Based on the findings from the existing literature, more work is necessary to establish the true prevalence of anemia in COPD. Robust and prospective clinical studies are needed to improve the management of COPD patients with comorbid anemia. COPD is a disease characterized by severe incurable air-flow limitation and reduced functional capacity, associated with multiple comorbidities and markers of systemic inflammation.
This, however, may represent merely the tip of the iceberg, as the full extent of the disease's financial burden is unknown. Some of the common comorbidities that contribute to the increased risk associated with morbidity and mortality in patients with COPD include cardiovascular disease, hypertension, diabetes mellitus, hypercholesterolemia, osteoporosis, and anemia. Therefore, clinical surveys and studies utilize different anemia definitions when defining anemic and non-anemic COPD patients.
This has led to a lack of consensus to determine the prevalence of anemia in patients with COPD. Findings from recent studies that investigated the prevalence of anemia indicate varying results. Thus, the prevalence of coexisting anemia in patients with COPD is highly variable and depends on the severity of the lung disease, the presence of other comorbidities, and other factors such as socioeconomic status and race.
Fatigue and dyspnea are the major symptoms of anemia, and these can be related to reduced oxygen carrying capacity of blood.
This review intends to update and synthesize the available data on the prevalence of anemia and its physiological consequences for patients with COPD, with particular focus on quality of life, healthcare utilization, morbidity, and mortality. An extensive literature search was conducted to identify relevant published articles evaluating COPD and anemia as a single associated comorbidity.
The search was performed using the following subject terms and key words: COPD, COPD, an a emia, h a ematocrit, erythropoietin, iron deficiency, red blood cells, and h a emoglobin level.
Studies were included that set limits for human studies attainable in English. An iterative procedure was used to certify that all pertinent articles were obtained. A supplementary hand search of bibliographic references of extracted articles and existing reviews was also conducted to identify potential studies not ascertained in the electronic database searches.
A single member of our team screened article titles from the preliminary search and acquired the abstracts from articles considered potentially relevant.
Each abstract was independently evaluated by the same research member, who then retrieved the full text. This procedure was followed by a second reviewer for independent confirmation. An article was considered relevant for full text retrieval if it met the following inclusion criteria:. Studies that explored the relationship between anemia and COPD, in either community, in-patient, or out-patient settings.
Of these, were classified as potentially appropriate. After the initial screening, were excluded. Nine full-text articles were determined appropriate for this analysis Fig. Details of the findings from these 7 studies are presented in Table 1. The inclusion and exclusion criteria for the selected articles are shown in Table 2.
John and colleagues 18 estimated the prevalence of anemia at However, they noted that neither age nor spirometric measures differed between the anemic and non-anemic COPD patients. Those with notably lower hemoglobin levels, however, had evidence for a greater level of systemic inflammation as indicated by increased levels of both interleukin 6 IL-6 and C-reactive protein.
By multivariable analysis they were able to account for prior healthcare utilization and other factors associated with the severity of COPD. Resource utilization rates and payments among the COPD patients with anemia were higher in every resource category.
This included in-patient hospital stay and stay in intensive care, purchasing durable medical equipment, home health assistance, and provision of skilled nursing facilities. Anemic COPD patients had greater comorbidity and were more likely to be male, older, and to utilize healthcare resources to a greater extent than non-anemic patients. Anemia was also correlated with age and disease severity.
The results also supported the clinical impression that hematocrit is an independent predictor of survival, hospital admission, and hospital stay. For example, hematocrit was only measured once during the study, at the initiation of long-term oxygen therapy. In addition, the stability of the oxygen prescription and smoking status was not established, and both of those variables may influence the likelihood of anemia.
Also there was no identification of comorbidities, which may be responsible for anemia in COPD patients. Cote and colleagues 19 retrospectively analyzed data that was prospectively collected at one of the sites Bay Pines Veterans Affair Medical Center, Bay Pines, Florida of the multicenter BODE body-mass index, air-flow obstruction, dyspnea, and exercise capacity index study.
However, the confinement of the study sample solely to the Veterans Affair Medical Center may diminish the generalizability of the findings. John and co-workers, 18 with a sample of 7, patients, compared the prevalence of anemia between hospital-admitted COPD and other chronic diseases asthma, chronic heart failure, chronic renal insufficiency, and cancer. Although the precise cause of anemia in COPD patients is unknown, there appears to be a relationship with certain pro-inflammatory markers Fig.
