Relationship between fraction of exhaled nitric oxide and peripheral eosinophilia in asthma.

BACKGROUND: Achieving disease control is the goal of asthma management. Serum or sputum eosinophil counts have been known traditional means of assessing eosinophilic airway inflammation in asthma, which is vital in predicting response to corticosteroid therapy which ultimately promotes control of the disease. Evidence suggests that fraction of exhaled nitric oxide (FeNO) may be a more useful non-invasive surrogate biomarker for the assessment of eosinophilic airway inflammation and could help with the timely adjustment of inhaled corticosteroid therapy in the uncontrolled asthma patient. The relationship between FeNO and other markers of airway inflammation has been variable in literature, with limited data in sub-Saharan Africa where FeNO testing is very sparse. We sought to define the relationship between FeNO levels, serum eosinophil counts, spirometry measures and symptom control among asthma patients. MATERIALS AND METHODS: The study was conducted at the Asthma Clinic of a large tertiary hospital. This study included 82 patients with physician-diagnosed asthma being regularly managed at the clinic. All participants were taken through the asthma control test (ACT), had FeNO and spirometry measurements taken according to the American Thoracic Society (ATS) guidelines. Blood samples were obtained from all participants for serum eosinophil counts. Correlation coefficient was used to ascertain the relationship between FeNO levels and serum eosinophil counts, ACT scores, and spirometry measurements. Logistic regression was used to examine the association between high FeNO and abnormal FEV1 percentage predicted (<80%) with adjustments for age, sex, and BMI. RESULTS: A total of 82 patients with asthma were included in the study, with higher prevalence of females (72%). Majority (40.2%) of the patients were found in the 60 and above age category. The median FeNO level and ACT score was 42.00 (26.00-52.50) parts per billion (ppb) and 20.0 (18-23) respectively. The median serum eosinophil counts was 0.25(0.90-0.38) × 109/L. The median FeNO levels were significantly higher in patients with partly and very poorly controlled asthma than in the well-controlled group (p < 0.001). A total of 47(57%) of the patients were classified as having well controlled asthma and 35 (42%) uncontrolled. FeNO correlated with serum eosinophil counts (r = 0.450, p < 0.001), ACT (r = -0.648, p < 0.001), and FEV1 percentage predicted (r = -0.353, p = 0.001). High FeNO (>50 ppb) was associated with an over fivefold increased risk of having an abnormal FEV1 percentage predicted. CONCLUSION: FeNO levels significantly correlated with the ACT scores, serum eosinophil counts and FEV1% predicted among the asthma patients who were on inhaled corticosteroid therapy. High FeNO was significantly associated with abnormal FEV1 percentage predicted. We suggest that the point of care assessment of FeNO is a reliable marker of eosinophilic inflammation in our cohort of patients and together with 'ACT scores' in our asthma clinics could increase asthma control rates.

Serum Iron Levels and Copper-to-Zinc Ratio in Sickle Cell Disease.

Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defense system and consequently lead to oxidative stress and associated complications in sickle cell disease (SCD) patients. Iron levels have been reported to increase in sickle cell patients due to frequent blood transfusion, chronic intravenous haemolysis and increased absorption of iron from the gastrointestinal tract. These elevated levels of iron may also lead to extensive oxidative damage. The current study evaluated serum levels of iron, copper and zinc in SCD patients and "healthy" controls. Materials and Methods: The study was a cross-sectional one, comprising 90 SCD patients with Haemoglobin SS and Haemoglobin SC genotypes and 50 HbAA "healthy" controls. Serum levels of iron, copper and zinc were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd, VIC, Australia). Copper and zinc ratios were calculated and analyzed. Results: Serum levels of iron and copper were significantly elevated in the SCD patients, compared to their "healthy" counterparts (p < 0.001). These levels were further increased in patients with haemoglobin SS in vaso-occlusive crises (HbSS VOCs). Serum zinc levels were, however, significantly lower in the SCD patients, particularly during vaso-occlusion. The copper-to-zinc ratio was also found to be significantly higher in the SCD patients. Conclusion: Elevated copper-to-zinc ratio may be a biomarker of sickle cell oxidative stress and associated complications. The ratio may also be informative for the management of sickle cell oxidative burden. The significantly lower levels of zinc in the SCD patients may warrant zinc supplementation.

Oxidative Profile of Patients with Sickle Cell Disease.

