Comparison between 20 and 30 meters in walkway length affecting the 6-minute walk test in patients with chronic obstructive pulmonary disease: A randomized crossover study.

BACKGROUND: A 30-m walkway length for the 6-minute walk test (6MWT) is the standard recommendation established by the American Thoracic Society to assess patients with chronic obstructive pulmonary disease (COPD). This study aimed to compare between the distances of 20 and 30 m long corridor affecting 6MWT in COPD patients.
METHODS: A randomized crossover study was conducted with patients. COPD patients were randomized 1:1 to either a 20-m or a 30-m walkway in the first test, then switched to the other in the second test. Physiologic parameters and 6-minute walking distance (6MWD) were recorded.
RESULTS: Fifty subjects (92% men) were included: age 69.1±7.4 years, body mass index 22.9±5.5 kg/m2, FEV1 63.0±21.3%, and 50% having cardiovascular disease. The 6MWD in a 20-m and a 30-m walkway were 337.82±71.80 m and 359.85±77.25 m, respectively (P<0.001). Mean distance difference was 22.03 m (95% CI -28.29 to -15.76, P<0.001). Patients with a 20-m walkway had more turns than those with a 30-m walkway (mean difference of 4.88 turns, 95% CI 4.48 to 5.28, P<0.001). Also, higher systolic blood pressure was found in patients with a 20-m walkway after 6MWT (4.62 mmHg, P = 0.019). Other parameters and Borg dyspnea scale did not differ.
CONCLUSIONS: The walkway length had significant effect on walking distance in COPD patients. A 30-m walkway length should still be recommended in 6MWT for COPD assessment. CLINICAL TRIAL REGISTRATION: Clinicaltrials.in.th number: TCTR20200206003.

Introduction

Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible inflammatory disease that makes it difficult to breathe. It was the fourth leading cause of death in the world by 2020 [1]. Common symptoms include a chronic cough, dyspnea, more sputum secretion, lung wheezing, and chest tightness. It’s caused by exposure to tobacco smoke, occupational chemicals, indoor and outdoor air pollution [1], and genetics [1, 2]. In patients with disease progression COPD limits physical activity and is related to a higher risk of exacerbation and increased risk of mortality [3, 4]. Therefore, assessment of physical activity is important for clinical management of COPD patients.

The 6-minute walk test (6MWT) is submaximal exercise that corresponds to functional activity used in daily activities. 6MWT is an effective exercise which is low cost, uncomplicated and provides a measure for evaluation of cardiopulmonary, musculoskeletal and nervous systems. In clinical practice, 6MWT is often used to evaluate patients with various diseases, especially COPD. 6MWT is a tool for evaluating physical activities, comparing pre-post treatment and predicting morbidity and mortality rates in COPD patients [5]. A guideline of the American Thoracic Society (ATS) suggests the walkway distance should not be less than 30-m [5]. Previous studies reported that a difference of 10 meters in the total walking distance affects the 6MWT results [6, 7]. In contrast, another study found that course length had no significant effect on walking distance 50 feet (15.24 m) to 164 feet (49.99 m) [8]. However, there are conflicting data on different walkway lengths of 6MWT in the COPD patient population with varying ethnicities. The aim of this study was to measure the difference of walking distance and other effects in walkways of 20-m and 30-m.

Methods

Study design and participants

A randomized crossover study of COPD subjects was conducted in Thammasat University Hospital, Thailand between June 2018 –January 2019. COPD diagnoses using post-bronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) < 0.7 were reviewed by chest physicians. The inclusion criteria were Thai COPD patients, age 40 to 80 years, smoking history ≥10 pack-years, and post-bronchodilator FEV1/FVC < 0.7. The exclusion criteria were recent COPD exacerbation, eye surgery or abdominal surgery within 6 weeks, inability to walk or failure to cooperate in walking, O2 saturation < 90% in resting stage, blood pressure below 90/60 or above 180/100 mmHg prior to testing, heart rate less than 50 or more than 120 beats per minute, disease other than COPD; e.g. lung cancer, pulmonary fibrosis, and pulmonary tuberculosis, myocardial infarction. Patients’ characteristics, treatment profiles, exacerbation history and comorbidities were collected.

