Incremental Shuttle Walking Test: A Reproducible and Valid Test to Evaluate Exercise Tolerance in Adults With Noncystic Fibrosis Bronchiectasis

Accepted Manuscript Incremental shuttle walking test: a reproducible and valid test to evaluate exercise tolerance in adults with non-cystic fibrosis bronchiectasis Anderson Alves de Camargo, PT, MSc Tatiane Soares Amaral, PT Samia Zahi Rached, MD Rodrigo Abensur Athanazio, MD Fernanda de Cordoba Lanza, PT, PhD Luciana Maria Malosa Sampaio, PT, PhD Celso Ricardo Fernandes de Carvalho, PT, PhD Alberto Cukier, MD, PhD Rafael Stelmach, MD, PhD Simone Dal Corso, PT, PhD PII:

S0003-9993(13)01239-2

DOI:

10.1016/j.apmr.2013.11.019

Reference:

YAPMR 55684

To appear in:

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION

Received Date: 19 June 2013 Revised Date:

5 November 2013

Accepted Date: 25 November 2013

Please cite this article as: Alves de Camargo A, Amaral TS, Rached SZ, Athanazio RA, de Cordoba Lanza F, Malosa Sampaio LM, Fernandes de Carvalho CR, Cukier A, Stelmach R, Corso SD, Incremental shuttle walking test: a reproducible and valid test to evaluate exercise tolerance in adults with non-cystic fibrosis bronchiectasis, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2014), doi: 10.1016/j.apmr.2013.11.019. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Incremental shuttle walking test: a reproducible and valid test to evaluate exercise tolerance in adults with non-cystic fibrosis bronchiectasis

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Running title: Incremental shuttle walking test and bronchiectasis

Anderson Alves de Camargo1, PT, MSc, Tatiane Soares Amaral1, PT, Samia Zahi Rached2, MD, Rodrigo Abensur Athanazio2, MD, Fernanda de Cordoba Lanza1, PT,

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PhD, Luciana Maria Malosa Sampaio1, PT, PhD, Celso Ricardo Fernandes de

Dal Corso1, PT, PhD

Affiliations

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Carvalho3, PT, PhD, Alberto Cukier2, MD, PhD, Rafael Stelmach2, MD, PhD, Simone

1- Postgraduate Program in Rehabilitation Sciences, Universidade Nove de Julho -

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UNINOVE, São Paulo, Brazil

2- Pulmonary Division, Heart Insitute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (SP), São Paulo, Brasil

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Brazil

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3- Physiotherapy Department, Faculty of Medicine, University of São Paulo, São Paulo,

Corresponding author: Simone Dal Corso Rua Vergueiro, 235/249 – 2o subsolo Zip code: 01504-001 Sao Paulo, Brazil Phone: 55 11 3385-9226 e-mail: [email protected]

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All authors have no conflicts of interest to disclose regarding this paper.

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INCREMENTAL SHUTTLE WALKING TEST: A REPRODUCIBLE AND VALID

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TEST TO EVALUATE EXERCISE TOLERANCE IN ADULTS WITH NON-

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CYSTIC FIBROSIS BRONCHIECTASIS

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Running title: Incremental shuttle walking test and bronchiectasis

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ABSTRACT

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Objective: To analyze the reliability, validity, and the determinants of the incremental shuttle

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walk test (ISWT) in adults with non-cystic fibrosis bronchiectasis.

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Design: Cross-sectional study

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Setting: Outpatient clinic from a tertiary university hospital

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Participants: Seventy-five subjects (26 male) underwent, on different days, the

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cardiopulmonary exercise testing (CPET) and two ISWTs, 30 min apart. Number of

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steps (steps/day) in daily life was recorded. Concurrent validity was tested by the

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relationship between distance walked with peak load, and oxygen uptake (VO2).

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Interventions: None

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Main Outcome Measures: Distance walked (meters) was compared between the first and

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second ISWT; the greatest distance walked was correlated with peak load and VO2 obtained

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from CPET, steps/day, and dyspnea evaluated by the Medical Research Council (MRC) scale;

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desaturation was compared between CPET and ISWT.

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Results: Distance walked was equivalent between the ISWT-1 (441±152 m) and ISWT-

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2 (445±153 m) with an excellent intraclass correlation coefficient (0.995 [95% CI:

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0.990-0.997]). There were significant correlations between distance walked and peak

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load (r =0.82), VO2 (r =0.72), steps/day (r =0.61), and MRC (r =-0.69). Age, body mass

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index, gender, forced vital capacity (%predicted), dyspnea, and steps/day explained

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70% of the variation in distance walked as expressed in meters and 60% when

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expressed as %predicted. Higher desaturation was observed during ISWT (-4±4%) than

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cycling (-2±3) (p <0.0001).

