Correlation of severity of chronic obstructive pulmonary disease with health-related quality of life and six-minute walk test in a rural hospital of central India

Abstract

Background:

Chronic obstructive pulmonary disease (COPD) patients experience a progressive deterioration and disability leading to worsening of their health-related quality of life (HRQoL) and functional exercise capacity. We performed this study to identify the correlation of HRQoL assessed by St George's Respiratory Questionnaire (SGRQ) and the functional exercise capacity assessed by the six-minute walk test (6MWT) with severity of COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria among spirometry-confirmed COPD patients, admitted in a tertiary care rural hospital.

Materials and Methods:

The study included 129 spirometry-confirmed COPD patients defined by the GOLD criteria from a tertiary care hospital in central India. They underwent HRQoL measurement using the disease-specific (SGRQ). Functional exercise capacity was measured by 6MWT, as per the American Thoracic Society (ATS) guidelines.

Statistical Analysis:

We analyzed the various SGRQ scores and six-minute walk distance (6MWD) percentage predicted with various stages of COPD using the Student's t-test. The Pearson's correlation coefficient (r) was used to assess the relationships between various SGRQ scores and 6MWD with FEV₁ % predicted.

Results:

We found that COPD patients with GOLD III and IV, but not GOLD II, had significantly poor HRQoL measured by SGRQ, as compared to patients with mild COPD (GOLD I). An inverse linear relation was found between 6MWD and the severity of COPD. Correlation of FEV₁ % predicted with various SGRQ scores varied from - 0.40 to - 0.53, with a maximum correlation of FEV₁ % predicted with an SGRQ symptom score (- 0.53) and SGRQ total score (- 0.50). A strong positive correlation was found between 6MWD and FEV₁ % predicted (0.57).

Conclusions:

Staging COPD according to the GOLD guidelines does correspond to important differences in the HRQoL of COPD patients having severe disease, but not for mild disease, whereas, the functional exercise capacity of COPD patients deteriorates in a linear fashion with the severity of disease assessed by the GOLD staging criteria.

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is the leading cause of mortality and morbidity worldwide and its burden is projected to rank fifth with respect to the overall burden of diseases in 2020.[1] COPD is currently the fourth cause of morbidity and mortality in the developed world. The 2013 updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines define COPD[2] as a common preventable and treatable disease, which is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. As the condition progresses, patients with COPD experience a progressive deterioration and disability, which lead to worsening conditions in their health-related quality of life (HRQoL). GOLD has developed a four-stage classification system of COPD severity based on forced expiratory volume in one second (FEV₁ ) to guide the therapeutic approach.[1] Although airflow limitation measured by spirometry is essential for diagnosis and provides a useful description of the severity of pathological changes in COPD, the current management of COPD is focused on symptom relief and to improve the health status and exercise tolerance of the patients. Hence, it is important to know whether FEV₁ % predicted correlates with the HRQoL, so that therapeutic intervention aimed at improving FEV₁ or reducing the rate of decline in FEV₁ in COPD, really changes the patient's centered outcome, such as, the HRQoL-related quality of life and exercise capacity.

Often during the course of COPD, patients subconsciously reduce their physical activity, which leads to deconditioning, which further increases breathlessness. On account of this interaction, the assessment of exercise tolerance is necessary to evaluate the impact of COPD on an individual patient. In general, measures of lung function, such as FEV₁, have a limited ability to predict exercise capacity in an individual. The six-minute walk test (6MWT) is a simple objective and inexpensive tool used to assess the functional exercise capacity in patients with COPD.[3] As recently the GOLD initiative stated that improvement in exercise tolerance should be an important goal of COPD treatment,[1] it is necessary to know whether the GOLD staging based on FEV₁ % predicted, which forms the basis for the treatment modality of COPD patients, really correlates with the functional capacity of patients. In India, the prevalence of COPD is estimated by the World Health Organization (WHO) to be 4.4% in males and 3.4% in females,[4] and with improvement in the socioeconomical status of developing countries, prevalence of the disease is likely to increase dramatically. The disease is more prevalent in smokers as compared to non-smokers and almost all forms of smoking products such as cigarettes, ‘bidis,’ and tobacco chewing used in different states are found to be significantly associated with COPD. Among non-smokers, especially women, an exposure to indoor air pollution from domestic combustion of solid fuels is an important risk factor. On an average, an Indian COPD patient spends about 15% of his income on smoking products and up to 30% on disease management.[5] All these factors influence not only the financial condition, but also disturb the social and psychological functioning of COPD, which overall affects their HRQoL and functional exercise capacity.

