(PDF) Six minute walk test Z score: Correlations with cystic fibrosis severity markers

Journal of Cystic Fibrosis 11 (2012) 253–256www.elsevier.com/locate/jcf

Short Communication

Six minute walk test Z score: Correlations with cystic fibrosisseverity markers

Fabíola Stollar a,⁎, Joaquim C. Rodrigues a, Maristela T. Cunha b,Claudio Leone c, Fabíola Villac Adde a

a Pulmonology Division, Instituto da Criança, Hospital das Clínicas, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 647, zip code 05403900, São Paulo, Brazilb Physiotherapy Division, Instituto da Criança, Hospital das Clínicas, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 647, zip code 05403900, São Paulo, Brazilc Department of Maternal and Child Health, College of Public Health, University of Sao Paulo, Av. Dr. Arnaldo, 715, zip code: 01246–904, São Paulo, Brazil

Received 7 September 2011; received in revised form 23 November 2011; accepted 24 November 2011Available online 20 December 2011

Abstract

Background: The six-minute-walk-test (6MWT) has been increasingly used in cystic fibrosis (CF) patients. However, few studies in children havecorrelated 6MWT with current parameters used to evaluate CF severity. Moreover, no study transformed the values of distance walked from metersinto Z scores to avoid bias like age and gender, which are sources of 6MWT variability.Methods: A cross-sectional descriptive study was performed to analyze the correlations (Spearman) among forced expiratory volume in one second(FEV1), body mass index (BMI), chest radiography (CXR), chest tomography (CT), and 6MWT Z score (Z-6MWT). Clinically stable CF patients,aged 6–21 years, were included.Results: 34 patients, 14F/20M, mean age 12.1±4.0 years were studied. The mean Z-6MWT was −1.1±1.106. The following correlations versus Z-6MWT were found: FEV1 (r=0.59, r

2=0.32, p=0.0002), BMI Z score (r=0.42, r2=0.17, p=0.013), CXR (r=0.34, r2=0.15, p=0.0472) and CT(r=−0.45, r2=0.23, p=0.0073).Conclusions: In conclusion there was a significant, but poor, correlation between the six minute walk test Z score and the cystic fibrosis severitymarkers currently in use.© 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Keywords: Chest imaging; function tests; minute walk test; fibrosis

1. Introduction

In cystic fibrosis (CF) disease progression is assessedthrough spirometry, chest radiography and tomography andclinical data [1–3]. In the last decade, the six-minute walk test(6MWT) has been widely used to evaluate global exercise ca-pacity in patients with cystic fibrosis [4–8] and it has been pro-posed as a simple and reliable test for the periodic evaluation ofCF patients' exercise program [4,9]. It is a low cost test, easy to

Abbreviations: CF, cystic fibrosis; CXR, chest radiography; CT, chest computedFVC, forced vital capacity; FEV1, forced expiratory volume in one second; FEF25-75%index.⁎ Corresponding author at: Pulmonology Division, Instituto da Criança, Hospital da

Paulo, Brazil. Tel.: +55 11 26618566.E-mail address: [emailprotected] (F. Stollar).

perform, reproducible and may serve as a predictor of mortalityand morbidity in patients with cardiopulmonary diseases[4,10,11,12]. It is also useful for longitudinal assessment, tomonitor response to treatment and to guide therapy [11,13].

The 6MWT has been increasingly used in young children,for whom performing cardiopulmonary exercise tests is espe-cially problematic, requiring a high degree of cooperation,good coordination and motivation [10,14]. It has to be takeninto account that there is a degree of practice bias with the

tomography scan; PFT, pulmonary function tests; 6MWT, six minute walk test;, forced expiratory flow between 25 and 75% of vital capacity; BMI, body mass

s Clínicas, University of São Paulo, Av. Dr Enéas Carvalho de Aguiar, 647, São

mailto:[emailprotected]

http://dx.doi.org/10.1016/j.jcf.2011.11.009

254 F. Stollar et al. / Journal of Cystic Fibrosis 11 (2012) 253–256

6MWT so that the more the children do it, the better they be-come [10]. Up to now, few studies in children have correlated6MWT with current parameters used to evaluate CF severity.Moreover, no study transformed the values of distance walkedfrom meters into Z scores to avoid bias like age and gender,which are sources of 6MWT variability.

