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Severe Asthma (SA) in children is relatively rare, affecting 2-5% of the asthmatic pediatric population. However, its burden is disproportionally high, as children with SA experience frequent asthma attacks, have a reduced quality of life, and account for approximately half of pediatric asthma healthcare costs. Asthma is now considered to encompass multiple conditions characterized by common symptoms (wheeze, cough, shortness of breath, chest tightness), variable degrees of airflow limitation, and various patterns of inflammation. Little data are available concerning airway inflammation (AI) and airway remodeling (AR) in pediatric asthma and the pathogenesis of pediatric SA cannot be completely extrapolated from adult studies. For example, although eosinophilic airway inflammation is a key feature of SA in schoolchildren, there is no evidence for the presence of Th2-type cytokines in bronchial mucosa or bronchoalveolar lavage (BAL) in this population. In this issue of Pediatric Pulmonology, Castro-Rodriguez et al4) present an extensive review of the intervention studies conducted in children with SA symptoms, in which direct analysis of AI and/or AR has been performed on BAL and/or bronchial biopsy. The authors sought to analyze the relationship between inflammation and remodeling and determine whether remodeling affects lung function (LF). AR has long been thought to result from repeated acute and chronic inflammation. However, this paradigm has been challenged by findings showing that some remodeling markers, especially increased reticular basement membrane (RBM) thickness, and airway smooth muscle (ASM) area can be observed early in the course of asthma, as early as in the preschool years, and that remodeling and inflammation appear to be unrelated in preschoolers with SA symptoms. AI can be assessed directly by bronchial biopsy or BAL. However, CastroRodriguez et al found only seven studies in which AI was analyzed in both BAL and biopsy. The extent to which the inflammatory cell counts in BAL correlate with those in the bronchial mucosa is unclear. Lex et al found that the eosinophil counts in BAL and bronchial mucosa were unrelated in children and adolescents with SA. The most reliable samples for analyzing AI in children with SA are those obtained from the bronchial mucosa, because they are collected directly from the pathological organ. In addition, most published biopsy studies have reported eosinophilic and neutrophilic infiltration of the bronchial mucosa, with a few focusing on other inflammatory cells, such as mast cells, lymphocytes, and macrophages. An important limitation of endoscopy studies in children is that they cannot include control subjects without any airway diseases for obvious ethical reasons. In many cases, the control subjects have upper or lower airway diseases other than asthma, whereas in others, no control subjects are included. It is therefore difficult to determine whether the observed features are pathological and specific to SA. This, along with the use of different technical procedures, limits the relevance of comparing studies and interpretation of the data. As expected, the authors showed that the datawere insufficient to make conclusions concerning potential influence of inflammation on remodeling in children with SA. However, they highlight that eosinophilic inflammation of the airways is always accompanied by the presence of remodeling markers. This does not mean that eosinophils cause remodeling, nor that inflammation precedes it. However, this is of major importance, because the presence of eosinophilsmay indicate an ongoing active inflammatory process in the airways, despite the use of high doses of inhaled steroids. Evidence suggest that AI in preschoolers with SA symptoms is more neutrophilic than eosinophilic, whereas SA in schoolchildren is more eosinophilic. This raises the question of whether SA in preschool and school-age children is based on a common pathological process, or whether they represent two different types of asthma. Interestingly, our group recently showed that some preschoolers with SA symptoms may display both eosinophilic and neutrophilic inflammation, and that those with more eosinophils at preschool age may be at increased risk of frequent severe exacerbations at school age. Analysis of the relationship between remodeling and LF showed an inverse correlation between ASM area and RBM thickness and FEV1 or FEV1/FVC. These findings are not surprising and support that 50% of children with asthma show a reduced increase in LF during childhood, with only 25% reaching 26 years of age with normal LF. However, most studies have focused only on RBM thickness and/or ASMarea, and the other remodelingmarkers, such asmucus gland area and epithelial integrity and vascularity are rarely described in children with SA. Their potential influence on LF or, more generally, on asthma is still poorly understood. Interventional studies with biopsy and extensive analysis of all AR markers are therefore needed to improve our understanding of how histological changes within the airway wall may affect the disease. For example, high vascularity in preschoolers with SA symptomsmay be associatedwith poor LF at school age.We have shown that there may be a substantial overlap between AR markers in preschoolers and school children, including RBM thickness, ASM, and mucus gland area, and epithelial integrity and vascularity. This finding suggests that the remodeling process may be progressive,