There is lack of published literature on the correlation of the severity of COPD with HRQoL and exercise capacity of COPD patients from India. We performed this study to identify the correlation of HRQoL assessed by the St George's Respiratory Questionnaire (SGRQ) and functional exercise capacity assessed by the 6MWT, with severity of COPD defined according to the GOLD criteria among spirometry-confirmed COPD patients, admitted to a rural tertiary care hospital.

MATERIALS AND METHODS

Setting and screening

We conducted this study in the Internal Medicine department of a rural-based, 972-bedded, teaching tertiary hospital in central India. We screened all the patients above 40 years admitted to the Medicine Ward with a history of chronic cough and breathlessness of more than one year duration, to confirm the presence of COPD by spirometry, as defined by the GOLD criteria.[1] Patients having a coexisting lung lesion on chest radiograph, evidences of ischemic heart disease on electrocardiography, and serum creatinine more than 1.4 mg/dl were excluded from screening. We performed pulmonary function tests on all these screened patients using a Spirolab III portable spirometer. A trained investigator performed a pre- and postbronchodilator (inhaled salbutamol 400 mcg) test, as per the standard recommendations given by American Thoracic Society (ATS).[6] Patients fulfilling the GOLD definition of COPD[2] by spirometry, that is, post bronchodilator forced expiratory volume in 1 second (FEV₁ )/forced vital capacity (FVC) less than 70% predicted were included in the study. These patients were classified into four stages as per the GOLD criteria. Patients with FEV₁ more than or equal to 80% of the predicted were classified as Stage I, more than or equal to 50%, but less than 80% of the predicted, as Stage II, more than or equal to 30%, but less than 50% of the predicted as Stage III, and less than 30% of the predicted as Stage IV. The Institutional Ethics Committee approved the study design and all patients gave a written informed consent for participation in the study.

Inclusion criteria

All confirmed cases of COPD defined by GOLD and determined by postbronchodilator spirometry detected in the above-mentioned screening procedure were included in the study.

Exclusion criteria

All patients confirmed to have COPD determined by postbronchodilator spirometry and having any contraindications for 6MWT, as given by the ATS,[3] were excluded from the study sample.

Six-minute walk test

The 6MWT was performed in all enrolled patients, to assess the functional exercise capacity as per the standard guidelines given by the ATS.[3] The test was performed in a 46-meter indoor corridor by an expert investigator and the primary measurement was the distance walked in six minutes (6MWD). The predicted 6MWD for the patients was calculated from the published reference equations,[7] which calculated the predicted 6MWD based on age, gender, height, and weight. The 6MWT was then expressed in absolute values and as percentage predicted for that age, gender, weight, and height.

St George's Respiratory Questionnaire

We measured the HRQoL of all patients included in the study by using a disease-specific questionnaire, namely, the (SGRQ). The SGRQ is a disease-specific questionnaire used extensively for patients with COPD and several other chronic pulmonary diseases. SGRQ contains 50 items with 76 weighted responses, divided into 17 questions that cover three domains: symptoms, activity, and impact. It has two parts. Part I produces the symptom score and Part 2 the activity and impact scores. A total score is also produced. Part I (Questions 1-8) covers the patients’ recollection of their symptoms over a period of one month to one year in order to assess the patients’ perception of their recent respiratory problems, their frequency, and severity. Part II (Questions 9-17) addresses the patients’ current state. The activity score measures disturbances to patients’ daily physical activity that cause or are limited by breathlessness. The impact score is the broadest component of the questionnaires, covering a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A total score has also been calculated, which summarizes the impact of the disease on the overall health status. Scores are expressed as a percentage of overall impairment where 100 represents the worst possible health status and 0 indicates the best possible health status. An Excel-based scoring calculator system was used in all patients, to calculate the symptoms, activity, impact, and total score.

