Iron deficiency (ID) and iron deficiency anemia (IDA) are common nutritional disorders in children. Hepcidin, a peptide hormone produced in the liver, is a central regulator of systemic iron metabolism. We evaluated whether serum hepcidin levels can diagnose ID in children.
Sera from 59 children (23 males and 36 females; 5 months to 17 years) were analyzed for hepcidin-25 by ELISA. Patients were classified according to hemoglobin level and iron parameters as: IDA, (N=17), ID (N=18), and control (N=24).
Serum hepcidin, ferritin, soluble transferrin receptor (sTfR), transferrin saturation, and hemoglobin levels differed significantly between groups (P<0.0001). Serum hepcidin and ferritin levels (mean±SD) were 2.01±2.30 and 7.00±7.86, 7.72±8.03 and 29.35±24.01, 16.71±14.74 and 46.40±43.57 ng/mL in the IDA, ID, and control groups, respectively. The area under the receiver operating characteristic curve for serum hepcidin as a predictor of ID was 0.852 (95% CI, 0.755-0.950). Hepcidin ≤6.895 ng/mL had a sensitivity of 79.2% and specificity of 82.8% for the diagnosis of ID. Serum hepcidin levels were significantly correlated with ferritin, transferrin saturation, and hemoglobin levels and significantly negatively correlated with sTfR level and total iron binding capacity (P<0.0001).
Serum hepcidin levels are significantly associated with iron status and can be a useful indicator of ID. Further studies are necessary to validate these findings and determine a reliable cutoff value in children.
Serum hepcidin; Iron deficiency; Children
Cigarette smoking and advanced age are well known as risk factors for chronic obstructive pulmonary disease (COPD), and nutritional abnormalities are important in patients with COPD. However, little is known about the nutritional status in non-COPD aging men with smoking history. We therefore investigated whether reduced lung function is associated with lower blood markers of nutritional status in those men.
Subjects and methods:
This association was examined in a cross-sectional study of 65 Japanese male current or former smokers aged 50 to 80 years: 48 without COPD (non-COPD group), divided into tertiles according to forced expiratory volume in one second as percent of forced vital capacity (FEV1/FVC), and 17 with COPD (COPD group).
After adjustment for potential confounders, lower FEV1/FVC was significantly associated with lower red blood cell count (RBCc), hemoglobin, and total protein (TP); not with total energy intake. The difference in adjusted RBCc and TP among the non-COPD group tertiles was greater than that between the bottom tertile in the non-COPD group and the COPD group.
In non-COPD aging men with smoking history, trends toward reduced nutritional status and anemia may independently emerge in blood components along with decreased lung function even before COPD onset.
anemia; chronic obstructive pulmonary disease; lung function; nutritional assessment; nutritional status; smoking
The aim of this study was to analyze the relationship between serum pro-hepcidin concentration and the anemia profiles of rheumatoid arthritis (RA) and to estimate the pro-hepcidin could reflect the disease activity of RA. RA disease activities were measured using Disease Activity Score 28 (DAS28), tender/swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Anemia profiles such as hemoglobin, iron, total iron binding capacity (TIBC), ferritin, and transferrin levels were measured. Serum concentration of pro-hepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay (ELISA). Mean concentration of serum pro-hepcidin was 237.6±67.9 ng/mL in 40 RA patients. The pro-hepcidin concentration was correlated with rheumatoid factor, CRP, ESR, and DAS28. There was a significant correlation between pro-hepcidin with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. The pro-hepcidin concentration was significantly higher in the patients with active RA (DAS28>5.1) than those with inactive to moderate RA (DAS28≤5.1). However, the pro-hepcidin concentration did not correlate with the anemia profiles except hemoglobin level. There was no difference of pro-hepcidin concentration between the patients with anemia of chronic disease and those without. In conclusion, serum concentration of pro-hepcidin reflects the disease activity, regardless of the anemia states in RA patients, thus it may be another potential marker for disease activity of RA.
Arthritis, Rheumatoid; Anemia; Hepcidin; Prohepcidin
Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD).
There are differences in serum biomarker levels between women and men with COPD.
Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD.
We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction. We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life. We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD.
The plasma biomarkers level explored were similar in men and women without COPD. In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men. Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels. There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes.
In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables. Further studies should confirm our findings.
Little is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD). We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.
To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.
Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects. Rbm fragmentation correlated with smoking history in COPD but not with age. There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05). The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004). In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).
Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences.
Hepcidin is the key mediator of renal anemia, and reliable measurement of serum hepcidin levels has been made possible by the ProteinChip system. We therefore investigated the iron status and serum hepcidin levels of peritoneal dialysis (PD) patients who had not received frequent doses of an erythrocytosis-stimulating agent (ESA) and had not received iron therapy. In addition to the usual iron parameters, the iron status of erythrocytes can be determined by measuring reticulocyte hemoglobin (RET-He). The mean serum hepcidin level of the PD patients (n = 52) was 80.7 ng/mL. Their serum hepcidin levels were significantly positively correlated with their serum ferritin levels and transferrin saturation (TSAT) levels, but no correlations were found between their serum hepcidin levels and RET-He levels, thereby suggesting that hepcidin has no effect on the iron dynamics of reticulocytes. Since low serum levels of CRP and IL-6, biomarkers of inflammation, were not correlated with the serum hepcidin levels, there is likely to be a threshold for induction of hepcidin expression by inflammation.
Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10–15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown.
To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers.
Prospective cohort study.
The city of IJsselstein, a small town in the Netherlands.
Smokers aged 40–65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 ≥80% predicted, n = 107) and follow-up measurements were conducted in 2003.
After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25).
In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.
incidence; middle-age; moderate COPD; patient characteristics; smokers
Hepcidin is a central regulator of iron metabolism. Serum hepcidin levels are increased in patients with renal insufficiency, which may contribute to anemia. Urine hepcidin was found to be increased in some patients after cardiac surgery, and these patients were less likely to develop acute kidney injury. It has been suggested that urine hepcidin may protect by attenuating heme-mediated injury, but processes involved in urine hepcidin excretion are unknown.
To assess the role of tubular reabsorption we compared fractional excretion (FE) of hepcidin-25 with FE of β2-microglobulin (β2m) in 30 patients with various degrees of tubular impairment due to chronic renal disease. To prove that hepcidin is reabsorbed by the tubules in a megalin-dependent manner, we measured urine hepcidin-1 in wild-type and kidney specific megalin-deficient mice. Lastly, we evaluated FE of hepcidin-25 and β2m in 19 patients who underwent cardiopulmonary bypass surgery. Hepcidin was measured by a mass spectrometry assay (MS), whereas β2m was measured by ELISA.
In patients with chronic renal disease, FE of hepcidin-25 was strongly correlated with FE of β2m (r = 0.93, P <0.01). In megalin-deficient mice, urine hepcidin-1 was 7-fold increased compared to wild-type mice (p < 0.01) indicating that proximal tubular reabsorption occurs in a megalin- dependent manner. Following cardiac surgery, FE of hepcidin-25 increased despite a decline in FE of β2m, potentially indicating local production at 12–24 hours.
Hepcidin-25 is reabsorbed by the renal tubules and increased urine hepcidin-25 levels may reflect a reduction in tubular uptake. Uncoupling of FE of hepcidin-25 and β2m in cardiac surgery patients suggests local production.
AKI; β2-microglobulin; Hepcidin; Megalin; Kidney tubules
Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD) patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory- and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7±13.9 [mean SD]) enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556) were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory- and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p<0.001), hsCRP (p<0.001) and the presence of diabetes (p = 0.02) and inversely with the estimated glomerular filtration rate (p = 0.01), absolute reticulocyte count (p = 0.02) and soluble transferrin receptor (p<0.001). Men had lower hepcidin-25 levels as compared to women (p = 0.03). Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA) or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but challenges its function as a clinical parameter for ESA resistance.