Tassiopoulos and colleagues, 23 in , were among the first to study anemia and its compensatory erythropoietic action in COPD patients. Their findings indicated an inverse correlation between the hemoglobin and erythropoietin concentrations, which suggests that in COPD patients low hemoglobin correlates with a compensatory erythropoietin response.
The causes of anemia in patients with COPD are probably multifactorial and include nutritional deficits, stress ulcer especially those on steroids , and carboxyhemoglobin effects of cigarette smoking. A particularly important cause of anemia in these patients may relate to the chronic inflammatory nature of COPD.
The anemia of chronic inflammation, which was previously termed the anemia of chronic disease, is one of the major causes of normocytic anemia in man. Indeed, anemia of chronic inflammation may be multifactorial, as it is associated with infection, inflammation, neoplastic disease, acute or chronic immune activation, and other conditions, including simple tissue injury, surgery, myocardial infarction, heart failure, and diabetes mellitus.
The mechanism whereby inflammation causes anemia is incompletely established. However, cytokines such as the IL-1, IL-6, and tumor necrosis factor TNF-alpha , released by activated monocytes in patients with underlying inflammatory conditions, 23 , 29 are certainly involved.
Several studies have demonstrated that these and other cytokines are associated with the appearance of anemia and may be involved in the pathogenesis by mechanisms such as blunting erythropoietin production in response to hypoxia or decreasing bone marrow responsiveness to erythropoietin.
The role of IL-6 in the pathogenesis of anemia first became apparent in the cancer setting, where severe anemia was found to be associated with very high levels of this and other inflammatory cytokines. Its role may actually be broader, in that hepcidin, itself, can suppress erythroid progenitor cell responses to erythropoietin. The prevalence of anemia in the general population increases with age, 42 irrespective of COPD or other chronic conditions.
For this reason, studies with a predominance of elderly COPD patients need to take this into consideration. It is also worth noting that many comorbid conditions are associated with COPD, and those comorbid conditions are more frequent and severe in older patients. Anemia can compromise oxygen deliveries to tissues and thus be a cause of dyspnea.
Yet it remains unclear whether correction of anemia favorably influences the clinical course of patients with COPD. In one study, minute ventilation and work of breathing WOB were significantly reduced following blood cell transfusion.
In control subjects without COPD, hemoglobin was increased to a similar level, but there was no change in ventilation or gas exchange. Although these findings demonstrate the potential benefit of blood cell transfusion on minute ventilation and WOB, it should be noted that the fall in minute ventilation increased P aCO 2 from 38 mm Hg to 44 mm Hg and a simultaneous fall in P aO 2 from 57 mm Hg to 53 mm Hg—a finding comparable to the inverse correlation between hematocrit and P aCO 2 demonstrated by Chambellan and colleagues.
The advantages of increasing the hemoglobin level may be countered by the potentially severe consequences of negatively altering blood gases. Frequent hospitalizations and duration of stay were also inversely correlated with higher hematocrit. Caution is also required with the age of transfused red blood cell.
Older cells are most likely to become stiffer and to be unable to penetrate the tissue microcirculation, so these transfusions may provide useful volume expansion but may not increase oxygen delivery. Further research is warranted into the effects of blood transfusion as a remedial intervention in anemic COPD patients.
A recent study found that a low preoperative hematocrit was also a predictor of a poor postoperative outcome. Nevertheless, it may be argued that the higher mortality was the result of greater blood loss during surgery, especially as both studies had patients who underwent surgery for upper-gastrointestinal bleeding 45 or abdominal aortic aneurysm. However, the populations of COPD patients in the studies by Chambellan and colleagues 9 and Celli and colleagues 47 were very different. In the Chambellan study the patients were on long-term oxygen therapy for severe COPD, whereas the patients in the Celli study had various levels of respiratory impairment.
Although that study included , COPD patients, it was a retrospective analysis of administrative claims data, so only patients who had Medicare claims with appropriate ICD-9 diagnosis codes were identified, and the presence of those codes is not a guarantee of correct diagnoses.
Although the sample size was large, relying on the ICD-9 codes, as opposed to threshold hemoglobin values as advocated by the World Health Organization, would suggest that the observed prevalence and consequences of anemia in that cohort was underestimated and unaccounted. Health-related quality of life is an important clinical outcome for individuals with advanced air-flow limitation and for their healthcare providers. This clinical measure helps to differentiate between people with different severities of lung disease and permits the evaluation of the impact of a specific intervention on patients' lives.
