Chronic Obstructive Pulmonary Disease Stage and Health-Related Quality of Life

The 1995 American Thoracic Society statement on the diagnosis and care of patients with chronic obstructive pulmonary disease [1] proposed that a staging system would have many potential applications, including clinical recommendations, prognostication, and health resource planning. Because FEV1 is highly correlated with morbidity and mortality and because knowledge about other potential dimensions of staging was lacking, the American Thoracic Society adopted FEV1 as the basis for staging patients with chronic obstructive pulmonary disease. Health-related quality of life in chronic obstructive pulmonary disease is thought to vary with severity: Stage I chronic obstructive pulmonary disease (FEV1 > 49% of the predicted value) minimally affects health-related quality of life, whereas stage II (FEV1, 35% to 49% of the predicted value) and stage III (FEV1 < 35% of the predicted value) disease are associated with profound deterioration in health-related quality of life [1]. However, little empirical evidence documents the suspected relation between disease stage and health-related quality of life. The European Respiratory Society [2] proposed a staging system that is based on FEV1 but uses different cut-off points. We examined the relation between the American Thoracic Society's system for staging chronic obstructive pulmonary disease and health-related quality of life. Particular attention was given to the influence of self-reported chronic comorbid conditions on the relation between health-related quality of life and severity of chronic obstructive pulmonary disease. Methods Study Sample Between April 1993 and July 1994, we recruited all consecutive male patients with clinical symptoms of chronic obstructive pulmonary disease who were attending outpatient respiratory clinics of participating centers. Two university public referral hospitals and one primary health care center for the population of Barcelona, Spain (an urban area); a public referral hospital for the population of Osona County, Spain (a semirural area in Barcelona Province); and a public referral hospital for the inhabitants of Castellon (an urban area) participated in the study. Inclusion criteria were 1) chronic airflow impairment [defined as FEV1 < 80% of the predicted value, a ratio of FEV1 to FVC 70%, and clinical stability of respiratory disease for at least 1 month before study entry with neither acute clinical decline nor a hospital admission] and 2) an increase in FEV1 less than both 200 mL and 15% after bronchodilator therapy. The study protocol was approved by the institutional review boards of the participating centers. Seventeen of 352 patients recruited were ineligible: Nine had airflow obstruction reversibility, 5 had an FEV1 greater than 80%, 2 had a ratio of FEV1 to FVC greater than 70%, and 1 was mentally incapacitated. Of the 335 patients who met the inclusion criteria, 14 (4.2%) refused to participate. Thus, 321 patients participated in the study. Patient Evaluation We measured FEV1 and FVC by using standard techniques [3] in the 2 months before or after the patient interview. For 90% of patients, questionnaires were administered and spirometry was performed no more than 23 days apart. Results of blood gas analysis done for diagnostic or therapeutic purposes up to 6 months before study enrollment were obtained from patient medical records; these values were available for 98% of patients with an FEV1 of 49% of the predicted value or less and 29% of patients with an FEV1 greater than 49% of the predicted value. Dyspnea was assessed by using an adapted version of the American Thoracic Society dyspnea questionnaire [4, 5] and a 10-point visual analogue scale [6]. The presence of comorbid conditions was determined by asking patients if they had any of 11 chronic conditions. Social class was assigned according to occupation by using an adapted version of the British Registrar General's Social Classes [7]: class I (professional), class II (intermediate occupations [such as nurse, manager, or schoolteacher]), class III (skilled nonmanual occupations), and classes IV and V (manual occupations). Most patients completed the Spanish versions of the St. George's Respiratory Questionnaire [8], the Nottingham Health Profile [9], and the 5-item Mental Health Inventory of the Medical Outcome Study 36-item short form health survey [10] on their own. Trained interviewers administered questionnaires to those patients (27%) who had vision problems or were functionally illiterate. Questionnaires were randomly ordered: Half of the study sample responded to the Nottingham Health Profile first, and the other half responded to the St. George's Respiratory Questionnaire first. The St. George's Respiratory Questionnaire is a standardized questionnaire that is designed to be completed without assistance. It measures health status and perceived well-being in persons with obstructive airway diseases. The Spanish version