losartan-potassium and Pulmonary-Disease--Chronic-Obstructive

The important association of erythropoietin (EPO) serum levels and chronic obstructive pulmonary disease (COPD) with anemia has been inadequately studied and remains a controversial issue. We aimed to shed light on this matter by comparing EPO levels in anemic and non-anemic COPD patients, along with a review of published literature. This cross-sectional study was conducted on COPD patients referred to the pulmonary clinic of Shahid Faghihi Hospital and Motahari clinic, Shiraz, Iran, for one year. We measured complete blood count, red blood cell indices, serum iron, TIBC and ferritin levels, serum EPO levels, and body mass index. Among 35 patients in this study, 28 males and 7 females were enrolled with a mean age of 54.57 ± 8.07 years. The average Forced expiratory volume in first second (FEV1) was 37.26 ± 7.33% and FEV1/FVC was 0.46 ± 0.12. Mean EPO levels were 30.29 ± 2.066 mU/mL. No statistically significant association was observed among erythropoietin levels and Hb, COPD severity, and age. There was no significant difference in EPO levels between anemic and non-anemic patients. EPO level, against the traditional expectation, didn't increase in COPD patients. EPO production also didn't compensate for the anemia of chronic disease which considers as a common comorbid disorder in these patients.

Topics: Anemia; Chronic Disease; Cross-Sectional Studies; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

Although polycythemia has been considered a common adverse event in COPD, anemia is reported more often and has gained more importance than polycythemia over the last thirty years.. Factors considered to be associated with the development of anemia in COPD have included: Aging and kidney dysfunction with erythropoietin deficiency and bone marrow suppression due to uremic toxins; heart failure (HF), often encountered in COPD and accompanied by anemia in one-third of the cases; Low-grade chronic inflammation, directly suppressing bone marrow and diminishing iron absorption and utilization via increased hepcidin levels; long-term oxygen therapy (LTOT), ameliorating chronic hypoxia, and most important, RAS inhibitors, which are widely used for the comorbidities associated with COPD (hypertension, HF, CKD, diabetes) and have previously been shown to lower hematocrit values or cause anemia in various clinical conditions.. Introduction of LTOT in COPD and especially the established use of RAS inhibitors form the basis for the shift from polycythemia to anemia in COPD. Interestingly, when the SGLT2 inhibitors are introduced for cardiorenal protection in COPD, one could anticipate correction of anemia or even reemergence of polycythemia, since this new class of drugs can augment erythropoietin secretion and increase hematocrit values.

Topics: Anemia; Antihypertensive Agents; Erythropoietin; Humans; Polycythemia; Pulmonary Disease, Chronic Obstructive; Renin-Angiotensin System

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic diseases, with an increasing rate in morbidity and mortality. In recent years, there has been a greater awareness about the clinical importance of systemic effects and other chronic conditions associated with COPD, as these significantly impact on the course of disease. The most studied extrapulmonary manifestations in COPD include the presence of concomitant cardiovascular disease, skeletal muscle wasting, osteoporosis and lung cancer. Anaemia is a recognised independent marker of mortality in several chronic diseases. Recent studies have shown that anaemia in patients with COPD may be more frequent than expected, with a prevalence ranging from 5% to 33%. Some evidence suggests that systemic inflammation may play an important pathogenic role, but anaemia in COPD is probably multifactorial and may be caused by others factors, such as concealed chronic renal failure, decreased androgenic levels, iron depletion, angiotensin-converting enzyme inhibitor treatment and exacerbations. Low levels of haemoglobin and haematocrit in COPD patients have been associated with poor clinical and functional outcomes as well as with mortality and increased healthcare costs. Despite the potential clinical benefit of successfully treating anaemia in these patients, evidence supporting the importance of its correction on the prognosis of COPD is uncertain.