Oxidative stress plays a very significant role in the pathophysiology of sickle cell disease (SCD) and associated complications. Oxidative stress, which is often experienced by SCD patients as a result of continuous production of reactive oxygen species (ROS), may lead to endothelial dysfunction and acute inflammation. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), often play a protective role. The current study aimed at determining the oxidative profile of persons with SCD at a tertiary hospital in Ghana. This was a case-control study involving 90 patients with SCD (34 HbSS patients at steady state, 30 HbSC at steady state, 15 HbSS with vaso-occlusive crisis, 11 HbSC with vaso-occlusive crisis), and 50 HbAA control group. Whole blood samples were collected from the study participants and analyzed for full blood counts. The blood samples were assayed for SOD and CAT as a measure of antioxidant defense, while lipid peroxidation was quantified as malondialdehyde (MDA). The results showed that the levels of SOD and CAT were significantly lower in SCD patients as compared to the control group. Patients with HbSS vaso-occlusive crisis had the lowest levels of SOD and CAT. The difference in SOD levels between HbSS at steady state and HbSC with vaso-occlusive crisis was, however, not significant (p = 0.228). The MDA level was significantly higher in SCD patients compared to the control group. This study concludes that the levels of various antioxidant enzymes (erythrocyte SOD and erythrocyte CAT) and oxidative marker (MDA) and are altered in SCD patients.

Correlation Between Soluble Endothelial Adhesion Molecules and Nitric Oxide Metabolites in Sickle Cell Disease.

Nitric Oxide (NO) and soluble adhesion molecules are promising biomarkers, which predict endothelial dysfunction in sickle cell disease (SCD). Several studies have investigated the relationship between NO (as well as its metabolites) and endothelial adhesion molecules in SCD. However, these studies were done mainly in the developed world, and it is difficult to extrapolate the findings to SCD populations in other geographical regions such as Africa due to significant disparities in the results. The aim of the current study was to determine the correlation between levels of nitric oxide metabolites (NOx) and adhesion molecules in SCD patients in a tertiary hospital in Ghana. A case control cross-sectional study involving 100 SCD (made up of HbSS and HbSC patients) and 60 healthy controls was conducted. Concentrations of NOx and soluble endothelial adhesion molecules (ICAM-1, VCAM-1 and E-selectin) were measured in all the study participants (n = 160) by the Griess reagent system and enzyme-linked immunosorbent assay (ELISA). Correlation analysis was performed to determine a possible link between the variables. Levels of soluble adhesion molecules were higher in the HbSS patients. Correlation of NOx with ICAM-1 almost approached significance (r = 0.565, p = 0.058) in the HbSS patients. There were no correlations between NOx and E-selectin in both HbSS and HbSC patients. There were no significant correlations between NOx and VCAM-1 in all the study participants (p > 0.05). Of the soluble adhesion molecules, ICAM-1 showed a significant positive correlation with VCAM-1 in the HbSC patients. There were no significant differences between the adhesion molecules and the age of participants in the various study groups. Whether or not a significant correlation exists between NOx and soluble adhesion molecules may not depend on the sickle cell genotype. The expression of adhesion molecules may not depend on age.

Hematological parameters in Ghanaian sickle cell disease patients.

BACKGROUND: Effective treatment and management of sickle cell disease (SCD) has been a challenge in Africa over the years. Hematological parameters are very useful profiles in the effective management of the disease. However, there is scarcity of studies on the hematological parameters of SCD in Ghana. This study aimed at determining hematological parameters among SCD patients with vaso-occlusion, those in the steady state as well as healthy controls at a teaching hospital in Ghana. METHODOLOGY: This was a cross-sectional study involving a total of 628 subjects, including 148 HbAA controls, 208 HbSS patients in steady state, 82 HbSC patients in steady state, 156 HbSS patients in vaso-occlusive crises (VOC), and 34 HbSC patients in VOC. Venous blood sample was collected from all study participants. A full blood count was done within 2 hours of collection, and hemoglobin (Hb) concentration, packed cell volume, red blood cell (RBC) concentration, mean corpuscular Hb, mean cell volume, mean corpuscular Hb concentration, and white blood cells (WBC) and platelet (PLT) counts were recorded. RESULTS: WBC and PLT counts were significantly higher in both female and male patients with SCD, compared with their healthy counterparts (P<0.05). The level of WBC was, however, significantly higher in patients with HbSS VOC among the SCD patients (P<0.001). Levels of Hb, RBC, and hematocrit were significantly higher in the controls (P<0.001). There was no significant difference in mean cell Hb among male patients with SCD (P=0.274) and female patients with SCD (P=0.5410). CONCLUSION: The SCD patients had lower Hb and RBC than the controls; however, higher PLT and WBC are noted in various status of SCD, possibly reflecting spleen effect in these patients. Further studies are needed to confirm these findings.

