Focus area: Physicians
Inflammation and remodeling in childhood asthma
The relationship between airway inflammation and airway remodeling is controversial. Are we able to determine, to date, if there is a real correlation?
Data from worldwide birth-cohort studies show that lung function is reduced in the early preschool years in children who develop asthma, and that the loss in lung function by the age of 5 years tracks into adulthood without recovering.
Castro-Rodriguez JA et al have perform a systematic review of all studies with direct measurements of both airway inflammation and remodeling in the subgroup of children with repeated wheezing and/or persistent asthma severe enough to warrant bronchoscopy, to address whether airway inflammation precedes remodeling or is a parallel process, and also to assess the impact of remodeling on lung function. They found 526 references, and 39 studies (2390 children under 18 years old) were included. Airway inflammation (eosinophilic/neutrophilic) and remodeling were not present in wheezers at a mean age of 12 months, but in older pre-school children (mean 2.5 years), remodeling (mainly increased reticular basement membrane [RBM] thickness and increased area of airway smooth muscle) and also airway eosinophilia was reported. This was worse in school-age children. RBM thickness was similar in atopic and non-atopic preschool wheezers. Airway remodeling was correlated with lung function in seven studies, with FeNO in three, and with HRCT-scan in one. Eosinophilic inflammation was not seen in patients without remodeling. There were no invasive longitudinal or intervention studies. For these results, it can be concluded that the relationship between inflammation and remodeling in children cannot be determined and the failure to demonstrate eosinophilic inflammation in the absence of remodeling is contrary to the hypothesis that inflammation causes these changes. If the relationship between inflammation and remodeling is to be resolved, a key research priority is to identify reliable non-invasive marker of inflammation and remodeling that can be used at all ages, including infants and preschool children. This would allow longitudinal assessments and enable us to determine which if any aspects of remodeling are protective and should be augmented, and which worsen airflow obstruction and should be treated.