Four-meter gait speed predicts daily physical activity in patients with chronic respiratory diseases

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Respiratory Investigation journal homepage: www.elsevier.com/locate/resinv

Original article

Four-meter gait speed predicts daily physical activity in patients with chronic respiratory diseases Chieko Yoshida, Hidenori Ichiyasu*, Hideharu Ideguchi, Susumu Hirosako, Aiko Masunaga, Keisuke Kojima, Sho Saeki, Kazuhiko Fujii, Takuro Sakagami, Hirotsugu Kohrogi Department of Respiratory Medicine, Kumamoto University Hospital, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan

article info

abstract

Article history:

Background: Physical activity measures are valuable for assessing the progression of chronic

Received 16 September 2018

respiratory diseases. The 4-m gait speed (4MGS) test is an established functional assess-

Received in revised form

ment in the elderly. However, the relationship between the 4MGS and daily activity in

4 February 2019

patients with chronic respiratory diseases has not been fully understood. The present

Accepted 15 March 2019

study aimed to investigate whether the 4MGS predicted daily activity, including physical

Available online 13 May 2019

activity level (PAL), in patients with chronic respiratory diseases. Methods: We enrolled 57 patients with chronic respiratory diseases, including interstitial

Keywords:

lung disease and chronic obstructive pulmonary disease, and evaluated the correlations

Four-meter gait speed

between the 4MGS and various clinical parameters, including respiratory function, the 6-

Chronic respiratory diseases

min walk test (6MWT), and daily activities, by using an accelerometer. Linear regression

Physical activity level

analysis was performed to identify significant predictors of daily activity.

Chronic obstructive pulmonary dis-

Results: The 4MGS was significantly correlated with daily step counts and PAL, as well as

ease

the 6 min walk distance (r ¼ 0.477, p < 0.001; r ¼ 0.433, p ¼ 0.001; and r ¼ 0.593, p < 0.001,

Interstitial lung disease

respectively). In the multivariate linear regression analysis, the 4MGS, % predicted forced expiratory volume in 1 s, and body mass index were independent predictors of PAL. Receiver operating characteristic analysis revealed that a 4MGS <1.07 m/s was the optimal cutoff for predicting an inactive PAL (area under the curve, 0.728; 95% confidence interval, 0.589e0.866). Patients with a slower 4MGS had significantly reduced daily activity than did

Abbreviations: 4MGS, 4-m gait speed; PAL, physical activity level; 6MWT, 6-min walk test; COPD, chronic obstructive pulmonary disease; ILD, interstitial lung disease; 6MWD, 6-min walk distance; SpO2, percutaneous oxygen saturation; DLco, diffusing capacity of the lung for carbon monoxide; IPF, idiopathic pulmonary fibrosis; GOLD, Global Initiative for Chronic Obstructive Lung Disease; PR, pulse rate; ATS, American Thoracic Society; WHO, World Health Organization; DSI 90, desaturation index 90; BMI, body mass index; mMRC, modified Medical Research Council; ROC, receiver operating characteristic; PaO2, partial pressure of arterial oxygen; PaCO2, partial pressure of arterial carbon dioxide; AaDO2, alveolarearterial oxygen difference. * Corresponding author. Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. E-mail addresses: [email protected] (C. Yoshida), [email protected] (H. Ichiyasu), [email protected] (H. Ideguchi), [email protected] (S. Hirosako), [email protected] (A. Masunaga), [email protected] (K. Kojima), [email protected] (S. Saeki), [email protected] (K. Fujii), [email protected] (T. Sakagami), [email protected] (H. Kohrogi). https://doi.org/10.1016/j.resinv.2019.03.009 2212-5345/© 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

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those with a preserved 4MGS, despite similar modified Medical Research Council dyspnea scale measures and respiratory parameters, such as oxygenation profiles. Conclusions: The 4MGS test is a simple screening test and a useful predictor of worsening daily activity in patients with chronic respiratory diseases. © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

1.

