Relation Between Quality of Life and Morbidity and Mortality in COPD Patients: Two-Year Follow-Up Study

ABSTRACT

Quality of life (QoL) is being recognized as an important outcome when evaluating chronic obstructive pulmonary disease (COPD) patients. This study aims at identifying the relation between QoL parameters and mortality and morbidity in COPD patients by using the St. George Respiratory Questionnaire (SGRQ). In this prospective study, 251 COPD patients as defined by American Thoracic Society (ATS) criteria were included. A total of 218 patients (86.85%) were male and mean age was 65.55 years. A pulmonary function test (PFT) and SGRQ were performed at the beginning, first, and second years. During a two-year follow-up, the first exacerbation day, the number of exacerbations and intubations, the number and duration of hospitalizations, hospitalizations in an intensive care unit, and exitus day were recorded. When the correlation between FEV₁, SGRQ scores, and these parameters was investigated, there was significant correlation between these parameters, and this correlation was more significant in SGRQ scores than FEV₁ (Pearson correlation test). The activity score of SGRQ was found to be more useful than other scores (Cox regression analysis). Not only PFT but also QoL questionnaires are useful in determining the prognosis of COPD. QoL questionnaires provide a valid and standardized estimate of the overall impact of COPD, and can complement spirometric measurements of baseline assessment of patients in routine practice.

Keywords: :

• COPD
• Quality of life
• Morbidity
• Mortality

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is the only disease that has an increasing trend in prevelance and mortality, with hospital mortality rates of 10%–49% and reported one-year mortality rates of 20%–59%, whereas all other major causes of death are declining (1–4).

COPD is a very important reason for healthcare utilization, such as emergency room visits and hospitalizations, and probably one of the major causes of disability, particularly in the elderly population. As hospitalization accounts for such a major portion of the cost in managing COPD patients, it would undoubtedly be helpful to identify those who are at the highest risk for hospitalization in order to target preventive interventions. Several studies have investigated the risk factors for rehospitalization among hospitalized COPD patients (5–7).

COPD has a complex pathophysiology. The systemic manifestations of the disease have been shown to be as important as the functional parameters such as FEV₁. FEV₁ has long been known to reflect airflow limitation and is a good marker for disease progression, but FEV₁ is not adequate to evaluate the multisystemic nature of COPD.

Health-related quality of life (HRQoL) is being recognized as an important outcome when evaluating patients with COPD. An increased number of past exacerbations is one of the best predictors of future exacerbations, and COPD patients with more frequent exacerbations have worse quality of life (QoL) (7). The magnitude of the short- and long-term impacts of exacerbations on QoL should be worth studying, and QoL scores might therefore be expected to predict mortality in COPD.

Two studies using a disease-specific measure of QoL in patients with severe COPD have found that patients with worse scores are more likely to have frequent exacerbations and hospitalizations, and furthermore found that QoL was an important predictor for hospitalization. These suggest studies that disease-specific QoL also may predict exacerbations in patients with less severe COPD (5, 8).

This study aims at identifying the relationship between QoL parameters and the mortality and morbidity in COPD by using a disease-specific quality of life questionnaire, the St. George Respiratory Questionnaire (SGRQ).

MATERIAL AND METHOD

Between December 2005 and October 2008, 286 patients with stable COPD were approached to participate in the study, but on follow-up 35 patients did not accept due to various reasons. A total of 251 patients with stable COPD were recruited in our outpatient respiratory clinic, and all patients were reinterviewed every 6 months. The diagnosis of COPD was based on the definition of the American Thoracic Society (9). Inclusion criteria at entry were chronic airflow impairment (percentage of FEV₁ <80% and FEV₁/FVC <0,7), with a change in FEV₁ less than 200 ml and 15% in the bronchodilator test, smoking history more than 20 pack-years, no history suggestive of asthma, no exacerbation of airflow limitation in the preceding 6 weeks, no changes in treatment regimen in the preceding 4 weeks, and quality of life questionnaire completion. Sociodemographic variables, smoking status, exacerbations in the past year, comorbid conditions, and physical examination findings were noted. PFT was performed using the Jaeger Master Screen Pneumo by the same person. Spirometric parameters, FEV₁, forced vital capacity (FVC), vital capacity (VC), FEV₁/FVC, and peak expiratory flow (PEF) were measured. Patients were classified according to GOLD as stage 1 (FEV₁ > 80%), stage 2 (80% > FEV₁ > 50%), stage 3 (50% > FEV₁ > 30%), and stage 4 (FEV₁ < 30%).

