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(Chest. 2007;131:217-222.)
© 2007 American College of Chest Physicians

Six-Minute Walk Test for the Evaluation of Pulmonary Disease Severity in Scleroderma Patients*

Wander O. Villalba, RT, MSc; Percival D. Sampaio-Barros, MD, PhD; Mônica C. Pereira, MD, PhD; Elza M. F. P. Cerqueira, MD, MSc; Cid A. Leme, Jr, MD, MSc; João F. Marques-Neto, MD, PhD and Ilma A. Paschoal, MD, PhD

* From the Department of Physiotherapy (Mr. Wander), Rheumatology Unit (Drs. Sampaio-Barros and Marques-Neto), Pulmonary Diseases Unit (Drs. Pereira and Paschoal), Department of Radiology (Dr. Cerqueira), and Cardiology Unit (Dr. Leme), School of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil.

Correspondence to: Wander O. Villalba, RT, MSc, Department of Physiotherapy, School of Medical Sciences, State University of Campinas, UNICAMP, Cidade Universitaria Zeferino Vuz, PO Box 6142, Campinas, São Paulo, Brazil; e-mail: wander{at}hc.unicamp.br

Abstract

Background: Pulmonary involvement is the leading cause of systemic sclerosis (SSc)-related deaths. A simple test to evaluate exercise capacity is the 6-min walk test (6MWT), and the walk distance is used as a primary outcome in clinical trials. Hemoglobin desaturation during a 6MWT is predictive of mortality in patients with primary pulmonary hypertension. Our objectives were to evaluate the walk distance and resting oxygen saturation – oxygen saturation after the 6-min period ({Delta}Sat) during the 6MWT in patients with SSc, and to establish correlations between the 6MWT results and other clinical variables.

Methods: We analyzed 110 SSc patients. {Delta}Sat was defined as a fall of end-of-test saturation ≥ 4%. Clinical and demographic data were collected. All the patients were submitted to chest radiographs and high-resolution CT (HRCT) and underwent pulmonary function testing and echocardiography, and the presence of autoantibodies was determined.

Results: The variables associated with a walk distance < 400 m (p < 0.05) were age, dyspnea index, fibrosis on radiography, pulmonary arterial systolic pressure (PASP) ≥ 30 mm Hg, and desaturation. The variables associated with {Delta}Sat (p < 0.05) were age, positive anti-Scl-70 autoantibody, dyspnea index, fibrosis on radiography, FVC < 80% of predicted, PASP ≥ 30 mm Hg, and ground-glass or reticular opacities on HRCT. In the multivariate logistic regression analysis, three variables were significant when tested with walk distance: age, race, and dyspnea index; four variables were significant when tested with {Delta}Sat: age, dyspnea index, positive anti-Scl-70 autoantibody, and FVC < 80% of predicted.

Conclusions: Desaturation during a 6MWT provides additional information regarding severity of disease in scleroderma patients with pulmonary manifestations.

Key Words: exercise test • exertion • hypoxemia • pulmonary fibrosis

The etiology and pathogenesis of systemic sclerosis (SSc) remain incompletely understood. SSc is unique in displaying features of three distinct pathophysiologic processes: cellular and humoral autoimmunity, vascular injury, and tissue fibrosis. Vascular injury, both functional and structural, is frequently the earliest manifestation of SSc and may antedate other manifestations by years. Immune abnormalities, especially serum autoantibodies, may also occur early in the course of SSc. Fibrosis, characterized by excessive accumulation of collagen and extracellular matrix components, is usually a late feature. Genetic factors may play a role in the pathogenesis of the disease by affecting host susceptibility or by modifying clinical presentation and organ damage.1

Survival is significantly diminished in scleroderma patients compared with age-matched populations. Poor prognostic factors include diffuse skin involvement, male sex, black race, and visceral organ involvement.234 Pulmonary fibrosis and pulmonary arterial hypertension (PAH) are the leading causes of disease-related deaths. SSc patients with lung involvement show a significant reduction in exercise capacity and in oxygen uptake.5

A simple test to evaluate exercise capacity is the 6-min walk test (6MWT).6 Hemoglobin desaturation, as measured by pulse oximetry during a 6MWT, is predictive of mortality in patients with primary pulmonary hypertension7; and the 6-min walk distance (6MWD) has been increasingly used as a primary outcome in clinical trials of new drugs indicated in the treatment of pulmonary hypertension in SSc.8910

The objectives of this study were to evaluate the walking distance and oxygen desaturation during the 6MWT in patients with SSc, and to establish correlations between the 6MWT results and other clinical findings. As our main hypothesis, we propose that desaturation at the end of the walk test would be at least as informative of severity of lung involvement as the decrease in walk distance.