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Conclusions: The ISWT is reliable, represents functional capacity, and induces greater

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desaturation in comparison with cycling. Age, body composition, pulmonary function,

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dyspnea, and physical activity in daily life are determinants of the distance walked on

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ISWT.

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Keywords: Bronchiectasis, exercise tolerance, exercise test, shuttle walking test,

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hypoxemia

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LIST OF ABBREVIATIONS

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BMI: Body mass index

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Bpm: Beats per minute

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COPD: Chronic obstructive pulmonary disease

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CPET: Cardiopulmonary exercise testing

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FEV1: Forced expiratory volume in one second

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FVC: Forced vital capacity

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HR: Heart rate

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ICC: Intraclass correlation coefficient

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IQR: Interval quartile range

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ISWT: Incremental shuttle walk test

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ISWT-1: first incremental shuttle walk test

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ISWT-2: second incremental shuttle walk test

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L: liters

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m/s: meters/second

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MRC: Medical Research Council

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min: Minute

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SpO2: oxyhemoglobin saturation

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VO2: oxygen uptake

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Non-cystic fibrosis (CF) bronchiectasis is characterized by a progressive loss of

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lung function and a decline in lung diffusing capacity.1-3 It is also associated with

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recurrent exacerbations leading to dyspnea and fatigue,4,5 contributing to reduced

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exercise tolerance.

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Cardiopulmonary exercise testing (CPET) is the gold standard for assessing

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exercise capacity, but it is not easily available in clinical practice. In this context, field

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walking tests have been used to evaluate functional capacity in patients with chronic

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respiratory diseases since these tests are more representative of the demands required

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during activities in daily life.6 Additionally, field walking tests are more sensitive in

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detecting desaturation than cycling tests.7,8

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Although non-CF bronchiectasis is a chronic and debilitating disease, few

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studies have assessed functional capacity in these patients, and the incremental shuttle

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walk test (ISWT) has been the field test of choice in the majority of these studies.9-12

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Interestingly, the reproducibility and/or validity of the ISWT have been tested in

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patients with chronic obstructive pulmonary disease (COPD),13 cystic fibrosis,14

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pacemakers,15 advanced cancer,16 and fibrotic interstitial pneumonia17 but not in those

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with bronchiectasis. With the growing interest in pulmonary rehabilitation for other

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chronic lung diseases such as non-CF bronchiectasis,18 it is crucial to know the within-

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subject reproducibility of the ISWT to correctly interpret the impact of interventions on

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functional capacity when using this test. Moreover, due to the similarity of symptoms

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and pulmonary impairment in relation to COPD, the ISWT may determine a greater

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desaturation compared with cycling in patients with non-CF bronchiectasis.

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Therefore, this study investigated three questions: (1) Is the ISWT reproducible

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and a valid test for measuring exercise tolerance in patients with non-CF

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bronchiectasis? (2) Is exercise-induced desaturation higher on the ISWT than for

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cardiopulmonary exercise testing (CPET)? (3) What are the determinants of the

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distance walked in the ISWT?

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METHODS

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Subjects

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Patients were recruited from a tertiary referral university hospital in the State of São

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Paulo. The inclusion criteria were as follows: diagnosis of bronchiectasis confirmed by

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high-resolution computed tomography, ≥ 18 years of age, clinical stability (no change in

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medication dosage, quantity, color of secretions, and symptoms of dyspnea in the

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preceding 4 weeks), and have never participated in a rehabilitation program. Patients were excluded if they had other lung diseases, unstable heart diseases, smoking history

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≥ 10 pack years, and any inability to perform the tests due to musculoskeletal

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limitations. There are 348 patients registered in this outpatient clinic. During the

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recruitment period, between November 2011 and October 2012, 83 patients met the

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inclusion criteria, representing 21% of the total number of subjects treated in this clinic.

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Eight patients were excluded for the following reasons: one performed regular physical

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activity, one was a smoker, three did not complete all the evaluations, one had severe

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kyphoscoliosis, one had a previous pneumonectomy, and one had severe heart disease.

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Then, 75 patients (26 males) were assessed. The ethical committees (Universidade Nove

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de Julho – 921/11 and University of São Paulo - 451538) approved the study. All the

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procedures and any associated risks were described to the participants and informed

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consent was obtained from all patients.

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Study design

This is a cross-sectional study. Patients rated dyspnea according to the Medical

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Research Council (MRC) scale19 and underwent bioelectrical impedance. Afterwards,

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they performed the CPET. On another day (48 hours apart), two ISWT were performed

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(30 min apart), and an accelerometer was given to the patients.

