10

Prediction of Pulmonary Rehabilitation in Patients

with Chronic Lung Disease Using 6-minute Walk
Distance

Yu-Shan Li1, Hui-Chuan Chen1, Jung-Yien Chien2, Huey-Dong Wu1,

Li-Ying Wang3,4, Ping-Lun Hsieh3,4

Background: Pulmonary rehabilitation (PR) is an important part of the management and

health maintenance of chronic lung disease (CLD) patients. This study aimed to identify the
predictor of the percent predicted of the 6-minute walk distance (6MWD) in CLD patients.
Methods: Patients suffering from CLD, including both chronic obstructive pulmonary
disease (COPD) (n=102) and non-COPD (n=39), who received an outpatient 8-week
structured PR program between 2017 and 2019, were included, and their performance was
analyzed.
Results: A total of 141 patients were included in the study. The patients were divided
into 2 groups depending on whether the increase in the 6MWD reached the minimal clinically
important difference (MCID) of 30 m after PR. A total of 78 and 63 patients were classified
into the responders (> 30 m) and non-responders (≤ 30 m) group, respectively. All patients
showed significant improvements in the 6MWD and modified Medical Research Council
dyspnea scale. Multivariable logistic regression analysis showed that younger age (p= 0.005,
OR = 0.89, 95% CI: 0.83 – 0.97) and < 60% predicted of the 6MWD value were independent
factors predicting PR responders.
Conclusion: This study found that physical performance was improved after 8-week
structured PR in patients with CLD. Younger age and 6MWD < 60% of the predicted value
could predict a significant functional exercise capacity response to PR. (Thorac Med 2023;
38: 10-19)

Key words: Pulmonary rehabilitation, chronic lung disease (CLD), 6-minute walk distance (6MWD)

1
Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei 10002, Taiwan,
2
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of
Medicine, Taipei, Taiwan, 3Physical Therapy Center, National Taiwan University Hospital, Taipei, Taiwan, 4School
and Graduate Institute of Physical Therapy, National Taiwan University
Address reprint requests to: Dr. Hui-Chuan Chen, Department of Integrated Diagnostics & Therapeutics, National
Taiwan University Hospital, Taipei 10002, Taiwan

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 Pulmonary Rehabilitation Prediction in Chronic Lung Disease 11

widely used, practical basic test for assessing

Introduction exercise performance, and reflects the func-
tional exercise level for daily physical activi-
Patients with chronic lung disease (CLD) ties [12-13]. The 6MWD and percent predicted
are markedly inactive in daily life and are often 6MWD (% 6MWD) are important measures for
characterized by a downward spiral of symp- assessing cardiopulmonary function [14-15].
tom-induced inactivity, leading to decondition- Previous studies have proposed that % 6MWD
ing and muscle weakness [1], and consequently, was a better method for assessing subjects’
reduced time being spent walking and standing clinical status [16]. Several reference equations
compared with sedentary healthy elderly sub- already exist to calculate % 6MWD based on
jects. an individual's age, gender, height and weight,
There is convincing evidence of the posi- and can be used to assess functional exercise
tive effects of pulmonary rehabilitation (PR), capacity [17-20]. However, studies on the %
as a comprehensive intervention that includes 6MWD predictor of PR program outcomes are
exercise training, education and behavioral lacking. In this study, we hypothesized that the
change, on the progression of various pulmo- % 6MWD may be a reliable predictor of PR re-
nary diseases, particularly for patients with sponders among patients with CLD. We aimed
chronic obstructive pulmonary disease (COPD) to assess 8-month PR outcome predictions us-
[2-3]. Even seriously ill lung patients without ing the % 6MWD in patients with CLD.
COPD can experience significant and clinically
relevant improvements with PR [4]. Materials and Methods
In patients post-acute COPD exacerba-
tion, PR significantly reduces the number of re- Study Population
hospitalizations and can possibly even lead to a One hundred forty-one COPD patients
reduced risk of mortality [5]. In CLD patients, were screened at the Outpatient Chest Clinic of
the main adverse effects are ventilatory limita- National Taiwan University Hospital between
tion and skeletal muscle dysfunction; in lung 2017 and 2019. All subjects were > 20 years of
fibrosis patients, in addition to impaired gas age. Subjects with concomitant confounding
exchange, cardiovascular dysfunction appears diseases, such as malignant disorders, cardio-
to be a limiting factor [6-9]. There is substantial vascular abnormalities or recent surgery, were
evidence to support the importance of PR in excluded. All subjects underwent physical ex-
the management of COPD. Daily symptoms, aminations, assessment of lung function and
exercise performance and health status are gen- anthropometric measurements, including body
erally improved following PR. However, this mass index (BMI). BMI was calculated as body
is not true for all patients [10]. There is some weight in kilograms divided by height in meters
evidence that approximately 30% of patients squared.
who completed a PR course did not respond in
aspects of quality of life and physical perfor- Pulmonary function and 6MWD
mance [11]. Patients were instructed to walk in a 15-m
The 6-minute walk distance (6MWD) is a corridor for 6 minutes, receiving standard en-

