الفهرس 
Bronchial Bronchial Bronchial Bronchial Bronchial Bronchial Bronchial Bronchial Bronchial AsthmasthmasthmasthmasthmaOnly 14 pages are availabe for public view
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Abstract
A
sthma is a disease characterized by airway chronic inflammation and bronchial hyperactivity, involving the imbalance of oxidative and antioxidative agents. There is an increased free radical generation and a decreased antioxidant enzyme activity, which correlate with the severity of the disease.
Endothelial dysfunction is a systemic pathological state of the endothelium and can be broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by (or acting on) the endothelium.
This current study aimed at assessment of endothelial function parameters namely flow mediated dilatation (FMD), flow mediated resistive index,(FMRI), and circulating endothelial cells count (CEC) in asthmatic children of various functional and clinical severity and correlating the studied endothelial function parameters with the level of disease control and severity.
This study included 40 asthmatic children (28 males and 12 females) attending the Pediatric Chest Clinic, Children’s Hospital, Ain Shams University. According to clinical severity those patients were divided functionally into mild persistent asthma (11 patients, 8males, 3 females), moderate persistent (15 patients, 11 males, 4 females), and severe persistent asthma (14 patients, 9 males, 5 females). According to level of control, they were classified into controlled (19 patients, 13 males, 6 females), partially controlled (10 patients, 6 males, 4 females) & uncontrolled (11 patients, 9 males, 2 females). According to exposure to smoking, they were classified into positive second hand smoke (25patients, 18 males, 7 females), and negative second hand smoke (15 patients, 10 males, 5 females).
12 Age and sex matched apparently healthy children were been selected as a control group.
For all studied case and control group through history, clinical examination, CBC, and IgE, were done and spirometric pulmonary function (FEV1, FVC) % of predicted were measured in pulmonary function lab, pediatric hospital, Ain shams university, and then we asses endothelium function through ultrasonographic evaluation of brachial artery measuring flow mediated dilatation (FMD ),and flow mediated resistive index (FMRI) ,also we asses laboratory circulating endothelial cell (CEC) and correlate endothelium function with asthma severity and level of control.
Studied groups were well matched as regards age, gender, and residence distribution (p>0.05 for all) respectively.
Studied asthmatics had significantly higher mean values of absolute esinophilic count and IgE level compared to controls (P < 0.01 for both).
There were statistically insignificant differences between both studied groups as regards the mean values of the performed pulmonary function tests (p > 0.05).
Studied asthmatics had significantly higher mean values of circulating endothelial cell count compared to controls (P< 0.05).
Regarding sonographic evaluation of endothelial cell functions, flow mediated dilatation (FMD) % and brachial artery diameter (mm) were measured before and after exercise. The mean values of flow mediated dilatation (FMD) of brachial artery was statistically highly significant lower in studied asthmatics compared to controls (P < 0.01), while there was statistically insignificant differences between studied groups concerning brachial artery diameter before and after exercise (P > 0.05 for both).
Resistive index (RI) of brachial artery after exercise was significantly higher in studied asthmatics compared to controls (P<0.01), while, it showed statistically non significant differences between studied groups before exercise. On the other hand, flow mediated resistive index (FMRI) was statistically significantly higher in studied asthmatics compared to controls (P<0.01).
Receiver Operating characteristic curve (ROC) showed that FMD of brachial artery had a sensitivity of 72.2%, a specificity of 83.3%, a PPV (positive predictive value) of 93.5%, and a NPV (negative predictive value) of 47.6% with a cutoff point <24 between asthmatics and controls. Also, it showed that FMRI had a sensitivity of 90%, a specificity of 100%, a PPV (positive predictive value) of 100% and a NPV (negative predictive value) of 75% with a cutoff point > -11.11.
Severely persistent asthmatics were significantly older than those moderately, and mildly persistent asthmatics with significantly longer disease duration than them (P<0.05).
According to the performed pulmonary function tests, severely persistent asthmatics had significantly higher reduction of FEV1 and FVC % of predicted compared to those with mild and moderate persistent asthma (P< 0.01).
According to disease severity, there was significantly higher association between severe degree of asthma and lower flow mediated dilatation, (FMD) % (P<0.01). Meanwhile, severely persistent asthmatics had both significantly higher flow mediated resistive index (FMRI)% and absolute circulating endothelial cell count compared to mild persistent asthmatics (P<0.01).
According to the degree of control of asthma, studied asthmatic subgroups showed no statistically significant association between level of control of asthma ,age, age of onset, duration of asthma, and IgE level; (P> 0.05) for all.
Regarding asthma control, uncontrolled asthmatics had highly significant lower FEV1 and FVC% of predicted compared with partially controlled and controlled (P< 0.01) for both. Also, partially controlled asthma had significantly lower means values of the FEV% of predicted compared to controlled asthmatics.
According to control of disease, uncontrolled asthmatics had statistically significantly lower FMD% in comparison to controlled and partially controlled (P<0.01). Meanwhile uncontrolled asthmatics had statistically significantly higher FMRI and circulating endothelial cells count in comparison to controlled asthmatics (P< 0.01) for both.
FMD% of the brachial artery was significantly negatively correlated with FMRI% of brachial artery, age of patients, duration of disease, and absolute count of circulating endothelial cell count; i.e., “the lower the FMD the higher the fMRI, the older the patient, the longer duration of the disease, and the more reduction in circulating endothelial cell count”. On the other hand, FMD% of the brachial artery was significantly positively correlated with FEV1% and FVC% of predicted; i.e., “the lower the FMD, the lower the FEV1, FVC% of predicted”.
On the other hand, FMRI was significantly negatively correlated with FMD%, FEV,and FVC% of predicted and; i.e., “the higher FMRI, the lower FMD, the lower FEV, FVC% of predicted”.
Absolute count of circulating endothelial cells showed significantly negative correlation with FMD% of brachial artery, FEV1 (% of predicted), and FVC (% of predicted) i.e., “the higher circulating endothelial cell count, the lower FMD, the lower FEV1, and FVC% of predicted”. On the other hand, it showed a significantly positively correlated with age, and duration of asthma i.e., “the higher circulating endothelial cell count, the older the patient and the more duration of disease”.
There were statistically insignificant differences between the mean values of all studied parameters of endothelial cell function when 2nd hand smoke asthmatics compared to non 2nd hand smoke asthmatics (P<0.05).
The previous study showed that Flow Mediated Dilatation (FMD) of the brachial artery was lower in asthmatic children in comparison to controls, also the lower FMD the more severe degree of asthma, and the poor control of disease. Meanwhile Flow Mediated Resistive Index (FMRI) of the brachial artery and circulating endothelial cells count was higher in asthmatics in comparison to controls, also the higher (FMRI) and circulating endothelial cell count, the more severe degree of asthma, and the poor control of disease.
In conclusion, asthmatic children showed evidence of endothelial dysfunction which was correlated to level of control and severity this may extend our understanding of asthma from airway inflammation to systemic inflammatory disease.