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Assessments

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Body composition

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Body height was determined to the nearest 0.1 cm with subjects standing barefoot. Body

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weight was assessed with the beam scale to the nearest 0.1 kg, with subjects standing

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barefoot and in light clothing. Body mass index (BMI) was calculated as weight/height

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(kg/m2). Fat-free mass was estimated with a body composition analyzer.a

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Cardiopulmonary exercise testing

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The

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electromagnetically braked cycle ergometerb with gas exchange and ventilatory

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variables analyzed breath-by-breath.c The test was performed as previously described.20

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The main outcome for this test were pulmonary oxygen uptake (VO2, mL/min), peak

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load (Watts), and oxyhemoglobin saturation (SpO2) measured with pulse oximetry.d

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Change in SpO2 between rest and exercising ≥ 4 was considered desaturation.21 Subjects

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were asked to rate dyspnea and leg fatigue at exercise cessation by using the 0–10 Borg

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category-ratio scale.22

incremental

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maximal

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Incremental shuttle walking test

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The tests were conducted in an unobstructed and quiet 10-m corridor. Two ISWT were

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performed with at least 30 min of rest in between. The walking speed was dictated by an

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audio signal, started at 0.5 m/s, and progressively increased 0.17 m/s every minute

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according to the triple beep.13 The tests were ended by the patient due to dyspnea and/or

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fatigue or by the physiotherapist if the patient was unable to complete the shuttle at the

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time of the audio signal for the second time. Heart rate (HR), saturation (SpO2)

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measured by pulse oximetry,d perception of effort22 for dyspnea, and leg fatigue were

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assessed before and immediately after the test was interrupted. The distance walked was

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expressed in meters and in predicted values.23 The test with the longest distance walked

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was used for correlation with the CPET and the number of steps recorded by the

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pedometer.

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Assessment of daily physical activity

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Daily physical activity was assessed with an accelerometer.e The patients received the

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accelerometer and were instructed to use it in the right pocket on the anterior surface of

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the pants for five consecutive days during the weekdays and then to return to our

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laboratory with the device. Patients were instructed not to change their daily physical

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activity behavior on the days using the device. They attached the accelerometer in the

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morning, used it throughout the day, and removed it only to shower and to sleep. For

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analysis, the first and last days were discarded and daily number of steps was the mean

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over three consecutive days, because it has been demonstrated that three days provides

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the best reliability in comparison to other combinations of days in comparison with a

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week of measurement.24 The main outcome from this assessment was the steps/day.

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Statistical analysis

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The normality of the data was analyzed by the Kolmogorov-Smirnov test. MRC scale,

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steps/day, Borg dyspnea and Borg fatigue are expressed as median (interquartile range,

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IQR) and other variables are expressed as means (95% confidence interval). To analyze

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the reliability of ISWT, three steps were followed. First of all, paired Student´s t test

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was used to compare distance walked (m), HR (bpm), %HR predicted, SpO2%,

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∆SpO2% at the peak of exercise while a Wilcoxon test was used to compare Borg

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dyspnea and Borg fatigue. Secondly, intraclass correlation coefficients (ICC) and 95%

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confidence intervals (95%IC) were calculated to verify the reproducibility of these

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variables between the ISWT-1 and ISWT-2. Finally, agreement between the two tests

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(ISWT-1 and ISWT-2) was evaluated by the Bland-Altman analysis. Comparisons

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between the farthest distance walked between sexes were made with the unpaired

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Student´s t-test. To answer the second question of the study, a chi-square (Fisher’s

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exact) test was used to evaluate the association between desaturation in the best ISWT

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and CPET. For the concurrent validity Pearson´s correlation was used (distance walked

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vs. peak VO2, and peak workload). This correlation was also used to analyze the

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strength of association between distance walked and steps/day. Spearman`s correlation

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was performed to correlate distance walked with MRC scores. To observe the

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determinants of distance walked in the ISWT (the third question of the study), a

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hierarchical multiple regression analysis was used. In the first model (block 1) of

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hierarchical regression were included: age, BMI, and gender because these variables

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usually explain the variability of the distance walked,23,25 and in the second model

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(block 2), FVC (% predicted), MRC, and steps/day were included because they

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contemplate different clinical aspects of the patients such as lung function, dyspnea, and

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functional capacity, respectively. The probability of a type I error was set at 5% (p <

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0.05). Statistical tests were performed with the SPSS 14.0, Chicago, Illinois.

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RESULTS

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The etiologies of bronchiectasis were idiopathic in 30 patients (40%), post-

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infectious in 18 patients (24%), primary ciliary dyskinesia in 9 patients (12%), chronic

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aspiration in 5 patients (6.7%), bronchiolitis obliterans in 3 patients (4%), Mounier-

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Khun Syndrome in 3 patients (4%), common variable immunodeficiency in 2 patients

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(2.7%), rheumatoid arthritis in 2 patients (2.7%), following chemotherapy, α1-

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antitrypsin deficiency, and Sjögren`s syndrome, in one patient each (4%). Pulmonary

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gas exchange was not performed in 19 patients (5 males) during the CPET, because they

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needed oxygen supplementation. Then, the concurrent validity of the distance walked

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with VO2 was conducted with 56 patients, but in the total sample (75 patients) with

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peak load. The characteristics of the subjects are summarized in Table 1.