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12 Yu-Shan Li, Hui-Chuan Chen, et al.

couragement during the test. Spirometry was condition that might influence their exercise re-
performed with a computerized spirometer sponses [26-27]. Our PR program also included
(MST-PFT, Germany) by a trained technician, instructions in breathing techniques (pursed-lip
according to the American Thoracic Society breathing and diaphragmatic breathing), air-
(ATS) criteria. The tests were performed with way clearance techniques, energy-conservation
the patient seated in an upright position, using techniques, and medication use. The exercise
a nose-clip and breathing through a non-com- prescription included supervised dyspnea or
pressible mouthpiece. All baseline spirometric fatigue-limited exercise training. Supplemental
measurements (forced expiratory volume in 1 oxygen was used during training for patients
second [FEV1], forced vital capacity [FVC], with exercise-induced oxygen desaturation (and
and FEV1/FVC) were obtained. COPD was exercise SpO2 less than 90%) and in patients
diagnosed as stable airway obstruction with who were already using home oxygen. Educa-
FEV1/FVC 70%, according to the Global Ini- tion included the importance of exercise and
tiative for Chronic Obstructive Lung Disease physical activity, proper use of medications, in-
(GOLD) criteria. Subjective scores of dyspnea haler technique, diet, hypoxemia management,
included a modified version of the Borg vi- oxygen treatment, coping and relaxation strate-
sual analog scale (Borg scale) and the modi- gies, bronchial hygiene techniques, and breath-
fied Medical Research Council dyspnea scale ing retraining, as well as self-management plans
(mMRC). The Dyspnea Scale quantifies disabil- for exacerbations. Supervised PR included at
ity attributable to breathlessness and is useful least 2 hours of exercise conditioning and edu-
for characterizing baseline dyspnea in patients cation.
with respiratory diseases.
Data collection
The outpatient PR program Demographic data (current age, sex, BMI,
The PR program consisted of 1 supervised and age at diagnosis) were obtained from the
session per week over an 8-week period, for subject’s medical records. A 6MWD was per-
a total of 8~10 sessions. The PR program was formed before and after completion of the PR
conducted by a multidisciplinary team, including program using published guidelines. % 6MWD
physicians, nurses, physiotherapists, respiratory prediction equations from a study are profiled
therapists and a dietician. Participants received below [17]:
an individually tailored exercise program. The Men: % 6MWD = (7.57 × height cm) – (1.76
supervised exercise training in this study con- × weight kg) – (5.02 × age) – 309 m
sisted of moderate-intensity aerobic exercises Women: % 6 MWD = (2.11 × height cm) –
and strengthening exercises that focused on (2.29 × weight kg) – (5.78 × age) + 667 m
upper and lower extremities. The intensity of The patients were divided into 2 groups
exercise training was targeted at 60-80% of the depending on the change in the 6MWD (re-
age-predicted maximal heart rate, 40-60% of sponders > 30 m and non-responders ≤ 30 m)
the heart rate reserved, or the modified Borg during PR. The “minimum clinically important
Dyspnea Scale 4-6/10, depending on the par- difference” (MCID) of 30 m was reported by
ticipants’ vital signs, medication use, and any Polkey [21]. The total distance walked, and the

