The 15-Step Oximetry Test: a Reliable Tool to Identify Candidates for Lung Transplantation Among Patients With Idiopathic Pulmonary Fibrosis

Transcription

1 CLINICAL LUNG AND HEART/LUNG TRANSPLANTATION The 15-Step Oximetry Test: a Reliable Tool to Identify Candidates for Lung Transplantation Among Patients With Idiopathic Pulmonary Fibrosis David Shitrit, MD, a,b Victorya Rusanov, MD, a,b Nir Peled, MD, a,b Anat Amital, MD, a,b Leonardo Fuks, MD, a,b and Mordechai R. Kramer, MD a,b Background: Methods: Results: Conclusions: Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease with a median survival of approximately 3 years. Measurements of lung volumes and diffusion capacity at rest are generally used to monitor the clinical course of IPF. Due to its high mortality, identification of patients at high risk is crucial for treatment strategies such as lung transplantation. This study was design to determine whether the simple 15-step climbing exercise oximetry test accurately characterizes disease severity and survival in patients with IPF. The study population consisted of 51 patients with progressive IPF. Findings on the 15-step climbing test, pulmonary function tests, cardiopulmonary exercise test and 6-minute walk distance test were assessed at baseline. Participants were prospectively followed for 2 years to determine the relationship between the test parameters and survival. On univariate analysis, there were strong correlations between the 15-stair climbing test parameters and survival. On stepwise linear regression analysis, independent significant predictors of mortality were lowest saturation levels on the 15-step test and the 6-minute walk distance test. The lowest saturation and desaturation areas on the 15-step oximetry test are significantly associated with long-term outcome in patients with IPF. We suggest that the 15-step test be used as a simple and reliable tool to predict severity and prognosis in IPF and to identify candidates for lung transplantation. J Heart Lung Transplant 2009;28: Copyright 2009 by the International Society for Heart and Lung Transplantation. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease resulting in severe morbidity and death due to progressive respiratory failure, 1 usually within 3 to 5 years. 2 5 Factors that have been variably associated with IPF severity include age, 6 smoking status, 7 gender, 8 resting pulmonary function, 9 histopathology score, 7 fibrosis score based on highresolution computed tomography 10,11 and initial response to treatment with corticosteroids. 10 A recent study described a composite score of clinical, radiographic and physiologic variables. 12 Although survival is the most important treatment outcome in IPF, its evaluation requires a large number of patients with this From the a Pulmonary Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqwa; and b Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Submitted August 12, 2008; revised November 4, 2008; accepted December 29, Reprint requests: David Shitrit, MD, Pulmonary Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqwa 49100, Israel. Telephone: Fax: davids3@ clalit.org.il Copyright 2009 by the International Society for Heart and Lung Transplantation /09/$ see front matter. doi: / j.healun uncommon disease and long-term prospective followup. Therefore, researchers are seeking a measure of disease and functional status that can accurately reflect the risk of progression to death. The cardiopulmonary exercise test (CPET) is considered the gold-standard index of functional capacity in IPF, but it has several important drawbacks. This is also true of common alternative methods, such as the 6-minute walk distance (6MWD) test, a clinical tool and outcome measure used in patients with heart disease, 13 obstructive lung disease 14 and vascular 15 and neuromuscular disease. 16 The 15-step climbing exercise oximetry test has been found useful for estimating ventilatory reserve in patients with chronic obstructive pulmonary disease (COPD) and for predicting post-operative complications of lung resection. 8 The results with this test also showed a good correlation with pulmonary function tests (PFTs). 9,10 Others reported that the 15-step test is effective for assessing arterial hypoxemia and recommended its use as a marker of disease severity and the need for oxygen supplementation The aim of the present study was to evaluate the relationship of the 15-step climbing test with measures of disease severity conventionally used in patients with 328

