الفهرس | Only 14 pages are availabe for public view |
Abstract lasminogen activator inhibitor (PAI)-1 is the main inhibitor of the fibrinolytic system and is known to play an essential role in tissue remodeling and the progression of pulmonary fibrosis. We sought to investigate the expression of PAI-1 in the blood and sputum of a sample of Egyptian atopic children with persistent asthma in relation to other clinical and laboratory parameters. The ultimate objective was to open a new path towards understanding the pathogenic mechanisms of asthma and paving the way for adjuvant non-conventional lines of therapy. We enrolled 45 physician-diagnosed cases of persistent bronchial asthma belonging to the age group 6-12 years from the Pediatric Allergy and Immunology Unit of Ain Shams University Children’s Hospital as well as 45 age and sexmatched healthy children as a control group after informed consent from the parents. We only recruited atopic asthmatics as evidenced by positive SPT results to common environmental allergens. SPT reactivity was an exclusion criterion in the control group to avoid enrollment of undiagnosed atopic subjects. Patients were subjected to clinical evaluation for the duration of illness, family history of allergy, history of breast feeding, co-existense of other forms of allergy, therapy received, and the severity grade of asthma. They were subjected to a general clinical examination to exclude other diseases. Weight and height measurements were recorded and plotted against the normal percentiles for age. The patients and controls underwent complete blood counting especially for the absolute eosinophil count, Serum total IgE assay and measurement of the PAI-1 in the plasma and induced sputum by enzymatic immune assays. In our study, the plasma and sputum PAI-1 levels of the asthmatic children during acute exacerbation of bronchial asthma were significantly higher than the corresponding values of the same patients when studied after quiescence. The healthy controls had a significantly lower PAI-1 expression as compared to the patients’ data whether during asthma exacerbation or quiescence. The upregulation of PAI-1 after subsidence of asthma exacerbation points to the continuing inflammatory process in this disease and the risk of remodeling even during quiescence of symptoms. Plasma and sputum PAI-1 expression did not vary in our series with the grade of asthma severity during stability. Children with mild persistent asthma were comparable to those with moderate and severe persistent asthma as far as their mean PAI-1 values were concerned. However, the severe persistent asthma category was limited to nine children in our sample being enrolled consecutively. The duration of illness did not correlate significantly to the blood or sputum PAI-1 levels in the current study. The co-existence of skin and/or nasal allergy did not have a significant impact on plasma or sputum levels of PAI-1 in our series neither did the family history of allergy. Gender did not influence the expression of PAI-1 in the blood or induced sputum in our study and there are no published data that support any impact of gender on fibrinolysis inhibitors. The plasma and sputum PAI-1 levels were comparable between asthmatics with normal total serum IgE and those with elevated levels during asthma exacerbation. Similarly, the presence of elevated levels of plasma or sputum PAI-1 failed to have a significant relation to the absolute eosinophil counts during exacerbation. Neither plasma nor sputum levels of PAI- 1 bore any significant variation with the use of inhaled corticosteroid therapy. It seems that control of PAI-1 expression, and hence its effect on remodeling and pulmonary fibrosis, needs new non-conventional lines of therapy. Plasma PAI-1 during asthma exacerbation had a significant positive correlation with plasma and sputum PAI-1 after remission. Again, sputum PAI-1 during acute asthma exacerbation bore a significant positive correlation with its level after remission. Otherwise, we could not elicit any significant linear relations between PAI-1 and other numerical variables studied including the age, weight and height percentiles for age, breast feeding duration, ESR, total leukocyte count, absolute eosinophil count, total serum IgE, and number of positive SPTs for common environmental allergens. Also, the SPT wheal diameter showed no linear relationship to the levels of PAI-1 in the blood or sputum. It seemed that the PAI-1 upregulation is related to the mere presence of atopy without respect to the extent of sensitization. The current results have several limitations. First, the sample size is relatively small and this hinders solid conclusions. Second, the sample, being consecutively recruited, was not evenly distributed among some variables which could be somewhat misleading on data analysis. Third, the relationship between PAI-1 expression and the duration of illness could not be accurately evaluated due to the narrow age range of the sample. Last, we are not confident on the relationship between asthma severity and PAI-1 expression due to the uneven distribution of the sample on various grades. from this pilot study, we report the over-expression of PAI-1 in the blood and sputum of a group of atopic school-aged children with persistent asthma as compared to a matched group of healthy controls. The levels were significantly higher during asthma exacerbations than after quiescence of symptoms and signs. The latter, however, did not decline to the control levels pointing to the continuing asthmatic inflammatory process between exacerbations. This and relevant future studies might pave the way for the development of adjuvant lines of therapy. PAI-1 may one day prove to be a novel target of treatment of airway remodeling in asthma. |