Introduction

Sustained physical inactivity in patients with chronic respiratory diseases leads to a “negative spiral,” including worsening exertional dyspnea, muscle atrophy, and malnutrition. Waschki et al. [1] reported that physical activity was the strongest predictor of all-cause mortality in patients with chronic obstructive pulmonary disease (COPD). Thus, evaluating physical activity and exercise tolerance in patients with chronic respiratory diseases is important. The 6-min walk test (6MWT) is used to evaluate functional exercise capacity across a wide range of respiratory diseases, including interstitial lung disease (ILD) and COPD [2]. The 6 min walk distance (6MWD) is positively associated with peak exercise capacity and negatively associated with the risk of disease exacerbation and clinical outcomes in patients with chronic respiratory diseases [3]. However, this test is difficult to conduct in clinical settings where the test space is poorly equipped and time is limited. Furthermore, debilitated and elderly individuals do not find it easy to walk for 6 min. Therefore, a test that is easy and of shorter duration has advantages in some clinical settings, such as outpatient clinics. Usual gait speed measured over 4 m (4-m gait speed [4MGS]) is a potentially useful marker of multisystemic wellbeing in community-dwelling elderly adults [1,4e6]. Reduced gait speed has been accepted as one of the main determinants of disability, age-related subclinical conditions, institutionalization, and mortality in healthy elderly adults [4]. In a metaanalysis, gait speed predicted the survival of elderly adults [5]. Recently, several studies proposed that the 4MGS was valuable for evaluating functional abilities in patients with COPD [7e10]. However, few reports have documented the relationship between gait speed and physical activity, including physical activity level (PAL), lung function, and oxygenation profile, in other chronic pulmonary diseases, including ILD. Thus, the utility of the 4MGS in patients with various respiratory diseases is still controversial. The objective of this study was to assess the usefulness of the 4MGS as an indicator of daily physical activity and to compare its utility with that of the 6MWD in patients with chronic respiratory diseases. Some of the results of this study were previously reported as abstracts [11].

informed written consent was obtained from all subjects. Fifty-seven outpatients with stable chronic respiratory diseases undergoing treatment at Kumamoto University Hospital were recruited between December 2013 and March 2016. The inclusion criteria were as follows: 1) patients with chronic respiratory diseases including ILD and COPD, and clinically stable over the previous 4 weeks; 2) age 20 years; 3) percutaneous oxygen saturation (SpO2)  90% at rest in room air and not receiving supplemental oxygen; and 4) the ability to perform the 6MWT and pulmonary function tests, including the diffusing capacity of the lung for carbon monoxide (DLco) test. ILD diagnoses included idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia, chronic hypersensitivity pneumonia, and connective tissue diseaseassociated lung diseases. These diagnoses were confirmed using previously reported criteria [12e14]. COPD was diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria [15]. Other disorders included obstructive respiratory diseases that did not meet the GOLD criteria, bronchiectasis, and pulmonary lymphangioleiomyomatosis. The exclusion criteria were as follows: 1) patients with concomitant confounding diseases that could affect their performance during the 6MWT, such as uncontrolled cardiovascular diseases, neuromuscular diseases, orthopedic diseases, or unstable respiratory conditions, including respiratory tract infections; 2) respiratory disease exacerbation; or 3) difficulties in detecting the patient's pulse or measuring oxygen saturation via pulse oximetry.

2.2.

Four-meter gait speed

We measured the 4MGS on the basis of the Short Physical Performance Battery protocol available from the National Institution on Aging (www.grc.nia.nih.gov/branches/ledb/ sspb/). Briefly, a 4-m flat, unobstructed course was prepared and marked out with tape. The subjects were asked to walk at their usual speed. We measured the time the subjects took to walk completely across the 4 m by using a stopwatch. The test was repeated without rest, and the faster of the two times was considered the 4MGS, expressed in m/s. During and after the test, the SpO2 and pulse rate (PR) were monitored using pulse oximetry (PULSOX-Me 300, TEIJIN Co., Ltd., Japan) until the values returned to baseline. The subjects were allowed to use walking aids such as canes and walkers, if required.

2.

Materials and methods

2.3.

2.1.

Subjects

The 6MWT was performed in the hospital on a flat, straight, 30-m walking course according to the American Thoracic Society (ATS) guidelines [16]. Subjective scores of dyspnea, determined using the modified Borg scale, were measured and

This study was approved by the Kumamoto University Research Ethics Committee (approval number: 1708), and

Six-minute walk test

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recorded before and after the 6MWT. The SpO2 and PR were measured during and after the test via pulse oximetry.

2.4.