2 The Journal of Heart and Lung Transplantation Shitrit et al. 329 Volume 28, Number 4 IPF and its possible value in predicting survival and identifying candidates for lung transplantation. METHODS Patients and Setting A prospective, open study design was used. The study group comprised 51 patients with IPF attending the Pulmonary Institute of Rabin Medical Center, a tertiary hospital in central Israel, during the 6-month period from January to June Diagnoses were made according to the criteria of the American Thoracic Society (ATS). 1 Individuals with collagen vascular disease, occupational lung disease, sarcoid, hypersensitivity pneumonitis and/or other idiopathic interstitial pneumonias were excluded. All patients with IPF who were entered into this study had progressive symptomatic and/or physiologic deterioration despite treatment with prednisone with or without additional immunosuppressive agents. The study was approved by the ethics committee of the Rabin Medical Center. Procedure The demographic, clinical and laboratory data of the patients were retrieved from the files. The 15-step exercise test was administered to all patients as part of their routine follow-up evaluation. The PFTs were performed first, and were followed, on the same day, by the upright maximal CPET, the 6MWD test and the 15-step climbing exercise oximetry test. The interval between tests was at least 2 hours. The order of the exercise tests was randomized. All tests were performed according to ATS guidelines Pulmonary Function Tests The PFTs were performed according to ATS/European Respiratory Society (ERS) guidelines using a pulmonary function system (1070-Series 2; Medical Graphics, St. Paul, MN). Lung volumes were obtained by body plethysmography (Model 1085; Medical Graphics). Maximal voluntary ventilation (MVV) was assessed by asking the patient to breathe as fast and as deeply as possible for 12 seconds, and the result was multiplied by 5. Carbon monoxide diffusion capacity (DLCO) was measured with a gas mixture containing air, 10% helium and 0.3% carbon monoxide; each measurement was adjusted to standard temperature and pressure. The predicted values of the parameters were obtained from the regression equations of the European Community for Coal and Steel. Cardiopulmonary Exercise Test The CPET was performed according to the ATS statement. 17 The test was administered between 8:30 a.m. and 12:00 noon. Patients were encouraged to take their medications as usual. An incremental exercise test was given first according to the protocol of Wasserman et al. 19 On arrival at the exercise laboratory, patients were connected to a 12-lead electrocardiogram (Cardiofax; Nihon Kohden, Tokyo, Japan) with a single-lead (V5) monitor (VC-22; Nihon Kohden). Oxygen saturation (SaO 2 ) was measured by pulse oximetry (NPB-190; Nellcor, Pleasanton, CA), and blood pressure with a sphygmomanometer. Each patient was then positioned on an electrically braked cycle ergometer (Ergometrics 800S; Ergoline, Bitz, Germany). After a 2-minute rest (arms at sides), they were asked to performed unloaded pedaling for 2 minutes at a rate of 60 rpm. The load was then progressively increased by 15 W/min (ramp protocol). The duration of the test was symptom-limited; the end-point was defined as the point at which the patient could not maintain a pedaling rate of 40 rpm. Cardiopulmonary data were collected and analyzed with an exercise metabolic unit (CPX, Medical Graphics). Heart rate, minute ventilation (VE), tidal volume (VT), oxygen consumption (VO 2 ), carbon dioxide production (VCO 2 ), respiratory rate (RR), total ventilation (VD/VT), oxygen pulse (O 2 P) and SaO 2 were recorded and calculated over 30-second intervals using standard formulas. Blood pressure was measured with a sphygmomanometer at rest and every 2 minutes until peak exercise. The dyspnea index (VE/MVV), expressed in percent, was calculated manually. The 6-Minute Walk Test The 6MWD test was performed according to ATS guidelines. 18 The test was administered along a measured indoor corridor at our institute. Participants were encouraged to cover as much distance as possible. The 15-Step Climbing Exercise Oximetry Test A finger oximeter (Model 8500; Nonin Medical, Plymouth, MN) was connected to each patient for continuous online recording of pulse rate and oxygen saturation. The data were sampled every 2 seconds, and the mean value was recorded every 10 seconds. A step measuring 25 cm (length) 50 cm (width) 20 cm (height) was used; patients were asked to climb up and down the step 15 times as fast as they could, without any fixed pacing. No supplemental oxygen was used during the 15-step climbing test. Each test was repeated twice, and the mean oximeter values were recorded. When oximeter readings were not optimal, as detected by a yellow or red signal, the data were discarded. The exercise time was recorded, as was the time from the start of exercise to lowest saturation (desaturation time), and the time from lowest saturation to recovery to baseline (recovery time) (Figure 1). The total test time was defined as the time from the start of exercise to complete recovery (sum of desaturation and recovery