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The majority of patients (n = 37) performed their best distance walked during the

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ISWT-2, 27 patients during the ISWT-1, and 11 patients walked the same distance

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during both ISWTs. In both tests, the distance walked ranged from 190 m to 940 m. No

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difference was observed in the variables between both tests either at rest or at the peak

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of exercise (Table 2). On average, the distance walked increased by 4 m (95% CI: -11; 2

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m). The distance walked was higher for men than for women (532 m [176] vs. 411 m

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[122], p = 0.001). Both sexes showed reduced distance walked in predicted values (47%

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[13] and 55% [12], respectively, p = 0.008).

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INSERT TABLE 2

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The Bland-Altman plot shows that patients walked the farthest distance during

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the second test represented by a negative mean difference (-4.4 m; Figure 1). The limits

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of agreement ranged from -57 m to 48 m.

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Nineteen patients performed the tests with oxygen supplementation, and the

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same amount was used during the two ISWTs and the CPET. Higher desaturation was

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observed during the ISWT (-4% [4]) than cycling (-2% [3]; p = 0.0001). Twenty-one

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percent of the patients presented with desaturation on the ISWT but not during the

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CPET (p = 0.01).

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There were significant positive linear correlations (p < 0.001 for all) between the

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distance walked in the ISWT and the workload, peak VO2, and steps/day, and a negative

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association with the MRC scale (Figure 2).

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In the hierarchical multiple regression analysis, the results of block 1 indicated that the variance accounted for (R2) with the first three independent variables (age, BMI,

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and gender) equaled 0.397 (adjusted R2 = 0.372), which was significantly different from

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zero (F=15.583, p<0.001). In block 2, the other three independent variables were

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entered into the regression equation (FVC % predicted, MRC, and steps/day). The

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change in variance accounted for (∆R2) was equal to 0.328, which was significantly

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different from zero (F=27.101, p<0.001). The percent of variability in the dependent

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variable that can be accounted for by all the predictors together is 70%. When distance

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walked was expressed as % predicted, the results of block 1 indicated that the variance

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accounted for (∆R2) was 0.104 (adjusted R2 = 0.066, F=2.745, p=0.049). In block 2, the

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change in variance accounted for (∆R2) was equal to 0.496 (F=28.069, p<0.001). All

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predictors explained 60% of the variation in distance walked (% predicted).

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DISCUSSION

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The major findings of this study were as follows: ISWT showed be reproducible

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when performed at the same day, a valid test for quantifying exercise capacity, and

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more sensitive than the CPET for detecting oxygen desaturation. Additionally, the

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determinants of the distance walked on ISWT in patients with non-cystic fibrosis

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bronchiectasis are related to age, body composition, pulmonary function, dyspnea, and

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physical activity in daily life.

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In our study, patients increased the distance walked by an average of 4 m, which

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represented less than a 1% improvement in relation to the first test. In the Bland and

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Altman analysis, the mean bias was close to zero (-4.4 m). This was much lower than

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that observed between the first and second trials of the ISWT (-31 m) in the study

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describing the ISWT for the first time in patients with COPD.13 However, it was higher

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compared with patients with cystic fibrosis (0 m)14 even though the 95% confidence

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intervals (CIs) of the differences were similar among the studies (-57 m to 48 m, -49 m

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to 13 m, and -40 m to 40 m, respectively). Additionally, the test-retest reliability of the

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distance walked (Table 2) was similar to that recently reported involving COPD

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patients less than 70 years of age (0.93 [0.89–0.96]).26 Then, a small learning effect for

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the ISWT occurred in our patients. The smaller variability in the ISWT can be

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attributed to an externally-paced characteristic that overcomes the motivation

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limitations present in the six-minute walk test (6MWT) whose learning effect varies

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from 2.6% to 22%.27 Taking into consideration that 51% of our patients had already

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performed better than, or the same as, the first ISWT (27 and 11 patients, respectively),

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we believe that the best performance can be achieved when two tests are undertaken on

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the same day in patients with non-cystic fibrosis bronchiectasis.

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While the minimum important difference has not yet been established for

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patients with non-cystic fibrosis bronchiectasis, we suggest using the lower limit of

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agreement from the Bland Altman analysis (57 m) as the variability of ISWT and a

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difference more than this could be considered as the minimal detectable change after

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interventions.

