Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma

Abstract

Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma.

Causal associations between pediatric asthma and united airways disease: a two-sample Mendelian randomization analysis

“…The findings of a 50 year cohort study demonstrate a significant association between pediatric asthma and an increased risk of developing COPD in later life ( 53 ); children with a prior history of asthma exhibit a 3.45-fold increased likelihood of developing COPD compared to children without such a medical background ( 54 ). Pediatric asthma can impair lung development, hindering the attainment of normal peak lung function during adolescence and diminishing adult lung function, thereby augmenting the susceptibility to developing COPD ( 55 ). Nevertheless, early suppression of airway inflammation and prevention of asthma exacerbations in childhood can foster optimal lung development and maturation, culminating in enhanced lung function and a reduced risk of COPD in adulthood ( 55 ).…”

“…Pediatric asthma can impair lung development, hindering the attainment of normal peak lung function during adolescence and diminishing adult lung function, thereby augmenting the susceptibility to developing COPD (55). Nevertheless, early suppression of airway inflammation and prevention of asthma exacerbations in childhood can foster optimal lung development and maturation, culminating in enhanced lung function and a reduced risk of COPD in adulthood (55). In a cross-sectional survey conducted on 851 patients with chronic sinusitis in seven cities across China, the prevalence of Chronic sinusitis Frontiers in Medicine 09 frontiersin.org among individuals with asthma was observed to be 24%, which is significantly higher compared to the 7% prevalence found among non-asthmatic participants (56).…”

Ιnterleukin-17A-Enriched Neutrophil Extracellular Traps Promote Immunofibrotic Aspects of Childhood Asthma Exacerbation

“…Remarkably, recent data focusing on severe non-eosinophilic forms of asthma have shown that neutrophils, inflammatory cytokines and/or mesenchymal cells may play a decisive role in the severity and progression of the disease [ 7 , 51 , 52 , 53 , 54 , 55 ]. In the same context, studies have supported that disease progression in adulthood may be predisposed by repeated exacerbations of asthma in childhood [ 56 , 57 ].…”

The Evolution of Scientific Knowledge in Childhood Asthma over Time: A Surprising History

“…The available studies have been conducted only in adults and in small size samples, showing a potential in vivo effect in airway remodeling evaluated through CT (omalizumab [75][76][77] and mepolizumab [78]) with a reduction in airway wall thickness and wall area, and increase in the tracheal lumen area, and through bronchial biopsies (omalizumab [79][80][81] and benralizumab [82]) with a reduction in reticular basement membrane thickness, in airway smooth muscle proteins, and in fibronectin deposit in airway submucosa. To date, no studies are available on the in vivo effects of dupilumab on airway remodeling [83]. Furthermore, even after discontinuation, biologic therapies possibly induce better control of asthma, thanks to their effect on airway remodeling.…”