Topics: Acute Disease; Androgens; Anemia; Chronic Disease; Erythropoiesis; Erythropoietin; Exercise Tolerance; Glomerular Filtration Rate; Health Resources; Hemoglobins; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Renal Insufficiency, Chronic; Renin-Angiotensin System

Topics: Acute Kidney Injury; Conscious Sedation; Critical Care; Diuretics; Erythropoietin; Humans; Positive-Pressure Respiration; Pulmonary Disease, Chronic Obstructive

Conventional treatment with epoetin to manage anaemia in chronic kidney disease needs frequent administrations, changes of dose, and close monitoring of haemoglobin concentrations. We aimed to compare the effectiveness of methoxy polyethylene glycol-epoetin beta, given intravenously at 2-week or 4-week intervals, with epoetin treatment one to three times per week for haemoglobin control in haemodialysis patients.. We screened 1115 adult patients from 96 centres who had stable chronic renal anaemia and were on dialysis treatment and intravenous maintenance epoetin. We did an open-label, parallel-group, non-inferiority trial to compare two dosing intervals of methoxy polyethylene glycol-epoetin beta with standard epoetin treatment. We established baseline haemoglobin concentration and eligibility over a 4-week run-in period. 223 patients were randomly assigned to receive methoxy polyethylene glycol-epoetin beta every 2 weeks, and 224 to receive it every 4 weeks. The initial dose was based on the average epoetin dose given during the week before the switch. The primary endpoint was change in haemoglobin concentration between baseline and the assessment period. We analysed patients both by intention to treat and per protocol. This study is registered with ClinicalTrials.gov, number NCT00077610.. We excluded 133 of the 673 randomised patients from the per-protocol analysis because they had inadequate iron status or fewer than five haemoglobin measurements during the assessment period or needed red blood cell transfusions. The mean change from baseline haemoglobin for patients who had switched to intravenous methoxy polyethylene glycol-epoetin beta every 2 weeks (-0.71 g/L, 95% CI -2.20 to 0.77) or every 4 weeks (-0.25 g/L, -1.79 to 1.29) was non-inferior to the mean change for patients who continued treatment with epoetin (-0.75 g/L, -2.26 to 0.75) (p<0.0001 for both comparisons). Of the 666 patients who received at least one dose of study drug, the incidence of adverse events or serious adverse events did not differ between groups (p=0.30 and p=0.40, respectively).. This long-acting erythropoiesis-stimulating agent is as safe as conventional epoetin treatment, and can maintain anaemia management in haemodialysis patients when given intravenously at 4-week dosing intervals.

Topics: Anemia; Drug Administration Schedule; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Peritoneal Dialysis; Polyethylene Glycols; Pulmonary Disease, Chronic Obstructive; Recombinant Proteins; Renal Dialysis; Solvents

Despite the severe derangement of gas exchange in the advanced stages of idiopathic pulmonary fibrosis (IPF), secondary erythrocytosis is either absent or much lower than is seen in chronic obstructive pulmonary disease (COPD) with comparable hypoxemia. This study investigates the differences in erythropoiesis between IPF and COPD, searching for the possible underlying mechanisms.. The study included 32 patients with COPD, 18 patients with IPF, all with overt hypoxemia (PO(2) <65 mmHg), and 34 healthy controls. Erythrocytic parameters and serum erythropoietin (EPO) levels were assessed for all subjects. In a number of patients from both groups, the development of erythroid colonies grown from peripheral blood mononuclear cells was assayed in semisolid methylcellulose cultures and compared to cultures of control cells, in the presence of patient or control serum.. Hb and serum EPO levels were significantly higher in the COPD group than in IPF patients and controls. However, the number of BFU-E colonies obtained from mononuclear cells of IPF patients was clearly higher than in COPD patients when the same culture medium was used. Unlike COPD sera, IPF sera induced a significant growth inhibition of erythroid bursts arising from mononuclear cells of both patients and controls.. Our findings suggest a kind of ineffective erythropoiesis in IPF. Defective EPO production and inhibitory effect on erythropoiesis exerted by pro-inflammatory cytokines released from alveolar macrophages may be implicated in the suboptimal erythropoietic response. However, the possible involvement of other factors affecting erythropoiesis in IPF requires further investigation.