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 Pulmonary Rehabilitation Prediction in Chronic Lung Disease 13

initial and final dyspnea scores were recorded. During the study period, 141 patients who
Dyspnea was scored with the mMRC Dyspnea came to the outpatient clinic for PR and com-
Scale [22], and measured during exercise using pleted > 8 sessions between 2017 and 2019
a modified Borg scale [23-24]. were reviewed. Our study demographic char-
acteristics revealed that more than 75% of the
Outcome measures patient groups were males. This is similar to
All subjects completed PR if they attended other studies that have shown a male predomi-
100% of the PR sessions (minimum of 8 ses- nance (78.9%) among combined COPD cohorts
sions). In the present study, the patients were in Taiwan. The prevalence rates of COPD in
divided into 2 groups depending on the change Taiwan seem to have peaked in men. However,
in 6MWD MCID (responders > 30m and non- it is possible there was selection bias in our
responders ≤ 30m) before and after PR. All pa- study population, since the outpatient chest
tients were assessed to determine whether there clinic indicated that patients be referred to the
was a subjective and/or objective improvement PR department. The mean (± SD) age of the
following the structured PR program. participants was 67.9±11.4 years, with 111 male
subjects (78.7%). Subject demographics and
Data analysis characteristics included spirometry use, inclu-
Data analyses and graphs were produced sion in the COPD group or non-COPD group,
using SPSS V.21 (IBM, USA). Descriptive cardiovascular co-morbidity, and hospital uti-
statistics (means, SD, counts, and frequen- lization, such as emergency department (ED)
cies in percent) were used to present patients’ visits and hospitalizations (Table 1).
baseline characteristics. Differences between The COPD and non-COPD groups were
the responder and non-responder groups were compared using the Dyspnea Severity Scale in
calculated using unpaired t-tests. P-values were response to PR. The COPD group results ac-
derived from an independent sample t-test for cording to GOLD stage are shown in Table 2.
continuous variables and from the chi-square Among the 141 patients, 102 (72.3%) were
test for categorical variables. Multivariate re- classified as having COPD. The non-COPD
gression analysis was used to identify patient subjects were diagnosed as having bronchiecta-
variables associated with response to PR. sis (13, 33.3%), pulmonary fibrosis (7, 17.9%),
and other diseases (19, 48.7%), classified as in-
Ethical approval terstitial lung disease or asthma associated with
The study was performed in accordance dyspnea. Seventy-eight participants (55%) had
with current ethical guidelines (Declaration of a responder outcome after PR. Patients in the
Helsinki) and was approved by the Research responder group were significantly younger (P=
Ethics Committee of National Taiwan 0.001), with a mean FEV1 of 51.3% ± 22.7%
University Hospital (No. 201905059RINB). versus 61.4% ± 23.4% in the non-responder
group (P= 0.012). The responder group had less
Results cardiovascular co-morbidity (P= 0.015). The
gender distribution, BMI, smoking history, ED
Subjects Baseline Characteristics: visits, and hospitalizations were not significant-

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14 Yu-Shan Li, Hui-Chuan Chen, et al.