Visual analog scale (VAS) used for dyspnea assessment (9) and quality of life was assessed using a Turkish translation of the SGRQ (10). The SGRQ contains 50 items divided into three dimensions (symptoms, activity, and impact), and their scores range from 0 to 100 (worst status), and total score is also calculated.

PFT, VAS, and SGRQ were performed at the beginning, first, and second years. During a two-year follow-up, the first exacerbation day, the number of exacerbations, the number and duration of hospitalizations, the number and duration of hospitalizations in an intensive care unit, the number of intubations, and exitus day were recorded.

Informed consent was obtained from all subjects and the study protocol was approved by the ethics committee.

Baseline differences of patients according to their vital status were tested using the Fisher exact test for proportions, t-test or Mann–Whitney U test, as appropriate. The Kaplan–Meier survival curves and long-rank tests were performed after stratifying by tertiles of baseline SGRQ scores. Semiparametric Cox models were used to assess the association between baseline SGRQ total score and survival time. Different analyses were performed by all causes and by specific causes for the total follow-up period. Deaths were classified as due to respiratory or other causes. The Spearmen correlation test was used to assess the relationship between FEV₁ values, SGRQ scores and morbidity parameters (first exacerbation day, the number of exacerbations, the number and duration of hospitalizations, the number and duration of hospitalizations in an intensive care unit, and number of intubations).

RESULTS

In this prospective study, 251 patients with COPD as defined by ATS criteria were included. A total of 218 patients (86.85%) were male and mean age was 65.55 ± 8.82 years (43–82 years). There were 100 patients (39.8%) in stage 2, 131 patients (52.2%) in stage 3, and 20 patients (8.0%) in stage 4. Mean duration of disease was 7.0 ± 5.0 years. Mean VAS was 63.6 ± 13.7 mm and mean SGRQ scores, namely, activity, symptom, impact, and total were 58.6 ± 17.2, 57.2 ± 13.9, 42.7 ± 16.6, and 48.9 ± 15.4, respectively. A total of 81 (32.2%) patients died by the end of the two-year follow-up.

The baseline characteristics of patients divided in two groups as alive and dead are shown in Table 1. Subjects who died during the follow-up were older, had a cardiac comorbidity (cardiac failure, cardiac arrhythmias, ischaemic heart disease, valvular heart disease, and hypertension), were more likely to be a current smoker, and were more imparied in the clinical characteristics studied. There were no differences according to disease duration, body mass index (BMI), usage of inhaled corticosteroid therapy and long-term oxygen therapy. Differences in health-related quality of life scores were observed. Differences for all SGRQ dimensions were seen.