Daily physical activity

To measure daily physical activity, we attached a uniaxial accelerometer (Lifecorder GS; Suzuken, Co., Ltd., Japan) to each subject's waist from the time he or she got up in the morning, and it was worn until bedtime (excluding when bathing or swimming). The Lifecorder GS recorded the following: daily step counts, walking distance, momentum, activity time, and energy expenditure. A maximum pulse over 4 s was taken as the acceleration value, and the intensity of the activity was categorized into 11 grades based on the accelerometer signal pattern. The activity intensity was subsequently converted into energy expenditure by using an algorithm. Data from the subjects who wore the accelerometer for at least 12 h a day were considered valid [17]. PAL was calculated as the total daily energy expenditure divided by the basal metabolic rate, as estimated using gender-age equations [18]. According to the World Health Organization (WHO), people with a PAL  1.70 are considered moderately to extremely active; those with a PAL of 1.40e1.69 are considered sedentary; and those with a PAL < 1.40 are considered extremely inactive [18,19].

2.5.

Pulse oximetry monitoring

To monitor each subject's SpO2 and PR for at least 24 h, the pulse oximeter probe was attached to a fingertip, and the oximeter was secured to the subject's wrist. All the oximetry data were downloaded to a computer for analysis. We defined the percent of diurnal registered oximetry time with SpO2 < 90% as the “desaturation index 90 (DSI 90).”

2.6.

Other measurements

We recorded the subjects’ demographic data, including age, sex, height, weight, body mass index (BMI), and smoking history. Dyspnea was measured using the modified Medical Research Council (mMRC) dyspnea scale. Spirometry was performed using a Chestac-8800 (Chest Co. Ltd., Tokyo, Japan), according to ATS/European Respiratory Society consensus guidelines [20,21]. The functional residual capacity was measured using a closed-circuit helium-gas dilution system. The Japanese Respiratory Society pulmonary function reference values were used to evaluate the % predicted values [22]. DLco was measured using the single breath-hold method. Arterial blood gas analysis was performed in room air, with the subject at rest and seated, by using a RAPID Point 500 system (Siemens Healthcare Ltd., Tokyo, Japan).

2.7.

Analysis

Data were expressed as means and standard deviations and were compared using the ManneWhitney U test. Categorized variables were analyzed using the chi-square test or Fisher's exact test, as appropriate for the sample size. Correlations between the 4MGS and other variables, including daily physical activities, were evaluated using Spearman's rank

correlation coefficient. A stepwise multivariate linear regression model was used to establish the independent explanatory variables for decreased daily physical activity. By using a receiver operating characteristic (ROC) curve, we determined the cutoff points of the 4MGS for identifying subjects who were extremely inactive (PAL < 1.40). A p value < 0.05 indicated statistical significance. Statistical analyses were performed using IBM SPSS Statistics for Windows/Macintosh, Version 22.0 (IBM Corp., Armonk, NY, USA).

3.

Results

3.1.

Baseline characteristics

During the study period, 57 subjects (44 men and 13 women) satisfied the inclusion criteria, agreed to participate, and completed all study procedures. Table 1 summarizes their clinical characteristics. Their mean age was 68.1 years, mean %FEV1 was 71.8%, and mean %DLco was 66.9%. The most common disease was ILD (64.9%), followed by COPD (28.1%), and other miscellaneous conditions (7.0%). The mean partial pressure of arterial oxygen at rest and 6MWD were preserved, but the mean minimum SpO2 during the 6MWT was 88.1%, and approximately half (51.8%) of the subjects had SpO2 levels < 90% during the 6MWT. The mean diurnal DSI 90 was 5.6%, suggesting hypoxemia during daily activities. The mean 4MGS was 1.06 m/s. Objectively measured daily physical activity, including step counts, was low, and the mean PAL was 1.37 ± 0.10. According to the WHO classification, 36 of 57 (63.2%) patients were classified as “extremely inactive,” and the remaining 21 (36.8%) were classified as “sedentary.”

3.2.

Comparison between the 4MGS test and 6MWT

The 4MGS correlated significantly with the 6MWD (Fig. 1; r ¼ 0.593, p < 0.001). The PR did not significantly differ before and after the 4MGS test, whereas it significantly increased after the 6MWT (Fig. 2A; 4MGS test, p ¼ 0.101; 6MWT, p < 0.001). The SpO2 significantly decreased after both tests (Fig. 2B; 4MGS test, p ¼ 0.014; 6MWT, p < 0.001). The degrees of decreased changes in SpO2 were significantly smaller with the 4MGS test than with the 6MWT (Fig. 2C; p < 0.001). These results indicated that the 4MGS test was easier and less exhausting to perform than was the 6MWT.

