Interstitial lung diseases and, in particular, idiopathic

Assessment of Health-Related Quality of Life in Patients With Interstitial Lung Disease* Jacqueline A. Chang, MD; J. Randall Curtis, MD, MPH; Donald L. Patrick, PhD, MSPH; and Ganesh Raghu, MD, FCCP Study objectives: Health-related quality of life associated with interstitial lung disease has received little attention in clinical studies because there have been no validated methods for directly measuring it. We have assessed the validity of several generic and respiratory-specific quality-of-life instruments in patients with interstitial lung disease. Design: Cross-sectional study. Setting: Outpatient pulmonary clinic at a university referral center. Patients: Fifty patients with interstitial disease such as idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis, and asbestosis. Interventions: Patients were administered four quality-of-life questionnaires, the Medical Outcomes Study Short Form 36 (SF-36), the Quality of Well-being scale (QWB), the Chronic Respiratory Questionnaire (CRQ), and the St. George s Respiratory Questionnaire (SGRQ). Patients concomitantly underwent pulmonary function testing and performed a 6-min walk. Measurements and results: Validation of these instruments was based on testing an a priori hypothesis that worse quality-of-life scores should correlate with more severe physiologic impairment demonstrated by pulmonary function tests, exercise tolerance on the 6-min walk, and dyspnea scores. Our patients, on average, had a moderate degree of physiologic impairment and demonstrated moderately decreased quality-of-life scores. Scores from all four quality-of-life questionnaires correlated significantly with 6-min walk distance and dyspnea score. Scores from the SF-36, QWB, and SGRQ showed significant correlation with FVC, FEV 1, and diffusing capacity as well. The SF-36 and SGRQ consistently showed the strongest correlation with physical impairment. Conclusions: Our findings indicate that preexisting quality-of-life instruments can be applied to patients with interstitial lung disease and suggest that the SF-36 and the SGRQ, in particular, are sensitive tools for assessing quality of life in these patients. Future intervention studies of patients with interstitial lung disease should consider using these measures. (CHEST 1999; 116:1175 1182) Key words: health status indicators; lung diseases; interstitial; pulmonary fibrosis; quality of life Abbreviations: CRQ Chronic Respiratory Questionnaire; Dlco diffusing capacity of the lung for carbon monoxide; MCS Mental Component Score; 6MW 6-min walk; 6MWD 6-min-walk distance; PCS Physical Component Score; QWB Quality of Well-Being Scale; SF-36 Medical Outcomes Short Form 36; SGRQ St. Gearoge s Respiratory Questionnaire; TLC total lung capacity *From the Division of Pulmonary and Critical Care Medicine, Department of Medicine (Drs. Chang, Curtis, and Raghu), and the Department of Health Services (Drs. Curtis and Patrick), University of Washington, Seattle, WA. Supported in part by the Respiratory Research Training grant, No. 5 T32 HL07287. Additional project support was provided by the Firland Sheltered Workshop Foundation, a nonprofit agency with a mission of support for projects relating to care of individuals with tuberculosis and other chronic respiratory problems. Manuscript received February 22, 1999; revision accepted June 8, 1999. Correspondence to: Ganesh Raghu, MD, FCCP, Division of Pulmonary and Critical Care Medicine, University of Washington, Box 356522, Seattle, WA 98195; e-mail: graghu@ washington.edu Interstitial lung diseases and, in particular, idiopathic pulmonary fibrosis are chronic progressive diseases with significant morbidity and mortality. The median survival for idiopathic pulmonary fibrosis is 3 to 5 years with half of the deaths resulting from progressive respiratory failure. 1,2 As the disease progresses, patients invariably become severely limited in their activities and dependent on supplemental oxygen. Current medical regimens have not been shown to improve survival but, nevertheless, are routinely prescribed with the hope of slowing progression of disease. 3 5 Currently available medica- CHEST / 116 / 5/ NOVEMBER, 1999 1175