Table 1.  Baseline characteristics of the patients

	Alive (n = 170)	Dead (n = 81)	p
Age (year)	64.4 ± 8.4	68.1 ± 9.2	.002
Gender (M–F)%	86.5–13.5	87.6–12.4	>.05
Body mass index	25.2 ± 2.1	24.9 ± 1.9	>.05
Disease duration (year)	6.7 ± 4.9	7.7 ± 5.2	>.05
Presence of cardiac comorbidity, n (%)	68 (40%)	52 (64%)	.001
Current smoke, n (%)	25 (14.7%)	19 (23.5%)	.002
Usage of corticosteroid therapy, n (%)	51 (30%)	28 (34.5%)	>.05
Long-term oxygen therapy, n (%)	10 (5.9%)	8 (9.1%)	>.05
FEV1 (lt)	1.42 ± 0.46	1.02 ± 0.32	.000
FEV1 (% predicted)	50.7 ± 12.4	39.0 ± 11.6	.000
GOLD staging
Stage 2, n (%)	89 (52.3%)	11 (13.6%)
Stage 3, n (%)	75 (44.1%)	56 (69.1%)
Stage 4, n (%)	6 (3.6%)	14 (17.3)
St. George Respiratory Questionnaire
Symptoms	48.3 ± 12.3	60.7 ± 13.5	.000
Activity	53.0 ± 14.8	71.1 ± 14.5	.000
Impact	37.1 ± 14.3	54.6 ± 14.9	.000
Total	43.5 ± 13.2	60.4 ± 13.5	.000
First exacerbation day	286.2 ± 129.2	158.7 ± 88.1	.000
Total number of exacerbations	2.5 ± 2.3	3.5 ± 1.8	.002
Total number of hospitalizations	1.1 ± 1.5	2.8 ± 1.6	.000
Total duration of hospitalization (days)	15.1 ± 23.6	39.3 ± 23.4	.000
Total number of hospitalizations in an intensive care unit	0.3 ± 0.8	1.4 ± 1.1	.000
Total number of intubations	0.1 ± 0.4	0.7 ± 0.5	.000

Of the 81 deaths, 50 corresponded to a respiratory cause. The distribution of specific causes of death was as follows: COPD, 50 deaths (61.7%); cardiovascular diseases, 15 deaths (18.5%); cerebrovascular accident, 6 deaths (7.4%); lung cancer, 5 deaths (6.2%); other causes, 3 deaths (3.7%); unknown, 2 deaths (2.5%). Of the 81 deaths, 30 were seen in the first year, and 21 of them (70%) were related to COPD.

BMI, long-term oxygen therapy, inhaled corticosteroid usage, FEV₁, cardiac comorbidity, age, visual analog score, SGRQ scores, disease duration, and smoking status were put in Cox models. In a multivariate model, total SGRQ score, age, cardiac comorbidity, and FEV₁ were associated with all causes of mortality and respiratory causes of mortality. FEV₁ was not associated with nonrespiratory causes of mortality (Table 2).

Table 2.  Adjusted association (Cox models) between baseline health-related quality of life and complete follow-up mortality by different mortality events

	All causes of mortality		Respiratory causes of mortality		Nonrespiratory causes of mortality
	Standard HR	HR (95% CI)	Standard HR	HR (95% CI)	Standard HR	HR (95% CI)
Total score	1.05	1.05 (1.02–1.07)	1.03	1.04 (1.00–1.07)	1.05	1.05 (1.02–1.08)
Cardiac comorbidity	2.82	2.80 (1.74–4.51)	2.36	2.47 (1.27–4.82)	4.99	4.29 (2.22–9.03)
FEV1 (%predicted)	0.96	0.96 (0.94–0.99)	0.93	0.92 (0.88–0.97)	0.98	0.98 (0.94–1.03)
Age (year)	1.04	1.04 (1.02–1.07)	1.03	1.03 (0.99–1.07)	1.11	1.11 (1.05–1.17)

Mortality was closely related with SGRQ scores. According to the Kaplan–Meier survival curves, in relation to SGRQ scores, survival was shorter in patients with the worst SGRQ scores, and differences between tertiles being statistically significant for SGRQ total score (long-rank test, p <0,000) (Figure 1). Mean SGRQ scores of the first, second, and third tertiles were 31.73 ± 6.54 (17.41–41.84), 48.41 ± 3.59 (42.07–55.38), and 66.57 ± 7.46 (56.12–94.05), respectively.

Figure 1.  Kaplan–Meier survival curves according to tertiles of SGRQ total score.

Aiming to determine if there is an association between baseline SGRQ scores and morbidity parameters, a Spearman correlation test was applied. When the correlation between FEV₁ values, SGRQ scores, and morbidity parameters (first exacerbation day, number of exacerbations, number and duration of hospitalizations, number and duration of hospitalizations in an intensive care unit, number of intubations) were investigated, there was significant correlation between these parameters, and this correlation was more significant in SGRQ scores (total, symptom, activity, and impact) than FEV₁ values (Spearman correlation test) (Table 3).