Elevated Proangiogenic Markers are Associated with Vascular Complications within Ghanaian Sickle Cell Disease Patients.

: Sickle cell disease (SCD) is an inherited blood disorder that can result in vasculopathy and end organ damage. Angiogenesis has been implicated as a key contributing factor to vascular mediated tissue injury in SCD. The relative plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) greatly influence angiogenesis. Dysregulation of these growth factors, leading to a pro-angiogenic state in SCD patients, has been documented in the developed world but there is very little data in Africa. There is the need, therefore, for studies in Ghanaian SCD patients. The aim of this study was to assess plasma levels of Ang-1, Ang-2, and VEGF in homozygous (HbSS) SCD patients with or without complications and healthy controls (HbAA) in Ghana. The study was a case-control study involving 544 participants: 396 HbSS SCD patients and 148 HbAA healthy controls. The study was conducted at the Center for Clinical Genetics (Sickle Cell Clinic) and Accra Area Blood Centre for National Blood transfusion at the Korle-Bu Teaching Hospital, Accra, Ghana. The plasma levels of Ang-1, Ang-2, and VEGF of study participants were measured with a double sandwich enzyme-linked immunosorbent assay (ELISA) technique. Complete blood count (CBC) was measured with an autoanalyser. The mean plasma Ang-1, Ang-2, and VEGF were significantly higher in HbSS SCD patients with or without complications than healthy controls (p < 0.001). The Ang-2/Ang-1 ratio was significantly lower in the controls than the HbSS patients (p < 0.001). The Ang-2/Ang-1 ratio was higher in the HbSS patients with leg ulcers as compared with patients with other complications and healthy controls (p < 0.001). There were higher leucocyte counts in HbSS patients than healthy controls. Overall, there was elevated plasma levels of Ang-1, Ang-2, and VEGF in SCD patients. The higher Ang-2/Ang-1 plasma levels in patients with leg ulcers suggests a possible ongoing angiogenesis and response to inflammatory stimuli. The study provides a first report on plasma levels of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factors in homozygous sickle cell disease patients in Ghana.

Levels of Soluble Endothelium Adhesion Molecules and Complications among Sickle Cell Disease Patients in Ghana.

BACKGROUND: Soluble adhesion molecules are involved in the gathering and joining of inflammatory cells to vascular endothelium. Therefore, they serve as potential markers of endothelial dysfunction in vascular diseases including sickle cell disease (SCD). In Ghana, there are scarcely any report on the levels of adhesion molecules among SCD patients. The current study aimed to determine plasma levels of ICAM-1, VCAM-1 and E-Selectin as markers of endothelial dysfunction in SCD patients in steady state, complications and controls. METHODOLOGY: This was a cross-sectional study involving 60 HbAA controls, 46 HbSS steady state, 57 HbSS VOC, 18 HbSC VOC, 21 HbSS with leg ulcer and 11 HbSS with priapism. Blood samples were collected from all the study subjects (n = 213) and processed into plasma. The plasma levels of VCAM-1, ICAM-1 and E-Selectin concentrations of SCD patients and controls were measured using a double sandwich ELISA technique. Demographic information was also collected from the study subjects. RESULTS: Levels of all soluble proteins (ICAM-1, VCAM-1 and E-Selectin) were significantly higher in HbSS steady-state patients compared to non-SCD controls (p < 0.001). Generally, SCD patients with complications had relatively higher levels of the soluble proteins compared to those in the steady-state. Of the SCD patients with complications, those with vaso-occlusion crisis (HbSS VOC) had relatively higher levels of ICAM-1, VCAM-1 and E-Selectin at (62.42 ng/mL ± 26.09), (634.99 ng/mL ± 324.31) and (236.77 ng/mL ± 114.40) respectively; Conclusion: Although levels of adhesion molecules were high in all the SCD patients with complications, those with vaso-occlusive crisis had higher levels. This might reflect an ongoing endothelial dysfunction in these patients. SCD patients with vaso-occlusive crisis presents with a more severe pathophysiology condition.