This study was approved by the Institutional Review Board of the Human Ethics Committee of Thammasat University No.2 (Project No. 001/2561, Certificate of Approval CoA 005/2561) (see S1–S6 Files). This study was registered in the Thai Clinical Trials Registry (TCTR); thaiclinicaltrials.org (number: TCTR20200206003). All participants provided written informed consent. This study started the first enrollment on June 1, 2018 and completed the follow-up on March 31, 2019. However, this study was not registered before enrolment of participants started because we initially judged that the study was an observational study rather than an interventional trial. The authors confirm that all ongoing and related trials for this intervention are registered.

Procedures and outcomes

Each patient performed the 6MWT twice in accordance with the ATS 2002 guidelines [5]. Patients were randomized 1:1 with block of four using a computer program to a 20-m walkway or a 30-m walkway in the first test, then the patient rested until all vital signs had stabilized. The other walkway test was performed in the second test (see Fig 1). In each test, bronchodilator was administered before each walk and the patient had to walk as fast as possible in a 6-minute period. The patient was encouraged walk the entire distance (20 or 30m). The patient was allowed a period of rest if shortness of breath developed. We collected demographics, spirometry variables, and physiologic variables including blood pressure, heart rate, respiratory rate, oxygen saturation and 10-point Borg dyspnea scale. After each test, we measured the same data variables as before test and recorded the number of turns, and 6-minute walking distance (6MWD). The patients were allowed to stop or rest during testing. All 6MWDs were recorded.

Fig 1

Flow chart of participant recruitment to the study.

Statistical analysis

Based on a previous study [9], the difference in 6MWD between 10-m walkway and a 30-m walkway in COPD patients was 49.5±33.6 meters. We hypothesized that the difference in 6MWD between 20-m walkway and a 30-m walkway in those patients was 34 meters. Thus, 50 patients were needed to be studied with 90% power and 5% type I error.

Statistical analyses were performed using SPSS version 23.0 software (IBM Corp., Armonk, NY, USA). Data is presented as mean ± standard deviation and number (%). Paired t-test was used to compare continuous variables between two groups. A two-sided p-value < 0.05 was considered statistically significant.

Results

Fifty-nine patients were screened. Of these, 50 patients were eligible for inclusion (see Fig 1). Males numbered 46 (92%). Mean age was 69.1±7.4 years. FEV1 was 63.0±21.3%. The patients having cardiovascular disease, dyslipidemia and lung disease other than COPD were 50%, 38% and 16%, respectively. The characteristics of the patients are shown (see Table 1).

Table 1

Baseline characteristics of the COPD patients.

Characteristics	N = 50
Age, years	69.1 ± 7.4
Male/Female	46/4 (92.0/8.0)
Body mass index, kg/m2	22.9 ± 5.5
Smoking history, pack-years	32.7 ± 23.0
Active smoking	15 (30)
FEV1/FVC, %	59.8 ± 10.8
FEV1, L	1.50 ± 0.55
FEV1, % predicted	63.05 ± 21.29
FVC, L	2.45 ± 0.74
FVC, % predicted	78.20 ± 19.43
Patients with exacerbation history	7 (14.0)
COPD medications
LABA	2 (4.0)
LAMA	19 (38.0)
LABA and LAMA	6 (12.0)
LABA and ICS	27 (54.0)
SABA	1 (2.0)
SABA and SAMA	30 (60.0)
Xanthine	19 (30.0)
Oral prednisone	1 (2.0)
Oral N-Acetylcysteine	23 (46.0)
Long-term Azithromycin	3 (6.0)
Comorbidities
Cardiovascular disease	25 (50.0)
Lung disease other than COPD	8 (16.0)
Dyslipidemia	19 (38.0)
Diabetes mellitus	6 (12.0)
Liver disease	6 (12.0)
Kidney disease	3 (6.0)

Data shown as mean ± SD or n (%).

kg = kilogram, m = meter, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, L = liter, LABA = Long-acting beta2-agonist, LAMA = Long-acting muscarinic antagonist, SAMA = Short-acting beta-agonist, SAMA = Short-acting muscarinic-antagonist, ICS = Inhaled corticosteroid, COPD = chronic obstructive pulmonary disease.