3 330 Shitrit et al. The Journal of Heart and Lung Transplantation April 2009 and 2 continued to smoke during the study period. Most of the patients (94%) were New York Heart Association (NYHA) Functional Class II to IV. Twentyfive (50%) patients were being treated with oxygen supplementation. Twenty patients (39%) were on the waiting list for lung transplantation. Figure 1. Mean oxygen saturation levels during the 15-step climbing exercise oximetry test in patients with IPF who survived (n 29) or did not survive (n 22). Diamonds: alive; squares: transplant/death. We defined desaturation area as the triangular area under the oxygen saturation curve between baseline and 98% saturation during the whole maneuver [(baseline SaO 2 lowest SaO 2 ) 0.5 test time (98% baseline SaO 2 ) test time]. times). Baseline oxygen saturation, lowest saturation and highest pulse were recorded. We also calculated the triangular area under the oxygen saturation curve between baseline and 98% saturation during the whole maneuver ( desaturation area ) [(baseline SaO 2 lowest SaO 2 ) 0.5 test time (98% baseline SaO 2 ) test time] (Figure 1). Statistical Analysis Results are shown as mean standard deviation. Pearson s correlation coefficient (r) and its statistical significance (p-value) were calculated between the variables. To analyze differences in the distribution of categorical data, the chi-square test or Fisher s exact test was used, as appropriate. Survival time was measured in days from enrollment into the study until death or lung transplantation. The end-point tested in the univariate and regression analyses was death at any time during follow-up. Univariate models were used to assess the relative hazard corresponding to overall mortality for each parameter, and multivariate analyses were used to assess the effects of other demographic and baseline variables. Logistic regression models of timed walking test (TWT) parameters predicting survival to the end of follow-up were used to corroborate the findings of the survival analyses. p 0.05 was considered significant. RESULTS Demographic Data All 51 patients completed the PFTs and the three exercise tests (CPET, 6MWD test and 15-step oximetry test). Table 1 summarizes the demographic and clinical data. Twenty-nine patients were male. Mean age was years (range 17 to 80 years). Twenty-four patients were non-smokers, 25 had smoked in the past, Exercise Tests Table 2 summarizes the main results of the three exercise tests. Mean maximum oxygen consumption (VO 2 max) on the CPET was 11 3 ml/kg/min (range 5.7 to 23.5 ml/kg/min); mean breathing reserve was liters (range 2 to 99 liters), and mean saturation at the end of exercise was 88 6% (range 73% to 95%). Mean distance on the 6MWD test was m (range 180 to 613 m). Mean post-exercise saturation was 86 8% (range 61% to 97%), and mean difference between saturation at rest and post-exercise saturation was 8 7% (range 0% to 38%). On the 15-step test, mean values were as follows: lowest saturation, 86 7% (range 70% to 93%); difference between saturation at rest and lowest saturation, 9 5% (range 0% to 19%); desaturation time, seconds (range 0 to 120 seconds); recovery time, seconds (range 0 to 220 seconds); and desaturation area, 1,314 1,078 sec% (range 156 to 4,200 sec%) (Figure 1). Table 1. Demographic and Clinical Data of 51 Patients With Idiopathic Pulmonary Fibrosis Characteristics Value Age, years (mean SD) a Male:female ratio 29:22 Smoking history Past 25 (50) Current 2 (4) Non-smoker 24 (47) NYHA Functional Class I 3 (6) II 18 (35) III 20 (39) IV 10 (20) Diagnosis by biopsy Yes 33 (65) No 18 (35) Treated for IPF In the past 1 (2) Current treatment 42 (82) No 8 (16) Oxygen supplementation Yes 25 (49) No 26 (51) IPF, idiopathic pulmonary fibrosis; NYHA, New York Heart Association. a All data except age are given as number (%).