Topics: Aged; Blood Gas Analysis; Erythrocyte Count; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Humans; Hypoxia; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis

Topics: Anemia; Chronic Disease; Critical Care; Erythrocyte Transfusion; Erythropoietin; Hematocrit; Hemoglobinometry; Humans; Lung Volume Measurements; Oxygen; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Reference Values; Ventilator Weaning; Work of Breathing

The occurrence and development of chronic obstructive pulmonary disease (COPD) are regulated by environmental and genetic factors. In hypoxia, Erythropoietin (. We conducted a case-control study enrolled 1095 COPD patients and 1144 healthy controls in Guangdong Province to evaluate the association between. In conclusion, this study found that

Topics: Case-Control Studies; Erythropoietin; Female; Genetic Predisposition to Disease; Humans; Hypoxia; Male; Polymorphism, Single Nucleotide; Protective Factors; Pulmonary Disease, Chronic Obstructive

To investigate the value of erythrocyte sedimentation rate (ESR) and serum EPO levels in evaluating the condition and prognosis of chronic obstructive pulmonary disease (COPD) in the elderly. 120 elderly patients with acute exacerbation of COPD admitted to our hospital from May 2016 to April 2019 were selected. Pulmonary function tests and CT scans were performed on all patients. According to Gold's guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease, patients with different degrees of illness were divided into mild group, moderate group and severe group. The levels of EPO and ESR were measured in the morning after admission and the differences of EPO and ESR between the three groups were compared. The correlation between EPO, ESR and FEV1% of lung function index was analyzed by linear correlation analysis. There was no significant difference in age, sex, BMI index and course of disease among the three groups (P>0.05); ESR and EPO increased in turn among mild, moderate and severe groups, while FEV1% decreased in turn, with significant differences between the two groups (P<0.05). Negative correlation (r values were - 0.33, - 0.49, P<0.05). ESR and serum EPO levels can reflect the severity of COPD in elderly patients to some extent, and are negatively correlated with FEV1% of lung function indicators, which can provide some clues to the condition and prognosis of COPD in elderly patients.

Topics: Aged; Blood Sedimentation; Erythropoietin; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Prognosis; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease associated with cigarette smoking. Alterations in local lung and systemic iron regulation are associated with disease progression and pathogenesis. Hepcidin, an iron regulatory peptide hormone, is altered in subjects with COPD; however, the molecular role of hepcidin in COPD pathogenesis remains to be determined. In this study, using a murine model of smoke-induced COPD, we demonstrate that lung and circulating hepcidin levels are inhibited by cigarette smoke. We show that cigarette smoke exposure increases erythropoietin and bone marrow-derived erythroferrone and leads to expanded but inefficient erythropoiesis in murine bone marrow and an increase in ferroportin on alveolar macrophages (AMs). AMs from smokers and subjects with COPD display increased expression of ferroportin as well as hepcidin. Notably, murine AMs exposed to smoke fail to increase hepcidin in response to Gram-negative or Gram-positive infection. Loss of hepcidin in vivo results in blunted functional responses of AMs and exaggerated responses to

Topics: Animals; Bone Marrow; Cation Transport Proteins; Cigarette Smoking; Disease Models, Animal; Disease Progression; Erythropoietin; Hepcidins; Humans; Iron; Lung; Macrophages, Alveolar; Mice; Mice, Inbred C57BL; Peptides; Pulmonary Disease, Chronic Obstructive; Smoke; Smoking

Hyperhemolysis is a serious transfusion reaction, most often described in patients with hemoglobinopathies. Hyperhemolysis is characterized by the destruction of host red blood cells (RBCs), in addition to donor RBCs, via an unknown mechanism.. We present the case of a 58-year-old woman with treated human immunodeficiency virus and a normal hemoglobin (Hb) electrophoresis who developed hyperhemolysis in the setting of a delayed hemolytic transfusion reaction (DHTR).. The patient was ABO group B and had a previously identified anti-Fy(b) alloantibody. After transfusion of Fy(b)--RBCs, she developed a DHTR and was found to have anti-E, anti-C(w), anti-s, and an additional antibody to an unrecognized high-frequency RBC alloantigen. Subsequent transfusion of ABO-compatible RBCs that were negative for Fy(b), E, C(w), and s antigens resulted in immediate intravascular hemolysis. In the absence of bleeding, her hematocrit (Hct) decreased to 10.2%. An extensive serologic evaluation failed to identify the specificity of the high-frequency antibody. Severe hemolytic reactions also occurred despite pretransfusion conditioning with eculizumab. The Hct and clinical symptoms slowly improved after the cessation of transfusions and treatment with erythropoietin and steroids. This case demonstrates several noteworthy features including hyperhemolysis in a patient without a Hb disorder, the development of an antibody to an unknown RBC antigen, and the failure of eculizumab to prevent intravascular hemolysis after transfusion.. Hyperhemolysis is not restricted to patients with hemoglobinopathies. Whether eculizumab offers any benefit in the hyperhemolysis syndrome or in the prevention of intravascular hemolysis due to RBC alloantibodies remains uncertain.