of the St. George's Respiratory Questionnaire has been shown to be conceptually equivalent to the original instrument and similarly valid and reliable [8]. It contains 50 items (76 levels) divided into three sections: Symptoms deals with the frequency and severity of respiratory manifestations, activity relates to activities that cause or are limited by breathlessness, and impacts covers aspects of social function and psychosocial disturbances that result from respiratory diseases. Scores on the St. George's Respiratory Questionnaire range from 0 (no disturbance of health-related quality of life) to 100 [11]. Mean scores obtained from a sample of persons (n = 74) between 17 and 80 years of age (mean age, 46 years) who had no history of respiratory disease (mean FEV1, 95%) served as reference values (Jones PW. Scoring Manual of the St. George's Respiratory Questionnaire). The Nottingham Health Profile is a multidimensional health status questionnaire that has been found to be appropriate for Spanish patients with chronic obstructive pulmonary disease [12]. It contains 38 items divided into six aspects of health (energy, pain, emotional reactions, sleep, social isolation, and physical mobility). A total score on the Nottingham Health Profile is calculated as the proportion of affirmative answers and ranges from 0 (no perceived distress) to 100 (maximum perceived distress). Scores from a representative sample of 610 men older than 40 years of age from the general population of Barcelona served as reference values [13]. Mental Health Inventory scores range from 0 (worst psychological well-being) to 100 (best psychological well-being) [14]. The severity of chronic obstructive pulmonary disease was staged according to the American Thoracic Society guidelines [15] as follows: stage I, FEV1 greater than 49% of the predicted value; stage II, FEV (1) 35% to 49% of the predicted value; and stage III, FEV1 less than 35% of the predicted value. Predicted FEV1 values were taken from a sample of Mediterranean persons [16]. Categories of Pao 2 included no hypoxemia (Pao 2 >87 mm Hg), mild hypoxemia (Pao 2, 75 to 87 mm Hg), and moderate to severe hypoxemia (Pao 2 <75 mm Hg). Statistical Analysis The Kruskal-Wallis test (with correction for ties when necessary) was used to compare health-related quality-of-life scores with clinical and functional categories of chronic obstructive pulmonary disease. The Spearman correlation coefficient (r) was calculated to assess the association between health-related quality-of-life scores and clinical or functional variables. Differences in health-related quality-of-life scores and other continuous variables according to the presence of comorbid conditions were tested by using the t-test. The Statistical Package for the Social Sciences [17] was used for calculations. Multivariate linear regression was used to identify variables that were associated with total scores on the Nottingham Health Profile and the St. George's Respiratory Questionnaire. Residual values from parametric regression were distributed normally. We used SAS software [18] to assess the adjusted least-squares means. Results Demographic and clinical characteristics of the study sample are shown in Table 1. The mean age of the patients was 64.9 9.6 years; more than two thirds of the patients were retired. One hundred thirty-one patients (41%) had stage I disease (mean percentage of predicted FEV1 SD, 62.9% 8.4%), 76 patients (24%) had stage II disease (mean percentage of predicted FEV1, 41.8% 4.2%), and 114 patients (35%) had stage III disease (mean percentage of predicted FEV1, 25.3% 6.0%). Eighty-four percent of patients reported at least one coexisting chronic condition; osteoarthritis was the most prevalent (37.7% of patients). Table 1. Characteristics of 321 Men with Chronic Obstructive Pulmonary Disease Both specific and generic health-related quality-of-life instruments showed decreased health-related quality of life with increased stage of chronic obstructive pulmonary disease (Table 2). This pattern was shown most clearly and consistently by the St. George's Respiratory Questionnaire scores (Figure 1). In all sections of the St. George's Respiratory Questionnaire, scores were moderately to strongly associated with FEV1 categories (r = 0.27 to 0.51). Of note, values for patients with stage I disease showed substantial and statistically significant impairment compared with reference values in all sections of the St. George's Respiratory Questionnaire (total score, 34 compared with 6; P < 0.001) and the Nottingham Health Profile (total score, 11 compared with 21; P < 0.001). Dyspnea also decreased in a statistically significant manner as FEV1 worsened (Table 2). The association between level of hypoxemia and staging categories for chronic obstructive pulmonary disease was statistically significant only for the activity section of the St. George's Respiratory Questionnaire. Table 2. Mean Health-Related Quality-of-Life Scores by Clinical and Functional Char