Dyspnea and fatigue are also well known manifestations of anemia, 50 so it is logical to assume that patients with COPD and anemia may have substantially worse dyspnea and fatigue.
Krishnan and colleagues 16 performed a post-hoc analysis of a study that enrolled participants from a general population in New York city. The SF has been supported as a valid instrument for quantifying health-related quality of life, 16 but there are other disease-specific health-related quality of life questionnaires for individuals with COPD.
The findings of this review indicate the prevalence of comorbid anemia in COPD patients to be 7. We extended these previous observations by showing the association between high Hb concentration and in-hospital death in CKD patients, which was particularly significant in the advanced CKD group. According to these preliminary reference intervals, high Hb levels were observed in patients 4. A high Hb concentration is double-edged. It not only is considered an adaptive physiological response to hypoxemia in the COPD population [ 22 ] but also plays a detrimental role in CKD [ 12 , 13 , 14 , 15 , 16 ].
The mechanism of the association between high Hb and death is unclear. Several hypotheses have been suggested, including increased blood volume and viscosity and improved platelet function after correction of anemia [ 23 , 24 ]. These mechanisms cause hyperviscosity of the blood and contribute to increased pulmonary vascular resistance.
Thromboembolic disease attributed to polycythemia affecting the pulmonary vascular bed again increases pulmonary vascular resistance.
Polycythemia also inhibits the endothelial-dependent relaxation response to acetylcholine [ 25 , 26 ]. In addition, erythropoiesis-stimulating agents and iron may play detrimental roles independent of their therapeutic roles in hemopoiesis [ 14 , 24 , 27 , 28 , 29 , 30 ].
No previous studies have reported a clinical threat of a high Hb level in COPD patients [ 6 , 7 , 31 ]. In such studies, the authors defined a high Hb level based on the standard for polycythemia, i. The study subjects were primarily stable COPD outpatients whose pathogenetic conditions were less severe and who had a lower mortality than inpatients, and patients with heart disease, kidney disease and malignancies were often excluded, as these conditions might serve as confounding diseases of COPD [ 6 , 7 , 31 ].
These features not only explain the major differences between this study and previous studies but also allow the current team to move forward to explore the upper reference limit for Hb in COPD patients. The exploration of the optimal upper Hb target in the CKD population has gone through a long journey. In early studies, exploring the optimal Hb target was difficult due to the considerable heterogeneity in the criterion for high Hb [ 16 ].
However, none of these trials focused on the COPD population. While exploring the upper reference limit for Hb, the current team adopted a stratification method to avoid the interaction of CKD with abnormal Hb levels.
These results provide evidence for future work on optimal Hb limits. This study has the following limitations. First, the CCS-AKI databank suffers from a lack of information regarding erythropoietin- and COPD-related medicine and hematologic testing indices except for Hb, as the initial designed endpoint of the databank was renal events.
Therefore, the potential influence of these factors on mortality failed to be corrected for. Second, because the data were derived from retrospective electronic medical records, supplemental oxygen use, pulmonary function and blood gas analysis indices were not available, and the severity of hypoxia and patient conditions were not evaluated.
Third, the adverse outcome observed in this study was limited to in-hospital mortality, and other adverse events, such as quality of life, cardiovascular events, shock and long-term death, were not included. Therefore, the possibility that the mechanisms underlying the influence of high Hb on these adverse events were different from those underlying mortality cannot be excluded. Finally, Hb levels in actual clinical practice may not be consistent with the target limits for Hb management.
The management of erythrocyte abnormalities in COPD should not be limited to anemia, but due attention should be given to CKD stratification and increased Hb levels. All data generated or analyzed during this study are included in this article and its supplementary information files. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
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Curr Opin Pulm Med. My Dr has referred me to a hemoglobinist. Will they be able to find the cause of my anemia? Unfortunately, much as we would like to help, a blog is not the place to answer a question such as this, even if we had a complete copy of your blood work and a physical examination. I assume you have seen the response given by Dr. We agree that your referral to a hematologist is the best way to find the cause of your anemia. I am so sorry we are not able of offer more help at this time.
If you find out something from your hematologist that might be interest to share with other readers, please come back and let us know what you discover! There are many causes of anemia. A hematologist is skilled in dissecting out the possibilities. Seeing a hematologist is an excellent idea. Save my name, email, and website in this browser for the next time I comment.
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