4 The Journal of Heart and Lung Transplantation Shitrit et al. 331 Volume 28, Number 4 Table 2. Main Results of Cardiopulmonary Exercise Test, 6-Minute Walk Distance Test and 15-Step Climbing Test in 51 Patients With Idiopathic Pulmonary Fibrosis Parameters Value Resting pulmonary function FEV 1 (% predicted) FVC (% predicted) 62 2 TLC (% predicted) RV (% predicted) DLCO (% predicted) Cardiopulmonary exercise test VO 2 max (ml/kg/min) 11 3 Breathing reserve (liters/min) Saturation at the end of exercise (%) minute walk distance test Saturation at rest (%) 94 3 Saturation after exercise (%) 86 8 Saturation difference (%) 8 7 Distance (m) step climbing test Saturation baseline (%) 95 3 Saturation lowest (%) 86 7 Saturation difference (%) 9 5 Exercise time (sec) Desaturation time (sec) Recovery time (sec) Desaturation area (sec%) 1,314 1,078 Parameters of the cardiopulmonary exercise test: VO 2 max (maximum volume of oxygen utilization). Parameters of 6-minute walk distance test: distance (walk distance). Parameters of 15-step climbing test: saturation lowest (lowest level of oxygen saturation during the test); saturation difference (difference between baseline and lowest saturation); exercise time (time of the exercise); desaturation time (time from start to lowest saturation); recovery time (recovery time (time from lowest saturation to recovery to baseline level); desaturation area [calculated triangular area between baseline saturation and 98% saturation during the complete maneuver (baseline SaO 2 lowest SaO 2 ) 0.5 test time (98% baseline SaO 2 ) test time]. Association of Function and Exercise Test Results With Survival Patients were prospectively followed from enrollment for a median of 2.4 years (range 2.0 to 3.1 years). Seven of the 51 patients (13.7%) died over the entire follow-up period. Three patients (5.8%) died within 12 months of study onset. All the deaths in the study population were related to the progression of IPF. Fifteen patients (29.4%) underwent lung transplantation at an average of 1.5 years (range 0.3 to 2.4 years) from enrollment and were censored in the analysis at the time of transplantation. Two lung transplant recipients died during follow-up, 2 of acute lung rejection and 1 of sepsis. Table 3 compares the findings for the PFT and exercise test parameters by patient survival/death at the end of follow-up. On univariate analysis, strong correlations were noted between the 15-step climbing test parameters and survival. To identify the parameters that independently predicted survival, a stepwise linear regression model was fitted to the data. The only significant predictors were lowest saturation on the 15-step test ( p 0.002) and the 6MWD test ( p 0.003), with odds ratios of (95% confidence interval to 1.092) and (95% confidence interval to 1.011), respectively. DISCUSSION The main finding of the present study is that the lowest saturation on the simple step-climbing test is an accurate predictive parameter of mortality in IPF. To provide patients with IPF with proper prognostic information, researchers have suggested various protocols with potential predictive value. It has been reported that increasing pulmonary artery pressure is a risk factor for death after single-lung transplantation in IPF. 20 PFTs are traditionally used to evaluate patients with interstitial lung disease, based on findings that survival in patients with pulmonary fibrosis depends on the forced vital capacity and DLCO. 21 However, PFTs do not measure the fall in oxygen saturation during exercise or requirements of oxygen supplementation. 22,23 The CPET provides the best index of functional capacity and global oxygen transport (VO 2 max), 7 and it Table 3. Comparison of Clinical Data of Patients Who Survived and Patients Who Did Not Survive or Underwent Lung Transplantation (n 51) Characteristic Survived (n 29) Did not survive or lung transplanted (n 22) p-value Age (years) M:F 22:7 12: FVC (% predicted) FEV 1 (% predicted) TLC (% predicted) RV (% predicted) DLCO (% predicted) Saturation at rest (%) Saturation after 6MWD (%) MWD (m) VO 2 max (kg/ml/min) Lowest saturation for 15-step test (%) Saturation differences 15-step test (%) Exercise time, 15-step test (sec) Desaturation time (sec) Recovery time (sec) Desaturation area (sec%) ,901 1, IPF, interstitial pulmonary fibrosis; FVC, forced vital capacity; FEV 1, forced expiratory volume in 1 second; TLC, total lung capacity; RV, respiratory volume; DLCO, carbon monoxide diffusion in the lung; 6MWD, 6-minute walk distance; VO 2 max, maximum volume of oxygen utilization.