3.3. Relationship between the 4MGS and 6MWD and clinical parameters Table 2 shows the correlations between the 4MGS and 6MWD and clinical parameters. In the 4MGS test, significant correlations with %FEV1 (r ¼ 0.298, p < 0.024) and daily physical activities (step counts, r ¼ 0.477, p < 0.001; PAL, r ¼ 0.433, p ¼ 0.001) were observed. In the 6MWT, significant correlations were observed with the BMI (r ¼ 0.293, p ¼ 0.028), mMRC score (r ¼ 0.382, p ¼ 0.004), %FEV1 (r ¼ 0.418, p < 0.001), and daily physical activities (step counts, r ¼ 0.420, p < 0.001; PAL, r ¼ 0.456, p < 0.001). When the subjects were divided into groups with ILD and COPD, the 4MGS significantly correlated with daily physical activities in both groups (s-Tables 1 and 2;

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Table 1 e Baseline characteristics of the study subjects. Subjects (N ¼ 57) 68.1 ± 11.3 44/13 22.6 ± 3.4 21/36/0 37 16 4 8/30/9/7/3 81.4 71.9 71.8 66.9

5,077 ± 3,753 1.37 ± 0.10 5.6 ± 6.3 94.8 ± 1.4

ILD group: step counts, r ¼ 0.403, p ¼ 0.013; PAL, r ¼ 0.361, p ¼ 0.028; COPD group: step counts, r ¼ 0.674, p ¼ 0.020; PAL, r ¼ 0.526, p ¼ 0.036). In contrast, the 6MWD correlated with PAL and step counts in patients with ILD alone (step counts, r ¼ 0.397, p ¼ 0.016; PAL, r ¼ 0.413, p ¼ 0.012). However, the DSI 90 and diurnal SpO2 did not significantly correlate with either the 4MGS or 6MWD. During the stepwise multiple linear regression analysis, the 4MGS (b, 0.307; p ¼ 0.011), %FEV1 (b, 0.262; p ¼ 0.038), and BMI (b, 0.304; p ¼ 0.012) were independent explanatory variables of decreased PAL (Table 3).

Prediction of the extremely inactive condition

By using a ROC curve for identifying inactive patients (PAL < 1.40), a 4MGS < 1.07 m/s was found to be the best cutoff point, yielding 71.7% sensitivity and 66.7% specificity (area under the curve ¼ 0.728) (Fig. 3). Therefore, the subjects were stratified according to the 4MGS with “slow” gait speed defined as a 4MGS <1.07 m/s and “preserved” gait defined as a 4MGS 1.07 m/s. The slow gait speed group showed significant

400 300

100 0

80.3 ± 11.8 40.9 ± 6.1 18.5 ± 11.6 405.6 ± 86.2 88.1 ± 5.4 1.06 ± 0.19

500

200

± 21.8 ± 19.2 ± 22.3 ± 26.0

Data are expressed as group means ± standard deviations or the number of subjects. Abbreviations: BMI, body mass index; ILDs, interstitial lung diseases; COPD, chronic obstructive pulmonary disease; mMRC, modified Medical Research Council; FVC, forced vital capacity; FEV1, forced expiratory volume in 1 s; DLco, diffusing capacity for carbon monoxide; PaO2, partial pressure of arterial oxygen; PaCO2, partial pressure of arterial carbon dioxide; AaDO2, alveolarearterial oxygen difference; 6MWT, 6-min walk test; 6MWD, 6-min walk distance; SpO2, percutaneous oxygen saturation; 4MGS, 4-m gait speed; PAL, physical activity level; DSI; desaturation index.

3.4.