In this study we transformed the values of distance walkedin the 6MWT from meters into Z scores and investigated thecorrelations between six minute walk test Z score (Z-6MWT)and other current parameters used to evaluate CF severity,such as forced expiratory volume in one second (FEV1), bodymass index (BMI), chest radiography (CXR) and chest computedtomography (CT).

2. Methods

This was a cross-sectional descriptive study. Between June2006 and August 2008, we studied 34 CF patients (between 6and 21 years old) recruited from the outpatient clinic of ourhospital. The diagnosis of cystic fibrosis was made accordingto established criteria [15]. Only patients with stable diseasewere included in this study. Exclusion criteria were pulmonaryexacerbation [16] in the month preceding the tests or a chest CTdone in the previous year to avoid another radiation exposure.Spirometry, chest radiography and CT and the 6MWT wereall carried out on the same morning.

This study was approved by the Human Ethics Committeeof Hospital das Clínicas — Medical School of University ofSão Paulo, Brazil (approval number 1074/05). Written in-formed consent was obtained from all subjects or their parents.

2.1. Spirometry

Spirometry was performed by a single technician with expe-rience in pediatric tests, using the standards recommended bythe American Thoracic Society (ATS) [17]. A Master Screenspirometer (Multispiro Creative Biometcs) was used. The re-sults were expressed as the percentage of predicted values forforced vital capacity (FVC), FEV1 and forced expiratory flowbetween 25 and 75% of vital capacity (FEF25-75%). The equa-tions of Polgar and Promadhat were used as a reference for sub-jects up to 17 years of age, and the equation of Knudson et al.was used for patients aged between 18 and 21 years [18,19].The severity of the ventilatory obstruction was classifiedaccording to ATS/ERS (European Respiratory Society) [20].

2.2. Chest radiography and chest CT scan

The Brasfield score [21] was used to evaluate chest radiogra-phy. Five categories were scored: air trapping, linear marks,nodular cystic lesions, large lesions, and overall severity. Chestroentgenograms showing more severe changes received a lowerscore.

The CT scans were scored using the scoring system describedby Bhalla et al. [22]. In 25 patients chest CT during expirationwas also performed and it was possible to calculate a modifiedBhalla score [23]. Bhalla score was used instead of the modified

Bhalla score for the correlation analysis because it was applied inall patients and a significant correlation between the modifiedBhalla score and the Bhalla score was found (r=0.97,pb0.0001).

Scanning was performed with a GE LightSpeed Ultra CTScanner. Thin-section CT scans were obtained using a beamcurrent automatically adjusted by the machine (70–100 mA), anexposure time of 0.5 s, a beam potential of 120 kV from lungapex to lung base at 10 mm intervals using 1.25 mm thick singleslices, non volumetric, and a field of view of 15–40 cm. MeanCTDI vol was 1.3 mGy. All scans were reconstructed with ahigh spatial frequency algorithm (bone) and printed with windowsettings appropriate for the imaging of pulmonary parenchyma(window width—600 HU; window level—1.500 HU).

The radiographic and tomographic scores were calculatedindependently in a blinded manner by three radiologists (twopediatric radiologists and a chest radiologist). The final scorewas the average of the three radiologists' scores.

2.3. Six-minute walk test

All 6MWTs were done using a lap 30 m in length, on a flat,hard surface, according to the ATS guidelines [10]. Two testswere performed on the same day with an interval of at least30 min and after all clinical variables had returned to theirbasal values. The patients were asked to walk as far as possiblefor 6 min up and down the measured lap, but not to run. Stan-dardized encouragement was given by the same person afterevery 1 min (“You are doing well!”, “Keep up the goodwork!”). The distance was measured in meters and the testwith the greatest distance was selected. The values were trans-formed into Z scores based on Geiger et al. data [24], using thefollowing formula: value found−normal value/standarddeviation.

