Published ahead of print on April 26, 2007, doi:10.1164/rccm.200607-883OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200607-883OC
Standard Reference for the Six-Minute-Walk Test in Healthy Children Aged 7 to 16 Years1 Department of Pediatrics and Centre for Epidemiology and Biostatistics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong Correspondence and requests for reprints should be addressed to Dr. Albert Martin Li, M.B., Clinical Lecturer, Department of Pediatrics, 6th Floor, Clinical Sciences Building, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. E-mail: albertmli{at}cuhk.edu.hk
Rationale: We have previously reported that the six-minute-walk test (6MWT) is a reliable and valid functional test for assessing exercise tolerance and endurance. There is a lack of pediatric standard reference for the 6MWT. Objectives: To construct height-specific standards for the 6MWT for children aged 7 to 16 years. Methods: The anthropometric data, spirometric lung function, and six-minute-walk distance (6MWD) of Chinese children aged 7 to 16 years were prospectively measured using standardized protocols. The findings were used to construct height-specific standards for the 6MWT. The least mean square (LMS) method using maximum penalized likelihood was used to facilitate model fitting. Factors significantly associated with 6MWD were also determined. Measurements and Main Results: From January 2005 to April 2006, a total of 1,445 subjects were studied. The measured variables showed a normal distribution. Height-specific reference standards for 6MWT were constructed for both male and female children. Forward stepwise multiple regression analysis revealed height and difference in heart rate before and after the walk test to be important clinical variables associated with 6MWD. Conclusions: These 6MWD standards will provide useful references for the care of pediatric patients.
Key Words: six-minute-walk test • child • reference curves
The individual response to exercise is an important clinical assessment tool because it provides a composite assessment of the respiratory, cardiac, and metabolic systems. The current gold standard for assessing one's aerobic exercise response is the maximum incremental cardiopulmonary exercise test. However, most daily activities are performed at submaximal levels of exertion; thus, using submaximal functional tests would provide a more realistic simulation of one's physical capability (1). The ability to walk for a distance is a quick, easy, and inexpensive way to assess the physical function of an individual. It is also an important component of quality of life as it reflects the ability to undertake day-to-day activities. Balke developed a simple test to examine the functional capacity by measuring the distance walked during a defined period of time (2). A 12-minute performance test was then developed to evaluate the physical fitness of healthy individuals (3). This test was subsequently modified for use in patients with chronic bronchitis (4). To allow patients with respiratory diseases for whom walking a 12-minute distance was too demanding, a shortened version, of 6 minutes, was found to provide comparable clinical information (5). A recent review of functional walking tests concluded that the six-minute-walk test (6MWT) is easy to perform with better acceptability by participants, and provides a better reflection of activities of daily living than other walk tests (1). The American Thoracic Society has also recently endorsed and published guidelines for performing the 6MWT in clinical settings (6). The 6MWT has been frequently used to measure outcomes before and after treatment in patients with moderate to severe heart and lung diseases (7). It has also been used to measure cardiopulmonary functional status and in epidemiologic research. The distance covered in 6 minutes (6MWD) has been shown to accurately predict morbidity and mortality from cardiopulmonary diseases (7). Previous studies involving children using the 6MWT were performed in groups of diseased patients with physical dysfunction and did not include healthy subjects (8–11). The lack of 6MWD reference values from normal, healthy children hinders the clinical usefulness of this test in the pediatric age group. Our study group had recently reported preliminary data involving 74 healthy subjects aged between 12 and 16 years and found the 6MWT to be a reliable, reproducible, and valid functional test for assessing exercise tolerance and endurance (12). In the current study, we aimed to establish height-specific reference standards for the 6MWD of healthy children aged between 7 and 16 years.
Subjects Data collection took place over a 15-month period from January 2005 to April 2006 when healthy children aged between 7 and 16 years were recruited from randomly selected local primary and secondary schools. Before recruitment, a health talk was given at each participating school by the principal investigator to explain the purpose of the study. The school principal at each school then arranged suitable students to attend our unit for assessment. A questionnaire was completed by the subject or his or her parent on the day of testing and informed consent obtained from the parent, as well as the subject as appropriate. The questionnaire identified children with cardiorespiratory problems, including asthma, bronchiectasis, congenital heart deficit and hypertension, exercise problems (e.g., neuromuscular or musculoskeletal diseases), hospital admissions within the past 3 months, a common cold within the last 4 weeks, or long-term medication that could interfere with the walk test. Children with any such history were excluded from the study. The remaining children with negative disease and medication history, and written parental informed consent, constituted the target study population. Each eligible subject was then interviewed by an investigator to confirm his or her health status before undergoing a thorough physical examination. Subjects' weight and standing height were measured with a calibrated weighing scale and stadiometer by standard anthropometric methods (13). All subjects underwent spirometry and a standardized 6MWT. We had obtained approval for the study from the ethics committee of the Chinese University of Hong Kong.