We found that the 6MWD in a 20-m and a 30-m walkway was 337.82±71.80 m and 359.85±77.25 m, respectively (P<0.001). Mean distance difference was 22.03 m (95% CI -28.29 to -15.76, P<0.001). Patients had 16.46±3.51 turns in 20-m walkway and 11.58±2.56 turns in 30-m walkway (mean difference of 4.88 turns, 95% CI 4.48 to 5.28, P<0.001).

Subsequently, we studied differences of effects of walkway distance on multivariable data include Borg dyspnea scale and physiologic variables. Systolic blood pressure was found to be higher in patients with a 20-m walkway after 6MWT (4.62 mmHg, 95% CI 0.77 to 8.46, P = 0.019). Other physiologic variables are shown in Table 2. All physiologic variables of perceived exertion after testing were higher than before testing in the 20-m test, but the 30 m test did not seem to affect diastolic blood pressure (see Table 3). The dataset of 6MWT in COPD patients is shown in S7 File.

Table 2

The effects of walking length on total distance and physiologic variables.

Variables	20 meters	30 meters	P-value
6MWD, meters	337.82±71.80	359.85±77.25	<0.001
Number of turns, times	16.46±3.51	11.58±2.56	<0.001
Before 6MWT
Systolic blood pressure, mmHg	130.26±18.04	128.56±16.78	0.220
Diastolic blood pressure, mmHg	79.56±11.19	80.52±12.83	0.196
Borg dyspnea scale	0.75±0.71	0.81±0.65	0.060
SpO2, %	97.17±1.50	97.10±1.36	0.699
Heart rate, bpm	79.64±11.99	80.06±13.07	0.150
Respiratory rate, bpm	20.16±3.89	19.80±2.95	0.237
After 6MWT
Systolic blood pressure, mmHg	139.56±19.39	134.94±21.40	0.019
Diastolic blood pressure, mmHg	83.22±12.82	81.02±21.40	0.210
Borg dyspnea scale	2.29±0.81	2.39±0.99	0.280
SpO2, %	96.14±2.41	96.14±2.37	1.000
Heart rate, bpm	86.16±14.17	88.24±14.25	0.077
Respiratory rate, bpm	22.68±3.47	22.88±3.19	0.547

Data shown as mean ± SD.

6MWD = six-minute walk distance, mmHg = millimeters of mercury, SpO2 = oxygen saturation using a pulse oximeter, bpm = beats per minute.

Table 3

The effects of walking length on physiologic variables after 6MWT.

Variables	Before 6MWT	After 6MWT	P-value
20-m walkway length
Systolic blood pressure, mmHg	130.26±18.04	139.56±19.39	<0.001
Diastolic blood pressure, mmHg	79.56±11.19	83.22±12.82	0.003
Borg dyspnea scale	0.65±0.71	2.29±0.81	<0.001
SpO2, %	97.14±1.50	96.14±2.41	<0.001
Heart rate, bpm	77.64±11.99	86.16±14.17	<0.001
Respiratory rate, bpm	20.16±3.79	22.68±3.47	<0.001
30-m walkway length
Systolic blood pressure, mmHg	125.56±16.78	134.94±21.40	<0.001
Diastolic blood pressure, mmHg	80.52±12.83	81.02±15.02	0.816
Borg dyspnea scale	0.81±0.65	2.39±0.99	<0.001
SpO2, %	97.10±13.6	96.14±2.37	<0.001
Heart rate, bpm	80.06±13.07	88.24±14.25	<0.001
Respiratory rate, bpm	19.80±2.95	22.88±3.19	<0.001

Data shown as mean ± SD.

6MWT = six-minute walk test, mmHg = millimeters of mercury, SpO2 = oxygen saturation using a pulse oximeter, bpm = beats per minute.

Discussion

This is the first randomized crossover study to compare between the distances of 20-m and 30-m long corridors affecting 6MWT in COPD patients. Our study found significant difference of 6MWD between a 20-m and a 30-m walkway in that walking distance on 20-m walkway is shorter than on a 30-m by an average of 22.03 m and had 4.88 more turns. These results correspond to the study of Klein SR, et al [10]. They found that, in COPD patients, 6MWD with 30-m walkway was significantly longer than 20-m walkway (mean difference in 22.1 m) [10]. We think that our sample size has sufficient power to detect a statistically significant difference by the 2-sided test for walking distance between two walkway lengths. Sample size estimation was based on findings from a previous study of Beekman E, et al [9].