tions, particularly corticosteroids and immunosuppressives, are all associated with significant side effects and morbidity. Colchicine has been used without significant side effects but does not appear to be significantly more effective than corticosteroids. 5 Toxicity of therapy is one important reason why quality of life should be considered a separate therapeutic end point in addition to stability of disease by pulmonary function or radiographic severity. However, clinicians and researchers have primarily followed physiologic and radiographic end points because there are no validated methods for directly measuring quality of life in this patient population. Standardized and validated methods for assessing the health-related quality of life in interstitial lung disease are needed to better understand the effect of these diseases and to evaluate standard and new therapies. Since the early 1980s, several standardized generic quality-of-life questionnaires have been developed to measure health-related quality of life for a variety of diseases. 6 10 Subsequently, respiratory-specific quality-of-life questionnaires were created to specifically address the problems faced by patients with chronic pulmonary disease. 11 Although many of these questionnaires were designed originally for patients with COPD, they have been applied to other patient populations as well. 12 14 In this study we have evaluated whether these generic and respiratory-specific questionnaires could be used to assess quality of life in patients with interstitial lung diseases. The validity of quality-of-life instruments is established primarily by demonstrating their content and construct validity. In applying well-established instruments to new patient populations, however, it is perhaps most important to demonstrate construct validity. 15 The premise of construct validation is that quality-of-life instruments should provide unique information not provided by objective measurements but, nevertheless, should correlate to some degree with severity of disease measured by these physiologic variables. Our hypothesis a priori was that worse quality-of-life scores should moderately correlate with more severe physiologic impairment demonstrated by pulmonary function tests, 6-min-walk distance (6MWD), and dyspnea. Most of the instruments also have subscale scores, which are designed to evaluate specific aspects of quality of life. Subscale scores focusing on physical or functional impairment would be expected to correlate better with pulmonary function than subscale scores focusing on mental or emotional health. We have used construct validation as the basis of our evaluation of four health-related quality-of-life instruments for patients with interstitial lung disease. Patients Materials and Methods All patients with documented interstitial lung disease referred to or followed by the University of Washington Chest Clinic from September 1997 through July 1998 were identified by screening clinic appointment books and were asked to participate if they met entry criteria. Interstitial lung disease was defined by the clinical presentation of otherwise unexplained dyspnea in conjunction with (1) linear or reticulonodular interstitial infiltrates on chest radiograph or CT scan, and (2) restrictive pulmonary function or consistent histopathologic findings. A total lung capacity (TLC) 80% of predicted was used as the criterion for defining restrictive physiology. Patients were excluded if they had any of the following: interstitial lung disease secondary to collagen vascular disease, nonparenchymal restrictive lung disease such as neuromuscular weakness or skeletal abnormality, obstructive lung disease such as COPD or asthma, or active coronary artery disease or other comorbid illness precluding performance of the 6-min walk (6MW) test. This case definition included patients with idiopathic pulmonary fibrosis, chronic sarcoidosis, chronic hypersensitivity pneumonitis, and asbestosis. Patients with idiopathic pulmonary fibrosis had histopathology consistent with either usual interstitial pneumonitis or nonspecific interstitial pneumonitis or met the clinical criteria of slowly progressive dyspnea of unknown cause and bibasilar infiltrates. Chronic sarcoidosis was diagnosed by the presence of noncaseating granulomas in all patients except one, who had typical radiographic features and a high CD4/CD8 ratio within a lymphocyte-predominant lavage fluid. The diagnosis of chronic hypersensitivity pneumonitis was based on the clinical history of exposure to a known offending antigen and confirmatory histopathology. Asbestosis was diagnosed primarily by clinical criteria including a history of heavy occupational exposure, although some patients had ferruginous bodies on tissue biopsy as well. Seventy-seven eligible patients were identified, and 50 patients participated after providing written informed consent. The most common reason patients did not participate was the traveling distance to the study center (n 10). Other reasons for nonenrollment were time conflicts with work (n 5), inability to contact patients (n 4), and patient disinterest (n 5). Only three patients were too sick to participate or died before study enrollment. All study procedures were approved by the University of Washington Human Subjects Committee. Study Design The study was a cross-sectional comparison of scores from two generic and two respiratory-specific health-related quality-of-life instruments with physiologic data from pulmonary function tests and a 6MW test. Patients were asked to complete the four quality-of-life questionnaires in a randomized order based on a random numbers table. After completing each questionnaire, patients were asked to rate how well the content of the questionnaire addressed quality-of-life issues relevant to their disease on a 1 (worst) to 10 (best) scale. Immediately after answering the questionnaires, the patients performed a modified 6MW test. The standard 6MW has been shown to be a reliable, valid, and safe method of assessing functional status in both patients with COPD and congestive heart failure. 