Hepcidin is upregulated by inflammation and iron. Inherited (HFE genotype) and treatment-related factors (blood units (BU), Iron overload) affecting hepcidin (measured by C-ELISA) were studied in 42 consecutive patients with AML prior to and after allogeneic hematopoietic cell transplantation (HCT). Results. Elevated serum ferritin pre- and post-HCT was present in all patients. Median hepcidin pre- and post-HCT of 358 and 398 ng/mL, respectively, were elevated compared to controls (median 52 ng/mL) (P < .0001). Liver and renal function, prior chemotherapies, and conditioning had no impact on hepcidin. Despite higher total BU after HCT compared to pretransplantation (P < .0005), pre- and posttransplant ferritin and hepcidin were similar. BU influenced ferritin (P = .001) and hepcidin (P = .001). No correlation of pre- or posttransplant hepcidin with pretransplant ferritin was found. HFE genotype did not influence hepcidin. Conclusions. Hepcidin is elevated in AML patients pre- and post-HCT due to transfusional iron-loading suggesting that hepcidin synthesis remains intact despite chemotherapy and HCT.
AIM: To investigate stepwise sedation for elderly patients with mild/moderate chronic obstructive pulmonary disease (COPD) during upper gastrointestinal (GI) endoscopy.
METHODS: Eighty-six elderly patients with mild/moderate COPD and 82 elderly patients without COPD scheduled for upper GI endoscopy were randomly assigned to receive one of the following two sedation methods: stepwise sedation involving three-stage administration of propofol combined with midazolam [COPD with stepwise sedation (group Cs), and non-COPD with stepwise sedation (group Ns)] or continuous sedation involving continuous administration of propofol combined with midazolam [COPD with continuous sedation (group Cc), and non-COPD with continuous sedation (group Nc)]. Saturation of peripheral oxygen (SpO2), blood pressure, and pulse rate were monitored, and patient discomfort, adverse events, drugs dosage, and recovery time were recorded.
RESULTS: All endoscopies were completed successfully. The occurrences of hypoxemia in groups Cs, Cc, Ns, and Nc were 4 (9.3%), 12 (27.9%), 3 (7.3%), and 5 (12.2%), respectively. The occurrence of hypoxemia in group Cs was significantly lower than that in group Cc (P < 0.05). The average decreases in value of SpO2, systolic blood pressure, and diastolic blood pressure in group Cs were significantly lower than those in group Cc. Additionally, propofol dosage and overall rate of adverse events in group Cs were lower than those in group Cc. Finally, the recovery time in group Cs was significantly shorter than that in group Cc, and that in group Ns was significantly shorter than that in group Nc (P < 0.001).
CONCLUSION: The stepwise sedation method is effective and safer than the continuous sedation method for elderly patients with mild/moderate COPD during upper GI endoscopy.
Upper gastrointestinal endoscopy; Adverse events; Sedation; Monitoring; Chronic obstructive pulmonary disease
Rationale: Oxidative stress is a key contributor in chronic obstructive pulmonary disease (COPD) pathogenesis caused by cigarette smoking. NRF2, a redox-sensitive transcription factor, dissociates from its inhibitor, KEAP1, to induce antioxidant expression that inhibits oxidative stress.
Objectives: To determine the link between severity of COPD, oxidative stress, and NRF2-dependent antioxidant levels in the peripheral lung tissue of patients with COPD.
Methods: We assessed the expression of NRF2, NRF2-dependent antioxidants, regulators of NRF2 activity, and oxidative damage in non-COPD (smokers and former smokers) and smoker COPD lungs (mild and advanced). Cigarette smoke–exposed human lung epithelial cells (Beas2B) and mice were used to understand the mechanisms.
Measurements and Main Results: When compared with non-COPD lungs, the COPD patient lungs showed (1) marked decline in NRF2-dependent antioxidants and glutathione levels, (2) increased oxidative stress markers, (3) significant decrease in NRF2 protein with no change in NRF2 mRNA levels, and (4) similar KEAP1 but significantly decreased DJ-1 levels (a protein that stabilizes NRF2 protein by impairing KEAP1-dependent proteasomal degradation of NRF2). Exposure of Bea2B cells to cigarette smoke caused oxidative modification and enhanced proteasomal degradation of DJ-1 protein. Disruption of DJ-1 in mouse lungs, mouse embryonic fibroblasts, and Beas2B cells lowered NRF2 protein stability and impaired antioxidant induction in response to cigarette smoke. Interestingly, targeting KEAP1 by siRNA or the small-molecule activator sulforaphane restored induction of NRF2-dependent antioxidants in DJ-1–disrupted cells in response to cigarette smoke.