Topics: Acute Disease; Adrenal Cortex Hormones; Anemia, Hemolytic; Antibodies, Monoclonal, Humanized; Blood Group Incompatibility; Cholecystitis; Coombs Test; Drug Resistance; Duffy Blood-Group System; Dyspnea; Erythrocyte Transfusion; Erythropoietin; Female; Hematocrit; Hepatitis C, Chronic; HIV Infections; Humans; Isoantibodies; Middle Aged; Oxygen Inhalation Therapy; Premedication; Pulmonary Disease, Chronic Obstructive; Receptors, Cell Surface; Syndrome; Transfusion Reaction

Hepcidin is the main regulator of systemic iron homeostasis and its expression is modulated by iron status, hypoxia, erythroid factors and inflammation. The aim of our study was to examine a relationship between level of hepcidin and iron status, erythropoietic activity, hypoxia and inflammation in exacerbations and stable COPD patients. We hypothesized that hepcidin concentration is changed in COPD patients and is substantially influenced by inflammation and/or hypoxia.. The study included 40 COPD patients and 30 healthy subjects. We measured haemoglobin, serum level of hepcidin and parameters indicative for inflammation: interleukin-6 (IL-6) and C reactive protein (CRP); hypoxia: partial oxygen pressure and haemoglobin oxygen saturation; iron status: iron, total iron binding capacity (TIBC), transferring saturation and ferritin; and erythropoietic activity: soluble transferrin receptors, reticulocytes, and erythropoietin.. Hepcidin was elevated in exacerbations and in a stable phase compared to the control group and we found positive correlations of hepcidin with inflammatory markers IL-6 and CRP. Hepcidin also correlated positively with ferritin and inversely with TIBC. However, in COPD patients reticulocyte count was significantly reduced and negative correlation with hepcidin was established in exacerbation. No correlations were observed with iron, or indices of hypoxia. In the control group, positive associations were observed only with indices of iron status, positive with ferritin and negative one with TIBC.. Systemic inflammation and elevated values of IL-6 present in exacerbations and stabile COPD might be responsible for the observed increased hepcidin level.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Case-Control Studies; Disease Progression; Erythropoietin; Female; Gene Expression; Hemoglobins; Hepcidins; Humans; Hypoxia; Inflammation; Interleukin-6; Iron; Male; Middle Aged; Oxygen; Pulmonary Disease, Chronic Obstructive; Receptors, Transferrin; Reticulocytes; Transferrin

Hypoxia inducible factor (HIF)-1 plays an important role in cellular adaptation to hypoxia by activating oxygen-regulated genes such as vascular endothelial growth factor (VEGF) and erythropoietin. Sputum VEGF levels are reported to be decreased in COPD, despite hypoxia. Here we show that patients with COPD fail to induce HIF-1α and VEGF under hypoxic condition because of a reduction in histone deacetylase (HDAC) 7.. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with moderate to severe COPD (n = 21), smokers without COPD (n = 12), and nonsmokers (n = 15). PBMCs were exposed to hypoxia (1% oxygen, 5% CO(2), and 94% N(2)) for 24 h, and HIF-1α and HDAC7 protein expression in nuclear extracts were determined by sodium dodecyl sulfate poly acrylamide gel electrophoresis (SDS-PAGE)/Western blotting.. HIF-1α was significantly induced by hypoxia in each group when compared with the normoxic condition (12-fold induction in nonsmokers, 24-fold induction in smokers without COPD, fourfold induction in COPD), but induction of HIF-1α under hypoxia was significantly lower in patients with COPD than in nonsmokers and smokers without COPD (P < .05 and P < .01, respectively). VEGF messenger RNA detected by quantitative real-time polymerase chain reaction was correlated with HIF-1α protein in nuclei (r = 0.79, P < .05), and HDAC7 protein expression was correlated with HIF-1α protein in nuclei (r = 0.46, P < .05). HDAC7 knockdown inhibited hypoxia-induced HIF-1α activity in U937 cells, and HIF-1α nuclear translocation and HIF-1α binding to the VEGF promoter in A549 cells.. HDAC7 reduction in COPD causes a defect of HIF-1α induction response to hypoxia with impaired VEGF gene expression. This poor cellular adaptation might play a role in the pathogenesis of COPD.