Statistical analysis

We entered the data in the Epidata software and analyzed it using statistical the software STATA version 10 (College Station, TX). We presented the descriptive data for the continuous variable as mean ± SD and for the categorical variable as a percentage. We classified disease severity as per the GOLD criteria. The Pearson's correlation coefficient (r) was used to assess the relationships between continuous variables. We analyzed the various SGRQ scores and 6MWD percentage predicted with various stages of COPD, keeping GOLD Stage I as the baseline and using one-way ANOVA. A P < 0.05 was considered to be statistically significant.

RESULTS

Out of 175 patients screened between 1 July, 2009, and 30 June, 2010, 19 patients were excluded due to focal lung lesions, associated ischemic heart disease or renal failure. Twenty-two patients had an FEV₁ /FVC ratio of more than 70% and five had contraindication to the 6MWT. Thus, a total of 129 spirometry-confirmed COPD patients were included in the study and underwent SGRQ and 6MWT. Table 1 shows the clinical characteristics of patients included in the study. The mean age of the study population was 60.96 ± 11.5 years. Out of the 129 patients included in the study, 99 patients (76.74%) were male. The mean body mass index of the study population was 19.13 ± 3.55 kg/m². The median symptom duration of the study group was 4.60 ± 3.05 years; 68.2% of the patients were either current or ex-smokers, with an average smoking history of 22 pack year. Five patients (3.87%) gave a history of significant occupational exposure. Forty-five patients (34.88%) were on regular treatment in the form of inhaled bronchodilator or inhaled steroids. The remaining patients were on intermittent treatment. The mean FEV₁ and FEV₁ % predicted was 1.19 ± 0.62 L or 53.68 ± 21.1%, respectively. The mean symptom, activity, impact, and total score of SGRQ were 49.81 ± 16.32, 46.60 ± 13.9, 25.19 ± 7.3, and 36.42 ± 9.75, respectively. The mean 6MWD and 6MWD% predicted were 317.62 ± 88.85 and 61.22 ± 17.04%, respectively. As per the GOLD criteria, 15 (11.6%) patients were in Stage I, 60 (46.5%) patients were in Stage III, 37 (28.6%) and 17 (13.3%) patients were in Stage III and IV, respectively.

Table 1.

Baseline characteristics of COPD patients (n=129)

Table 2 shows the comparison of various characteristics of the study population across disease severity defined as per the GOLD. There was no significant difference in age or gender between GOLD Stage II, III, and IV, as compared to Stage I, however, patients with severe COPD (Stage IV) had a significantly longer symptom duration and low body mass index as compared to patients with mild COPD (Stage I) (P = 0.03 and P = 0.005, respectively). There was no significant difference in the various SGRQ scores (symptom, activity, and impact scores) and the total scores between GOLD I and II. Patients with severe COPD (Stage III and IV) had a significantly higher SGRQ total score as compared to those with mild COPD (Stage I) (P < 0.01) implying an overall poor quality of life and health status in severe COPD. In addition, severe COPD (Stage III and IV) patients had significantly higher scores for each of the three SGRQ domains (symptom, activity, and impact scores) as compared to mild COPD (Stage I). The 6MWD% predicted, which assessed the functional exercise capacity in COPD patients was found to be significantly low in GOLD Stage II to IV, as compared to Stage I [Figure 1].

Table 2.

Various St George respiratory questionnaire scores and 6MWD% predicted across GOLD stages

Figure 1.