ATS 2002 guidelines recommended at least 30-m corridors for 6MWT [5]. The study of Ng SS and coworkers, studied 25 healthy subjects aged 50 years and over to compare the walkway lengths of 10-m, 20-m and 30-m. Their results revealed that the walkway length affects the total walking distance [7], which is consistent with the study of Beekman E and coworkers comparing 10-m and 30-m corridors for COPD patients. They found that the average walking distance on the 10-m was less than on the 30-m by (approximately 49.50-m) [9]. These findings were similar to our study because the longer walkways have fewer turns than shorter walkways. In contrast, the study of Sciurba F and coworkers showed that the effect on walking distance of walkway lengths of 50 feet (15.24-m) to 164 feet (49.99-m) made no difference [8]. There are also studies of patients with chronic stroke and cirrhotic patients waiting for liver transplants. In chronic stroke patients, the study by Ng SS and coworkers showed significant difference between walkway lengths of 10-m, 20-m and 30-m [6], but the study of cirrhotic patients by Veloso-Guedes CA and coworkers found no difference of effect between 20-m and 30-m [11].

Interestingly, our COPD patients had a little above 2 points of Borg dyspnea scale after exercise testing (see Table 2). This finding may result from low dyspnea perception and high symptom variability of COPD patients. There are several established evidences of poor correlation between symptom perception and FEV1 [12]. COPD symptoms show high seasonal, weekly, and daily variability [12]. Moreover, oxygen saturation did not differ before and after exercise testing in our study. It is possible that our COPD patients had less-severe airway obstruction (FEV1 of 63%), therefore desaturation after walking test is not shown according to an established definition; a fall in SpO2 ≥ 4% or SpO2 < 90% [13]. 6MWDs in our patients (around 350 m) are similar to another study on stable COPD patients in Thailand [14]. In this study, the majority of COPD patients were spirometric grade 2 (mean FEV1 of 66%) with a mean 6MWD of 317 m [14].

Beside shorter walkway had more turns than longer walkway. Most of physical variables after tests were higher than before tests due to increased physical activity in our study. These results indicated that the short walkway length affects physiologic changes and decrease in 6MWD.

Our study had a few limitations. To decrease the learning effect in walking tests, participants were randomized to short or long walkway length in the first test, then switched to the other test. Moreover, to assure accurate test results, participants had to rest between tests until all physiologic and dyspnea variables had stabilized. However, 6MWD may be expected to increase as participants become increasingly familiar with the exercise.

Conclusion

The walkway length had significant effect on walking distance in COPD patients. A 30-m walkway length should still be recommended in 6MWT for COPD assessment.

(DOC)

Click here for additional data file.

Study protocol in English.

(PDF)

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Study protocol in Thai.

(PDF)

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Information sheet in English.

(PDF)

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Information sheet in Thai.

(PDF)

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Consent form in English.

(PDF)

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Consent form in Thai.

(PDF)

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Dataset of 6-minute walk test in COPD patients.

(XLSX)

Click here for additional data file.

19 Oct 2021

PONE-D-21-27964Comparison between 20 and 30 meters in walkway length affecting the 6-minute walk test in patients with chronic obstructive pulmonary disease: a randomized crossover studyPLOS ONE

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Reviewer #1: Few comments:

Introduction

- the parameter FEV1/FVC is not usual to express in percentage, rather is expressed in decimal number: not < 70%, but 0.70

- METHODS. It is not written which Borg scale was used, with 10 or 11 points – it should be added.

- It is not emphasized wheather patient was encouraged or not, because it is important in a methodology of 6MWT.

- RESULTS

- In Table No 1, I suggest to delete in Legend PDE4=phosphodiesterase 4, because there was none patient with such therapy

- It is very unusual that, as we can see in table 2, the Borg Dyspnea scale was just a little above 2 points after exercize, especially because the walking distance was rather short, around 350 m, when most of COPD patients has more pronounced dyspnea...It is also unexpected that oxygen saturation did not differ befere and after exercize while such short distance was achieved. Also when FEV1 in COPD is arround 63%, we could expect longer distance in 6MWT. Please, comment that in a discussion.

Reviewer #2: The article can benefit from some minor grammatical and syntax corrections.

Example: “ However, there are few published data on 6MWT in the COPD

patient population“ should be rephrased because there are 718 results in PubMed for 6MWT and COPD.