600

6MWD (m)

Age (years) Sex (male/female) BMI (kg/cm2) Smoking status (never/ex/current) Underlying diseases ILDs COPD Others mMRC score (0/1/2/3/4) Pulmonary function test FVC (% predicted) FEV1/FVC (%) FEV1 (% predicted) DLco (% predicted) Arterial blood gas analysis PaO2 (Torr) PaCO2 (Torr) AaDO2 (Torr) 6MWT 6MWD (m) Minimum SpO2 (%) 4MGS (m/s) Daily activity Step counts (steps/day) PAL DSI 90 (%) Diurnal mean SpO2 (%)

r = 0.593 p < 0.001

700

0.4

0.6

0.8

1

1.2

1.4

1.6

4MGS (m/s) Fig. 1 e Correlations between the 4-m gait speed (4MGS) and the 6-min walk distance (6MWD). The 4MGS significantly correlates with the 6MWD (r ¼ 0.593, p < 0.001).

impairment in exercise capacity and poor daily activity performance. However, no differences were observed in the mMRC score and respiratory parameters, including alveolarearterial oxygen difference, %DLco, DSI 90, and diurnal mean SpO2, except for %FEV1, between the two groups (Table 4).

4.

Discussion

This was the first study to show a significant correlation between the 4MGS and 6MWD and daily physical activity including step counts and PAL in patients with chronic respiratory diseases. The 4MGS, BMI, and %FEV1 were independent explanatory variables of an inactive PAL. A cutoff value of 4MGS <1.07 m/s was optimal for predicting an inactive PAL. The 4MGS test appears useful as a screening test for predicting daily activity performance. The changes in the PR and SpO2 during the 4MGS test were less than those during the 6MWT, suggesting that the 4MGS test was easier and more comfortable than was the 6MWT for patients with chronic respiratory diseases. Although patients with mild to moderate respiratory dysfunction showed nearly normal SpO2 levels at rest, the 4MGS test revealed likely inactivity. Patients with mild to moderate pulmonary impairment are often normoxemic at rest, but they develop hypoxemia during exercise and daily living tasks. This exercise-induced hypoxemia strongly correlates with the severity of COPD and is associated with decreased lung function and poor prognosis [23,24]. Moreover, some patients tend to limit, consciously or subconsciously, their physical activity to avoid exerciseinduced hypoxemia and subsequent worsening of symptoms. This assertion is supported, in part, by our data, given that the %FEV1 was an independent predictor of PAL. In

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(A)

(B) p = 0.014 100

140

95

120

90

100

p < 0.001

0

85

80

80

60

75

40

70

p < 0.001 5

∆ SpO2 (%)

p < 0.001

160

SpO2 (%)

Pulse rate (bpm)

N.S.

(C)

-5

-10

-15

-20

4MGS 6MWT 4MGS

6MWT

4MGS

6MWT

Fig. 2 e Comparisons of the pulse rate (PR) and percutaneous oxygen saturation (SpO2) before and after the 4-m gait speed (4MGS) test and 6-min walking test (6MWT). (A) The PRs significantly increase after the 6MWT, whereas no significant difference is noted before and after the 4MGS test. (B) The SpO2 values after both the tests are significantly decreased compared with the pre-test values. (C) SpO2 changes (DSpO2) during the test are significantly smaller during the 4MGS test than during the 6MWT (p < 0.001). The box-and-whisker plot shows the 25th and 75th percentiles (box), the median (the horizontal line within the box), and the 10th and 90th percentiles (whiskers). N.S, not significant. particular, the evaluation of daily physical activity is critical for patients with chronic respiratory diseases, including ILD and COPD, thus underscoring the need for a simple and reliable test to predict physical activity. A novel finding in the present study was that the 4MGS, as well as %FEV1, explained PAL and daily step counts. Furthermore, the 4MGS was well-correlated with the 6MWD, a historically strong predictor of daily activity in patients with COPD and IPF [25,26]. Hence, our results seem to correspond to those of previous reports confirming the relationship between walking performance and daily physical activity [17]. The

Table 2 e Relationship between the 4MGS and 6MWD and clinical parameters. 4MGS

Age (years) BMI (kg/m2) mMRC FVC (% predicted) FEV1 (% predicted) DLco (% predicted) AaDO2 (Torr) Step counts (steps) PAL DSI 90 (%) Diurnal mean SpO2 (%)