Conclusions: NRF2-dependent antioxidants and DJ-1 expression was negatively associated with severity of COPD. Therapy directed toward enhancing NRF2-regulated antioxidants may be a novel strategy for attenuating the effects of oxidative stress in the pathogenesis of COPD.
chronic obstructive pulmonary disease; NRF2; DJ-1; oxidative stress; antioxidants
In this case report we describe the relationship between ferritin levels and hepcidin in a patient with alcohol-related spur cell anemia who underwent liver transplantation. We demonstrate a reciprocal relationship between serum or urinary hepcidin and serum ferritin, which indicates that inadequate hepcidin production by the diseased liver is associated with elevated serum ferritin. The ferritin level falls with increasing hepcidin production after transplantation. Neither inflammatory indices (IL6) nor erythropoietin appear to be related to hepcidin expression in this case. We suggest that inappropriately low hepcidin production by the cirrhotic liver may contribute substantially to elevated tissue iron stores in cirrhosis and speculate that hepcidin replacement in these patients may be of therapeutic benefit in the future.
Alcohol; Iron; Anaemia; Hepcidin; Cirrhosis
Recently, hepcidin expression in adipose tissue has been described and shown to be increased in patients with severe obesity. We tried to assess the effect of obesity on hepcidin serum levels and treatment outcome of iron deficiency anemia in children.
This was a case control study included 70 children with iron deficiency anemia "IDA" (35 obese and 35 non-obese) and 30 healthy non-obese children with comparable age and sex(control group). Parameters of iron status (Serum iron, ferritin, transferrin, total iron binding capacity and transferrin saturation) and serum hepcidin levels were assessed initially and after 3 months of oral iron therapy for IDA.
Compared to the control group, serum hepcidin was significantly lower in non-obese children with IDA(p < 0.01) and significantly higher in obese children with IDA (p < 0.01). Hepcidin increased significantly in non-obese children with IDA after 3 months of iron therapy (P < 0.01). On the other hand, obese children showed non-significant change in hepcidin level after iron therapy (p > 0.05). Although hepcidin showed significant positive correlations with Hb, serum iron and transferrin saturation in non-obese children with IDA, it showed significant negative correlations with Hb, serum iron and transferrin saturation in obese children with IDA (P < 0.05).
Obesity increased hepcidin levels and was associated with diminished response to oral iron therapy in childhood iron deficiency anemia.
Obesity; Hepcidin; Iron deficiency; Children
Several matrix metalloproteinases (MMPs) are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). In mice, MMP‐12 plays a crucial role in the development of cigarette smoke induced emphysema. A study was undertaken to investigate the role of MMP‐12 in the development of COPD in human smokers.
Induced sputum samples were collected from patients with stable COPD (n = 28), healthy smokers (n = 14), never smokers (n = 20), and former smokers (n = 14). MMP‐12 protein levels in induced sputum were determined by ELISA and compared between the four study groups. MMP‐12 enzymatic activity in induced sputum was evaluated by casein zymography and by cleaving of a fluorescence quenched substrate.
Median (IQR) MMP‐12 levels were significantly higher in COPD patients than in healthy smokers, never smokers, and former smokers (17.5 (7.1–42.1) v 6.7 (3.9–10.4) v 4.2 (2.4–11.3) v 6.1 (4.5–7.6) ng/ml, p = 0.0002). MMP‐12 enzymatic activity was significantly higher in patients with COPD than in controls (4.11 (1.4–8.0) v 0.14 (0.1–0.2) μg/μl, p = 0.0002).
MMP‐12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP‐12 in the development of COPD in smokers.
chronic obstructive pulmonary disease; matrix metalloproteinases; induced sputum; MMP‐12; smoking
Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level.
Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters.
Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients.
Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential.
Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome). It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).
Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography. The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group). The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).
The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group. The peripheral eosinophil counts and sputum eosinophil counts were significantly higher. The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher. A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening. Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.
COPD patients with asthmatic symptoms had some clinical features. ICS should be considered earlier as a potential treatment in such patients. High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS.
COPD; asthma; HRCT; inhaled corticosteroid; pulmonary function
Surfactant Protein D (SP-D) is an important marker in chronic obstructive pulmonary disease (COPD). Serum SP-D levels increase while lung production of SP-D decreases in COPD. SP-D is a specific biomarker for monitoring COPD, assessment of exacerbation frequency and arrangement of treatment modalities. In the present study, we aimed to investigate the correlation between serum and induced sputum SP-D levels with severity and acute exacerbations of COPD.
20 healthy subjects, older than 40 years, with at least 10 pack/years smoking history (group 1), 20 stage I-II COPD patients (group 2) , and 20 stage III-IV COPD patients (group 3) were enrolled in the study. All subjects performed pulmonary function tests. Venous blood samples were taken to determine complete blood count, C-reactive protein(CRP) and serum SP-D levels. Induced sputum samples were obtained to determine SP-D level. COPD patients were followed up for acute exacerbations for 6 months.
Serum SP-D levels of group 3 were the highest and induced sputum SP-D levels of group 2 were the lowest among the three groups. SP-D levels of induced sputum decreased in patients with increasing number of cigarette pack/years (p = 0.03, r = −0.115), whereas serum SP-D levels increased in these patients (p = 0.0001, r = 0.6 ). Induced sputum SP-D levels in COPD patients receiving inhaled corticosteroid treatment were significantly higher than in patients who were not receiving inhaler corticosteroid treatment (p = 0.005). An inverse correlation between serum SP-D levels and FEV1 (%) was found and there was a positive correlation between the serum SP-D levels and exacerbations frequency in 6-month follow up period (p = 0.049 ,r = −0.252; p = 0.0001, r = 0.598 respectively).
Our study demonstrates the adverse effects of smoking on local SP-D levels since low levels of induced sputum SP-D were found in the group of current smokers, who were not receiving inhaled corticosteroid treatment. Relationship between serum SP-D and COPD exacerbations frequency suggests that serum SP-D level may be used as a lung-specific biomarker during the follow up and progression of COPD.
Chronic obstructive pulmonary disease; Induced sputum; Surfactant protein-D
It is uncertain if the presence and severity of airflow obstruction in chronic obstructive pulmonary disease (COPD) is predictive of surgical morbidity and mortality after coronary artery bypass grafting (CABG).
Retrospective study of patients who underwent CABG between 1998 and 2003 in a university-affiliated hospital for whom a preoperative spirometry was available. COPD was diagnosed in smokers or ex-smokers 50 years of age or older in the presence of irreversible airflow obstruction. Patients were divided into three groups depending on the spirometry: controls (forced expiratory volume in 1 s [FEV1] 80% or more, FEV1/forced vital capacity [FVC] greater than 0.7), mild to moderate COPD (FEV1 50% or more and FEV1/FVC 0.7 or less) and severe COPD (FEV1 less than 50% and FEV1/FVC 0.7 or less).
Among the 411 files studied, 322 (249 men, 68±8 years of age) were retained (controls, n=101; mild to moderate COPD, n=153; severe COPD, n=68). The mortality rate (3.0%, 2.6% and 0%, respectively) was comparable among the three groups. Patients with severe COPD had a slightly longer hospital stay than controls (mean difference 0.7±1.4 days, P<0.05). Pulmonary infections were more frequent in severe COPD (26.5%) compared with mild to moderate COPD (12.4%) and controls (12.9%), P<0.05. Atrial fibrillation tended to be more frequent in severe COPD than in the other two groups.
Mortality rate associated with CABG surgery is not influenced by the presence and severity of airflow obstruction in patients with COPD. The incidence of pulmonary infections and length of hospital stay were increased in patients with severe COPD.