2.4. Statistical analysis

Data were expressed as number of cases, mean and standarddeviation or median. Mean±SD was used for parametric data(age, BMI, 6MWT, spirometry) and median was used for non-parametric data (Bhalla and Brasfield scores). Linear regression(Spearman's correlation coefficient) was used for analysis of cor-relations between the tests, calculated by the GraphPadPrism 5program. The significance level considered was pb0.05.

It was calculated that a minimum sample size of 30 patientswas needed in order to estimate correlations with a level of sig-nificance of α=0.05 and a statistical power (1-ß) of 95% (Med-Calc software version 10.0.0).

The BMI of patients was calculated and transformed into Zscores (Z-BMI) using the program Nutrition Epi Info™, ver-sion 3.3.2 on the CDC website.

3. Results

Thirty-four patients were evaluated, 14 females and 20 males,mean age of 12.1±4 years. The descriptive characteristics of pa-tients are shown in Table 1. The mean distance walked was 596±

Table 1Characteristics of the CF patients (n=34).

Mean±sd Range

Age (years) male/female: 20/14 12.1±4.0 6.0–20.9Z-BMI −0.6±1.2 −2.9–2.1BMI (Kg/m2) 17.0±2.4 13.7–22Z-6MWT −1.1±1.106 −4.07–0.66MWT (m) 595.9±68.8 431.0–743.0FVC (% predicted) 70.4±25.9 20.4–126.0FEV1 (% predicted) 59.2±26.0 13.3–134.0FEF25-75% (% predicted) 47.4±35.8 4.8–172.4Bhalla score (median) 10.8 2.7–19.0Brasfield score (median) 15.7 6.0–23.7

Z-BMI, body mass index Z score; Kg, kilogram; m, meters; Z-6MWT, six-minute walk test Z score; FVC, forced vital capacity; FEV1, forced expiratoryvolume in 1 s; FEF25-75%, forced expiratory flow between 25 and 75% ofvital capacity.

255F. Stollar et al. / Journal of Cystic Fibrosis 11 (2012) 253–256

69 m and the Z-6MWT was −1.1±1.106. Regarding the nutri-tional status the average BMI was 17±2.4 Kg/m2. Spirometryshowed 11 children with mild obstructive lung disease(FEV1≥70%) or normal FEV1 (FEV1≥80%), seven moderate(FEV1 between 60 and 69%), five moderately severe (FEV1

between 50 and 59%), six severe (FEV1 between 35 and 49%)and five very severe (FEV1b35%).

For all patients the correlations between Z-6MWT and FEV1,Z-BMI, Brasfield score and Bhalla score were calculated. A sig-nificant correlation between all parameters was observed(Figs. 1A, B, C and D).

5 10 15 20 25-5

-4

-3

-2

-1

Brasfield score

Z-6

r = 0.34; r2=0.15 ; p = 0.0472

A B

0 5 10 15 20

-4

-2

Bhalla score

Z-6

r = -0.45; r2=0.23; p = 0.0073

C D

Fig. 1. A) Correlation between Brasfield score and six minute walk test Z score (Z-6MC) Correlation between Bhalla score and Z-6MWT; D) Correlation between forced

4. Discussion

In the present study, the Z-6MWT correlated significantlywith current parameters used to evaluate CF severity such asFEV1, Z-BMI, chest radiography and tomography. Despite thestatistically significant correlation that was found the correlationcoefficients and plots did not show a very tight correlation andthis may reflect that the 6MWT is affected by other extra pulmo-nary domains [10].

