الفهرس 
Persistent AsthmaOnly 14 pages are availabe for public view
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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.