COPD; Coronary artery bypass; Heart surgery; Postoperative complications
Elevated circulating levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen (FG) have been repeatedly associated with many adverse outcomes in patients with chronic obstructive pulmonary disease (COPD). To date, it remains unclear whether and to what extent systemic inflammation is primary or secondary in the pathogenesis of COPD.
The aim of this study was to examine the association between haplotypes of CRP, IL6 and FGB genes, systemic inflammation, COPD risk and COPD-related phenotypes (respiratory impairment, exercise capacity and body composition).
Eighteen SNPs in three genes, representing optimal haplotype-tagging sets, were genotyped in 355 COPD patients and 195 healthy smokers. Plasma levels of CRP, IL-6 and FG were measured in the total study group. Differences in haplotype distributions were tested using the global and haplotype-specific statistics.
Raised plasma levels of CRP, IL-6 and fibrinogen were demonstrated in COPD patients. However, COPD population was very heterogeneous: about 40% of patients had no evidence of systemic inflammation (CRP < 3 mg/uL or no inflammatory markers in their top quartile). Global test for haplotype effect indicated association of CRP gene and CRP plasma levels (P = 0.0004) and IL6 gene and COPD (P = 0.003). Subsequent analysis has shown that IL6 haplotype H2, associated with an increased COPD risk (p = 0.004, OR = 4.82; 1.64 to 4.18), was also associated with very low CRP levels (p = 0.0005). None of the genes were associated with COPD-related phenotypes.
Our findings suggest that common genetic variation in CRP and IL6 genes may contribute to heterogeneity of COPD population associated with systemic inflammation.
Weight loss is common in patients with chronic obstructive pulmonary disease (COPD). However, the mechanisms of this weight loss are still unclear.
Sixty male patients with stable COPD and 45 healthy male controls participated in this study. The COPD patients were divided into two groups, that is, the emphysema and chronic bronchitis groups, by the transfer coefficient of carbon monoxide. The body composition, resting energy expenditure (REE), plasma leptin levels and serum tumor necrosis factor-alpha (TNF-α) were measured in all the study participants. The difference and correlation of these parameters were investigated between the two groups.
Emphysematous patients were characterized by a lower body mass index (BMI) and fat-mass (FM)
compared with the chronic bronchitis patients (p<0.001). The plasma leptin levels, as corrected for the FM, were not different between the COPD patients and healthy controls (78.3±30.9 pg/mL/kg vs. 70.9±17.3 pg/mL/kg, respectively), and the plasma leptin levels, as adjusted for the FM, were also not different between the two groups of COPD patients. In the chronic bronchitis patients, the plasma leptin concentration was correlated with the BMI (r=0.866, p<0.001) but it was not correlated with the BMI in the emphysema patients. The serum TNF-α levels were higher in the stable COPD patients than those in the controls, but there was no statistical difference (10.7±18.6 pg/mL vs. 7.2×3.5 pg/mL, respectively, p0.05). The leptin concentration was well correlated with the BMI and %FM in the patients with chronic bronchitis and the leptin concentration was only correlated with the %FM (r=0.450, p=0.027) in emphysema patients. There was no correlation between the plasma leptin concentration, as adjusted for the fat mass, and the activity of the TNF-α system.
The interaction of leptin and the activity of the TNF-α system in the pathogenesis of tissue depletion may not play an important role in chronic stable COPD patients.