5 332 Shitrit et al. The Journal of Heart and Lung Transplantation April 2009 also estimates cardiac and pulmonary reserves, information that is not provided by other modalities. 24,25 However, VO 2 max cannot be measured in patients with advanced cardiac and lung disease, 26,27 and the use of the CPET requires complicated and expensive equipment and trained staff. 17 In addition, the test may be intimidating to frail, elderly or severely disabled patients because the rate of exercise is not under their control. The most common alternative methods available today are bicycle ergometry with different protocols, the 6MWD test and the stair-climbing test. Each differently assesses the relevant parameters, namely the lowest arterial oxygen pressure (SaO 2 ) achieved, mean partial arterial oxygen (PaO 2 )orsao 2 during exercise, and maximal drop in PaO 2 or SaO 2 from baseline. The 6MWD test is simple, inexpensive and convenient, and it requires minimal medical personnel and can be performed in an office setting. 18 It has excellent reproducibility, whereas maximal exercise variables do not. 24 Studies have shown that the 6MWD test provides more accurate prognostic information than resting PFTs in patients with COPD, 28 with good correlation with cardiopulmonary exercise parameters (VO 2 max and peak PaO 2 ). 19,29 In patients with IPF, a highly significant correlation was reported between the 6MWD test, DLCO and VO 2 max. 27,30 Flaherty et al found that changes in distance walked and quantity of desaturation during the 6MWT would add prognostic information to changes in FVC or diffusing capacity for carbon monoxide in patients with IPF. 31 Moreover, the amplitude of desaturation during the 6MWD test was the single strongest predictor of mortality. 27,30 Some researchers suggested that the test may be regarded as a surrogate marker for VO 2 in patients with IPF. 27,30 However, it does not fully characterize the physiologic abnormalities associated with the severity and progression of IPF 28 and, like the CPET, the 6MWD test may not be used in patients with advanced lung disease. The step-climbing test is used to assess exercise capacity in patients with severe lung disease. Like the 6MWD, it is simple to perform, inexpensive and convenient and, unlike the 6MWD, it can be used in patients with severe lung disease. In patients with COPD, the step-climbing test can be applied to effectively estimate ventilatory reserve, 8 assess arterial hypoxemia, and predict complications of lung resection. 9 It is also recommended for use in patients with COPD as a marker of disease severity and in need of oxygen supplementation. 11 Recently, we investigated the potential role of the step-climbing test in the assessment of exercise-induced hypoxemia and functional capacity in patients with IPF. We calculated the desaturation area, which takes into account the baseline saturation as well as the severity of desaturation and recovery to baseline, and compared it with findings on PFTs and two other exercise tests, the CPET and 6MWD test, performed in the same session. We noted a good correlation between all oximetry parameters (lowest saturation, saturation difference, recovery time and desaturation area) and both VO 2 max and DLCO. These findings indicate that the desaturation measured by the 15-step oximetry test is comparable to the desaturation measured by the CPET and the 6MWD test, making the 15-step test a reliable tool for monitoring disease progression in IPF and for evaluating the need for oxygen supplementation. In the present study, we found the step-climbing test parameters of lowest saturation, saturation difference, desaturation area and exercise time to be highly correlated with survival in patients with IPF (Table 3). On multivariate analysis, the lowest saturation on the stepclimbing test significantly predicted mortality. This finding may reflect the significance of the degree of desaturation during exercise in IPF, as highlighted in the study by Lama et al, 28 who assessed a subgroup of patients with IPF without resting hypoxemia and found that desaturation to 88% at any point during the 6MWD test was associated with an increased hazard of death. The present study has several potential limitations: (1) it was conducted at a single tertiary-care referral center with expertise in the management of IPF; (2) the stair-climbing test was not serially performed during follow-up; and (3) the treatment regimen subsequent to the stair-climbing test was not controlled for in the analysis. Given that there is no known effective therapy to date, individual therapies are unlikely to have confounded the relationship between the TWT and survival. In conclusion, the stair-climbing test is a simple clinical tool that can be performed in the ambulatory setting and relates to important aspects of disease severity and long-term outcome in IPF. This simple functional measurement may have a place in the clinical evaluation of individuals with IPF. It may serve as a reliable outcome measure in the assessment of treatment response, a guide to the timing of lung transplantation, and a predictor of long-term survival. Future studies in larger samples using continuous measurements of the stair-climbing test are needed to corroborate our findings. REFERENCES 1. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS) and European Respiratory Society (ERS). Am J Respir Crit Care Med 2000;161: Agusti AG, Roca J, Rodriguez-Roisin R, et al. Different pattens of gas exchange response to exercise in asbestosis and idiopathic pulmonary fibrosis. Eur Respir J 1988;1:510 6.