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We tested the criterion validity of the ISWT as a measure of exercise capacity by

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contrasting the distance walked with the main outcomes from CPET (peak load and

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VO2). The literature is replete with studies assessing correlations among the six-minute

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walk test, the ISWT, and the CPET, but generally these studies are performed in

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patients with COPD. The present study is the first to verify the strength of association

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between mean outcomes from the ISWT and CPET in patients with non-cystic fibrosis

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bronchiectasis. The higher values for the distance walked represents a better

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performance on functional capacity, which in turn is related to a better performance on

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the CPET (r = 0.82; Figure 2). The strength of association between the distance walked

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and peak VO2 in the present study (r = 0.72) was similar to that found in patients with

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COPD when the distance walked was correlated with the peak VO2 obtained from a

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treadmill test (r = 0.88) and with the VO2 measured at the peak of the ISWT (r = 0.81).28

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This result was expected since the higher the distance walked on an incremental

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walking test the greater the aerobic capacity. In adults with cystic fibrosis, the

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relationship between the distance walked and directly measured peak VO2 during a

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treadmill test was stronger (r = 0.95).29 However, those patients were younger (25 ± 7

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yrs), the majority of them (14 out of 20 patients) walked more than 800 m on the ISWT,

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and they had a high peak VO2 (32.9 ± 10.4 ml/kg/min, 74% of predicted). Also, the

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treadmill protocol chosen by Bradley et al. for comparison with the ISWT was very

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intense (12% inclination at a speed of 3–4 mph) providing a close correlation between

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the distance walked and VO2.29

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The objective quantification of physical activity has been increasingly

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incorporated into assessing patients with cardiopulmonary diseases. However, daily

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physical activity has never been assessed in patients with non-cystic fibrosis

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bronchiectasis and contrasted with a field-based test. In clinical practice, the steps/day is

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one of the most commonly measured outcomes used for determining a patient’s level of

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physical activity in daily life. For this purpose, we used a recently validated

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accelerometer in patients with COPD.30 The strength of association found between the

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steps/day and the distance walked on the ISWT is consistent with that observed between

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the 6MWT and the walking time measured with a triaxial accelerometer in patients with

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COPD.31 Similarly, in patients with non- cystic fibrosis bronchiectasis, higher levels of

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daily physical activity are associated with better functional capacity, as represented by

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the greater distance walked during the ISWT. On the other hand, patients with non-

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cystic fibrosis bronchiectasis may experience disabling dyspnea that could compromise

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their ability to perform daily activities. This assumption is supported by the negative

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correlation found between the MRC scale and the ISWT.

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This is the first study to analyze the determinants of the ISWT in patients with non-cystic fibrosis bronchiectasis. The finding that age, BMI, and gender (block 1 of the

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hierarchical regression analysis) were determinants of the ISWT is not surprising since

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they are commonly part of the prediction equations for the distance walked on this

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test.23,32 However, although these variables were statistically significant as predictors of

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distance walked, they did not explain the entire variation in distance walked (R2 = 0.372,

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p < 0.001). Adding markers of pulmonary function (FVC), dyspnea (MRC), and

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functional capacity (steps/day), the percentage of variability accounted for went up from

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37.2% to 70%. It means that these latter variables have an effect beyond of the effects of

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demographics and anthropometric data. For distance walked expressed as a percentage

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of predict, the first block, although statistically significant, contributed in a quite low

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proportion (R2 = 0.104, p = 0.049) to explain the distance walked, probably because

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distance walked in percentage of predicted values is already corrected for age, BMI, and

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gender.23 The second block predicted the distance walked (% predicted) above and

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beyond the effects of the first block, i.e., FVC, dyspnea, and steps/day are important

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predictors of the distance walked, even when it is expressed in predicted values.

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In a previous study, the FVC (% predicted) was positively correlated with the

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distance in the 6MWT, but this value did not remain in the multiple regression model

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possibly because the patients presented the pulmonary function relatively preserved.33

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In fact, FVC (89 ± 20 % predicted) and FEV1 (74 ± 23 % predicted) were higher than

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those attained by our patients (Table 2). In patients with cystic fibrosis, a disease very

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similar to the bronchiectasis, FVC has been one of the independent variables that

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explained the distance walked in the 6MWT.34 The breathlessness during daily activities

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evaluated by the MRC scale was also a predictor of the ISWT. Dyspnea is one of the

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most prevalent symptoms in patients with non-cystic fibrosis bronchiectasis1,4,5 and it

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has been related to reduced exercise capacity.35 Therefore, we can infer that dyspnea

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during daily activities may lead to a sedentary lifestyle and a progressive deterioration

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in functional capacity in these patients. This assumption is based on the reduced

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functional capacity presented by our patients, since they have walked, on average, 50%

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of the predict distance, and on the correlation between distance walked and MRC

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(Figure 2, panel D). Previous studies also show that the higher the MRC score, the

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lower scores for the activity domain in the Saint George`s Respiratory Questionnaire,10

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and the lower the maximum work rate achieved in the incremental cardiopulmonary

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exercise testing.35 In this line of reasoning, it was not surprising that the steps/day was

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one of the predictors of the distance walked because the 6MWT distance is considered

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representative of patient´s daily life physical activities.31

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The ISWT was more sensitive than cycling in detecting oxygen desaturation.