Box plot showing distributions of various St George Respiratory Questionnaire (SGRQ) scores and six-minute walk distance% predicted (6MWD% predicted) by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Error bars show SD. Box shows the SE. The central line in the boxes shows the median

Table 3 shows a correlation of severity of COPD assessed by FEV₁ % predicted, FEV₁ /FVC, symptom duration, and BMI with SGRQ and 6MWD (% predicted). FEV₁ % predicted, used to classify the severity of disease by GOLD, showed a significant correlation with the SGRQ total score (r = 0.50 P < 0.01). Similarly various domains of SGRQ, for example, the symptom score, impact score, and activity score, also showed significant correlation with FEV₁ % predicted (symptom score r = 0.53 P < 0.01, activity score r = 0.40 P < 0.01, impact score r = 0.42 P < 0.01) implying an overall poor quality of life in patients having severe COPD [Figure 2]. Similar to FEV₁ % predicted, FEV₁ /FVC showed significant correlation with the SGRQ total score and its various components [Figure 3]. The body mass index showed a significant correlation with the SGRQ total score, symptom score, and impact score. Only the impact score of SGRQ showed a significant correlation with symptom duration; otherwise the symptom score, activity score, and total score, did not show any significant correlation. The functional exercise capacity assessed by 6MWD% predicted showed strong correlation with FEV₁ % predicted (r = 0.57 P < 0.01) [Figure 2]. Furthermore 6MWD% predicted showed a significant correlation with FEV₁ /FVC, SGRQ total score, and its various domains (except activity score), body mass index, and symptom duration.

Table 3.

Correlation of severity of COPD with SGRQ and 6MWD% predicted (n=129)

Figure 2.

Scatterplot showing correlation of various St George Respiratory Questionnaire (SGRQ) scores and six-minute walk distance % predicted (6MWD% predicted) with FEV1% predicted

Figure 3.

Scatterplot showing correlation of various St George Respiratory Questionnaire (SGRQ) scores with FEV1 / FVC% predicted

DISCUSSION

The present study showed that patients with severe COPD (GOLD III and IV) had significantly poor HRQoL measured by disease-specific questionnaire SGRQ, as compared to patients with mild COPD (GOLD I). Studying the various domains of HRQoL, that is, symptom, activity, and impact, had not shown any significant impairment in HRQoL between GOLD II and I; however, GOLD III and IV had significant impairment of all three domains of quality of life, with the maximum effect on the symptom domain. An inverse linear relation has been found between 6 MWD and severity of COPD defined by the GOLD. Thus, staging COPD according to the GOLD guidelines does correspond to important differences in the health status of COPD patients having severe disease, but not for patients with mild disease, whereas, the functional exercise capacity of COPD patients deteriorates linearly with the severity of disease assessed by GOLD staging criteria.

Important differences in health status between stages III and IV and the lack of significant differences between stages I and II suggests that every effort should be made to prevent the progression of COPD, as passing the boundary of a forced expiratory volume in one second of < 50% of the predicted is likely to cause a dramatic decline in the health status of patients. A similar observation has been found in a study conducted by Antonelli et al.,[8] which shows that the FEV₁ % predicted of less than 49% marks a threshold for dramatic worsening of the health status, and the progression of COPD severity up to Stage II does not correspond to any meaningful difference in health status. Results of some studies[9,10] have shown a linear relationship between deterioration in HRQoL and severity of disease based on FEV₁ % predicted and patients with mild disease have also shown significantly compromised HRQoL. This is in contrast to our study results, which have shown significant deterioration in HRQoL only when the FEV₁ % predicted falls to less than 50%. Use of the ATS system for staging COPD, in this study, and the associated comorbid condition, may be responsible for the different results as compared to the present study.[9] The few studies conducted in the past have not shown any significant correlation between HRQoL and severity of COPD. A study conducted by Okubadejo et al.[11] has not shown any correlation between FEV₁ and the various SGRQ scores. However, a relatively small number of patients and a small range of measurements of FEV₁ with no patient having a FEV₁ value more than 1.5 L in the mentioned study, may be the possible reason for not detecting any significant correlation between HRQoL and disease severity.