6 The Journal of Heart and Lung Transplantation Shitrit et al. 333 Volume 28, Number 4 3. O Donnell DE. Physiology of interstitial lung disease. In: Schwarz M, King T Jr, eds. Interstitial lung disease. Hamilton, ON: B.C. Decker; 1998: Hansen JE, Wasserman K. Pathophysiology of activity limitation in patients with interstitial lung disease. Chest 1996;109: King TE Jr, Tooze JA, Schwarz MI, et al. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Med 2001;164: Timmer SI, Karamzadeh AM, Yung GL, et al. Predicting survival of lung transplantation candidates with idiopathic interstitial pneumonia: does PaO 2 predict survival? Chest 2002;122: Mogulkoc N, Brutsche MH, Bishop PW, et al. Pulmonary function in idiopathic pulmonary fibrosis and referral for lung transplantation. Am J Respir Crit Care Med 2001;164: Pollock M, Roa J, Benditt J, et al. Estimation of ventilatory reserve by stair climbing. A study in patients with chronic airflow obstruction. Chest 1993;104: Olsen GN, Randolph Bolton JW, Weiman DS, et al. Stair climbing as an exercise test to predict the postoperative complications of lung resection two years experience. Chest 1991;99: Bolton JW, Weiman DS, Hayness JL, et al. Stair climbing as an indicator of pulmonary function. Chest 1987;92: Kramer MR, Krivoruk V, Lebzelter J, et al. Quantitative 15 steps exercise oximetry as a marker of disease severity in patients with chronic obstructive pulmonary disease. Isr Med Assoc J 1999;1: Starobin D, Kramer MR, Yarmolovsky A, et al. Assessment of functional capacity in patients with chronic obstructive pulmonary disease: correlation between cardiopulmonary exercise, 6 minute walk and 15 step exercise oximetry test. Isr Med Assoc J 2006;8: Pate P, Tenholder MF, Griffin JP, et al. Preoperative assessment of the high-risk patients for lung resection. Ann Thoracic Surg 1996;61: American Thoracic Society; European Respiratory Society. ATS/ ERS statement: Standardisation of spirometry. Eur Respir J 2005; 26: American Thoracic Society; European Respiratory Society. ATS/ ERS statement: Standardisation of the measurement of lung volumes. Eur Respir J 2005;26: American Thoracic Society, European Respiratory Society. ATS/ ERS statement: Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 2005;26: American Thoracic Society; American College of Chest Physicians. ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003;167: American Thoracic Society. ATS statement: Guidelines for the six minute walk test. Am J Respir Crit Care Med 2002;166: Wasserman K. Anaerobic threshold and cardiovascular function. Mondaldi Arch Chest Dis 2002;58: Whelan TP, Dunitz JM, Kelly RF. Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis. J Heart Lung Transplant 2005; 24: Flaherty KR, Mumford JA, Murray S, et al. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003;168: Erbes R, Schaber T, Loddenkemper R. Lung function tests in patients with idiopathic pulmonary fibrosis: are they helpful for predicting outcome? Chest 1997;111: Noble PW, Morris DG. Time will tell: predicting survival in idiopathic interstitial pneumonia [editorial]. Am J Respir Crit Care Med 2003;168: Moloney ED, Clayton N, Mukherjee DK, et al. The shuttle walk exercise test in idiopathic pulmonary fibrosis. Respir Med 2003; 97: Eaton T, Young P, Milne D, et al. Six-minute walk, maximal exercise test reproducibility in fibrotic interstitial pneumonia. Am J Respir Crit Care Med 2005;171: Corra U, Mezzani A, Bosimini E, et al. Cardiopulmonary exercise testing and prognosis in chronic heart failure: a prognosticating algorithm for the individual patient. Chest 2004;126: American Association for Respiratory Care. AARC clinical practice guideline: exercise testing for evaluation of hypoxemia and/or desaturation. Respir Care 2001;46: Lama VN, Flaherty KR, Toews GB, et al. Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia. Am J Respir Crit Med 2003;168: Poulain M, Durand F, Palomba B, et al. 6-minute walk testing is more sensitive than maximal incremental cycle testing for detecting oxygen desaturation in patients with COPD. Chest 2003;123: Kadikar A, Maurer J, Kesten S. The six-minute walk test: a guide to assessment for lung transplantation. J Heart Lung Transplant 1997;16: Flaherty KR, Andrei AC, Murray S, Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test. Am J Respir Crit Care Med 2006;174:803 9.