JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2008, 59, Suppl 6, 297 301 www.jpp.krakow.pl M. GRABICKI 1, H. PARYSEK 1, H. BATURA-GABRYEL 1, I. BRODNICKA 2 COMORBIDITIES AS AN ELEMENT OF MULTIDIMENSIONAL PROGNOSTIC ASSESSMENT OF PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE 1 Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Sciences, Poland; 2 Hospital of Pulmonary Diseases and Tuberculosis, Wolica, Poland Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation, some significant extrapulmonary effects, and important comorbidities. The BODE index, a multidimensional scale, has been proposed to better identify severity of the disease and to predict survival. The goal of the study was to evaluate the prevalence of concomitant diseases in patients with COPD and to assess correlations between comorbidities and the BODE index. Eighty patients with COPD were enrolled. They were at least 40 years old and had more than a 10-year history of smoking. The most frequent comorbidities were: systemic hypertension, edema of lower limbs, movement disorders, varices of lower limbs. Subjects with higher scores in BODE index had significantly greater prevalence of arrhythmias and episodes of pneumonia. Evident correlation was observed between low FEV 1 and episodes of pneumonia. We also found that patients with higher BODE scores had more exacerbations of COPD. Comorbidities are very common in COPD. Results indicate a close connection between the BODE index and some comorbidities, which suggests that these conditions may aggravate the COPD course and increase risk of mortality. Key words: BODE index, comorbidities, COPD INTRODUCTION Chronic obstructive pulmonary disease (COPD) is characterized by not fully reversible chronic airflow limitation, a range of pathological changes in the lung, and some significant extra-pulmonary effects with important comorbidities, all of which may contribute to the severity of the disease (1). COPD often develops in
298 long-time smokers, who often have a variety of other diseases related to either smoking or aging (2-4). COPD, itself, also has significant extrapulmonary (systemic) effects that lead to comorbid conditions (5). COPD is currently the fourth leading cause of death in the world and is projected to be the third most common cause of death by 2020 (6, 7). Some studies evaluating the cause of death in patients with COPD suggest that these patients are more likely to die of comorbid conditions than from COPD (8-10). Comorbidities can be categorized in various ways to aid in a better understanding of their impact on the patient and disease management. Therefore, it has been proposed to divide them into 4 categories: comorbid diseases with a common pathophysiology, which in the case of COPD means other smokingrelated diseases such as ischemic heart disease and lung cancer, conditions that arise as a complication of COPD such as pulmonary hypertension and consequent heart failure, co-incidental comorbidities with unrelated pathogenesis particularly related to aging such as bowel or prostate cancer, depression, diabetes mellitus, dementia, arthritis, and, finally, acute illnesses (inter-current comorbidities) that may have a more severe impact or require different treatment in patients with a given chronic disease, e.g., upper respiratory tract infections (1). All comorbid conditions become harder to manage when COPD is present, either because COPD adds to the total level of disability, or because COPD therapy adversely affects the comorbid disorder. Comorbid conditions amplify the disability associated with COPD and can potentially complicate its management. The severity of comorbid conditions and their impact on a patient health status vary between patients and in the same patient over time. To better identify severity of the disease and to predict subsequent survival of the individuals affected by COPD, the BODE index has been proposed. This is a multidimensional 10-point scale which integrates body mass index, degree of airflow obstruction (FEV 1 - forced expiratory volume in 1 second) and dyspnea, and exercise capacity measured in 6-min walk test (11). The higher scores in BODE index indicate a higher risk of death. The BODE index was designed to show that it is important to consider a range of factors, rather than just a single component in the course of comprehensive assessment of COPD patients (11, 12). Nevertheless, up to date there is limited information on comorbidities as a prognostic factor and on the correlation between comorbidities and the BODE index. The goal of the present study was to evaluate the prevalence of concomitant diseases in patients with COPD and to assess correlations between comorbidities and the BODE index, to conclusively determine what coexisting diseases have the highest negative influence on the COPD course and on the patients' general condition. MATERIAL AND METHODS The study was approved by a local Ethics Committee and informed consent was obtained from each subject. Eighty patients with COPD, diagnosed based on Global Initiative for Chronic Obstructive Lung