16,17 Our protocol for the 6MW was adjusted slightly for patient comfort and safety. Patients were allowed to stop and restart during the 6 min if necessary. Although 6MW tests are sometimes performed multiple times to account for a learning effect, only one test was performed 1176 Clinical Investigations

because of many patients severe exercise limitation. 18 In addition, patients were deliberately allowed to use supplemental oxygen at the same inspired concentration normally used with their daily activities. After completing the walk, patients rated the amount of dyspnea experienced during the test on a standard Borg scale. 19 Patients underwent pulmonary function testing including spirometry, plethysmography, and diffusing capacity within 2 months of answering the questionnaires. Two months was believed to be the maximal length of time of stability in pulmonary function for this population. Two-thirds of the patients had pulmonary function tests within 1 week of the questionnaires, and half of the patients had tests on the same day. All tests were performed in accordance with published standards. 20 22 FVC, FEV 1, TLC, and diffusing capacity of the lung for carbon monoxide (Dlco) were expressed as percent of normal based on age, sex, race, and height-adjusted population standards. 23 Dlco was adjusted for hemoglobin concentration. Health-Related Quality-of-Life Questionnaires Medical Outcomes Short Form 36: The Medical Outcomes Short Form 36 (SF-36) is a generic health-related quality-of-life instrument, which has been used to assess quality of life in a variety of chronic medical conditions including COPD and asthma. 24,25 Its validity, reproducibility, and responsiveness to changes over time have been well demonstrated. 8 It assesses eight dimensions of quality of life: physical function, role limitation caused by physical impairment, bodily pain, general health, vitality, social function, role limitation caused by emotional impairment, and mental health. Each dimension is scored separately on a 0 to 100 scale, in which higher scores correspond to better quality of life. The SF-36 also incorporates the subscale scores into two summary measures, the Physical Component Score (PCS) and the Mental Component Score (MCS), which provide a measure of the overall effect of physical and mental impairment on quality of life. These summary scores are standardized to responses from the general population, whose mean score is 50. Quality of Well-Being Scale: The Quality of Well-Being Scale (QWB) is a general health outcome and health utility measure, which has been validated in patients with a variety of medical conditions including COPD. 9,10,26 Its questions focus on symptoms and medical problems, mobility, physical activity, and impact of illness on activities of daily living, and it summarizes these into one score ranging from 0 (death) to 1.0 (perfect health). Chronic Respiratory Questionnaire: The Chronic Respiratory Questionnaire (CRQ) is a respiratory-specific quality-oflife instrument originally developed for patients with COPD, which has been validated in patients with asthma as well. 13,27,28 It assesses four aspects of quality of life: dyspnea, fatigue, emotional function, and mastery. The questionnaire has a unique format, which allows patients to rate the severity of dyspnea associated with individually identified activities. Scores for each of the four domains and the summary score have a range from 0 to 100, in which higher scores signify better health-related quality of life. St. George s Respiratory Questionnaire: The St. George s Respiratory Questionnaire (SGRQ) is a respiratory-specific instrument developed for patients with COPD. Its validity, reproducibility, and response to change over time have been demonstrated in patients with COPD, asthma, and bronchiectasis. 