6MWD

r

p value

r

p value

1.181 0.123 0.246 0.207 0.298 0.064 0.017 0.477 0.433 0.073 0.009

0.179 0.361 0.065 0.122 0.024 0.635 0.900 <0.001 0.001 0.591 0.946

0.280 0.293 0.382 0.251 0.418 0.139 0.256 0.420 0.456 0.097 0.149

0.036 0.028 0.004 0.062 0.001 0.305 0.071 <0.001 <0.001 0.477 0.278

The r and p values were calculated using Spearman's rankcorrelation analysis. Abbreviations: 4MGS, 4-m gait speed; 6MWD, 6-min walk distance; BMI, body mass index; mMRC, modified Medical Research Council; FVC, forced vital capacity; FEV1 forced expiratory volume in 1 s; DLco, diffusing capacity for carbon monoxide; AaDO2, alveolarearterial oxygen difference; PAL, physical activity level; DSI, desaturation index; SpO2, percutaneous oxygen saturation.

major factor associated with the 4MGS is the strength of the leg muscles. Further, the 4MGS test is easier and less exhausting than is the 6MWT, and the 4MGS has been accepted as an indicator of whole functional status, including exercise tolerance, in the geriatric population. Therefore, it is feasible that the 4MGS correlated with both physical activity and exercise capacity, as did the 6MWD. To our knowledge, only one previous report has documented the ability of the 4MGS to independently predict PAL. DePew et al. [27] showed that PAL significantly affected the 4MGS in patients with chronic lung diseases by using multivariate analysis. However, unlike our subjects, those authors enrolled patients with severe lung dysfunction (e.g., mean %FEV1 of 31.5% and mean %DLco of 42.0%) and did not identify a 4MGS cutoff value for detecting inactivity. Moreover, by using a ROC curve, we expanded upon past findings by determining the cutoff value for identifying patients with an inactive PAL. Karpman et al. [9] showed that the 4MGS could detect low 6MWD, thus suggesting that the 4MGS is more closely related to exercise capacity than daily physical activity in patients with COPD. Gait speed is a well-established and potentially useful marker of physical performance, mobility, sarcopenia, and frailty among elderly adults [6,28]. Owing to its simplicity and

Table 3 e Relationship between daily physical activity and clinical variables assessed using multivariate linear regression analysis. Daily activity PAL

Covariate

b coefficient

p value

R2

4MGS %FEV1 BMI

0.307 0.262 0.304

0.011 0.038 0.012

0.335

Abbreviations: PAL, physical activity level; 4MGS, 4-m gait speed; FEV1, forced expiratory volume in 1 s; BMI, body mass index.

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Sensitivity

0.8

0.6 0.4 AUC=0.728 Cut-off: 4MGS=1.07 m/s PPV=55.6% NPV=80.0%

0.2 0

0

0.2

0.4

0.6

0.8

1

1 – Specificity Fig. 3 e The receiver operating characteristic curve analysis. A 4-m gait speed (4MGS) of 1.07 m/s has the highest accuracy and serves as the cutoff value for predicting the inactive physical activity level (<1.40). The vertical axis shows the number of true positives (sensitivity); the horizontal axis shows the number of false positives (1 ¡ specificity). AUC, area under the curve; PPV, positive predictive value; NPV, negative predictive value.

reduced time and space requirements, the 4MGS test is a widely used assessment tool in clinical settings. In patients with COPD, the 4MGS is associated with pulmonary function and functional capacity [7,29]. Recently, Kon et al. reported that the 4MGS correlated well with the health-related quality of life, risk of readmission, and responsiveness to pulmonary

Table 4 e Comparison of patients with chronic respiratory diseases with either slow or preserved 4MGS. 4MGS

Age, years Sex (male/female) BMI (kg/cm2) mMRC score (0/1/2/3/4) FVC (% predicted) FEV1 (% predicted) DLco (% predicted) AaDO2 (Torr) 6MWD (m) Step counts (steps) PAL DSI 90 (%) Diurnal mean SpO2 (%)

Slow (n ¼ 30)

Preserved (n ¼ 27)

70.6 ± 8.6 25/5 21.9 ± 3.8 3/15/4/5/3 76.6 ± 22.7 63.9 ± 21.6 69.0 ± 31.9 18.6 ± 11.9 372.0 ± 96.8 3896 ± 3362 1.33 ± 0.09 4.8 ± 4.9 94.7 ± 1.2

