Functional Analysis of Airway Remodeling is Related with Fibrotic
Mediators in Asthmatic Children
Abstract
Background: Asthmatic children present variable degrees of airway
inflammation, remodeling and resistance, which correlates with disease
control and severity. Chronic inflammatory process of the airways
triggers airway remodeling, which reflects the degree of airway
resistance. Pro-inflammatory and pro-fibrotic mediators are centrally
involved in this process. This study has investigated for the first
time, whether the levels of pulmonary and systemic pro-inflammatory and
pro-fibrotic mediators present correlation with the resistance of
respiratory system and of proximal and distal airways. Methods: 24
asthmatic children (persistent mild and moderate) and 24 non-asthmatic
children (both between 6-13 years old) were evaluated for anthropometric
characteristics, lung function and mechanics, pulmonary and systemic
immune response. Results: Asthmatic children showed an increased number
of blood eosinophils (p<0.04), basophils (p<0.04),
monocytes (p<0.002) and lymphocytes (p<0.03). In
addition, asthmatic children showed an impaired lung function, as
demonstrated by FEV1%pred. (p<0.0005) and FEV1/FVC
(p<0.004), decreased total resistance of respiratory system
(R5Hz; p<0.009), increased resistance of proximal airways
(R20Hz; p<0.02), increased elastance (Z5Hz; p<0.02)
and increased reactance (X5Hz; p<0.002). Moreover, the
following inflammatory factors were significantly higher in asthmatic
than non-asthmatic children: GM-CSF in the breath condensate (BC)
(p<0.0001) and in the serum (p<0.0001); TGF-beta in
the BC (p<0.0001) and in the serum (p<0.004); IL-5
in the BC (p<0.02) and in the serum (p<0.01); IL-4
in the serum (p<0.0002). Conclusions: Impulse oscillometry is
a sensitive method to detect airway resistance in asthmatic children,
reflecting airway remodeling, an event followed by increased levels of
pro-inflammatory and pro-fibrotic mediators.