Table 1. Baseline Characteristics Stratified According to Outcome

Response improved > 30 m No response improved ≤ 30 m
Variables Total (N=141) P
(n = 78) (n = 63)
Age (year) 67.9 ± 11.3 65.1 ± 11.3 71.4 ± 10.5 .001
Male 111 (78.7%) 63 (80.8%) 48 (76.3%) .509
BMI (kg/m ) 2
23.6 ± 10.1 22.9 ± 4.8 24.6 ± 14.0 .311
Smoking status .772
Non-smoker 63 (44.7%) 34 (43.6%) 29 (46.0%)
smoker 78 (55.3%) 44 (56.4%) 34 (54.0%) 0.09
COPD group 102 (72.3%) 59 (75.6%) 43 (68.3%) .330
a
Non-COPD .404
Bronchiectasis 13 (33.3%) 6 (31.6%) 7 (35.0%)
Lung fibrosis 7 (17.9%) 2 (10.5%) 5 (25.0%)
Others 19 (48.7%) 11 (57.9%) 8 (40.0%)
FEV1 % pred. 55.8 ± 23.5 51.4 ± 22.7 61.4 ± 23.4 .012
FEV1/FVC 55.7 ± 20.4 53.4 ± 19.9 58.6 ± 20.9 .137
Cardiovascular co-morbidity 69 (48.9%) 31 (39.7%) 38 (60.3%) .015
ED visits 1.5 ± 2.43 1.7 ± 2.41 1.3 ± 2.5 .352
Hospitalizations 0.9 ± 1.4 0.9 ± 1.2 0.9 ± 1.6 .917
Data are presented as the mean ± SD for continuous variables and n (%) for categorical variables. BMI: body mass index; COPD: chronic
obstructive pulmonary disease; FEV1: forced expiratory volume in the first second; FVC: forced vital capacity; ED: emergency department.

ly different between the 2 groups. 325.10 ± 93.19 m; P=0.014), as did the non-
responder group with COPD (349.49 ± 90.91 m
Six-minute walk distance, % 6MWD, and dys- versus 337.05 ± 95.70 m; P=0.013). In contrast,
pnea score the non-responder groups with COPD and with
COPD severity was staged by the degree non-COPD showed no significant change in %
of airflow limitation (i.e., GOLD stage). The 6MWD after 8 weeks of PR.
responder group had significant improvement The mMRC was significantly decreased be-
(P< 0.001) in both 6MWD (absolute values tween the responder group and the total group.
and percent of predicted) and mMRC, with However, the Borg score after PR was not sig-
equal effectiveness in different stages of COPD. nificantly decreased in either the responder or
After our comprehensive PR program, the % non-responder group.
6MWD was greatly improved in the responder
group (65.05% vs 82.42%). The 6MWD mean Predictors of response in CLD post-pulmonary
change of 113 m in the non-COPD group post- rehabilitation
PR was much more than the 90 m in the COPD Univariate logistic regression was used
group (Table 2). The non-responder group with to determine the associations between patient
COPD GOLD stages 1 and 2 had significant characteristics and response outcome variables,
decreases in 6MWD (absolute values) post-8 and showed a univariate association with re-
weeks of PR (mean 338.20 ± 86.03 m versus sponse post-PR (at P< 0.10). This was included

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 Pulmonary Rehabilitation Prediction in Chronic Lung Disease 15

Table 2. Six-minute Walk Distance and % 6MWD after Pulmonary Rehabilitation (PR)

