Diapositiva 1

1
Association between eosinophilic airway
inflammation and T-cells response in children
with bronchial asthma
J. Antipkin1, T. Umanets1, V. Lapshyn1, A.
Nakonechna2
Abstract 2160

• Institute of Pediatry, Obstetrics and
  Gynaecology, Kiev, Ukraine
• Royal Liverpool and Broadgreen University
  Hospitals NHS Trust, Liverpool, United Kingdom
• E-mail allergy_at_novidec.com

MATERIALS AND METHODS
INTRODUCTION
65 children aged 7-12 years with
moderate-to-severe bronchial asthma (Table 1)
37 age-matched healthy controls were observed
Diagnosis and assessment of asthma based on
Clinical questionnaire (respiratory symptoms,
frequency of episodes of asthma, family history,
medication) Physical examination with
quality-of-life assessment (QOL) Allergy skin
prick tests (SPTs) - cat, dog, house dust mite,
D. pharine, D.pteronissinus, grass mix, tree mix,
Alternaria, Aspergilus, Cladosporium, food
allergens (egg, milk, wheat, fish, soya, meat,
nuts). A negative control diluent and a positive
control (10 mg/ml histamine) were included. A
positive SPT was defined as giving a mean weal
diameter of 3 mm or more at 15 min. Total IgE
and antigen specific IgE (assessed by ELISA)
Lung functions (Pic.1) Induced sputum analysis
method Pizzichini IL-5, IL-10, gamma-IFN
levels (assessed by ELISA)
Eosinophilic airway inflammation plays a key
pathophysiological role in bronchial asthma (BA),
but there is evidence that T-cells and cytokines
are also involved, although the association
between these parameters is still unclear. Our
objective is to investigate the association
between induced sputum eosinophilia and cytokines
production by Th1 and Th2 cells in children with
BA.
Graphs and tables
Table 1 - Patients Table 1 - Patients Table 1 - Patients
Group I 41 moderate asthma
Group II 24 severe asthma
Control 37
All children with bronchial asthma (65) were
divided in 2 groups, according to asthma
severity, that was assessed by FEV1, peak
expiratory flow (PEF) variability and daily
symptom scores (Pic. 1) Group I children with
moderate asthma (41 pat.) - 63 Group II
children with severe asthma (24 pat.) - 37
Diagnosis of BA was confirmed by positive SPT
at least to one allergen (Pic. 2) increased
total IgE to 49810 KU/l in Gr. I and to 65712
KU/l in Gr. II elevated specific IgE levels,
that were more expressive in a group with severe
asthma (Pic. 3) evaluation of episodic
wheezing, nocturnal waking, dyspnoea/chest
tightness, which were more significant in severe
asthmatic children improvement in symptoms
following asthma therapy, which was more
revealing in moderate asthma group (plt0,001). The
investigation of airway inflammation showed that
all asthmatic children had induced sputum
eosinophilia, which directly correlated with
elevated peripheral blood eosinophils and was
more expressive in severe asthma group (12,20,5
vs. 24,32,5) (threshold of lt 3) (plt0,001).
There was also increased level of sputum
lymphocytes, basophils and mast cells and
bronchial epithelial desquamation and all these
indexes were more significant in Group II
(Pic.4). These results were the most important
evidence of our investigational purpose as sputum
eosinophilia directly associated with skin
sensitization increased level of total and
specific IgE clinical symptoms of BA reduced
lung function All there markers were more
significant in children with severe BA. More of
that, there was found direct correlation between
these parameters and levels of cytokines
production, especially in severe asthmatic
children. As it is shown on Pic. 5 level of
IL-5 production increased to 1425 pkg/ml in Gr.
I compared with 1718 pkg/ml in Gr. II
(N74.33.3) production of IL-10 increased
to 1027 pkg/ml in Gr. I and to 1337 pkg/ml in
Gr.II respectively (N5.90.25) level of
?-IFN production decreased to 2815 pkg/ml in Gr.
I and 2434 pkg/ml in Gr.II (N33135) (plt0.05).
The increasing of the of cytokines production
level (IL-4 and IL-5) by peripheral mononuclear
cells induce the expression of cell adhesion
molecules on inflamed endothelium and epithelial
production of chemokines, leading to the
recruitment of inflammatory cells, stimulating
the production of IgE by B cells and causing
bronchial hyper-reactivity. IL-5 is known as an
important cytokine for the growth,
differentiation and activation of tissue
eosinophils. Although IL-10 is often described
to have an immunosuppressive effect on both
Th1/Th2 cells, it can also favour the
polarization to Th2 cells. The presence of IL-10
at the site of T cell differentiation diminishes
the secretion of IL-12, thereby indirectly
attenuating the differentiation of Th1 cells.
All this immunological mechanism found the
reflection in the results of our clinical
investigation and proved the interaction between
eosinophilic airway inflammation and T-cells
response in bronchial asthma children, what was
confirmed by cytokines production, total and
allergenspecific IgE levels and the count of
sputum eosinophils.

• Investigation confirms that eosinophilic airway
  inflammation (induced sputum eosinophilia) is
  associated with increased functional activity of
  Th2 cells (increased cytokines production).
• Both these parameters are linked to disease
  severity in children with moderate to severe
  asthma.