Topics: Adaptation, Physiological; Aged; Cell Hypoxia; Cells, Cultured; Erythropoietin; Female; Gene Expression; Histone Deacetylases; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Middle Aged; Monocytes; Promoter Regions, Genetic; Pulmonary Disease, Chronic Obstructive; RNA, Messenger; Statistics as Topic; Transcriptional Activation; Vascular Endothelial Growth Factor A

Although a subset of patients with chronic obstructive pulmonary disease (COPD) display anemia, the role of elevated pro-inflammatory cytokines in COPD-related anemia of chronic disease (ACD) has not been fully investigated.. To examine the levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), C-reactive protein (CRP) and erythropoietin in stable COPD outpatients with and without ACD.. A case-control design was followed.. Fifty-four patients with stable COPD were studied. Among them, 27 had ACD according to strict clinical and laboratory criteria (group of cases), while another 27 nonanemic COPD patients, carefully matched to cases for age, gender, height, lung function and smoking status represented the controls. Serum levels of IL-1β, IL-6, IL-10, TNFα, IFNγ, CRP and erythropoietin were measured in both groups.. Patients with ACD had significantly higher levels of IL-10 [25.6 (1.9-95.2) vs. 4.1 (1.9-31.9) pg/ml, P = 0.049] and IFNγ [15.2 (2.2-106.9) vs. 2 (1.2-18.3) pg/ml, P = 0.026] and had more frequently elevated CRP than controls. Levels of IL-1β [26.2 (9.8-96.4) vs. 7.9 (2.1-28.4) pg/ml, P = 0.073], IL-6 [20.3 (2.1-125.4) vs. 6.2 (1.2-33.8) pg/ml, P = 0.688] and TNFα [30.1 (3.2-107.5) vs. 10.1 (3.2-50.4) pg/ml, P = 0.131] were also higher in cases, but the differences did not reach statistical significance. Patients with ACD also displayed significantly higher erythropoietin levels than controls [(21.9 (8.4-101.7) vs. 9.7 (6.3-21.7) mIU/ml, P = 0.010], indicating erythropoietin resistance.. This study shows that in stable COPD outpatients with strictly defined ACD, levels of inflammatory mediators and erythropoietin are elevated compared to nonanemic controls.

Topics: Aged; Anemia; Biomarkers; C-Reactive Protein; Case-Control Studies; Cytokines; Erythropoietin; Female; Humans; Inflammation Mediators; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

Systemic inflammation may represent a possible cause of anemia. Previous data support that anemic patients with COPD present high erythropoietin (EPO) levels, suggestive of EPO resistance, possibly mediated through inflammatory mechanisms.. We aimed to determine whether systemic inflammation, which is usually up-regulated during exacerbations of COPD (ECOPD) is associated with low hemoglobin levels expressing erythropoietin resistance.. Hemoglobin (Hb), EPO and serum biomarkers of systemic inflammation [CRP, TNF-α, fibrinogen and IL-6] were assessed at three time points (admission, resolution and stable phases) in a selected cohort of 93 COPD patients.. Hemoglobin levels were significantly lower on admission compared to resolution and stable phases (median 12.1 g/dl [interquartile ranges 11.2-12.7], vs 13.5 [12.4-14.3] vs 13.4 [12.7-14.08], respectively p=0.002), whereas EPO was significantly higher on admission compared to resolution and stable phases. A negative association between Hb and IL-6 and a positive association between EPO and IL-6 were observed only during the acute phase of exacerbation. EPO and Hb were negatively associated during the acute phase, whereas they were positively associated during discharge and stable phase.. In this observational study we have shown that during admission for ECOPD Hb levels are decreased and EPO levels are increased. We have also identified a negative association between Hb and EPO. The above association is mainly related to increased IL-6 levels, indicating a possible EPO resistance through the mechanism of increased systemic inflammatory process.