65.3 ± 13.3 19/8 23.3 ± 3.0 5/15/5/2/0 86.7 ± 19.7 80.4 ± 20.0 64.6 ± 17.5 18.4 ± 11.6 440.2 ± 55.8 6389 ± 3786 1.41 ± 0.10 6.5 ± 7.7 94.9 ± 1.6

p value

0.246 0.396 0.069 0.114 0.164 0.010 0.994 0.919 <0.001 0.004 0.004 0.502 0.350

Data are expressed as group means ± standard deviations or the number of subjects. The p values refer to comparisons between the two groups. Abbreviations: 4MGS, 4-m gait speed; BMI, body mass index; mMRC, modified Medical Research Council; FEV1, forced expiratory volume in the first 1 s; DLco, diffusing capacity for carbon monoxide; AaDO2, alveolarearterial oxygen difference; 6MWD, 6-min walk distance; PAL, physical activity level; DSI; desaturation index; SpO2, percutaneous oxygen saturation.

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rehabilitation in patients with COPD who were hospitalized with acute pulmonary exacerbations [7,8,30]. In a systematic review of studies on patients with COPD, Johnston et al. [31] showed that the cutoff values of the 4MGS for identifying patients with lower exercise capacities were 0.9 m/s (sensitivity, 64%; specificity, 90%) and 1.0 m/s (sensitivity, 80%; specificity, 50%). Our results also showed that a 4MGS cutoff value < 1.07 m/s was optimal for predicting an inactive PAL. This was similar to the results of the aforementioned report. However, the clinical significance of the 4MGS remains unclear in patients with various types of chronic respiratory diseases, including ILD. Several studies evaluated the clinical utility of the 4MGS in patients with ILD including IPF [32e34]. Nolan et al. found that the 4MGS was a reliable, valid, and responsive measure for detecting a worsening phenotype in patients with IPF. Further, the 4MGS had great potential for stratifying patients on the basis of disease severity. They speculated that the 4MGS test might play a specific role in assessing physical function in patients with advanced IPF, for whom the 6MWT was impossible to complete because of secondary to severe respiratory failure. Moreover, Nolan et al. showed that the 4MGS was an independent predictor of allcause mortality and non-elective hospitalization. These reports suggested that the 4MGS was valuable not only in COPD but also in IPF. One benefit of the 4MGS test, other than the time it took to perform the test, was the test's low demand on patients. Small changes in PR and oxygen saturation were observed during the tests; hence, most patients should be able to complete the 4MGS test. However, the 4MGS test did not identify patients who developed oxygen desaturation during physical activity, and if this were to be evaluated, the 6MWT would be favorable. The decision regarding the type of test to use should be based on the clinical setting. Only a few previous studies have reported using ambulatory pulse oximetry monitoring in patients with chronic respiratory diseases including COPD. The usefulness of ambulatory pulse oximetry monitoring is still controversial. The present study showed that the diurnal DSI 90 and mean SpO2 did not correlate with the 4MGS and PAL. This suggests that patients with chronic respiratory diseases regulate their daily activities to avoid oxygen desaturation and shortness of breath, and develop conditioned responses to unfavorable events. This study had several limitations. First, the number of recruited patients was small. A larger study will be required to determine the usefulness of the 4MGS test for estimating daily physical activity. Second, the heterogeneity of the underlying diseases made it difficult to examine the relationships. Third, only patients capable of performing both the 4MGS test and 6MWT without supplemental oxygen were included in this study. Hence, it is unclear if these results can be applied to patients with conditions that limit walking ability and to those who need supplemental oxygen. Fourth, the results of daily physical activities are influenced by various factors of daily life, including weather conditions. Pitta et al. showed that assessments performed over 2 days were valid for evaluating PAL [17]. However, we performed assessments for 1 day only, and the differences in frequency and duration of these assessments may have affected the results. Finally, this was a

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cross-sectional study, and hence, we could not detect serial changes in the 4MGS and daily physical activity.

5.

Conclusions

The 4MGS correlated with the 6MWD and measures of daily physical activity including PAL. Further, the 4MGS test was useful for identifying inactive patients with chronic respiratory diseases. Compared with the 6MWT, the 4MGS test is simple and can be performed quickly at any time and location. Moreover, the 4MGS test was well tolerated by our patients. Further explorations of the longitudinal associations of the 4MGS that characterize inactive patients are warranted.

Financial disclosure and conflicts of interest All of the authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Acknowledgements We would like to thank the patients who participated in this study. We would also like to thank Editage (www.editage.jp) for the professional English language review.

Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.resinv.2019.03.009.

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