The population in study (ethnicity) should be stated.

Reviewer #3: This is a well-designed crossover study. Randomization and sample size are clearly documented. But there is a significant problem in the introduction: the sentence is "We hypothesized that the results would not

differ between the two distances." In that case, it is an equivalence study, which must be powered and analyzed completely differently. So what is it? Clearly, the sample size computations indicate a difference. Please clarify.

1. Were the parameters estimated in the sample size realized in the trial? Please add to the discussion.

2. p<.05 has little meaning in the presence of so many hypothesis tests, as does the term "significance". Please modify the description to indicate that type I error rate is preserved for the primary outcome, and all other tests are exploratory in nature.

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Reviewer #1: Yes: Prof. Sanja Popović-Grle, M.D., Ph.D.

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5 Nov 2021

Dear Reviewer of PLOS ONE:

I submitted an original contribution to PLOS ONE entitled “Comparison between 20 and 30 meters in walkway length affecting the 6-minute walk test in patients with chronic obstructive pulmonary disease: a randomized crossover study” (Manuscript number: PONE-D-21-27964).

Thank you so much for your great reviews and comments regarding my manuscript. I would like to explain and submit a revised manuscript. My response to the comment is below.

RESPONSE TO REVIEWER 1:

REVIEWER #1 COMMENT 1: Introduction - the parameter FEV1/FVC is not usual to express in percentage, rather is expressed in decimal number: not < 70%, but 0.70

RESPONSE: I have corrected this number in the Method section, Study design and participants. Thank you for kindly reviews.

REVIEWER #1 COMMENT 2: METHODS. It is not written which Borg scale was used, with 10 or 11 points – it should be added.

RESPONSE: I have added these words in the Method section, Procedures and outcomes.

REVIEWER #1 COMMENT 3: It is not emphasized whether patient was encouraged or not, because it is important in a methodology of 6MWT.

RESPONSE: I have added more information about encouragement in the Method section, Procedures and outcomes.

REVIEWER #1 COMMENT 4: RESULTS - In Table No 1, I suggest to delete in Legend PDE4=phosphodiesterase 4, because there was none patient with such therapy

RESPONSE: I have removed this word from footnote in Table 1.

REVIEWER #1 COMMENT 5: It is very unusual that, as we can see in table 2, the Borg Dyspnea scale was just a little above 2 points after exercise, especially because the walking distance was rather short, around 350 m, when most of COPD patients has more pronounced dyspnea...It is also unexpected that oxygen saturation did not differ before and after exercise while such short distance was achieved. Also when FEV1 in COPD is around 63%, we could expect longer distance in 6MWT. Please, comment that in a discussion.

RESPONSE: I have added more discussion in the Discussion section, Paragraph 3.

RESPONSE TO REVIEWER 2:

REVIEWER #2 COMMENT 1: The article can benefit from some minor grammatical and syntax corrections.

Example: “However, there are few published data on 6MWT in the COPD patient population” should be rephrased because there are 718 results in PubMed for 6MWT and COPD.

RESPONSE: I have reorganized the sentence in the Introduction section, Paragraph 2. Thank you so much for kindly reviews.

REVIEWER #2 COMMENT 2: The population in study (ethnicity) should be stated.

RESPONSE: I have added this word in the Introduction section, Paragraph 2.

RESPONSE TO REVIEWER 3:

REVIEWER #3 COMMENT 1: This is a well-designed crossover study. Randomization and sample size are clearly documented. But there is a significant problem in the introduction: the sentence is "We hypothesized that the results would not differ between the two distances." In that case, it is an equivalence study, which must be powered and analyzed completely differently. So what is it? Clearly, the sample size computations indicate a difference. Please clarify.

1. Were the parameters estimated in the sample size realized in the trial? Please add to the discussion.

RESPONSE: I have added more discussion about power of the test in the Discussion section, Paragraph 1. Thank you so much for wonderful reviews.

REVIEWER #3 COMMENT 2:

2. p<.05 has little meaning in the presence of so many hypothesis tests, as does the term "significance". Please modify the description to indicate that type I error rate is preserved for the primary outcome, and all other tests are exploratory in nature.

RESPONSE: I have corrected the description of secondary outcomes in the Results section, Paragraph 3. Thank you for kindly suggestions.