Topics: Aged; Biomarkers; Cohort Studies; Erythropoietin; Female; Hemoglobins; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Recurrence; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha

Anemia may be present in patients with chronic obstructive pulmonary disease (COPD) and further impair their functional capacity.. This study investigated the prevalence of anemia of chronic disease (ACD) in COPD patients and its impact on dyspnea and exercise capacity, utilizing cardiopulmonary exercise testing (CPET).. ACD prevalence was assessed in 283 consecutive patients with stable COPD (263 males, 60 females; age 60.31 ± 5.34 years; percent forced expiratory volume in 1 s 46.94 ± 6.12). ACD diagnosis was based on a combination of clinical and laboratory parameters [hemoglobin (Hb) <13 g/dl for males, <12 g/dl for females; ferritin >30 ng/ml; total iron-binding capacity <250 μg/dl, and transferrin saturation rate between 15 and 50%]. Twenty-seven patients who were identified with ACD (cases) and 27 matched nonanemic patients (controls) completed maximal CPET, and data were compared between the groups.. ACD was diagnosed in 29 patients, which represents a prevalence of 10.24%; the severity of anemia was generally mild (mean Hb: 12.19 ± 0.66 g/dl). Patients with ACD had a higher Medical Research Council dyspnea score compared to controls (2.78 ± 0.44 vs. 2.07 ± 0.55; p <0.001) and lower peak O(2) uptake (VO(2)) (59.54 ± 17.17 vs. 71.26 ± 11.85% predicted; p <0.05), peak work rate (54.94 ± 21.42 vs. 68.72 ± 20.81% predicted; p <0.05) and peak VO(2)/heart rate (69.07 ± 17.26 vs. 82.04 ± 18.22% predicted; p <0.05). There was also a trend for a lower anaerobic threshold (48.48 ± 15.16 vs. 55.42 ± 9.99% predicted; p = 0.062). No exercise parameter indicative of respiratory limitation differed between the groups.. ACD occurs in approximately 10% of stable COPD patients and has a negative impact on dyspnea and circulatory efficiency during exercise.

Topics: Anemia; Case-Control Studies; Cross-Sectional Studies; Erythropoietin; Exercise Test; Female; Ferritins; Forced Expiratory Volume; Hemoglobins; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

It is known that pro-inflammatory cytokines suppress in vitro the gene expression and protein production of erythropoietin (Epo). We hypothesized that systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) may influence Epo production, particularly during episodes of exacerbation of the disease (ECOPD) where an inflammatory burst is known to occur.. We compared the plasma levels of Epo and high-sensitivity (hs) C-reactive protein (hsC-RP) in patients hospitalized because of ECOPD (n = 26; FEV(1): 48 +/- 15% predicted), patients with clinically stable COPD (n = 31; FEV(1): 49 +/- 17% predicted), smokers with normal lung function (n = 9), and healthy never smokers (n = 9).. Venous blood samples were taken between 9 and 10 a.m. after an overnight fast into tubes with EDTA (10 ml) or without EDTA (10 ml). Plasma levels of Epo (R&D Systems Inc., Minneapolis, Minn., USA) and hsC-RP (BioSource, Belgium) were determined by ELISA.. Log-Epo plasma levels were significantly lower (0.46 +/- 0.32 mU/ml) in ECOPD than in stable COPD (1.05 +/- 0.23 mU/ml), smokers (0.95 +/- 0.11 mU/ml) and never smokers with normal lung function (0.92 +/- 0.19 mU/ml) (p < 0.01, each). In a subset of 8 COPD patients who could be studied both during ECOPD and clinical stability, log-Epo increased from 0.49 +/- 0.42 mU/ml during ECOPD to 0.97 +/- 0.19 mU/ml during stability (p < 0.01). In patients with COPD log-Epo was significantly related to hsC-RP (r = -0.55, p < 0.0001) and circulating neutrophils (r = -0.48, p < 0.0001).. These results show that the plasma levels of Epo are reduced during ECOPD likely in relation to a burst of systemic inflammation.

