Sumber 1 Anemia In Copd Lungindia.docx

Malay Sarkar, Puja Negi Rajta, Jasmin Khatana, Departments of Pulmonary Medicine, Departments of Physiology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India (2015) http://www.lungindia.com/temp/LungIndia322142-2007091_053430.pdf ANEMIA IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE Abstrak Chronic obstructive pulmonary disease (COPD) is a common preventable and treatable lifestyle-related disease with high global prevalence. COPD is associated with significant morbidity and mortality worldwide. Comorbidities are important events in the natural history of the disease and have a negative effect on the morbidity and mortality of COPD patients. Cardiac diseases, lung cancer, osteoporosis, and depression are common comorbidities reported for COPD. Recently, anemia has been recognized as a frequent comorbidity in COPD patients. The prevalence of anemia in patients with COPD varies from 7.5% to 33%. Anemia of chronic disease (ACD) is probably the most common type of anemia associated with COPD. ACD is driven by COPD-mediated systemic inflammation. Anemia in COPD is associated with greater healthcare resource utilization, impaired quality of life, decreased survival, and a greater likelihood of hospitalization.

Matthias John, MD, PhD; Soeren Hoernig, MD; Wolfram Doehner, MD; Darlington D. Okonko, MD; Christian Witt, MD, PhD; Stefan D. Anker, MD, PhD CHEST. 2005;127(3):825-829. https://www.medscape.com/viewarticle/501430_4 ANEMIA AND INFLAMATION IN COPD Discussion This study documents that anemia occurs relatively frequently in COPD patients and is related to the presence of inflammation. Anemia is an understudied issue in COPD but may be of great importance in this disease. In our cohort, anemia (with hemoglobin concentrations < 12.0 g/dL in women and < 13.5 g/dL in men) was present in as many as 13% of all COPD patients. This may be an underestimation of the anemia prevalence, as we have excluded patients with anemia related to bleeding and known folate or vitamin B12 deficiency. Furthermore, anemic COPD patients showed increased levels of erythropoietin compared to nonanemic patients and normal control subjects.

Anemia of chronic illness is typically a normocytic anemia and is most commonly observed in patients with concurrent infectious, and inflammatory or neoplastic diseases. COPD fulfills the criteria of a chronic, inflammatory, multisystemic disease leading to the expectation of anemia. While anemia in chronic heart failure or renal insufficiency has been frequently investigated, it is understudied in COPD. The mechanism of anemia development in COPD might be similar to that in other chronic diseases. It has been shown that mediators of the immune and inflammatory response, such as tumor necrosis factor-α, IL-6, and interferon-γ are potentially involved in the development of anemia in chronic illness.[7] The increased levels of inflammatory cytokines lead to a shortened RBC survival, with a demand for a slight increase in RBC production. The bone marrow cannot adequately respond to the increased demand for RBCs. This is caused by a relative erythropoietin resistance due to an impaired ability of RBC progenitors to respond to erythropoietin. An impaired mobilization of reticuloendothelial iron stores is an additional pathophysiologic factor.[3,8] The observed increased inflammatory response in anemic patients confirms the pathophysiologic understanding of anemia in chronic disease, in that anemia is at least partially due to excessive production of inflammatory cytokines such as IL-6, which inhibit the production and the effect of erythropoietin and iron at the level of the bone marrow.[9–11] Once anemia has developed, an autoregulatory up-regulation of erythropoietin occurs to maintain the homeostasis. However anemic COPD patients do not respond to increased levels of erythropoietin. The increased levels indicate a relative peripheral erythropoietin resistance in COPD. This is similar to other diseases and fits into the pathophysiology of anemia in chronic disease. The hypothesized relationship of anemia to weight loss and cachexia was not observed in our cohort, indicating that the development of anemia is independent from nutritional factors. In chronic heart failure, it was demonstrated that the mortality rate correlated with the severity of anemia and that anemia is an independent risk factor for increased mortality. [12,13] Furthermore, it has been shown that a hemoglobin concentration below the physiologic range is a predictor of exercise limitation and mortality in chronic heart failure. [2] Whether anemia contributes to symptoms or exercise limitations in COPD is presently unknown. However, in our study overall COPD severity according to standard criteria of lung function was not related to frequency of anemia and hemoglobin levels ( Table 1 and Table 3 ). More studies are needed to study these issues. The present study is limited by a relative small number of patients. For future investigations, larger study populations are needed. This would allow investigating whether anemia is related to

the primary disease process per se or to secondary systemic manifestations such as weight loss, loss of lean tissue mass, hypoxia, or systemic inflammation. Anemia in COPD is understudied. There are no previous reports on anemia frequency and pathophysiology in COPD. More detailed investigations on hematologic and clinical parameters ( ie , prevalence of anemia in COPD and its gender relatedness, exercise capacity, 6-min walk test) and prognosis are required to provide indications whether anemia is merely a marker or a mediator of pathophysiologic processes that may impair physical functioning in COPD. Interventions with erythropoietin and iron supplementation would then seem very promising in order to improve the poor health status and prognosis of patients with COPD.

ANAEMIA OF CHRONIC DISEASE: AN IN-DEPTH REVIEW https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588399/ (2016) Anaemia is the most common haematological disorder affecting humanity and is usually observed in chronic disease states such as non-specific anaemia, which may cause diagnostic difficulties. In chronically ill patients with anaemia, this has a negative impact on quality of life as well as survival. This paper aims at reviewing the pathogenesis of this form of anaemia with a view to suggesting future targets for therapeutic intervention. The ability to diagnose this disorder depends on the ability of the physician to correlate the possible clinical pathways of the underlying disease with the patients' ferrokinetic state. It is important to rule out iron deficiency and other causes of anaemia as misdiagnosis will in most cases lead to refractoriness to standard therapy. The cytokines and acute-phase proteins play important roles in the pathogenesis of anaemia of chronic disease. Alterations in the metabolism of iron via the molecule hepcidin and ferritin are largely responsible for the consequent anaemia. Concomitant iron deficiency might be present and could affect the diagnosis and therapeutic protocol. Treatment options involve the use of erythropoiesis-stimulating agents, blood transfusion, and iron supplementation, in addition to treating the underlying disease. Key Words: Anaemia, Chronic disease/inflammation, Hepcidin, Ferritin, Pathogenesis, Cytokines

ANEMIA IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE - ASSOCIATION WITH COMORBIDITIES https://erj.ersjournals.com/content/48/suppl_60/PA3778 (2015)

Methods: Data was collected retrospectively from 96 patients diagnosed with COPD based on the GOLD criteria2. Oxygen saturation, Medical Research Council (MRC) dyspnoea score, COPD Assessment Test (CAT), Body Mass Index (BMI) and comorbidities were registered. Blood samples were analyzed for hemoglobin and C-reactive protein (CRP). Results: Patients were classified in A(n=35), B(n=20), C(n=14) and D(n=29) with reference to the GOLD criteria. Anemia was found in 14% of the patients (13/96). There was an equal distribution of patients with/without anemia in group A vs. group B+C+D but no significant association between COPD severity and the frequency of anemia (p=0.2). Patients with/without anemia were comparable on gender, age, CRP, CAT, BMI and lung function; but significantly different with respect to MRC score (p=0.0009) and comorbidities when comparing patients with 1 comorbidity with those with ≥2 (p=0.03). A significantly higher proportion of patients with concomitant kidney and/or heart disease had anemia compared to those without (p=0.03vs.0.009). Conclusion: COPD patients with anemia have more comorbidities, especially kidney and heart disease and have more respiratory symptoms than patients without anemia.