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 correlate with disease control and severity. The chronic inflammatory process of the airway triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process.

Objective

To investigate whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present a correlation with the resistance of the respiratory system and of the proximal and distal airways.

Methods

39 Asthmatic children (persistent mild and moderate) and 39 non-asthmatic children (both between 6 and 13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, and pulmonary and systemic immune responses.

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 impaired lung function, as demonstrated by FEV1 (p < 0.0005) and FEV1/FVC (p < 0.004), decreased total resistance of the respiratory system (R5Hz; p < 0.009), increased resistance of the proximal airways (R20Hz; p < 0.02), increased elastance (Z5Hz; p < 0.02) and increased reactance (X5Hz; p < 0.002) compared to non-asthmatic children. 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 persistent mild and moderate asthmatic children, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators.

Keywords:

• Lung function
• lung immunology
• lung remodeling
• lung mechanics
• asthma
• asthmatic children

Declaration of interest

No potential conflict of interest was reported by the author(s).

Data availability statement

The row data will be available upon reasonable request to the corresponding author.

Additional information

Funding

This study was supported by São Paulo Research Foundation (FAPESP), grants #2012/15165-2 and the National Council of Research and Development (CNPq), grants 427889/2016-2 and 313299/2018-8. MARBR holds a PhD fellowship from FAPESP (2019/05739-0). RMF holds a PhD fellowship from FAPESP (2019/11008-9), ACR holds a technical fellowship from FAPESP (2019/26116-1).