliminary
assessment of each trainable muscle characteristic and a further adjustment of the training
prescription according to the required number of repetitions, velocity of contraction, load,
and progression necessary to improve the specific aspect of muscle function being trained.
Healthcare 2021, 9, 1397 15 of 17

Furthermore, to obtain a complete framework of all the aspects of patients’ muscle

function, the evaluation of muscle strength, endurance, and power should be integrated
with the assessment of structural characteristics, such as muscle CSA and body FFM,
following the requirements of the clinical rehabilitation practice. A secondary aspect in
RT design, on the other hand, is the choice of the equipment for RT, which should be made
on the basis of its availability in the clinical setting and safety for patients since there are
no differences between, for example, weights or elastic resistance in terms of gain in
muscle strength. Finally, adopting training strategies, such as partitioning the exercising
muscle groups, namely exercising using a single limb at a time, might represent an
alternative to improve muscle dysfunction for those patients who are particularly limited
by exertional dyspnea. However, more studies on this topic are necessary to make
recommendations.

Supplementary Materials: The following are available online at

www.mdpi.com/article/10.3390/healthcare9101397/s1, Table S1: Database search strategy, Table S2:
Primary outcome results of the included studies.
Author Contributions: Conceptualization, S.P. and J.H.V.; methodology, J.H.V., N.F.L., and P.P.;
investigation, S.P. and P.P.; data curation, S.P. and P.P.; writing—original draft preparation, S.P.
and P.P.; writing—review and editing, S.P. and N.F.L.; supervision, J.H.V., L.N.C.B., and N.F.L.;
project administration, S.P. and N.F.L. All authors have read and agreed to the published version
of the manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflict of interest.

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