Although reference values for 6MWT in Brazilian childrenhave recently been published [25] we decided to use Geigeret al. [24] reference values because our sample consisted of pa-tients up to 21 years old and the Brazilian data only includedpatients younger than 12 years of age. Nevertheless, the Brazil-ian data on reference values for the 6MWT strongly correlatedwith the data of Geiger et al. (r=0.87).

Previous studies in CF patients did not show significant corre-lations between 6MWT and pulmonary function tests [4,26,27],BMI [8,26] and chest radiography [8]. Different from these stud-ies we decided to transform the values of distance walked frommeters into Z score based on reference values from healthypopulation to avoid bias like age and gender, which are sourcesof 6MWT variability [10,24,28,29]. The use of the Z score to rep-resent the distance walked was able to render uniform the data ofthe population studied, which had a wide age range (6 to 21 yearsold).

Only two studies found significant correlations between6MWT and FEV1 (r=0.53 to r=0.75), but one evaluated CF

-4 -2 0 2

-4

-2

Z-BMI

Z-6

r = 0.42; r2=0.17; p = 0.013

0 50 100 150

-4

-2

FEV1 (% predicted)

Z-6

r = 0.59; r2=0.32; p = 0.0002

WT); B) Correlation between body mass index Z score (Z-BMI) and Z-6MWT;expiratory volume in 1 s (FEV1) and Z-6MWT.

256 F. Stollar et al. / Journal of Cystic Fibrosis 11 (2012) 253–256

adolescents and adults [8] and in the other patients with CF andother obstructive lung disease were included [30].

The poor correlation we found between the Brasfield andBhalla scores and the Z-6MWT may be due to the fact thatthe 6MWT reflects the overall status of both lungs whileCXR and CT can help identify abnormalities that affect onlya small portion of the lung. The correlation between 6MWTand chest CT has not been described before.

One limitation of our study is that it is a cross-sectionalstudy and this precludes a longitudinal evaluation. It was notpossible to assess whether or not the parameters (CXR, CT,FEV1, 6MWT) would change in a similar way.

Acknowledgments

We thank Luiz Antonio N. Oliveira, Lisa Suzuki and CarmemL. Fujita who calculated the Bhalla and Brasfield scores.

References

[1] Brody AS, Tiddens HA, Castile RG, et al. Computed tomography in theevaluation of cystic fibrosis lung disease. Am J Respir Crit Care Med2005;172:1246–52.

[2] Milla CE. Association of nutritional status and pulmonary function in chil-dren with cystic fibrosis. Curr Opin Pulm Med 2004;10:505–9.

[3] Sawyer SM, Carlin JB, DeCampo M, Bowes G. Critical evaluation ofthree chest radiograph scores in cystic fibrosis. Thorax 1994;49:863–6.

[4] Gulmans VAM, van Veldhoven NHMJ, de Meer K, Helders PJMl. Thesix-minute-walking test in children with cystic fibrosis: reliability and va-lidity. Pediatr Pulmonol 1996;22:85–9.

[5] Chetta A, Pisi G, Zanini A, et al. Six minute walk test in cystic fibrosisadults with mild to moderate lung disease: comparison to healthy subjects.Respir Med 2001;95:986–91.

[6] Kadikar A, Maurer J, Kesten S. The six-minute-walk test: a guide to assess-ment for lung transplantation. J Heart LungTransplant 1997;16:313–9.

[7] Balfour-Lynn IM, Ammani Prasad S, Laverty A, Whitehead BF, DinwiddieR. A step in the right direction: assessing exercise tolerance in cystic fibrosis.Pediatr Pulmonol 1998;25:278–84.

[8] Ziegler B, Rovedder PME, Lukrafka JL, Oliveira CL, Menna-Barreto SS,Dalcin PTR. Submaximal exercise capacity in adolescent and adult pa-tients with cystic fibrosis. J Bras Pneumol 2007;33:263–9.

[9] Geiger R, Willeit J, Rummel M, et al. Six-minute walk distance in over-weight children and adolescents: effects of a weight-reducing program.J Pediatr 2011;158:447–51.