Table 3.  Spearman correlation between FEV₁ values, SGRQ scores and morbidity parameters

	FEV1 (% predicted) r		SGRQ Symptom score r		SGRQ Activity score r		SGRQ Impact score r		SGRQ Total score r
	Alive	Dead	Alive	Dead	Alive	Dead	Alive	Dead	Alive	Dead
First exacerbation day	0.39	0.45	0.40	0.31	0.37	0.38	0.37	0.40	0.41	0.42
Total number of exacerbations	0.47	0.27	0.44	0.1	0.45	0.04	0.42	0.19	0.47	0.12
Total number of hospitalizations	0.44	0.45	0.39	0.34	0.37	0.25	0.36	0.36	0.40	0.32
Total duration of hospitalization (days)	0.44	0.41	0.38	0.33	0.36	0.31	0.35	0.40	0.39	0.37
Total number of hospitalizations in an intensive care unit	0.33	0.62	0.33	0.52	0.36	0.48	0.33	0.51	0.37	0.51
Total number of intubations	0.31	0.42	0.24	0.40	0.24	0.36	0.27	0.31	0.28	0.33

DISCUSSION

During the past 10 years, measurements of HRQoL or health status have been widely used in the assessment of outcomes in COPD patients (11, 12). Because of the limitations of using physiological measurement, the importance of HRQoL in measuring the impact and outcome of COPD is increasingly being acknowledged. The measurement of FEV₁ is essential for the diagnosis and quantification of the respiratory impairment resulting from COPD (13). In addition, the rate of decline in FEV₁ is a good marker of disease progression and mortality; however, FEV₁ does not adequately reflect all the systemic manifestations of the COPD.

There has recently been some debate about the use of FEV₁ as the main single evaluative parameter for COPD. Nishimura and coworkers have reported that categorizing patients with COPD on the level of dyspnea was more closely related with mortality than classification based on disease severity, as assessed by the percentage of predicted FEV₁ (14). Celli proposed a systemic evaluation of COPD patients and stressed that there is a need to seek candidates for multidimensional disease staging (15). Exercise capacity and health status may also be important clinical indices to evaluate disease impairment in addition to FEV₁.

Our results showed that HRQoL scores were associated with mortality. After adjusment for BMI, long-term oxygen therapy, inhaled corticosteroid usage, FEV₁, cardiac comorbidity, age, visual analog score, SGRQ scores, disease duration, smoking status, SGRQ total score, age, cardiac comorbidity, and FEV₁ were independently associated with all causes of mortality and respiratory causes of mortality, but FEV₁ was not associated with nonrespiratory causes of mortality. This association was more prominent in a respiratory than in a nonrespiratory mortality.

There are many studies indicating the relationship between SGRQ scores and COPD severity (10, 12). Also, the relationship between mortality and SGRQ scores was shown. Domingo-Salvany and coworkers have reported that SGRQ total score was independently associated with mortality after adjusment for age, FEV₁, and BMI, and they furthermore reported that a worsening of one standard deviation in the SGRQ total score was associated with a 30% increase in total mortality (16). In the study performed with 150 male patients with COPD, SGRQ total score was significantly correlated with mortality (17). In our study, we also found that SGRQ total score was independently associated with mortality. In the Cox model for HRQoL, a wide range of variables such as BMI, long-term oxygen therapy, inhaled corticosteroid usage, FEV₁, cardiac comorbidity, age, visual analog score, SGRQ scores, disease duration, and smoking status were included. Only FEV₁, cardiac comorbidity, and age were retained in the final Cox models. Although there is strong evidence that long-term oxygen therapy increases survival in COPD patients (18), usage of long-term oxygen therapy was not statistically significant between the alive and dead groups. For this reason, usage of long-term oxygen therapy was also included into the Cox model.