Materials and Methods

Patient Selection
Our hospital (Teaching Hospital of the State University of Campinas) is a reference center for scleroderma patients, and > 250 patients are presently being followed up at the institution. A previous selection excluded from the study patients with severe organ involvement, articular disabilities, presence of ischemic cutaneous ulcers, or inadequate pulse signal on pulse oximetry (Raynaud phenomenon). If the resting oxygen saturation by pulse oximetry (SpO2) was < 90% in room air, patients were not considered eligible for the 6MWT.

One hundred fourteen patients were selected but 4 were excluded due to the fact that end-of-test saturation was not readable because of an inadequate pulse signal. This prospective study analyzed 110 patients with SSc diagnosed according to the American College of Rheumatology classification criteria11 and who attended the Scleroderma Outpatient Clinic between January 2003 and December 2004. The patients were classified as diffuse and limited clinical variants.12 Approval for the use of patient data was obtained from the Research Ethics Committee of the university.

Study Design
All patients were tested under standardized conditions13 by the same technician (W.O.V.). Baseline BP and heart rate were measured, and SpO2 was determined using finger probe pulse oximeter (Nonin Medical; Plymouth, MN). The pulse signal was carefully observed during at least 20 s, and the most frequent value on display, measured with a good pulse signal, was chosen. Saturation was measured at rest and immediately after the end of the 6-min period, and the patients were carefully observed during the test to avoid dangerously exceeding their exercise limits. According to the American Thoracic Society guidelines,13 SpO2 should not be used for constant monitoring during the exercise and the technician must not walk with the patient to observe SpO2. This procedure could interfere with the results of both the measurement of the oximeter, because of motion artifact and the final distance achieved by the patient. Pulse oximeters that better protect against motion artifacts and models that can be attached to the patients and are capable of sending data by telemetry could have been used, but these machines are not available at our institution.

For the purpose of data analysis, desaturation (resting oxygen saturation – oxygen saturation after the 6-min period [{Delta}Sat]) was defined as a decrease in SpO2 from baseline ≥ 4%. The 4% fall was validated in a study14 of exercise-induced hypoxemia during maximal exercise tests in athletes. The walk distance was considered abnormal when < 400 m.

All 110 patients underwent plain chest radiography. Pulmonary function tests were performed using a spirometer (model AM 4000 PC; Anamed; São Paulo City, São Paulo, Brazil). The severity of dyspnea was evaluated in all patients, and they were classified according the New York Heart Association (NYHA) classification of functional capacity.15

Chest high-resolution CT (HRCT) examinations were performed (Somaton AR; Siemens; Erlangen, Germany) and scored for ground-glass attenuation, reticular opacities, and honeycombing. The scoring system was based on the proposal of Wechsler et al,16 with modifications. To analyze each CT scan, the lungs were divided into six regions. For each abnormality, and in each one of the six regions, a score grade was chosen (between 0 and 3). The total score varied from 0 to 18. Doppler echocardiography was performed to estimate pulmonary artery systolic pressure (PASP).

Statistical Analysis
Two main dichotomic variables were chosen, {Delta}Sat ≥ 4% and walk distance < 400 m, and these categorical variables were used as dependent variables. Categorical data were compared using {chi}2 tests or Fisher Exact Test when necessary, and continuous data were compared using Mann-Whitney test. The analyses were performed using statistical software (Epi Info, Version 6.04d; Centers for Disease Control and Prevention; Atlanta, GA; and SPSS version 6.0; SPSS; Chicago, IL).

Multiple logistic regression analysis was used to determine whether baseline demographic, physiologic, serologic, and radiographic information could predict desaturation or a walk distance < 400 m. Appropriate tests determined the significance of interaction terms.