[10] American Thoracic Society (ATS) Committee on Proficiency Standardsfor Clinical Pulmonary Function Laboratories. ATS statement: guidelinesfor the six-minute walk test. Am J Respir Crit Care Med 2002;166:111–9.

[11] Enright PL. The six-minute walk test. Respir Care 2003;48:783–5.[12] Chetta A, Zanini A, Pisi G, et al. Reference values for the 6-min walk test

in healthy subjects 20–50 years old. Respir Med 2006;100:1573–8.[13] Hoeper MM, Markevych I, Spiekerkoetter E, et al. Goal-oriented treatment

and combination therapy for pulmonary arterial hypertension. Eur Respir J2005;26:858–63.

[14] Li AM, Yin J, Yu CC, et al. The six-minute walk test in healthy children:reliability and validity. Eur Respir J 2005;25:1057–60.

[15] Farrell PM, Rosenstein BJ, White TB, et al. Cystic Fibrosis Foundation.Guidelines for diagnosis of cystic fibrosis in newborns through olderadults: Cystic Fibrosis Foundation consensus report. J Pediatr 2008;153:S4–S14.

[16] Rabin HR, Butler SM, Wohl MEB, et al. Pulmonary exacerbations in cys-tic fibrosis. Pediatr Pulmonol 2004;37:400–6.

[17] Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A.Standardisation of spirometry. Eur Respir J 2005;26:319–38.

[18] Polgar G, Promeghat V. Pulmonary function testing in children: techniquesand standards. Philadelphia: Saunders; 1971.

[19] Knudson RJ, Lebowits ND, Holberg CJ, Burrows B. Changes in the normalmaximal expiratory flow-volume curve with growth and aging. Am RevRespir Dis 1983;127:725–34.

[20] Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lungfunction tests. Eur Respir J 2005;26:948–68.

[21] Brasfield D, Hicks G, Soong S, Tiller RE. The chest roentgenogram incystic fibrosis: a new scoring system. Pediatrics 1979;63:24–9.

[22] Bhalla M, Turcios N, Aponte V, et al. Cystic fibrosis: scoring system withthin-section CT. Radiology 1991;179:783–8.

[23] Dood JD, Barry SC, Barry RBm, Gallagher CG, Skehan SJ, Masterson JB.Thin-section CT in children with cystic fibrosis: correlation with peak ex-ercise capacity and body mass index. Radiology 2006;240:236–45.

[24] Geiger R, Strasak A, Treml B, et al. Six-minute walk test in children andadolescents. J Pediatr 2007;150:395–9.

[25] Priesnitz CV, Rodrigues GH, Stumpf CS, et al. Reference values for the 6-min walk test in healthy children aged 6–12 years. Pediatr Pulmonol2009;44:1174–9.

[26] Cunha MT, Rozov T, de Oliveira RC, Jardim JR. Six-minute walk test inchildren and adolescents with cystic fibrosis. Pediatr Pulmonol 2006;41:618–22.

[27] Guillén MAJ, Posadas AS, Asensi JRV, Moreno RMG, Rodríguez MAN,González AS. Reproductibilidad del test de la marcha (walking test) enpacientes afectos de fibrosis quística. An Esp Pediatr 1999;51:475–8.

[28] Ben Saad H, Prefaut C, Missaoui R, Mohamed IH, Tabka Z, Hayot M. Ref-erence equation for 6-min walk distance in healthy North African children6–16 years old. Pediatr Pulmonol 2009;44:316–24.

[29] Li AM, Yin J, Au JT, So HK, et al. Standard reference for the six-minute-walk test in healthy children aged 7 to 16 years. Am J Respir Crit CareMed 2007;176:174–80.

[30] Nixon PA, Joswiak ML, Fricker FJ. A six-minute walk test for assessingexercise tolerance in severely ill children. J Pediatr 1996;129:362–6.

(PDF) Six minute walk test Z score: Correlations with cystic fibrosis severity markers - DOKUMEN.TIPS (2024)

References