Anemia in Patients with Chronic Obstructive Pulmonary Disease in a Tertiary Care Hospital in Bangladesh

Background: Chronic obstructive pulmonary disease (COPD) is usually associated with polycythemia. It is assumed that systemic inflammatory components of COPD can interfere with erythropoietin and can result in anemia of chronic disease which will impair the functional capacity of these patients and also increase morbidity and mortality. Objective: To evaluate anemia status in COPD patients. Materials and Methods: This cross-sectional study was conducted in clinically stable 50 COPD patients in the outpatient department of Medicine in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period of July to December 2011. The demographic characteristics, smoking habit, duration of disease, types and severity of anemia, BMI and results of 6-minute walk test were recorded. Results: Out of 50 COPD patients, 76% were male and 24% were female. Among them 32% patients were anemic, 20% were polycythemic and 48% patients had normal hemoglobin. Among the anemic patients with COPD, 87% were male and 13% were female,75% were mildly anemic and 4% moderately anemic, 62.5% had normocytic and 37.5% had microcytic anemia. Conclusion: Anemia in COPD patients is often overlooked and underestimated. Clinicians should be aware of the presence of anemia in patients with COPD so that appropriate treatment could be initiated to improve the quality of life and prognosis.

literature describing the level of hemoglobin (Hb) and its impact on outcomes in the COPD.Anemia of chronic disease (ACD), with chronically low levels of circulating Hb, is an immune driven abnormality that occurs in many inflammatory diseases and also in chronic heart failure.If present in COPD, anemia could worsen dyspnea and limit exercise tolerance. 5treated hypoxemia is associated with secondary erythrocytosis, but like other chronic diseases, COPD potentially could affect hematopoiesis.The observed hematopoietic suppression in chronic inflammatory diseases is mediated by three different mechanisms such as shortened red blood cell survival, bone marrow erythropoietin resistance, and dysregulation of iron homeostasis.Underlying factors influencing these aforementioned mechanisms are thought to be related to smoking and smoking-related morbidities, malnutrition and probably the systemic inflammation that accompanies COPD.Systemic inflammation in COPD has been characterized by elevations in levels of IL-6, IL-8, CRP, and TNF-α with the later two mediators potentially contributing to a reduction in red blood cells lifespan, impaired iron utilization, and increased erythropoietin resistance. 6usti et al In regression models, anemia independently predicted dyspnea and reduced exercise capacity. 7PD patients with low hemoglobin levels have a poorer prognosis than patients with normal hemoglobin levels.Raising hemoglobin through transfusion decreases minute ventilation and work of breathing in COPD patients. 5This study was done to find out the frequency of anemia in COPD patients in a tertiary hospital in Bangladesh and to aware the physicians to diagnose it and to treat the patients accordingly.

Materials and Methods
This cross-sectional study was done in clinically stable 50 COPD patients attending in outpatient department of Medicine of Bangabandhu Sheikh Mujib Medical University (BSMMU) during the period of July to December 2011.COPD was defined by history of dyspnea, chronic cough or sputum production and history of exposure to risk factors and a ratio of FEV 1 (forced expiratory volume in 1 st second) to FVC (forced vital capacity) <0.7 measured 20 minutes after administration of broncodilator (salbutamol).Patients were defined as clinically stable if they had no hospital admission, respiratory infection or exacerbation in prior three months.Patients with bronchial asthma (defined as an increase in FEV 1 by 200 mL or 15% above the baseline value after administration of a bronchodilator), history of myocardial infarction within the preceding four months, unstable angina, congestive heart failure, thyroid disease, liver disease, renal disease, gastrointestinal or other hemorrhage, blood transfusion within the last three months and any malignancy were excluded from the study.
Anemia was defined as a hemoglobin level of <12 g/dL for women and <13 g/dL for men, according to WHO criteria. 8All study subjects underwent peripheral venous blood sampling to determine complete blood count, peripheral blood film, serum levels of urea, creatinine, liver transaminases and total protein.Body mass index (BMI) of all patients was recorded and 6minute walk test was performed.All data were documented in individual case record form.Statistical analysis was done by computer software (SPSS version 12.0).
Prior to the commencement of the study the research protocol was approved by Ethical Review Committee.Written informed consent was taken from each patient after informing them the objective of the study, the risks and benefits, confidential handling of personal information and the voluntary nature of participation and the rights to withdraw from the study.