Results

Among the 110 SSc patients analyzed in the present study, 96 patients (87.3%) were female. Regarding race, there were 76 whites (69.1%) and 34 African Brazilians (30.9%). For statistical purposes, patients were subclassified into groups ≥ 36 years old (82 patients, 74.5%) and < 36 years old (28 patients, 25.5%) because 25% of the patients in the study belonged to the first quartile. On the topic of the SSc clinical variant, 78 patients (70.9%) presented limited SSc and 32 patients (29.1%) presented diffuse SSc. Laboratory analysis revealed that antinuclear antibody was positive in 86.2% of the cases, while anticentromere antibody was present in 10.9%. Anti-Scl-70 autoantibody was positive in 28 patients (25.5%): 16 patients (20%) with limited SSc, and 12 patients (37%) with diffuse SSc.

According to the NYHA classification,15 91 patients (82.7%) were classified as grade I, and 19 patients (17.3%) were classified as grade II. An altered FVC (< 80% of predicted) was present in 45 patients (42.4%). The medians and range of FVC and FEV1 (expressed percentage of predicted value) and FEV1/FVC were 88.5% (35 to 124%), 81.5% (41 to 137%), and 80% (70 to 99%), respectively.

Thirty-three patients (30%) had chest radiographs showing reticular and heterogeneous opacities suggestive of pulmonary fibrosis. The scores for each of the analyzed patterns on HRCT can be seen in Table 1 . A score ≥ 6 points was observed for ground-glass opacities in 23% of the patients, for reticular opacities in 32.4% of the patients, and for honeycombing in 11.8% of the patients. Doppler echocardiography results revealed that PASP was ≥ 30 mm Hg in 32 patients (29.1%).


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  		Table 1. Tomographic Characteristics of the Subjects Studied

 
The two variables used in the statistical analysis as dependent, {Delta}Sat ≥ 4% and walk distance < 400 m, were present in 31 patients (29.5%) and in 32 patients (28.2%), respectively. These and further information regarding the 6MWT results are shown in Table 2 .


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  		Table 2. 6MWT Results (n = 110)

 
Statistical data concerning walk distance in 6MWT are stated in Table 3 . This table shows that the variables that presented statistical association with a walk distance < 400 m were age, dyspnea index, fibrosis on chest radiography, PASP ≥ 30 mm Hg, and {Delta}Sat ≥ 4%. The variables that presented statistical association with {Delta}Sat (Table 3) were age, positive anti-Scl-70 autoantibody, dyspnea index, fibrosis on chest radiograph, FVC < 80% of the predicted value, PASP ≥ 30 mm Hg, and presence of ground-glass or reticular opacities on HRCT.


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  		Table 3. 6MWT, Univariate Analysis: Variables Associated With Walk Distance and With {Delta} Sat

 
In the multivariate logistic regression analysis, three variables (age, race, and dyspnea index) presented statistical significance when tested with the walk distance, and four variables (age, dyspnea index, positive anti-Scl-70 autoantibody, and FVC < 80% of the predicted value) presented statistical significance when tested with {Delta}Sat (Tables 4, 5 ).


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  		Table 4. Multivariate Logistic Regression Analysis: Risk Prediction of Walk Distance < 400 m

 

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  		Table 5. Multivariate Logistic Regression Analysis: Risk Prediction of {Delta} Sat ≥ 4%

 
Multiple logistic regression analysis revealed that the probability of walking < 400 m in the 6MWT for a scleroderma patient in our study was 82.3% if all the following conditions were present: age ≥ 36 years, Afrrican-Brazilian origin, and NYHA class II classification of disability (Table 4). However, a probability of 98.3% for {Delta}Sat ≥ 4% was predicted if all the following conditions were present: age ≥ 36 years, FVC < 80% of predicted, positive anti-Scl-70 autoantibody, and NYHA class II classification of disability (Table 5).

Discussion

The 6MWT is a simple and inexpensive test that requires a minimum number of health-care staff and can be performed in an office setting. In patients with pulmonary hypertension, the 6MWT has been recognized as a strong and independent predictor of mortality.171819 Nevertheless, in most of these trials the parameter analyzed in 6MWT is the walk distance.

In fibrotic idiopathic interstitial pneumonia, Eaton et al20 found that the distance walked during the 6MWT is highly reproducible and unlikely to improve with repeated testing. Normal values of walk distance are not available. Troosters et al21 evaluated 51 healthy subjects aged 50 to 85 years and no history of chronic disease with the 6MWT. On average, subjects walked 631 ± 93 m (mean ± SD). Oxygen saturation remained unaltered throughout the tests.