The present study showed that a patient with severe disease tended to have more scores on SGRQ, thus a poorer quality of life, as compared to a patient with mild COPD. Correlation between the lung function test, other disease severity parameters and quality of life has been done in the previous studies. The present study has shown a strength of correlation of FEV₁ % predicted with SGRQ scores, varying from - 0.40 to - 0.53, with the maximum correlation of FEV₁ % predicted with SGRQ symptom score (- 0.53) and SGRQ total score (- 0.50). The results of the present study show that the symptom score and total score are the best variables to explain the 28 and 25% variation in the FEV₁ values, respectively. Hence while investigating these COPD patients, more attention must be paid to the recent symptoms of the patients and treatment should be directed toward improving the dyspnea and other symptoms, in order to improve the HRQoL of these patients. Comparing the results of the present study, few studies done in the past have shown a correlation only between the FEV₁ % predicted with SGRQ total scores, but not with other scores.[10,12,13,14] A study conducted by Kaplan et al.[13] using pre-randomized data from the National Emphysema Treatment Trial (NETT), analyzed 1218 COPD patients and showed a weak, but significant, correlation between the SGRQ total score and FEV₁ % predicted. However, this trial has recruited only severe COPD patients, and hence, the result of this study may not be applicable to all COPD patients.

In our study, a significant positive linear correlation was found between disease severity and 6MWT, an objective measurement of functional exercise capacity. A strong positive correlation was found between 6MWD and FEV₁ % predicted (r = 0.57) explaining 32% of the variance in FEV₁ % predicted. This is in agreement with the previous studies,[15,16,17,18] which had shown a similar positive correlation between the 6MWD and FEV₁ % predicted. Hence, as stated by GOLD, improvement in exercise tolerance by various rehabilitation programs must be an important target in the management of COPD patients. In this study, we have found a statistically significant negative correlation between 6MWT and HRQoL, as determined by the SGRQ, symptoms domain, SGRQ impact domain, and the SGRQ total score. Various previous studies have investigated the correlation between the SGRQ, a subjective measurement of HRQoL, and 6MWT, an objective measurement of exercise capacity,[12,14,17,19] and observed statistically significant correlations between various SGRQ scores and 6MWT.

Our study has certain strengths. We enrolled all consecutive inpatients that fulfilled our inclusion criteria and thus avoided sampling bias in our work. We enrolled only those patients who definitely had COPD based on the spirometry parameter and classified disease severity defined by the GOLD, thus providing objectivity to the diagnosis and severity of COPD. We assessed the HRQoL using a disease-specific questionnaire SGRQ and functional capacity by 6MWT, as per the guidelines given by the ATS. However our study has a few limitations too. First, as it is a hospital-based study, it is more likely that patients with more severe disease got enrolled in the study; hence, the results of this study may not be representative of the overall COPD patients from a community. Second, while assessing HRQoL by SGRQ, patients have to recall their symptoms from the last one year, which may have led to recall bias in assessing HRQoL. Finally, although the 6MWT has been performed as per the ATS guidelines, we have not taken into consideration other comorbid conditions that could affect the functional capacity in these patients, and hence, we have not been able to assess the effect of the associated comorbid conditions on the functional capacity of these patients.

CONCLUSION

Staging COPD according to the GOLD guidelines does correspond to important differences in the HRQoL of the COPD patients having severe disease and not for those with mild disease. The functional exercise capacity of COPD patients deteriorates linearly with severity of the disease assessed by the GOLD staging criteria. The present pharmacological modalities have not been seen to change the decline in lung function, which is the hallmark of the disease. Hence, improvement in the quality of life measured by self-assessment of the disease symptoms should be an important parameter in the management strategy of COPD patients, especially during the early stage of the disease.