12,14,29 It has three components: symptoms, which measures respiratory symptoms; activities, which measures impairment of mobility or physical activity; and impacts, which measures the psychosocial impact of disease. Scores for these components and the summary score are on a 100-point scale, which is opposite in direction to the other three instruments. Higher scores correspond to worse health-related quality of life. Statistical Analysis Correlation between quality-of-life scores and pulmonary function tests, 6MWD, and dyspnea score were evaluated using Pearson s coefficient. Quality-of-life scores were plotted against physiologic measures on scatter plots to ensure a linear relationship between the two (data not shown). Linear regression methods were then used to determine whether physiologic measures remained independent predictors of quality-of-life scores after considering patient demographics and comorbid illness. Two-sample Student s t tests were used to determine whether quality-of-life scores differed between patients who were dependent on supplemental oxygen and patients who were not. Analysis of variance was used to assess whether quality-of-life scores differed between patients by diagnosis. The criteria for statistical significance was set at p 0.05. The Friedman test, a nonparametric test similar to analysis of variance for repeated measures, was used to test for significant differences in patient ratings between the four questionnaires. 30 Results Clinical Characteristics We administered quality-of-life questionnaires to 50 patients with interstitial lung disease. The clinical characteristics of this group are described in Table 1. The median age of the patients was 60.5 years with a range from 29 to 81 years. The older age and male predominance of the study population reflect the epidemiologic features of its largest group, idiopathic pulmonary fibrosis. The majority of patients were currently taking or had been previously taking steroids and other immunosuppressives. Seventy-six percent of the patients were currently or previously taking high-dose steroids ( 40 mg/d), whereas 34% of the patients were currently maintained on steroids at lower doses ( 40 mg/d). A quarter of the patients were dependent on supplemental oxygen. Seventy-eight percent of the patients had at least one stable comorbid illness. Comorbid conditions included non insulin-dependent diabetes mellitus without end-organ damage, stable coronary disease, or arthralgia attributed to degenerative joint disease. Physiologic Characteristics On average, the study group had moderately severe restrictive lung disease indicated by their FVC and FEV 1 (Table 2). There was a larger decrement in the mean Dlco. However, the values for the FVC, FEV 1, and Dlco varied widely from values indicative of a severe restrictive defect to values within normal limits (defined as 80% of predicted). CHEST / 116 / 5/ NOVEMBER, 1999 1177

Table 1 Baseline Clinical Characteristics of 50 Patients With Interstitial Lung Disease* Table 2 Physiologic and Functional Severity of Disease for 50 Patients With Interstitial Lung Disease Variable Variable Median No. of Patients Percentage of Patients Sex Male 28 56 Female 22 44 Age 50 yr 37 74 50 yr 13 26 Diagnosis IPF 33 66 Sarcoidosis 10 20 Asbestosis, misc. 7 14 Biopsy-proven diagnosis Overall 39 78 IPF 24 73 Sarcoidosis 9 90 Asbestosis, misc. 6 86 Comorbidities Non-rheumatoid joint disease 13 26 Steroid use Currently on high dose ( 40 mg/d) 3 6 Currently on low dose ( 40 mg/d) 17 34 Not currently on steroids 30 60 Other immunosuppressives Azathioprine, currently 11 22 Azathioprine, previously 13 26 Cyclophosphamide, currently 1 2 Cyclophosphamide, previously 6 12 Supplemental oxygen use 14 28 *IPF idiopathic pulmonary fibrosis; misc. miscellaneous. Interquartile Range Minimum Maximum FVC, % predicted 65.0 49.0 81.0 31 115 FEV 1, % predicted 64.5 51.5 80.8 29 101 TLC, % predicted 69.0 55.5 78.8 38 109 Dlco, % predicted 49.0 36.5 59.8 11 88 6MWD, feet 1,421 1,130 1,626 315 2,235 Borg dyspnea score 2.8 0.6 4.0 0.0 5.0 Similarly, the study group had on average a moderate decrease in exertional capacity illustrated by the mean 6MWD of 1,360 feet (Table 2). The 6MWDs from other studies provide some comparison. The average 6MWD for a group of healthy men, whose average age was 60 years old, was 1,728 feet (576 m), and the average 6MWD for patients awaiting hip replacement was approximately 600 feet (300 m). 31,32 The 6MWD for our population, like the pulmonary function tests, encompassed a wide range from severe limitation (315 feet) to normal (2,235 feet). Most of the patients reported light to moderate dyspnea during the 6MW: dyspnea ratings on the Borg scale had a bimodal distribution with peaks at 0.5 and 4 (Table 2). Even though patients were allowed to perform the test using oxygen if they normally used it, 38% of the group still exhibited desaturations to 88%. Health-Related Quality of Life The summary scores from each of the four quality-of-life instruments are shown in Table 3. The summary scores of the SF-36, the PCS and the MCS, were standardized to scores from the general population, which conform to a normal distribution with a mean of 50. The mean PCS for our patients signified on average a moderately severe degree of impairment compared with the general population. The larger decrease in the PCS compared with the MCS suggested a more significant impairment in the physical aspects of quality of life than the