In this study, we chose 400 m as the cut-off limit of the 6MWD to compensate for differences in age, height, weight, sex, and muscle strength. Nevertheless, age retained a significant association with 6MWD of < 400 m, although the median age of the patients in the study was 45.5 years.

Another important association with walk distance in this study was the NYHA functional class.15 Class II patients had much greater probability of a 6MWD of < 400 m. Our results agree with the findings of Miyamoto et al,17 who demonstrated in patients with primary pulmonary hypertension that the distance walked during the 6MWT significantly decreased in proportion to the severity of the NYHA functional class.

We found an association between the evidence of fibrosis on radiography and the walk distance (p = 0.05). Nevertheless, there was no relationship between walk distance and the findings on chest HRCT. It is well known that the HRCT is more sensitive and specific to detect mild alterations in interstitial pulmonary diseases.22 The majority of our CT findings (Table 1) were scored in the lowest score levels (score < 6). According to Desai et al,23 interstitial lung disease in patients with SSc is less extensive, less coarse, and characterized by a greater proportion of ground-glass opacities than in patients with interstitial pulmonary fibrosis (IPF).

The reported rates of PAH in scleroderma patients have been wide ranging (5 to 50%), depending on the methodology used and the cut-off value of PASP considered for diagnosis.24252627 Doppler echocardiography is a helpful means of assessing PASP.24252627

The cutoff value of ≥ 30 mm Hg to define the presence of PAH28 is somewhat low, but in our study it was significantly associated with 6MWD < 400 m and {Delta}Sat ≥ 4%. According to MacGregor et al,26 a single echocardiography PASP reading ≥ 30 mm Hg in scleroderma is associated with 20% mortality in 20 months. The results of 6MWD in our study agree with the findings in studies1017 that evaluated 6MWD in patients with PAH of other etiologies.

It is quite common among patients with IPF and/or PAH to present with normal SpO2 at rest. However, during submaximal exercise some of them will show desaturation.29

End-exercise PaO2 during maximal exercise3031 and submaximal steady-state exercise31 are important measures of disease severity in IPF, and these observations allow us to raise the hypothesis that decrease in saturation during self-paced walking is a meaningful measure of disease status in patients with scleroderma lung disease. Lama et al32 demonstrated that patients with usual interstitial pneumonia who desaturate during a 6MWT ({Delta}Sat ≥ 4%) had a more than fourfold-higher hazard of dying during follow-up.

In another study of 41 patients with IPF, exercise-induced hypoxemia evaluated by {Delta}PaO2/{Delta}oxygen uptake on cardiopulmonary exercise testing was strongly correlated with survival.33 However, cardiopulmonary exercise testing is infrequently used to evaluate patients with IPF,34 probably because of the expense and limited availability of this diagnostic modality.

In the study by Eaton et al,20 the value of hemoglobin desaturation on pulse oximetry was found to be nonreproducible, with unacceptable measurement variation. However, they did not use this variable as a categorical one; instead, they computed the values of saturation in two 6MWTs. We believe that the important information here is the occurrence of desaturation per se, a fact that is not observed in normal subjects.21

In our study, {Delta}Sat ≥ 4% was significantly associated with age, NYHA class II of the classification of disability, a radiograph with signs of interstitial fibrosis, and PASP ≥ 30 mm Hg. These associations were also found with walk distance (p < 0.05). However, significant associations were observed with some variables and {Delta}Sat exclusively. This was the case with the presence of a positive anti-Scl-70 autoantibody, generally found positive in scleroderma patients with pulmonary fibrosis.35 Reduction in FVC in spirometry, another characteristic feature of pulmonary fibrosis, also had a significant association with {Delta}Sat (p < 0.001).

On HRCT, a score ≥ 6 for ground-glass opacities (p < 0.05) and reticular opacities (p < 0.001) was associated with {Delta}Sat, maybe reflecting the ability of desaturation on the 6MWT to detect these early interstitial abnormalities. The variable 6MWD < 400 m in the multiple logistic regression analysis model was significantly associated with age, race, and dyspnea, while {Delta}Sat ≥ 4% was associated with age, dyspnea, and two other variables related to pulmonary involvement: FVC < 80% of predicted and a positive Scl-70 antibody. But the statistical model applied to the data cannot indicate which of these dependent variables was stronger in predicting pulmonary disease. Nevertheless, it seems that {Delta}Sat ≥ 4% may supply more information on this topic (Table 6 ).