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This phenomenon has already been described in patients with COPD during walking

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compared with cycling.7,8,36,37 The magnitude of the difference in desaturation between

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walking and cycling in COPD patients is greater (≈ 7%)7,8 than that observed in our

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study (= 2%); possibly because the lung diffusing capacity for carbon monoxide in

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patients with bronchiectasis has been reported as normal except in the more severe

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disease state3. However, the percentage of our patients who demonstrated desaturation

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only during the ISWT is equivalent to that shown by patients with COPD (21% and

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28%, respectively).7 Although we have not measured the pulmonary gas exchange

370

parameters during the ISWT, two main mechanisms should be emphasized to explain

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the differences in desaturation compared with cycling: amount of muscle mass and

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ventilatory demand, both superior during walking, determining a lower mixed venous

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oxygen saturation in the ISWT.

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Implications of the study

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Although the ISWT has been used in patients with non-cystic fibrosis

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bronchiectasis, the reproducibility of the test has never been analyzed in this population.

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Based on our data, there is a learning effect, but the magnitude is small when compared

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to that described for the 6MWT in patients with COPD. Hence, in clinical practice, as

380

recommended for other chronic respiratory diseases, two tests performed on the same

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day appear to be sufficient to elicit the best performance in patients with non-cystic

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fibrosis bronchiectasis. However, we suggest that a third test must be performed when

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the difference between the first two tests exceeds 57m. Additionally, future studies

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comparing the performance in more than two tests should be performed to verify the

385

veracity of this suggestion. Two tests performed on the same day are also sufficient to

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ensure the best performance on the ISWT. However, we suggest that a third test be

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performed when the difference between the first two tests exceeds the 57m. Further

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studies should be done to define a minimum clinically important improvement for the

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ISWT in patients with non-cystic fibrosis bronchiectasis undergoing pulmonary

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rehabilitation. The strong linear association between the distance walked with variables

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from the CPET and daily physical activity confirm that the ISWT is representative of

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exercise capacity and functional status in patients with non-cystic fibrosis

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bronchiectasis. Since a subgroup of patients presented with desaturation only during the

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ISWT, the ISWT should be used as a complement of the CPET to obtain a complete

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evaluation of the limiting factors of exercise.

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Limitations of the study

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Our patients were recruited from a convenience sample, which could compromise the

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external validity of our results. Although 21% of all patients of our clinic have been

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evaluated, in comparison with other studies1-5,9-11,13 our patients presented MRC scores

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for dyspnea (2[2−3]) similar to King et al2,3 (1.9±1.1 and 2.3±0.9), and O´Leary et al9

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(2.1±1.0), and equivalent distance walked on ISWT (453±153 m) with the latter

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(473±153 m). In terms of pulmonary function and functional capacity, the range of

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FEV1 and distance walked is quite huge (Table 1), which leads us to assume that our

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studied group is representative of those patients who are frequently encountered in the

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outpatient clinics, because comprise a wide range of respiratory and functional

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impairment. We did not measure the pulmonary gas exchange during the ISWT. Future

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studies correlating the distance walked with the peak VO2 measured on the ISWT

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should substantiate this test as an objective measure of the cardiopulmonary capacity in

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non-cystic fibrosis bronchiectasis patients. In a recent validation study of the Power

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Walker accelerometer, patients wore it attached to the waist, in the hemi-clavicular

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line,30 since the present validation study was published after our study had already

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begun, we follow the recommendations of the manufacturer. Thus, we cannot affirm

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that the accelerometer presents the same performance when it is worn in a pocket. We

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used only the steps/day as an outcome of physical activity in daily life and future studies

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are needed to evaluate the duration, intensity, and amount of daily physical activity in

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these patients.

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Conclusions

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In conclusion, the ISWT is reproducible, represents functional capacity, and

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induces greater desaturation in patients with non-cystic fibrosis bronchiectasis in

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comparison to CPET. Age, body composition, pulmonary function, dyspnea, and

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physical activity in daily life are determinants of the distance walked on ISWT.

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References

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1- Nicotra MB, Rivera M, Dale AM, et al. Clinical, pathophysiologic and microbiologic

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characterization of bronchiectasis in an aging cohort. Chest 1995;108:955-956.

430

2- King PT, Holdsworth SR, Freezer NJ, et al. Outcome in adult bronchiectasis. COPD

431

2005;2:27-34.

432

3- King PT, Holdsworth SR, Freezer NJ, et al. Lung diffusing capacity in adult

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bronchiectasis: a longitudinal study. Respir Care 2010;55:1686-1692.

434

4- Neves PC, Guerra M, Ponce P, et al. State-of-the-art – Pulmonary non-cystic fibrosis

435

bronchiectasis. Interact CardioVasc Thorac Surg 2011;13:619-625.

436

5- King PT, Holdsworth SR, Freezer NJ, et al. Characterization of the onset and

437

presenting clinical features of adult bronchiectasis. Respir Med 2006;100:2183-2189.