Pulmonary Assessment
6MWT A light meal was acceptable before the test, but the subject was told to avoid vigorous exercise for 2 hours before testing. No "warm up" period before the test was allowed and the subject sat at rest in a chair, located near the starting position, for 10 minutes before commencement. During this period, resting pulse, oxygen saturation (NPB-40 Pulse Oximeter; Nellcor Puritan Bennett, Inc., Pleasanton, CA), and blood pressure were measured. The 6MWT was performed by a single investigator (J.Y.), who used a mechanical lap counter to count the number of laps completed, and an electronic timer with an alarm that sounded 6 minutes after the walk started. The words of encouragement during the testing were standardized ("Keep going," "You are doing fine," "Everything is going well") and were given by the same person at set times during the test. The distance in meters covered over the 6 minutes was recorded (6MWD). Pulse and oxygen saturation were recorded at the end of the test.
Statistical Analysis
The mean, SD, and 3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 97th centiles of 6MWD at 5-cm height intervals were computed independently for the male and female subjects. Centile charts were constructed using the maximum penalized likelihood LMS method. (15) The LMS method estimates the measurement centiles in terms of three height- and sex-specific cubic spline curves: the L curve (Box-Cox power to transform the data follow a normal distribution), M curve (median), and S curve (coefficient of variation). In brief, let Y(t) denote an independent positive datum (i.e., 6MWD) at t height in centimeters, so that the distribution of Y(t) can be summarized by a normally distributed SD score (Z) as follows:
Once the L(t), M(t), and S(t) have been estimated for each height t, the 100
 is the centile of the normal distribution (e.g., for the 97th centile, =0.97 and Z=1.88). Sample sizes at each exact height (measurements of 6MWD were normally distributed) were calculated using the method described by Healy (16).
One thousand five hundred Chinese subjects were approached and 1,469 attended our unit for assessment. Twenty-three participants had asthma and one subject was diagnosed to have a ventricular septal defect: these individuals were excluded from the study. Eight hundred and five males and 640 females completed the 6-minute walk. The mean (SD) age of the cohort was 12.0 (2.6) years. Ninety-eight subjects suffered from allergic rhinitis, for which 20 were taking an antihistamine on a regular basis and 5 were taking nasal spray corticosteroids at nighttime. Twenty-two subjects had eczema; only one was using topical corticosteroid cream, and the remainder used topical moisturizer on an as-required basis. One subject suffered from hypothyroidism and was receiving regular thyroxine replacement; and, at the time of the study, he was known to be euthyroid. One subject suffered from epilepsy and had been seizure free without medications for 2 years. Physical examination was unremarkable for all subjects and none admitted to be smokers. Their characteristics are shown in Table 1. Males were significantly heavier and taller than females and there was a sex difference in BMI (18.6 [3.6] vs. 18.2 [3.3], p = 0.02). The detailed demographic characteristics of the subjects separated into each age group are shown in Table 2.
During the study, none of the walk tests had to be prematurely terminated and none of the subjects required a rest. The overall 6MWD was 664 (± 65.3) m and was greater in males than females by 38.2 m (680.9 and 642.7 m, respectively). Resting heart rate was significantly faster in the females (85.9 [11.7] vs. 81.9 [11.3] beats/min [bpm], p < 0.0001), but there was no sex difference in end of exercise heart rate (154.5 [20.6] vs. 153.8 [22.0] bpm, p = 0.545]. Resting oxygen saturation was lower in the male subjects (98.1 [1.1] vs. 98.3% [1.1%], p = 0.001] but like resting heart rate, this was of little clinical significance. There was no sex difference in end of exercise oxygen saturation (97.7 [1.4] vs. 97.8% [1.3%], p = 0.155) (Table 1). Univariate correlation between 6MWD and 6MWD per kilogram of body weight and the various demographic, lung function, and 6MWT variables are presented in Tables 3 and 4. Forward stepwise multiple regression analysis for each sex revealed height and difference in heart rate before and after the walk test to be positively associated with 6MWD (Table 5). We obtained similar results if 6MWD per kilogram of body weight was used as the dependent variable. Age and FEV1, both highly correlated with height, were also found to have significant association with 6MWD. Height was chosen to be the more important clinical parameter because it is routinely measured in clinical settings and has the best correlation with 6MWD on univariate analysis.