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  		Table 6. Comparison of Relative Strength of the Dependent Variables 6MWD < 400 m and {Delta} Sat ≥ 4% in the Multiple Logistic Regression Model

 
Curiously, race appeared as an important association with walk distance on the multivariate analysis but not in the univariate analysis. It has become increasingly apparent that ethnicity influences susceptibility to scleroderma and other autoimmune diseases. Scleroderma is diagnosed almost twice as often in African-American women than in white women, and African-American women have more severe clinical disease, earlier age of onset, and worse survival rates.36

The most common functional impairment in patients with lung disease is impaired gas exchange. In early stages, SpO2 is normal at rest, but when the demand increases, as occurs during exercise, oxygen desaturation may appear. As it could be appreciated in this study, besides the walking distance, oxygen desaturation may be another valuable outcome variable in 6MWT.

Footnotes

Abbreviations: {Delta}Sat = resting oxygen saturation – oxygen saturation after the 6-min period; 6MWD = 6-min walk distance; 6MWT = 6-min walk test; HRCT = high-resolution CT; IPF = idiopathic pulmonary fibrosis; NYHA = New York Heart Association; PAH = pulmonary arterial hypertension; PASP = pulmonary artery systolic pressure; SpO2 = oxygen saturation by pulse oximetry; SSc = systemic sclerosis

This work was performed at the Department of Internal Medicine, School of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil.

The authors have no financial or other potential conflicts of interest to disclose.

Received for publication March 14, 2006. Accepted for publication July 21, 2006.