emotional aspects of healthrelated quality of life. However, there was a wide range among individuals. The extremely low minimal values observed indicated an extremely poor health-related quality of life on both a physical and an emotional level for some individuals. The mean QWB score was similarly decreased. However, individual responses fell within a narrower range. Both the total scores from the SGRQ and the CRQ indicated a moderate decrease in quality of life Table 3 Health-Related Quality-of-Life Scores for 50 Patients With Interstitial Lung Disease Instrument Median Interquartile Range Minimum Maximum SF-36 Physical function 55.0 30.0 71.3 0 100.0 Bodily pain 67.0 41.0 100.0 0 100.0 Role physical 0.0 0.0 56.3 0 100.0 General health 41.0 25.0 58.3 0 87.0 Vitality 45.0 20.0 70.0 0 95.0 Social function 75.0 37.5 90.6 0 100.0 Role emotional 100.0 33.3 100.0 0 100.0 Mental health 78.0 63.0 88.0 24.0 100.0 PCS 32.2 23.9 43.1 18.7 55.8 MCS 53.2 42.2 58.4 23.9 67.9 QWB 0.65 0.58 0.71 0.42 0.83 SGRQ Symptom score 50.5 31.5 69.8 8.8 92.5 Activity score 54.4 39.9 72.9 0.0 92.5 Impact score 28.4 18.8 45.1 1.6 90.3 Total score 38.9 28.7 55.2 2.3 91.3 CRQ Dyspnea 54.3 42.9 65.7 14.3 90.5 Fatigue 55.4 39.3 75.0 21.4 100.0 Emotional function 74.5 60.0 82.1 36.7 98.0 Mastery 78.6 60.7 89.3 32.1 100.0 Total score 67.1 54.3 75.4 31.4 94.0 1178 Clinical Investigations

because their medians were considerably below the midpoint of the scales. Individual responses on both questionnaires, but in particular the SGRQ, nearly covered the entire range of possible scores. Analysis of variance revealed no significant differences in the quality-of-life scores between patients with idiopathic pulmonary fibrosis and patients with other interstitial lung diseases (p values ranged from 0.6 to 1.0 for the four instruments.) Furthermore, the pattern of association between quality-of-life scores and physiologic variables for the subgroup of patients with idiopathic pulmonary fibrosis was similar to that seen for the entire cohort (data not shown). Therefore the results for the two groups were combined in the subsequent analysis evaluating the correlation between quality-of-life scores and physiologic measurements. Validation of Health-Related Quality-of-Life Measures With Physiologic Variables Scores from all four of the quality-of-life instruments showed statistically significant correlation with pulmonary function test results (Table 4). The PCS of the SF-36 and the QWB score were correlated with FVC, FEV 1, and Dlco. However, their correlation with TLC was not statistically significant. The CRQ score was only correlated with Dlco. Of the five quality-of-life scores, the SGRQ total score was most strongly correlated with pulmonary function. Its correlation with the FVC, FEV 1, and Dlco was stronger than its correlation with TLC. The MCS of the SF-36 did not show a statistically significant correlation with any of the pulmonary function tests. Scores from all four of the quality-of-life questionnaires were correlated with 6MWD and dyspnea rating. The PCS was more strongly correlated with 6MWD and dyspnea than the QWB score. Likewise the SGRQ score showed a stronger correlation than the CRQ score. The MCS did not show statistically significant correlation with either variable. Long-term supplemental oxygen use was statistically associated with lower PCS, QWB, SGRQ, and CRQ scores (t 2.774, 2.131, 4.718, and 3.355, respectively; p 0.05). However, resting oxygen saturation, exertional oxygen saturation, and the presence of exercise-induced desaturation were not associated with quality-of-life scores from any of the instruments. An additional method of validating the quality-of-life instruments was to assess the correlation between individual subscale scores and the physiologic data. Of the eight individual subscale scores of the SF-36, only physical function was statistically correlated with FVC% (r 0.38, p 0.01). Although the subscale scores of the SGRQ do not clearly delineate physical aspects of quality of life from emotional aspects, the activity score was expected to correlate with physiologic variables better than would the symptom score. The correlation coefficients for these subscale scores were consistent with our hypothesis: the FVC% was more strongly correlated with activity score (r 0.39, p 0.01) than the symptom score (r 0.31, p 0.05). Similarly, for the CRQ, the dyspnea score was significant correlated with the FVC% (r 0.32, p 0.05), whereas the fatigue score and the emotional score were not. Demographic and physiologic variables were entered into multiple linear regression models to ascertain whether pulmonary function, walk distance, and dyspnea were independent predictors of qualityof-life scores. Even after considering age, oxygen use, and comorbidity, pulmonary function tests, 6MWD, and dyspnea remained significant independent predictors of the SF-36 PCS score and the