Response group / Outcome pre-PR M ± SD post-PR M ± SD P

Responder (n = 78)
% 6MWD, % 63.27 ± 20.55 81.64 ± 18.05 <.001
6MWD, m 309.28 ± 101.95 405.28 ± 90.94 <.001
COPD GOLD 1,2 % 6MWD, % (n = 18) 71.77 ± 21.08 90.59 ± 17.95 <.001
COPD GOLD 1,2 6MWD, m (n = 18) 326.96 ± 105.27 428.42 ± 86.32 <.001
COPD GOLD 3,4 % 6MWD, % (n = 41) 59.02 ± 19.09 77.16 ± 16.51 <.001
COPD GOLD 3,4 6MWD, m (n = 41) 65.05 ± 20.67 82.42 ± 18.14 <.001
COPD group % 6MWD, % (n = 59) 71.77 ± 21.08 90.59 ± 17.95 <.001
COPD group 6MWD, m (n = 59) 310.08 ± 99.60 400.69 ± 87.92 <.001
Non-COPD group % 6MWD, % (n = 19) 57.73 ± 19.65 79.21 ± 18.02 <.001
Non-COPD group 6MWD, m (n = 19) 306.79 ± 111.77 419.53 ± 100.93 <.001
Borg scale 3.97 ± 1.37 4.05 ± 1.86 .726
mMRC 2.10 ± 0.95 1.63 ± 0.86 <.001
Non-responder (n = 63)
% 6MWD, % 72.87 ± 16.44 71.65 ± 16.93 .092
6MWD, m 342.37 ± 86.73 328.41 ± 100.18 .015
COPD GOLD 1,2 % 6MWD, % (n = 20) 76.23 ± 15.93 74.16± 16.95 .128
COPD GOLD 1,2 6MWD, m (n = 20) 338.20 ± 86.03 325.10 ± 93.19 .014
COPD GOLD 3,4 % 6MWD, % (n = 23 74.94 ± 17.85 74.28 ± 18.11 .583
COPD GOLD 3,4 6MWD, m (n = 23) 359.30± 95.77 347.43± 98.70 .151
COPD group % 6MWD, % (n = 43) 75.54 ± 16.80 74.22 ± 17.37 .139
COPD group 6MWD, m (n = 43) 349.49 ± 90.91 337.05 ± 95.70 .013
Non-COPD group % 6MWD, % (n = 20) 66.84 ± 14.22 65.83 ± 14.68 .435
Non-COPD group 6MWD, m (n = 20) 327.05 ± 76.88 309.85 ± 109.42 .250
Borg scale 3.79 ± 1.69 3.71 ± 1.34 .738
mMRC 2.14 ± 0.94 1.95 ± 1.07 .154
Total (n = 141)
% 6MWD, % 67.52 ± 19.37 77.21 ± 18.19 <.001
6MWD, m 324.06 ± 96.54 370.94 ± 102.30 <.001
COPD GOLD 1,2 % 6MWD, % (n = 38) 77.29 ± 17.73 83.64 ± 20.04 <.001
COPD GOLD 1,2 6MWD, m (n = 38) 345.08 ± 94.63 383.00 ± 105.98 .008
COPD GOLD 3,4 % 6MWD, % (n = 64) 64.83 ± 19.53 76.19 ± 16.55 <.001
COPD GOLD 3,4 6MWD, m (n = 64) 315.78 ± 98.34 368.44 ± 90.25 <.001
COPD group % 6MWD, % (n = 102) 69.47 ± 19.74 78.96 ± 18.19 <.001
COPD group 6MWD, m (n = 102) 326.70 ± 97.55 373.86 ± 96.15 <.001
Non-COPD group % 6MWD, % (n = 39) 62.28 ± 17.53 72.52 ± 17.57 <.001
Non-COPD group 6MWD, m (n = 39) 317.18 ± 94.76 363.28 ± 117.89 .003
Borg scale § 3.89 ± 1.52 3.90 ± 1.64 .965
mMRC 2.11 ± 0.94 1.77 ± 0.97 <.001
Data are presented as mean ± standard deviation
6MWD: 6-minute walk distance; % 6MWD: percent predicted for 6-minute walk distance; GOLD stage: Global Initiative for Chronic Obstructive
Lung Disease stage; mMRC: modified Medical Research Council.
§
This visual is designed for rehabilitation therapists to assess and document perceived exertion throughout a therapy task. Based on the Borg scale
and numbered 1-10

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16 Yu-Shan Li, Hui-Chuan Chen, et al.

Fig. 1. Distribution of responses and non-responses stratified by > 80%, 60-79%, 40-59%, < 39% predicted 6MWD (% 6MWD) before pulmonary
rehabilitation.

in stepwise backward multivariate logistic After adjustment for possible confound-

models to adjust for confounders. This study ing factors, including age, pre-PR % 6MWD <
addressed an important clinical issue regard- 60%, FEV1, and cardiovascular co-morbidity,
ing the role of % 6MWD in the predictors of multivariate analysis showed that age (OR =
response in CLD post-PR. The thresholds of % 0.89, P = 0.005) and % 6MWD < 60 % (OR =
6MWD on response between groups had obvi- 8.11, P = 0.032) were independently confirmed
ously changed to 57% (Figure 1). The univari- as predictors of response in CLD after PR (Table
ate analysis shows that < 60% 6MWD may be a 3).
stronger predictor of response.

