Timed walking tests have been used for a long time to evaluate functional exercise performance.1–4 The six-minute walk test (6MWT) is a safe, simple, submaximal test, for evaluating functional exercise capacity, assessing prognosis and evaluating response to treatment across a wide range of respiratory diseases4–15; it reflects the capacity of the individual to perform activities of daily living.3,8–10 The six-minute walk distance (6MWD) is the primary outcome of the 6MWT, which is a reliable measure associated with death in some diseases.5–7,16–19 There is strong evidence of learning effect for the 6MWD when two or more 6MWT are conducted.1,6,7

Demographic, anthropometric, clinical, psychological and physiological characteristics can affect the test performance.5,16 Since 6MWT is a self-paced test, the results are influenced by external factors such as energy expenditure, clinician's/investigator's encouragement and subject's motivation.4,9,10,15,16,20

The American Thoracic Society (ATS) published the 6MWT guidelines, which aimed to standardize this procedure and encourage researchers to establish reference values for each population.5,11 During the last decade, several studies have elaborated 6MWT reference values,1,4,8–11,13–17,21–29 using different populations and 6MWT protocols.1,10,13,20 To the best of our knowledge, there are no reference equations for predicting 6MWD for the Portuguese population.

The aims of the present study were: to measure anthropometric data and 6MWD in a sample of healthy Portuguese population aged 18–70 years, according to the standardized approach provided by the ERS/ATS guidelines5,6; to establish reference equations to predict 6MWD; and to compare the 6MWD obtained with our reference equations to those obtained using previously published equations.27,28

To the best of our knowledge, the present study was the first to describe the 6MWD in healthy Caucasian Mediterranean people aged 18–70 years-old and to present predictive equations.

The 6MWT is one of the several modalities available for the objective evaluation of functional exercise capacity.5 In our sample of healthy adults, no spirometry was performed because only subjects who never smoked and without respiratory diseases were included after applying a COPD Diagnostic Questionnaire.30 The original papers on reference values for the 6MWT (published in English) included: unhealthy individuals,23 six papers with age ranges greater than 4 decades4,10,17,20,26,29 and only eight had more than 150 individuals.1,11,14,17,21,25,28,29 In the present study, the 158 healthy subjects were balanced both by sex and decades of age.

The 6MWD is influenced by learning effect,1,5–7,11 being large enough to be clinically important.5 In order to avoid bias caused by the learning effect in our study, two standardized tests were performed, and the best of both was used in the analysis. Our results showed that 6MWT2 was, on average, 3% better than 6MWT1. 6MWT2 was higher than documented in the study of Casanova et al.,11 which included a population analysis of seven countries, but very similar to the data from 13 studies of COPD patients.7

There was a significant difference in the 6MWD between male and female, with men walking a greater distance than women. This may be due to the fact that men were significantly taller – a higher height is associated with a longer stride, which generates a longer distance.1,4,26,29 In addition, men have a greater absolute muscle strength and muscle mass.9,11,16

The average 6MWD measured in this study was relatively shorter than those of Caucasian studies20,22,24,27 and longer than those of North and South American1,9,13–15,28 and Asian studies.16,17,26,29 The explanation for these differences may lie not only in racial and demographic differences, but also in 6MWT methodology.

Age, sex, BMI and ΔHR were the most important factors that significantly influenced the 6MWD of our healthy subjects. Age is a variable that significantly influenced 6MWD in almost all29 previous studies on 6MWD reference equations. We found that age and BMI were negatively associated with the 6MWD. The negative association with age could be explained by the fact that muscle mass, muscle strength and maximal oxygen uptake gradually decreases with age.9,13,16 The six-minute walk work (6MWW) is the product of 6MWD and body weight. 6MWW increases with obesity; as a result, the obese walk shorter distances since changes in weight can significantly affect the energy requirement and, therefore, the amount of work performed.34 In our study, we found that the ΔHR was significantly positively associated with 6MWD, which may be because ΔHR represents the level of effort the subject expended while performing the test,17 the subjects who tried harder walking more. Another measure for level of effort may be the percentage of mHR, which in our study was 67.6%, a value lower than that described by Camarri et al. in a Caucasians study, where 6MWD was greater,20 reinforcing the idea that less effort may have influenced outcomes.

In the present study, three equations were derived for 6MWD in a sample of healthy Portuguese population aged 18–70 years old. The first proposed model seems advantageous given its simplicity. We considered the second model (with explanatory power of 38%), to be the reference equation for the Portuguese population aged 18–70 years old. In agreement with the literature,1,4,8–11,13–17,20–28 we verified that there was a decrease of 6MWD with increase in age. Consequently, it seemed pertinent to propose the third model in which the age range, by decade, was included.

The use of predictive equations for 6MWD created for populations other than the one studied, was associated with errors on the predicted distances. The difference between the measured and predicted 6MWD values might be caused by multiple factors. A systematic review identified many published studies from 1998 to 2017 that included 6MWD prediction equations from healthy adults.1,4,9–11,13–17,20–22,24–29 These studies were conducted using a wide variety of populations and methodologies. Casanova et al.11 studied a population of 7 countries, including Spain. In spite of having included a Mediterranean population, the conclusions reached by this group was that there were wide regional and geographic differences not explained by the variables used to obtain the reference equations. Thus, considering that a single reference equation was generated for a population of 6 American and one Mediterranean countries, we do not consider this equation to be representative of Mediterranean population. We selected the regression equations from the models of Gibbons et al.27 and Britto et al.,28 because these studies included populations with an age range similar to our study population. Applying the Gibbons and Britto equations, we found that there was an overestimation with the first and an underestimation with the equation 1 of the second one. Further, our study adds to the evidence that the predictive equations derived from other populations27,28 would not apply to Portuguese population.

Our research had some limitations: our sample may not be representative of the entire Portuguese population (although subjects were selected consecutively on the basis of inclusion criteria); the sample size was sufficient to elaborate a reference equation, but it was a relatively small sample, in particular the age group over 60 years old for which this test is widely used and has a particular interest (rehabilitation and exercise capacities in clinical groups); we did not recruit underweight and obese people, our reference equations are not applicable to the subjects with 18<BMI>30kg/m2 and although we have excluded high competition athletes we haven’t objectively measured physical activity. Despite the limitations, we found, for the first time, reference values for the 6MWD for Caucasian Mediterranean healthy population aged 18–70 years old.

The present study was the first to describe the 6MWD in healthy Portuguese people aged 18–70 years old and to propose predictive equations. Age, sex, BMI and ΔHR were the most significant predictors of the 6MWD and the regression equations explained approximately 34–38% of the variance in the 6MWD. We conclude that our equations can improve the evaluation of Caucasian Mediterranean patients with diseases that affect their functional capacity.

Conceptualization: Miguel Guimarães, Maria João Oliveira.

Data curation: Maria João Oliveira, Raquel Marçôa, José Moutinho.

Formal analysis: Pedro Oliveira.

Writing: Maria João Oliveira, Raquel Marçôa, Pedro oliveira.

Writing±review & editing: Maria João Oliveira, Raquel Marçôa, Pedro Oliveira, José Moutinho, Inês Ladeira, Ricardo Lima and Miguel Guimarães.

The protocol was approved by our ethics committee, and written informed consent was obtained from each patient prior to the study.

None declared.

The authors have no conflicts of interest to disclose.