Prediction equations for 6MWD were also derived for each sex. They were as follows: 6MWD (m) for males = 554.16 + (difference in heart rate x 1.76) + [height (cm) x 1.23], and 6MWD (m) for females = 526.79 + (difference in heart rate x 1.66) + [height (cm) x0.62]. Figures 1 and 2 show the height-specific smoothed centile curves for the 6MWD for male and female subjects, respectively. Figure 3 shows a composite graph overlapping both male and female standard curves at the 25th, 50th, and 75th centiles for comparison. At all height intervals, males were able to cover greater distances compared with their female counterparts. The 50th centile curve for males corresponded approximately to the 75th centile curve of females.
To our knowledge, these are the first reported data in the international literature on reference values for 6MWD in children. They may be used to obtain the predicted 6MWD for individual pediatric subjects aged between 7 and 16 years performing the test for the first time, when using the standardized protocol. We also demonstrated that height and difference in heart rate before and after the walk test were significantly associated with 6MWD. The 6MWT is increasingly being used in routine clinical practice because it provides useful information on the daily physical performance of healthy individuals and those with pulmonary diseases (14). The distance achieved within 6 minutes allows an estimation of individual response to incremental maximal exercise and has been found to accurately reflect physical capacity of patients with pulmonary disease (10, 14). In a previous study performed by our research group, we have shown that the 6MWT in healthy children was reproducible and reliable. There was no significant difference in the 6MWD reached at two time points, separated by a mean of 18 days, and the within-subject correlation coefficient was excellent (0.94 [95% confidence interval, 0.89–0.96]) (11). We were also able to demonstrate that the test was valid because a significant correlation was established between the 6MWD and maximum oxygen consumption obtained at treadmill exercise test (11). There was a significant sex difference in 6MWD. At all height intervals, males were found to have greater 6MWD than females, possibly as a result of their greater muscle mass and the ability to achieve higher levels of physical activity. We could not exclude the possibility of physical fitness as an important determining factor for 6MWD, and this could have explained the sex difference demonstrated. However, quadriceps strength has not been shown to be a predictor of 6MWD in healthy elderly subjects (17), and previous research has failed to demonstrate an association between self-reported physical activity and 6MWD in healthy adults (17, 18). Our cohort of male subjects had significantly greater height compared with their female counterparts and this could explain the sex difference seen in the distance covered in 6 minutes. Among all anthropometric measurements, height had the best correlation with 6MWD. Taller people could have larger stride length and thus greater walk distances; however, we did not measure leg length, which may also be an important predictor of 6MWD because it is a primary determinant of stride length (19). The effect of puberty on 6MWD was not examined in this study. A previous study demonstrated that absolute total energy expenditure and physical activity level increased after puberty (20). Difference in heart rate before and after the test would represent the effort levels individual subjects exerted during the test. On the other hand, lower resting heart rate, which is typically seen in trained athletes, would also give rise to a greater difference in heart rate before and after the test. Accordingly, resting heart rate was found to have a significant negative correlation with 6MWD (r = –0.25) in this study. Significant correlation between 6MWD and FEV1 has been shown in other studies involving patients with chronic pulmonary disease and, especially, cystic fibrosis (7–9). Webb and colleagues (21) recently demonstrated a positive association between FEV1 and the distance walked on the incremental shuttle walking test in healthy males aged 40 to 69 years. Because FEV1 and height were strongly correlated, it is likely that the correlation between FEV1 and the distance covered in 6 minutes simply reflects the correlation of FEV1 with height, especially given the normal pulmonary function of the sample. Height was used instead of age for the construction of these standard reference curves because, among all anthropometric factors that were proven to have a significant correlation with 6MWD, height was the most discriminative with the best correlation. Height is one of the anthropometric parameters that is routinely recorded in all medical records in pediatric clinics. In addition, height is a more robust parameter than age, because individuals of the same age but of different racial background can have very different height. Using height-specific curves could possibly lessen such racial variation, but further studies involving subjects from other races will be needed for formal comparison (22). Caution should also be taken when applying our centile curves to individuals who fall outside the characteristics of our cohort, such as those younger than 7 years. These centile curves are clinically relevant and provide a user-friendly method in the prediction of 6MWD. Although an abnormally low 6MWT result does not identify the cause of the limitation and a treadmill exercise test will be needed to delineate the underlying mechanisms, the 6MWT is easy to perform, well tolerated by the subjects, and serves as a good reflection of daily activities (1). It is a useful measure of functional capacity, and, in this study, reference standards for healthy Chinese children aged 7 to 16 years were derived.
Supported by the Department of Pediatrics, The Chinese University of Hong Kong. Originally Published in Press as DOI: 10.1164/rccm.200607-883OC on April 26, 2007 Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Received in original form July 1, 2006; accepted in final form April 23, 2007
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