Table 3. Multivariate Analysis for Identifying Predictors of Response Post-PR

Univariate Multivariate
Factors
OR (95%CI) P OR (95%CI) P
Age (years) 0.95 (0.92 - 0.98) .002 0.89 (0.83–0.97) .005
Pre-PR % 6MWD < 60% 2.40 (1.12–5.15) .024 8.11 (1.20 – 54.8) .032
FEV1% 0.98 (0.97 - 1.00) .016 0.94 (0.87 - 1.01) .094
CV co-morbidity 1.88 (0.22 - 0.86) .011 0.41 (0.55–10.7) .239
Factors included in the multivariate analysis in order to identify independent predictors of response. CV: cardiovascular; OR: odds ratio; CI:
confidence interval.

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 Pulmonary Rehabilitation Prediction in Chronic Lung Disease 17

Discussion Hence, knowledge of the factors predict-

ing response is crucial for ensuring better PR
The present study sought to identify factors efficacy. The role of baseline lung functions in
that could predict clinical outcomes after PR in predicting benefit after PR for COPD patients
CLD patients. The results showed that age and has been investigated previously. However, the
% 6MWD < 60 were independent predictors as- results have been discordant, with a few stud-
sociated with response to PR. In current clinical ies showing a negligible value, while others
practice, the 6MWD is the only critical factor demonstrated a positive association between a
for physicians when making clinical decisions, worse baseline lung function and improvement
but the significant value of % 6MWD is un- in exercise capacity [21-24]. In the present
known in CLD patients. In a past study, the % study, patients with FEV1 demonstrated that
6MWD was better correlated with respiratory the exercise capacity of a responder was signifi-
function than the actual 6MWD [17]. However, cantly lower than that of a non-responder, com-
no recent study has explored the correlations pared to those with a preserved lung function,
between the percentage values of % 6MWD and in the present population, FEV1 percent
and response to PR. In the present study, it was of predicted was a weak predictor for outcome
necessary to standardize the use of % 6MWD, of PR. Nevertheless, this study demonstrated
and we suggested that < 60% predicted 6MWD the positive outcomes of a comprehensive PR
would be a higher predicted response post-PR. program in COPD patients at all stages of the
Our study reinforced the existing scien- disease.
tific evidence regarding the benefit of PR in This study did not reveal an association be-
improving exercise capacity and decreasing tween BMI, smoking and the COPD group after
mMRC in all patients. Fifty-five percent of a PR response. Other variables such as dyspnea
patients in the study had a response post-PR. score and cardiovascular co-morbidity have
The response rates were comparable to those also been evaluated previously, but these factors
of previous studies that reported improvements did not yield a predictive response in this study.
of 50%–68% [18-19] and 50%–75% [20-21] Certain cardiovascular co-morbidities, such as
in 6MWD, respectively. These previous stud- coronary artery disease, heart attack, arrhyth-
ies showed that reference equations, actual mia, peripheral artery disease and heart failure,
6MWD and % 6MWD are important for as- have also been evaluated as predictors of re-
sessing cardiopulmonary function. Gender was sponse to PR. But, in our population, the inci-
an important bias factor for actual 6MWD, and dence of cardiovascular co-morbidities was sig-
%6MWD was better related to pulmonary func- nificantly lower in the responder group. Despite
tion than 6MWD. In the present study, we used the fact that impairment is different in patients
reference equations for 6MWD in CLD patients with CLD or cardiovascular co-morbidity, the
after outpatient PR, and assessed their value in underlying symptoms reported by these patients
reflecting exercise capacity. We endeavored to during exercise are common, and are related
demonstrate whether the percentage predicted predominantly to leg discomfort and shortness
value is a better predictor for the response post- of breath. A PR program significantly increases
PR. functional capacity in patients with CLD or

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18 Yu-Shan Li, Hui-Chuan Chen, et al.

congestive heart failure after completion of the Cochrane Database Syst Rev 2015(2): Cd003793.
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