COPD; Weight loss; Leptin; Tumor necrosis factor-alpha
Objectives; Pulmonary hypertension (PH) is a common and well established complication of chronic obstructive pulmonary disease (COPD). Its presence is associated with decreased survival. This study was designed to investigate the PH frequency and its relations in hospitalized tobacco and biomass related COPD patients. Methods and Results; The study was a retrospective review of inpatients with COPD defined as a history of tobacco or biomass smoking, Pulmonary function tests (PFT) within stable status, an echocardiogram within stable status. PH was defined as systolic pulmonary artery pressure (sPAP) >35 mmHg. Of the 694 individuals, 600 had suitable aspects for inclusion of study. All Females were biomass exposer and males were tobacco smoker. The Prevalence of PH was found more frequent in females than males. It was more prominent in moderate level COPD cases (56,2% and 37,5%, P<0,002). Both groups had airflow limitation, hypercapnia and hypoxemia, but no differences were found in terms of PaCO2 and PaO2. However, FEV1 % was lower in males than females (p<0,005). On the other hand, FVC % was lower in the females compared with the males (p < 0.02). When analyzing the influence of PFT and demographic parameters on PH in separate COPD level groups, the results a bit varied among the groups. Conclusion; Our study demonstrated that PH frequency is higher in female COPD cases due to biomass smoke than in male COPD cases due to tobacco smoke. The influence of FVC % on the risk of a person having PH increased with increasing COPD level.
COPD; Pulmonary Hypertension; Environmental pollutants; Smoking.
Though there are few studies addressing brainstem auditory evoked potentials (BAEP) in patients with chronic obstructive pulmonary disease (COPD), subclinical BAEP abnormalities in stable COPD patients have not been studied. The present study aimed to evaluate the BAEP abnormalities in this study group.
MATERIALS AND METHODS:
In the present study, 80 male subjects were included: COPD group comprised 40 smokers with stable COPD with no clinical neuropathy; 40 age-matched healthy volunteers served as the control group. Latencies of BAEP waves I, II, III, IV, and V, together with interpeak latencies (IPLs) of I-III, I-V, and III-V, and amplitudes of waves I-Ia and V-Va were studied in both the groups to compare the BAEP abnormalities in COPD group; the latter were correlated with patient characteristics and Mini–Mental Status Examination Questionnaire (MMSEQ) scores to seek any significant correlation.
Twenty-six (65%) of the 40 COPD patients had BAEP abnormalities. We observed significantly prolonged latencies of waves I, III, V over left ear and waves III, IV, V over right ear; increased IPLs of I-V, III-V over left ear and of I-III, I-V, III-V over right side. Amplitudes of waves I-Ia and V-Va were decreased bilaterally. Over left ear, the latencies of wave I and III were significantly correlated with FEV1; and amplitude of wave I-Ia, with smoking pack years. A weak positive correlation between amplitude of wave I-Ia and duration of illness; and a weak negative correlation between amplitude of wave V-Va and MMSEQ scores were seen over right side.
We observed significant subclinical BAEP abnormalities on electrophysiological evaluation in studied stable COPD male patients having mild-to-moderate airflow obstruction.
Brainstem auditory evoked potentials; chronic obstructive pulmonary disease; correlation analysis; Mini–Mental Status Examination
Recent research evidence suggests a central role for hepcidin in iron homeostasis. Hepcidin is a hormone synthesized in the liver. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. A 38-year-old female who presented with recurrent abdominal pain was found to have raised urinary porphyrins and a blood lead level of 779 μg/l. Her haemoglobin level was 8.3 g/dl. Her MCV was normal. Serum ferritin, B12 and folate were normal. Her serum prohepcidin level was 2,489 ng/ml (normal <450 ng/ml). To our knowledge, this is the first report of raised prohepcidin levels in a patient with anaemia of chronic disease resulting from lead poisoning.
Hepcidin; Prohepcidin; Lead poisoning; Porphyrins; Abdominal pain; Sideroblastic anaemia
Introduction. Anemia is a frequent problem in hospitalized geriatric patients, and the anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the 2 most prevalent causes. The aim of the study was to assess the possible role of serum hepcidin in the differential diagnosis between ACD and IDA. Methods. We investigated serum hepcidin, iron status, anemia, and C-reactive protein in 39 consecutive geriatric patients with ACD and IDA. Serum hepcidin levels were determined using a commercial ELISA kit (DRG Instruments, Marburg, Germany). We also measured hepcidin in 26 healthy controls. Results. The serum hepcidin levels were not significantly higher in the 28 patients with ACD as compared to the 11 patients with IDA. Conclusions. The serum hepcidin levels measured using the commercial ELISA kit (DRG) do not appear to increase in older patients with ACD. It should be noted that an assay-specific problem could explain our results.