References

  1. Varga, J, Korn, JH (2004) Pathogenesis of systemic sclerosis: emphasis on human data. Clements, PJ Furst, DE eds. Systemic sclerosis 2nd ed. ,63-88 Lippincott, Williams and Wilkins. Philadelphia, PA:
  2. Ferri, C, Valentini, G, Cozzi, F, et al Systemic sclerosis: demographic, clinical, and serologic features and survival in 1012 Italian patients. Medicine (Baltimore) 2002;81,139-153[CrossRef][Medline]
  3. Geirsson, AJ, Wollheim, FA, Akesson, A Disease severity of 100 patients with systemic sclerosis over a period of 14 years. Ann Rheum Dis 2002;60,1117-1122
  4. Scussel-Lonzeti, L, Joyal, F, Raynauld, JP, et al Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French-Canadian patients with emphasis of features at diagnosis as predictive factors. Medicine (Baltimore) 2002;81,154-167[CrossRef][Medline]
  5. Morelli, S, Ferrante, L, Sgreccia, A, et al Pulmonary hypertension is associated with impaired exercise performance in patients with systemic sclerosis. Scand J Rheumatol 2000;29,236-242[CrossRef][ISI][Medline]
  6. Guyatt, GH, Sullivan, MJ, Thompson, PJ, et al The 6-min walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J 1985;132,919-923[Abstract]
  7. Paciocco, G, Martinez, FJ, Bossone, E, et al Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension. Eur Respir J 2001;17,647-652[Abstract/Free Full Text]
  8. Badesch, DB, Tapson, VF, McGoon, MD, et al Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. Ann Intern Med 2000;132,425-434[Abstract/Free Full Text]
  9. Oudiz, RJ, Schilz, RJ, Barst, RJ, et al Treprostinil, a prostacycline analogue, in pulmonary hypertension associated with connective tissue disease. Chest 2004;126,420-427
  10. Rubin, LJ, Badesch, DB, Barst, RJ, et al Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346,896-903[Abstract/Free Full Text]
  11. Masi, AT, Rodnan, GP, Medsger, TA, et al Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980;23,581-590[ISI][Medline]
  12. LeRoy, EC, Black, C, Fleischmajer, R, et al Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988;15,202-205[ISI][Medline]
  13. American Thoracic Society.. ATS statement: guidelines for the 6-minute walk test. Am J Respir Crit Care Med 2002;166,111-117[Free Full Text]
  14. Préfaut, C, Durand, F, Mucci, P, et al Exercise-induced arterial hypoxemia in athletes: a review. Sports Med 2000;30,47-61[CrossRef][ISI][Medline]
  15. American Heart Association. 1994 revisions to classification of functional capacity and objective assessment of patients with diseases of the heart. Available at: http://www.americanheart.orghttp://www.americanheart.org. Accessed December 11, 2006
  16. Wechsler, RJ, Steiner, RM, Spirn, PW, et al The relationship of thoracic lymphadenopathy to pulmonary interstitial disease in diffuse and limited systemic sclerosis: CT findings. AJR Am J Roentgenol 1996;167,101-104[Abstract/Free Full Text]
  17. Miyamoto, S, Nagaya, N, Satoh, T, et al Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Am J Respir Crit Care Med 2000;161,487-492[Abstract/Free Full Text]
  18. Sitbon, O, Nunes, H, Parent, F, et al Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 2002;40,780-788[Abstract/Free Full Text]
  19. McLaughlin, VV, Sitbon, O, Badesch, DB, et al Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J 2005;25,244-249[Abstract/Free Full Text]
  20. Eaton, T, Young, P, Milne, D, et al Six-minute walk, maximal exercise tests: reproducibility in fibrotic interstitial pneumonia. Am J Respir Crit Care Med 2005;171,1150-1157[Abstract/Free Full Text]
  21. Troosters, T, Gosselink, R, Decramer, M Six-minute walking distance in healthy elderly subjects. Eur Respir J 1999;14,270-274[Abstract]
  22. Epler, GR, McLoud, TC, Gaensler, EA, et al Normal chest roentgenograms in chronic diffuse infiltrative lung disease. N Engl J Med 1978;298,934-939[Abstract]
  23. Desai, SR, Veeraraghavan, S, Hansell, DM, et al CT features of lung disease in patients with systemic sclerosis: comparison with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Radiology 2004;232,560-567[Abstract/Free Full Text]
  24. Azevedo, AB, Sampaio-Barros, PD, Torres, RM, et al Prevalence of pulmonary hypertension in systemic sclerosis. Clin Exp Rheumatol 2005;23,447-454[ISI][Medline]
  25. Denton, CP, Cailes, JB, Philips, GD, et al Comparison of Doppler echocardiography and right heart catheterization in systemic sclerosis. Br J Rheumatol 1997;36,239-243[Abstract/Free Full Text]
  26. MacGregor, AJ, Canavan, R, Knight, C, et al Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival. Rheumatology 2001;40,453-459[Abstract/Free Full Text]
  27. Mukerjee, D, St George, D, Coleiro, B, et al Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis 2003;62,1088-1093[Abstract/Free Full Text]
  28. Battle, RW, Davitt, MA, Cooper, SM, et al Prevalence of pulmonary hypertension in limited and diffuse scleroderma. Chest 1996;110,1515-1519
  29. Hallstrand, TS, Boitano, LJ, Johnson, WC, et al The timed walk test as a measure of severity and survival in idiopathic pulmonary fibrosis. Eur Respir J 2005;25,96-103[Abstract/Free Full Text]
  30. King, TE, Schwarz, MI, Brown, K, et al Idiopathic pulmonary fibrosis: relationship between histopathologic features and mortality. Am J Respir Crit Care Med 2001;164,1025-1032[Abstract/Free Full Text]
  31. King, TE, Tooze, JA, Schwarz, MI, et al Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Respir Crit Care Med 2001;164,1171-1181[Abstract/Free Full Text]
  32. 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 Care Med 2003;168,1084-1090[Abstract/Free Full Text]
  33. Miki, K, Maekura, R, Hiraga, T, et al Impairments and prognostic factors for survival in patients with idiopathic pulmonary fibrosis. Respir Med 2003;97,482-490[CrossRef][ISI][Medline]
  34. Mapel, DW, Samet, JM, Coutlas, DB Corticosteroids and the treatment of idiopathic pulmonary fibrosis: past, present, and future. Chest 1996;110,1058-1067
  35. Steen, VD Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 2005;35,35-42[CrossRef][ISI][Medline]
  36. Mayes, MD, Reveille, JD Epidemiology, demographics, and genetics. Systemic sclerosis 2nd ed. 2004,1-16 Lippincott, Williams and Wilkins. Philadelphia, PA:




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