Patients with COPD may suffer recurrent exacerbations, with worsening of symptoms and reduction in lung function that may not be recovered in a small proportion of patients (19). Moreover, exacerbations are associated with an impaired quality of life (8), reduced survival (20), and a high healthcare expenditure (21). Prevention of exacerbations is therefore an important goal in the managment of stable COPD (22), although knowledge about which factors relate to COPD exacerbations or hospital admissions for exacerbations is currently very limited (23, 24). In a study of COPD patients with severe disease, patients with lower scores on the sickness impact profile, which is the general measure of health-related QoL, had frequent exacerbations and hospitalizations (7). Two recent studies have used a respiratory specific QoL instrument, SGRQ. Among patients who were hospitalized for a COPD exacerbation, lower scores on SGRQ predicted hospital readmisson within the next 12 months, while sex, age, and pulmonary function did not (5). In another study of 61 stable outpatients, those with low SGRQ scores had more frequent exacerbations (8). A study using QoL questionnaire (Seattle Obstructive Lung Disease Questionnaire) found that lower QoL was a powerful predictor of hospitalization and all-cause mortality (25). We found that the SGRQ was an independent and important predictor for subsequent COPD exacerbations, hospitalization, and mortality. Lower scores on all scores of SGRQ were associated with exacerbation, hospital admission, hospitalization, and death.

The relationship between age and quality of life has not been shown, although a decrease in quality of life with advanced age is expected. Ketelaars and coworkers found no correlation between age and quality of life, and explained this with aged patient expectation that activity limitation is normal in advanced age (26). Moreover, an improved quality of life in old patients with COPD and asthma was shown, and it was related to the tolerance of aged patients to activity limitation (27). On the other hand, in a study done with 247 COPD patients, a positive correlation between disease severity and quality of life was found in patients over 65 years of age, but this correlation was not evident below this age (28). Peruzza and coworkers reported that elderly COPD patients show a substantial impairment in SGRQ depending on the severity of airway obstruction, and that symptoms related to the disease may be exaggerated by mood deflection (29). In another study, the COPD stage-free assessment of SGRQ scores with age showed high SGRQ scores, especially in activity scores in elderly patients, but this relation was not as evident as assessment of SGRQ by disease severity (12). In this study, age was also found to be related with mortality. This result suggests that it is an important parameter when the HRQoL is investigated.

Comorbidity may modify the specific HRQoL in patients with COPD (30). Antonelli and coworkers showed that comorbidities such as chronic renal failure or electrocardiogram signs of myocardial ischemia were associated with mortality in COPD patients (31). Also, Wijnhoven and coworkers reported that in studies on patients with asthma or COPD aged 40–75 years, comorbidity should be treated as a determinant of HRQoL (32). In our study, comorbidity was not found to be significantly different between the alive and dead subjects, but in the subgroup analysis, cardiac comorbidity was found as an important factor on mortality and it was independently related to mortality.

Of the 81 deaths, 30 were seen in the first year and 21 of them (70%) were related to COPD. FEV₁ was lower, and SGRQ scores, age, and disease duration were high in this group. Also, all of them were active smokers. The patients in this subgroup had more exacerbations than others.

To our knowledge, this is the first study reporting that specific baseline HRQoL scores are associated with the first exacerbation day, number of exacerbations, number and duration of hospitalizations, number and duration of hospitalizations in an intensive care unit, and number of intubations. There was correlation between FEV₁ values, SGRQ scores and morbidity parameters (first exacerbation day, number of exacerbations, number and duration of hospitalizations, number and duration of hospitalizations in an intensive care unit, number of intubations). This result suggests that reliable and valid measures of condition-specific HRQoL, such as SGRQ, can provide important prognostic information about the course of COPD. This showed that HRQoL in COPD patients, measured using the SGRQ, was a significant risk factor for important morbidity factors discussed above.

In conclusion, our results have shown that HRQoL is an independent risk factor of respiratory and all causes of mortality. Using the SGRQ, it was possible to identify a group of patients at high risk for exacerbation, hospitalization, and intubation, providing an opportunity to identify patients who would potentially benefit from preventive measures, and the risk assessment might be used to justify the added cost of prescribing inhaled corticosteroids or long acting bronchodilators, agents that reduce exacerbation rates when given singly or in combination.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.