299 Disease recommendations - GOLD 2006, were enrolled into this cross-sectional study (1). All participants were at least 40 years old and had more than a 10-year history of smoking. To determine the presence of comorbid diseases, all participants were asked questions according to a prepared questionnaire. This questionnaire included questions concerning other than COPD pulmonary problems, cardiovascular diseases, digestive system abnormalities, neoplasm, neurological pathologies, sleep apnea syndrome symptoms, and other not specified illnesses. Every subject underwent lung function test (flow-volume spirometry) after inhalation of bronchodilator, 6-min walk test, and ECG at rest to estimate the presence and type of arrhythmias. The study group consisted of 55 male (69%) and 25 female (31%). The mean age was 63 ±8.3 years. There were 50 subjects up to 65 years old and 30 over 65 years old. The mean BMI was 27.6 ±6.4. Fifty percent of the subjects smoked between 20-60 pack-years. The mean number of pack-years was 33. Fifteen patients (18.8%) were current smokers (13 male and 2 female). All data were analyzed using Statistica software. Shapiro-Wilk normality test, Spearman's rank correlation test, Kendall tau rank correlation and analysis of variance (ANOVA) were carried out. A P value of <0.05 was considered statistically significant. RESULTS The most frequent comorbidities in patients with COPD were: systemic hypertension, edema of lower limbs, movement disorders, and varices of lower limbs, sleeping disorders, angina pectoris, vertigo and digestive ulcers. The prevalence of all comorbid diseases was higher in older individuals (Table 1). Subjects with higher scores in BODE index had a significantly greater prevalence of arrhythmias, namely supraventricular tachycardia, atrial fibrillation and flutter. Table 1. Prevalence of comorbidities in patients with COPD. Comorbid disease All subjects n=80 Subjects aged <65 n 1 =50 Subjects aged 65 n 2 =30 n %n n 1 %n 1 n 2 %n 2 Hypertension 42 52.5 22 44.0 20 66.7 Edema of lower limbs 35 43.8 20 40.0 15 50.0 Movement disorders 31 38.8 14 28.0 17 56.7 Varices 31 38.8 13 26.0 18 60.0 Sleeping disorders 26 32.5 16 32.0 10 33.3 Angina pectoris 21 26.3 8 16.0 13 43.3 Vertigo 21 26.3 11 22.0 10 33.3 Digestive ulcers 17 21.3 8 16.0 9 30.0 Severe headache/ migraine 14 17.5 7 14.0 7 23.3 Arrhythmias 12 15.0 5 10.0 7 23.3 GERD 12 15.0 7 14.0 5 16.7 n, n 1, n 2 - number of subjects with comorbid diseases; %n, %n 1, %n 2 - percentage of subjects with comorbid diseases in relation to the total number of subjects in each group; GERD - gastroesophageal reflux disease.
300 There was a significant correlation between higher scores in BODE index and the number of episodes of pneumonia, mainly in male and in a subgroup of patients of 60-65 years old, regardless of the gender. Evident correlation was also observed between low FEV 1 in flow-volume spirometry and the number of episodes of pneumonia. Additionally, we noted that patients with higher BODE scores had a significantly greater prevalence of COPD exacerbations, and they were more frequently hospitalized because of pulmonary problems. DISCUSSION Comorbidities are very common in COPD. Most patients with COPD, especially older patients, suffer from other accompanying diseases (13, 14). The relevance and impact of comorbid diseases on COPD is not well understood. The results of the present study indicate close connection between BODE scores and some comorbidities (especially arrhythmias) and other pulmonary disorders, which suggests that these conditions may aggravate the COPD course and increase the risk of mortality. Therefore, there is a great need to take into special account the incidence and severity of comorbid conditions in a course of comprehensive assessment and treatment of COPD patients. A combination of BODE index and some comorbidities in one multidimensional scale seems a better way of estimating survival of COPD patients, mainly elderly individuals. Nevertheless, up to date it is not conclusively clear what comorbidities are the most predictive of a grave condition and should be included into such a new prognostic scale (14, 15). Further research is needed to elucidate the interrelationships among comorbidities, BODE index, and COPD. Moreover, the number of hospitalizations and COPD exacerbations can be well predicted based on the BODE index, which can help in choosing a better therapy regimen to avoid subsequent deterioration and a need of re-hospitalization in a short time. Acknowledgements: This study was supported by University of Medical Sciences in Poznan, Poland. Conflicts of interest: No conflicts of interest were declared with relation to this work. REFERENCES 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006; Available from URL: http://www.goldcopd.org. 2. Soriano JB, Visick GT, Muellerova H, Payvandi N, Hansell AL. Patterns of comorbidities in newly diagnosed COPD and asthma in primary care. Chest 2005; 128: 2099-2107. 3. Hasnis E, Bar-Shai M, Burbea Z, Reznick AZ. Cigarette smoke-induced NF-κB activation in human lymphocytes: the effect of low and high exposure to gas phase of cigarette smoke. J Physiol Pharmacol 2007; 58 Suppl 5: 263-274.
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