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6- Guyatt GH, Thompson PJ, Berman LB, et al. How should we measure function in

439

patients with chronic heart and lung disease? J Chronic Dis 1985;38:517-524.

440

7- Poulain M, Durand F, Palomba B, et al. 6-minute walk testing is more sensitive than

441

maximal incremental cycle testing for detecting oxygen desaturation in patients with

442

COPD. Chest 2003;123:1401-1407.

443

8- Turner SE, Eastwood PR, Cecins NM, et al. Physiological responses to incremental

444

and self-paced exercise in COPD. A comparison of three tests. Chest 2004;126:766-773.

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9- O’Leary CJ, Wilson CB, Hansell DM, et al. Relationship between psychological

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well-being and lung health status in patients with bronchiectasis. Resp Med

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2002;96:686-692.

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10- Wilson CB, Jones PW, O’leary CJ, et al. Validation of the St. George’s respiratory

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questionnaire in bronchiectasis. Am J Respir Crit Care Med 1997;156:536-541.

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11- Newall C, Stockley RA, Hill SL. Exercise training and inspiratory muscle training

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in patients with bronchiectasis. Thorax 2005;60:943-948.

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12- Lee AL, Cecins N, Hill CJ, et al. The effects of pulmonary rehabilitation in patients

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with non-cystic fibrosis bronchiectasis: protocol for a randomised controlled trial. BMC

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Pulm Med 2010;10:1-7.

455

13. Singh SJ, Morgan MD, Scott S, et al. Development of a shuttle walking test of

456

disability in patients with chronic airways obstruction. Thorax 1992;47:1019-1024.

457

14- Bradley J, Howard J, Wallace E, et al. Reliability, repeatability, and sensitivity of

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the modified shuttle test in adult cystic fibrosis. Chest 2000;117:1666-1671.

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15- Payne GE, Skehan JD. Shuttle walking test: a new approach for evaluating patients

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with pacemakers. Heart 1996;75:414-418.

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16- Booth S, Adams L. The shuttle walking test: a reproducible method for evaluating

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the impact of shortness of breath on functional capacity in patients with advanced

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câncer. Thorax 2001;56:146-150.

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17- Eaton T, Young P, Milne D, et al. Six-minute walk, maximal exercise tests.

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reproducibility in fibrotic interstitial pneumonia. Am J Respir Crit Care Med

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2005;171:1150-1157.

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18- Ries AL, Bauldoff GS, Carlin BW, et al. Pulmonary Rehabilitation - Joint

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ACCP/AACVPR Evidence-Based Clinical Practice Guidelines. Chest 2007;131(5

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19- Bestall J, Paul E, Garrod R, et al. Usefulness of the Medical Research Council

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(MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive

472

pulmonary disease. Thorax 1999;54:581-586.

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20- Neder JA, Nery LE, Castelo A, et al. Prediction of metabolic and cardiopulmonary

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responses to maximum cycle ergometry: a randomised study. Eur Respir J 1999;14:

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1304-1313.

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21. Hadeli KO, Siegel EM, Sherrill DL, et al. Predictors of oxygen desaturation during

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submaximal exercise in 8,000 patients. Chest 2001;120:88-92.

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22. Wilson RC, Jones PW. A comparison of the visual analogue scale and modified

479

Borg scale for the measurement of dyspnoea during exercise. Clin Sci 1989;76:277-282.

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23. Probst VS, Hernandes NA, Teixeira DC, et al. Reference values for the incremental

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shuttle walking test. Respir Med 2012;106:243-248.

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24. Tudor-Locke C, Burkett L, Reis JP, Ainsworth BE, Macera CA, Wilson DK. How

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many days of pedometer monitoring predict weekly physical activity in adults? Prev

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Med 2005;40(3):293-8.

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25. Enright PL, Sherril DL. Reference equations for the six-minute walk test in healthy

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adults. Am J Respir Crit Care Med 1998; 158:1384-1387.

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26- Campos LA, Chilingaryan G, Berg K, et al. Validity and reliability of the modified

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shuttle walk test in patients with chronic obstructive pulmonary disease. Arch Phys Med

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Rehabil 2006;87:918-922.

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27- Hernandes NA, Wouters EFM, Meijer K, et al. Reproducibility of 6-minute walking

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test in patients with COPD. Eur Respir J 2011;38:261-267.

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28- Singh SJ, Morgan MDL, Hardman AE, et al. Comparison of oxygen uptake during a

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conventional treadmill test and shuttle walking test in chronic airflow limitation. Eur

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Respir J 1994;7:2016-2020.

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29- Bradley J, Howard J, Wallace E, et al. Validity of a modified shuttle test in adult

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cystic fibrosis. Thorax 1999;54:437-439.

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30- Sant'anna T, Escobar VC, Fontana AD, et al. Evaluation of a new motion sensor in

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patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil

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2012;93:2319-2325.