SGRQ total score (data not shown). There were no significant differences in the patients ratings of the questionnaires in terms of the extent to which their content addressed relevant quality-of-life issues ( 2 0.98, p 0.81). The median ratings of the questionnaires (1 and 10 as the worst and best ratings, respectively) were as follows: 9.0 (SF-36), 8.5 (QWB), 8.5 (CRQ), and 8.5 (SGRQ). Table 4 Pearson Correlation Coefficients (r) Between Quality-of-Life Scores and Pulmonary Function Tests and 6MWD for 50 Patients With Interstitial Lung Disease FVC, % predicted FEV 1,% predicted TLC, % predicted Dlco, % predicted 6MWD, ft Dyspnea Score SF-36-PCS 0.31* 0.30* 0.20 0.32* 0.51 0.62 SF-36-MCS 0.20 0.19 0.11 0.10 0.12 0.04 QWB 0.29* 0.28* 0.23 0.30* 0.45 0.36 SGRQ total score 0.45 0.46 0.36 0.55 0.66 0.56 CRQ total score 0.23 0.24 0.21 0.41 0.36* 0.53 *p 0.05. p 0.01. CHEST / 116 / 5/ NOVEMBER, 1999 1179

Discussion Health-related quality of life in interstitial lung disease is a vital concern to both patients and their physicians. Patients experience decreased quality of life because of symptoms and treatment side effects as well as the progressive nature of the respiratory impairment and functional limitation caused by the disease. Physicians should be particularly concerned about quality-of-life issues with these diseases because medications currently available are of marginal effectiveness, particularly in the case of idiopathic pulmonary fibrosis, and are associated with significant adverse effects. Standardized quality-of-life measures are essential for characterizing and assessing the quality of life in this patient population. Our data support the validity of using preexisting health-related quality-of-life questionnaires to assess the health-related quality of life of patients with interstitial lung disease. Our evaluation of the SF-36, QWB, SGRQ, and CRQ was based on construct validation. Scores from all four of the quality-of-life instruments correlated with severity of physical impairment reflected by pulmonary function, 6MWD, and dyspnea rating. In addition to assessing whether these instruments were valid in this population, we were interested in determining whether some instruments were better than others. We based our judgment on the strength of the association between the quality-of-life scores and the physiologic measurements as well as the patient ratings of the questionnaire content. There were no significant differences in the patient ratings of the questionnaires. In comparing the two generic questionnaires, the PCS was consistently more strongly correlated with pulmonary function, 6MWD, and dyspnea rating than the QWB score. Likewise, between the two respiratory-specific instruments, the SGRQ total score was more strongly associated with all physiologic measurements than the CRQ score. Our findings suggested that the SF-36 and the SGRQ may be more-sensitive instruments for discriminating differences in quality of life between individuals with varying degrees of physical impairment caused by interstitial lung disease. Observations from the study suggested possible reasons why the QWB and the CRQ may be lesssensitive quality-of-life instruments. Although our study population represented the full spectrum of disease severity, their QWB scores fell within a relatively narrow range. Because of the lesser variability in QWB scores, this generic questionnaire may be less successful in distinguishing between patients with interstitial lung disease. The few questions that addressed respiratory symptoms were answered in a similar manner by most patients, whereas much of the variability in the scores resulted from nonrespiratory symptoms and problems. The scores on the CRQ had more variability than the QWB but less variability than the SF-36 and the SGRQ. Although the CRQ is a respiratory-specific quality-of-life instrument, its individualized format may have accounted for why its scores were less consistently correlated with pulmonary function than the SGRQ. With the CRQ, patients rated the severity of their dyspnea based on symptoms during their own daily activities. In our study we observed that patients with the most severe disease frequently scaled down their activities to minimize dyspnea and therefore did not consistently report more dyspnea on the questionnaire. This explanation could have accounted for the attenuated difference in scores between patients with mild and severe physiologic impairment. The CRQ may be better suited for longitudinal follow-up of patients than comparisons between individuals. The correlation between the quality-of-life scores and pulmonary function tests and 6MW tests in this population with interstitial lung disease were similar to those described in patients with COPD and asthma. Several investigators found significant correlation of similar magnitude between the SGRQ total score and subscale scores and FEV 1 and FVC in patients with COPD (r 0.28 to 0.51). 