Results
Among 50 COPD patients, 76% were male and 24% were female.Among 50 COPD patients, 32% were anemic, 20% were polycythemic and 48% patients had normal Hb (Table II).Among the anemic patients with COPD, 87% were male and 13% were female.Table III shows that among the anemic patients with COPD, 75% were mildly anemic and 25% were moderately anemic; 62.5% had normocytic and 37.5% had microcytic anemia.
Table II

Discussion
A large portion of COPD patients remain hypoxemic which contribute to polycythemia.Although COPD is usually associated with polycythemia, its systemic inflammatory components can interfere with erythropoietin and result in anemia of chronic disease.
There is no feasibility of regular health check-up due to various factors.Lack of knowledge and/or ignorance of signs and symptoms of anemia hinder early diagnosis of anemia.Patients with COPD usually come to a physician or other health care providers due to shortness of breath; so anemia may be overlooked.Patients with COPD also cannot eat well due to respiratory difficulty which leads to nutritional anemia.
In this study, among fifty COPD patients, 38 were male and 12 were female.Males were more affected than females, as smoking was more common in males.Maximum number of COPD patients were in the age group of 61-70 years.A study done by Shorr et al 9 in 2008 revealed that anemic patients are older and more likely to be male.Another study done by Chambellan et al 10 found that 21% patients were anemic with concomitant COPD and most of them were elderly.
In this study, 32% COPD patients were anemic.A study done by Stanbrook 11 found the prevalence of anemia 36% in COPD patients randomly selected from outpatient clinic.Another study done by Park et al 12 in which 58 patients were enrolled, the frequency was found 48%.John et al 13 evaluated anemia and inflammation in COPD patients and found prevalence of anemia 13% in patients with COPD.Two studies utilizing the International Classification of Diseases (ICD-9 or ICD-10) codes for hospital discharge diagnoses found that 21% and 23% of COPD patients had anemia. 14,15Cote et al 16 and John et al 13 used the World Health Organization's criteria 8 for diagnosis of anemia and found it in 13% and 17% in their study samples of COPD patients.Thus the prevalence of coexisting anemia in patients with COPD is highly variable.
In this study, among the anemic patients with COPD, 87% were male and 13% were female.A study done by Lainscak 17 revealed that women were significantly more likely than men to be anemic (21% versus 12%, P<0.001).
The frequency of mild, moderate and severe anemia was 75%, 25% and 0% respectively in this study.A study done by Boutou et al 18 found mild anemia in all patients.In present study, the most common variety of anemia was normochromic normocytic anemia (62.5%).The reasons may be multifactorial, specially due to anemia of chronic disease.In a study done by Tsantes et al 17  In this study COPD patients with high BMI were found to be anemic and there is a significant difference in BMI between anemic and nonanemic patients (P<0.05).Chambellan et al 10 found that there is a positive correlation between BMI and anemia in COPD patients.
This study shows that near about one-third of COPD patients are anemic with predominance of normocytic anemia.Most of the patients are male and disease duration is mostly more than 10 years.The present study is limited by a small number of patients.We recommend multicentered trial with large sample to find out the prevalence of anemia in COPD patients, to determine the correlation of anemia with disease severity and to follow-up the patients after appropriate treatment.

Table I
Only 4 patients were nonsmokers.Total 14 patients had COPD for more than 20 years, 24 for 10-20 years and only12 patients for less than 10 years.152

Table I :
Distribution of patients with COPD according to age, duration of smoking and duration of disease (n=50) 21macrocytosis (defined as MCV>94 fL) was found in 43.75% patients with COPD.The cause is still poorly understood.Another study conducted by García-Pachón and Padilla-Navas 20 also revealed the prevalence of macrocytosis in 29% COPD patients.Another study done by Cassanova et al21found no difference with respect to the dyspnea scale or in meters covered in the 6-minute walk test.