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31- Pitta F, Troosters T, Spruit MA, et al. Characteristics of physical activities in daily

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life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med

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2005;171:972-977.

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32. Jürgensen SP, Antunes LCO, Tanni SE, et al. The incremental shuttle walking test

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in older brazilian adults. Respiration 2011;81:223-28.

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33. Lee AL, Button BM, Ellis S, et al. Clinical determinants of the 6-minute walk test in

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bronchiectasis. Respir Med 2009;103:780-785.

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34. Troosters T, Langer D, Vrijsen B, et al. Skeletal muscle weakness, exercise

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tolerance and physical activity in adults with cystic fibrosis. Eur Respir J 2009;33:99-

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106.

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35. Koulouris NG, Retsou S, Kosmas E, Dimakou K, Malagari K, Mantzikopoulos G,

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Koutsoukou A, Milic-Emili J, Jordanoglou J. Tidal expiratory flow limitation, dyspnoea

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and exercise capacity in patients with bilateral bronchiectasis. Eur Respir J 2003; 21:

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743–748.

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36- Cockcroft A, Beaumont A, Adams L, et al. Arterial oxygen desaturation during

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treadmill and bicycle exercise in patients with chronic obstructive airways disease. Clin

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Sci 1985;68:327-32.

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37- Palange P, Forte S, Onorati P, et al. Ventilatory and metabolic adaptations to

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walking and cycling in patients with COPD. J Appl Physiol 2000;88:1715-1720.

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SUPPLIERS

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a. Tanita BC-554, Tanita Corporation of America, Inc, Arlington Heights, IL.

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b. Corival, LODE B.V. Medical Technology Groningen, the Netherlands.

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c. CPX Ultima, Medical Graphics Corporation-MGC, St. Paul, MO, USA.

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d. Ohmeda Biox 3740, USA.

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e. Yamax Power Walker, model PW-610, Tokyo, Japan.

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FIGURE LEGENDS

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Figure 1 – A Bland-Altman plot of the between-test difference in the distance walked

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on ISWT. The solid horizontal line represents the mean bias. The dashed horizontal

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lines represent the lower and upper limits of agreement.

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Figure 2- Correlations between the distance walked on incremental shuttle walk test

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(ISWT) and (A) peak load, (B) steps/day, (C) VO2 (oxygen uptake), (D) MRC (Medical

536

Research Council) score. * p < 0.001 for all.

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Table 1 – Characteristics of the subjects. N = 75 (26 male)

Minimum - Maximum

Age (yrs)

45 (40−47)

19 − 81

BMI (kg/m2)

25 (24−27)

16 − 35

FFMi (kg/m2)

17 (16−17)

FVC (L)

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13 − 21

0.95 − 4.2

2.4 (2.2−2.6)

FVC (% pred)

26 − 107

FEV1(L)

1.5 (1.4−1.7) 53 (49−58)

FEV1/FVC

65 (61−68)

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FEV1(% pred)

0.36 − 2.74

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68 (63−72)

16 − 98 29 − 92

2 (2-3)

1−5

8,753(5,158-12,632)

1,382 − 27,808

Peak load (watt)

77 (68−75)

7 − 178

Peak load (% pred)

63 (58−68)

13 − 117

a

Peak VO2 (ml/kg/min)

18 (16−19)

11 − 34

a

Peak VO2 (% pred)

62 (59−66)

23 − 90

a

n = 56 patients. BMI: body mass index; FFMi: fat free mass index; FVC: forced vital

MRC

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capacity; FEV1: forced expiratory volume in the first second; MRC: Medical Research

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Council scale; NS: number of steps; VO2: oxygen uptake.

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Table 2- Data at the peak of the two incremental shuttle walking test. P value

Distance (m)

441 (406−476)

445 (410−481)

0.20

HR (bpm)

136 (132−140)

137 (132−141)

% HR pred (% )

78 (75−80)

78 (76−80)

SpO2 (%)

91 (90−93)

91 (90−93)

∆SpO2 (%)

-4 (-5 − -3)

Borg Dyspnea (points) Borg Fatigue (points)

ICC (95%IC)*

Best ISWT

0.99 (0.99-0.995)

453 (415-489)

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ISWT-2

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ISWT-1

0.92 (0.88-0.95)

138 (134-143)

0.49

0.90 (0.85-0.94)

79 (76-81)

0.76

0.91 (0.85-0.94)

91 (90-93)

-4 (-6 − -3)

0.63

0.87 (0.80–0.92)

-4 (-5 − -3)

4 (2-5)

3 (2-5)

0.55

0.91 (0.86-0.94)

3 (2-5)

4 (1-5)

3 (2-5)

0.29

0.91 (0.86-0.95)

3 (2-5)

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Variables

Values are expressed as mean (95% CI). HR: heart rate, SpO2: oxygen saturation, ∆: resting – peak at exercise. P value for

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comparisons between ISWT-1 and ISWT-2. *p < 0.001 for all.

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