12,33 Similarly, they found a statistically significant association between quality-of-life scores and 6MWD (r 0.26 to 0.59). 12 The SF-36 has been tested less extensively in COPD, but the correlation found by Jones and colleagues 34 is similar to our findings. Other investigators have identified strong correlation between CRQ scores and the 6MW, but the correlation between CRQ scores and pulmonary function tests have been less consistent in other studies as well. 13,27,35 Kaplan and colleagues 10 also found a significant correlation between the QWB score and FVC and FEV 1 in patients with COPD. In our study, we found a significant correlation between health-related quality of life and the need for supplemental oxygen but no association between quality of life and oxygenation at rest or during exercise. The association between health-related quality-of-life scores and oxygenation reported by other investigators has been inconsistent. Although Jones and colleagues 12 found no significant correlation between scores from the SGRQ and resting oxygen saturation in patients with COPD, Okubadejo et al 36 did find a statistically significant association between scores on this questionnaire and Pao 2. Our results are not necessarily contradictory to the findings of Okubadejo and colleagues. 36 In their study, none of the patients were using long-term oxygen therapy although it was initiated in some 1180 Clinical Investigations

based on the low arterial oxygen noted. Impaired oxygenation may not necessarily be associated with poorer quality of life provided that patients can use long-term supplemental oxygen. Additionally, the amount of oxygen individual patients use may vary with their different daily activities and may not be the same as the average amount of oxygen use reported and consequently used during our 6MW tests. One potential limitation of our study is that the patient population was a referral population, which may differ from patients with interstitial lung disease in the community. Our patients had, on average, moderately severe restrictive lung disease by physiologic criteria supporting a possible referral bias. However, the severity of illness varied from severe physiologic defects to within normal limits, and therefore our sample provides a reasonable representation of the complete spectrum of disease. Another limitation of our study is the possibility that we did not accurately assess the patients maximal exercise tolerance because the 6MW was only performed once. The potential inaccuracy of the 6MWD is unlikely to jeopardize the validity of our results, because the association between the 6MWD and the quality-of-life scores was highly statistically significant (p 0.01). However, inaccuracy in measuring the 6MWD may have affected our estimate of the magnitude of the correlation. In summary, we have demonstrated that a general measure, the SF-36, and a respiratory-specific measure, the SGRQ, are sensitive instruments for evaluating health-related quality of life in patients with interstitial lung disease. These findings are an important first step to the application of standardized quality-of-life measurements in clinical research. Our cross sectional study has shown that the SF-36 and the SGRQ can be used to examine the healthrelated quality of life of this patient population and how it varies based on severity of disease. Future studies are needed to address the ability of these instruments to assess change over time. The outcomes of these studies, in combination with our results, will allow selection of specific quality-of-life instruments as end points in clinical trials to evaluate the efficacy of new therapies. ACKNOWLEDGMENT: The authors would like to thank the persons with interstitial lung disease who participated in this study. References 1 Tukiainen P, Taskinen E, Holsti P, et al. Prognosis of cryptogenic fibrosing alveolitis. Thorax 1983; 38:349 355 2 Hubbard R, Johnston I, Britton J. Survival in patients with cryptogenic fibrosing alveolitis. Chest 1998; 113:396 400 3 Johnson MA, Kwan S, Snell NJC, et al. Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis. Thorax 1989; 44:280 288 4 Raghu G, Depaso WJ, Cain K, et al. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebocontrolled clinical trial. Am Rev Respir Dis 1991; 144:291 296 5 Douglas WW, Ryu JH, Swensen SJ, et al. Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998; 158:220 225 6 McHorney CA, Ware JE, Rogers W, et al. The validity and relative precision of MOS short- and long-form health status scales and Dartmouth COOP charts. Med Care 1992; 30: MS253 MS265 7 Ware JE, Sherbourne CD. The MOS 36-item short form health survey (SF-36). Med Care 1992; 30:473 483 8 Stewart AL, Greenfield S, Hays RD, et al. Functional status and well-being of patients with chronic conditions. 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