I appreciate your consideration of my manuscript for publication in PLOS ONE.

Sincerely,

Narongkorn Saiphoklang, M.D.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

19 Nov 2021

PONE-D-21-27964R1Comparison between 20 and 30 meters in walkway length affecting the 6-minute walk test in patients with chronic obstructive pulmonary disease: a randomized crossover studyPLOS ONE

Dear Dr. Saiphoklang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================Please revise as suggested by reviewers.==============================

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Kind regards,

Davor Plavec, MD, MSc, PhD, Prof.

Academic Editor

PLOS ONE

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

Please revise as suggested by the reviewers.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

Reviewer #3: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: All questions and comments by me were included as good answers and reasonalble explantations, also methods are improved, so I find the manuscipt ready for publishing.

Reviewer #2: When I suggest the linguistic and semantic corrections i mean that the whole article should be rechecked for consistence. I can still find sentences that are at least not precise like: They found that 6MWD with 30-m walkway had significantly longer than 20-m walkway in COPD patients (mean difference in 22.1 m)

That should sound like: "They found that, in COPD patients, 6MWD with 30-m walkway is significantly longer than with 20-m walkway (mean difference of 22.1 m) [10]

Please recheck the whole article and correct such sentences. I have no other comments and the article is worth publishing.

Regards

Reviewer #3: The authors seem not to understand my comment on the last part of the Introduction where they say that we hypothesized that there would be NO difference. Clearly you found a difference, you powered for a difference, yet the sentence is still there. Either remove the sentence or change it to reflect that you are hypothesizing that there WILL BE a difference.

**********

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Reviewer #1: Yes: prof. dr.sc. Sanja Popović-Grle, M.D.Ph.D.

Reviewer #2: No

Reviewer #3: No

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23 Nov 2021

RESPONSE TO REVIEWER:

REVIEWER #1: All questions and comments by me were included as good answers and reasonable explanations, also methods are improved, so I find the manuscript ready for publishing.

RESPONSE: Thank you so much for wonderful reviews and accepting for my corrections.

REVIEWER #2: When I suggest the linguistic and semantic corrections. I mean that the whole article should be rechecked for consistence. I can still find sentences that are at least not precise like: They found that 6MWD with 30-m walkway had significantly longer than 20-m walkway in COPD patients (mean difference in 22.1 m)

That should sound like: "They found that, in COPD patients, 6MWD with 30-m walkway is significantly longer than with 20-m walkway (mean difference of 22.1 m) [10]

Please recheck the whole article and correct such sentences. I have no other comments and the article is worth publishing.

RESPONSE: I have corrected this sentence in the Discussion section. Thank you for kindly suggestions.

REVIEWER #3: The authors seem not to understand my comment on the last part of the Introduction where they say that we hypothesized that there would be NO difference. Clearly you found a difference, you powered for a difference, yet the sentence is still there. Either remove the sentence or change it to reflect that you are hypothesizing that there WILL BE a difference.

RESPONSE: I have removed the sentence to reflect the hypothesis in the Introduction section. Thank you for great suggestions and wonderful reviews.

I appreciate your consideration of my manuscript for publication in PLOS ONE.

Sincerely,

Narongkorn Saiphoklang, M.D.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

20 Dec 2021

Comparison between 20 and 30 meters in walkway length affecting the 6-minute walk test in patients with chronic obstructive pulmonary disease: a randomized crossover study

PONE-D-21-27964R2

Dear Dr. Saiphoklang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Davor Plavec, MD, MSc, PhD, Prof.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I am happy to announce that your paper is ready for acceptance with the minor revision suggested by the reviewer #2.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: I Don't Know

Reviewer #3: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Still minor problem. Please correct: "It is possible that our COPD patients were nonsevere airway obstruction (FEV1 of 63%)," to: "It is possible that our COPD patients had less-severe airway obstruction (FEV1 of 63%)" or something like that and there are no further objections from my point.

Regards

Reviewer #3: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

30 Dec 2021

PONE-D-21-27964R2

Comparison between 20 and 30 meters in walkway length affecting the 6-minute walk test in patients with chronic obstructive pulmonary disease: a randomized crossover study

Dear Dr. Saiphoklang:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Davor Plavec

Academic Editor

PLOS ONE