Topics: Aged; C-Reactive Protein; Erythropoietin; Humans; Inflammation; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Smoking

Topics: Erythropoietin; Heart Failure; Humans; Hypoxia; Prognosis; Pulmonary Disease, Chronic Obstructive; Risk Factors

Chronic lung disorders are usually associated with a hypoxia driven increase in red cell mass. However, patients with cystic fibrosis (CF) often have normal or decreased haemoglobin levels. The present prospective observational study in cystic fibrosis patients was performed to determine which factors were involved in alterations in the hematopoetic response to corresponding arterial oxygen pressure. Sixty adult patients (age 21-51) with stable CF were included. They all had vitamin A, D, E, and K but no vitamin B12 supplementation. Twenty-five patients were on oral Fe(2+) (100 mg/day). Resting arterial blood gases, lung function, complete blood counts, parameters of iron status, CRP, sputum microbiology and serum erythropoietin were measured at recruitment and after 3 and 6 months. Patients had varying degrees of pulmonary functional impairment and 9% were hypoxemic (arterial oxygen pressure <60 mm Hg). Low-grade systemic inflammation (CRP > 0.5 mg/dl) was present in 40% of the patients, who all had bacterial colonization. None of the patient had erythrocytosis and 12 patients had anemia. There was no significant difference in iron status between patients with or without chronic iron supplementation and erythropoietin levels were normal. During the 6 months observation period no significant changes occurred. The patients exhibited an impaired erythropoietic response to hypoxemia with normal or low hematocrit in spite of chronic lung disease which might be caused by chronic inflammation associated with CF. Linear multivariate regression analysis revealed CRP levels but neither iron substitution, nor erythropoietin levels nor lung function parameters as independent determinant of haemoglobin levels. CF may be associated with anemia of variable severity as expression of the chronic inflammation present in these patients. The therapeutic consequences are to treat the underlying inflammation rather than to supplement iron.

Topics: Adult; Anemia, Iron-Deficiency; Blood Gas Analysis; C-Reactive Protein; Cystic Fibrosis; Erythropoietin; Female; Follow-Up Studies; Forced Expiratory Flow Rates; Hemoglobins; Humans; Male; Middle Aged; Oxygen; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

As a noninvasive method, exhaled breath condensate (EBC) has gained importance to improve monitoring of lung diseases and to detect biomarkers. The aim of the study was to investigate, whether erythropoietin (EPO) is detectable in EBC. EBC was collected from 22 consecutive patients as well as from healthy individuals. Using a multiplex fluorescent bead immunoassay, we detected EPO in EBC, as well as tumour necrosis factor-alpha (TNF-alpha) in 13 out of 22 patients simultaneously (EPO 0.21 +/- 0.03 in U/mL and TNF-alpha 34.6 +/- 4.2 in pg/mL, mean +/- SEM). No significant differences for EPO levels or correlation between EPO and TNF-alpha were found but TNF-alpha was significantly higher in patients with chronic obstructive pulmonary disease (COPD) than in non-COPD (obstructive sleep apnoea, OSA, and lung healthy patients). This is the first report of detection of EPO in EBC. Due to the small study size more data is needed to clarify the role of EPO in EBC.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Breath Tests; Case-Control Studies; Erythropoietin; Exhalation; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha

Anemia in patients with COPD and its pathophysiology is an understudied issue.. In a group of 101 COPD patients (FEV(1) percentage of predicted, 37 +/- 2% [mean +/- SEM]; mean age, 61 +/- 1 years; 35% female gender), the prevalence of anemia and its relationship to body mass and weight loss, inflammatory parameters, and erythropoietin levels was determined. Data were compared to a control group (healthy persons with matched age) in order to identify potential factors that may influence the development of anemia in patients with COPD.. Anemia was diagnosed in 13 patients (hemoglobin levels < 13.5 mg/dL in male patients and < 12.0 mg/dL in female patients), which represents a prevalence of 13%. Anemic COPD patients showed elevated erythropoietin levels (41.8 +/- 25.4 U/L vs 16.3 +/- 2.9 U/L) and an increased inflammatory response compared to nonanemic patients. A significant inverse correlation of hemoglobin vs erythropoietin (r = - 0.84, p < 0.01) was observed in anemic COPD patients, but not in the nonanemic group.. Anemic COPD patients show high erythropoietin levels, which may indicate presence of erythropoietin resistance. The latter may be mediated through inflammatory mechanisms, which is typical for anemia of chronic illness.

Topics: Anemia; Body Mass Index; Erythropoietin; Female; Forced Expiratory Volume; Hemoglobins; Humans; Inflammation; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Vital Capacity; Weight Loss

In order to determine the initial values and dynamic changes of EPO (erythropoietin) after therapy, 57 consecutively presenting, typical COPD (chronic obstructive pulmonary disease) patients with chronic hypoxia and acute exacerbated serum EPO levels were serially measured. Initial mean EPO levels were slightly above the normal range (41.4 +/- 83.5 units/l), but in the majority of patients the initial EPO levels were significantly reduced. Following the correction of hypoxaemia, mean EPO levels decreased to 14.1 +/- 16.9 units/l (P=0.0093). However, not all COPD patients showed this pattern; in an important subset of patients (36.8%), who had initially lower EPO levels and lower erythrocyte count, EPO levels were significantly increased (by more than 60%; P=0.0028) on the second day of treatment, despite correction of the hypoxaemia. This finding was unexpected and paradoxical when compared with physiological studies addressing the same issue. The data presented support previous reports of variable EPO levels in severely hypoxic COPD patients and suggest that the haematological response is already hampered at an early stage, at the level of EPO production, and much less likely at later steps in the haemopoietic response by failure to respond to elevated EPO levels. Our data are consistent with recent discoveries that the O2 sensing and regulation of EPO production is a complex process in which multiple factors, including cytokines and therapeutic agents, play a role by enhancing or inhibiting the response. We believe that further studies on this clinical condition are complementary to basic physiological research and may help to elucidate the role of cytokines and other individual factors in complex clinical hypoxic situations.

Topics: Acute Disease; Aged; Carbon Dioxide; Erythropoietin; Female; Hemoglobins; Humans; Hypoxia; Male; Middle Aged; Oxygen; Partial Pressure; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency

To investigate the influence of theophylline on erythropoiesis in chronic obstructive pulmonary disease (COPD) and explore the potential underlying mechanisms.. We evaluated the haematological parameters and erythropoietin (EPO) values in 38 COPD patients, 18 of which had been treated with theophylline (8 mg/kg daily) for at least 1 year, and the other 20 had never received this drug; 38 sex- and age-matched healthy volunteers served as controls. We further studied the development of BFU-E (bursts forming units of erythrocyte precursors) -derived colonies in semisolid methylcellulose cultures in blood samples from 7 patients randomly selected from both groups. In addition, we studied the effects of theophylline on the erythroid cell development by adding this agent to erythroid cell cultures from 6 healthy volunteers at various concentrations.. Haemoglobin values were found to be significantly lower in COPD patients treated with theophylline than in those untreated ( P<0.05). Both groups of patients exhibited significantly higher haemoglobin values than normal subjects ( P<0.01 and P<0.001 for treated and untreated patients, respectively). Serum EPO levels did not differ among the three studied groups. Unlike untreated patients and controls, the serum of the theophylline-treated patients produced a significant growth inhibition of erythroid bursts ( P<0.05); the in vitro use of theophylline showed a concentration-dependent inhibition ( P<0.001).. Our findings confirm the decrease of red cell production, which occurs following administration of theophylline, exclude the possibility of decreased EPO synthesis and suggest a direct inhibitory action of theophylline on erythropoiesis.

Topics: Aged; Bronchodilator Agents; Cells, Cultured; Erythropoiesis; Erythropoietin; Female; Humans; Hypoxia; Male; Pulmonary Disease, Chronic Obstructive; Theophylline