Abstract
PURPOSE: To characterize the multidimensional phenotype of childhood asthma associated with obesity at initial diagnosis, prior to controller therapy. METHODS: We conducted a cross-sectional study of 130 treatment-naïve children with asthma, comprising 67 with normal weight and 63 with obesity. All participants underwent spirometry, assessment of inflammatory biomarkers, and immune cell profiling. Lipid profiles were measured solely in the obese subgroup (n = 63) to evaluate metabolic comorbidity. The Type 2 (T2)-high inflammatory phenotype was defined using standard clinical cut-offs (blood eosinophil count ≥ 0.3 × 10⁹/L and/or FeNO ≥ 20 ppb); dyslipidemia was defined according to the 2012 National Cholesterol Education Program (NCEP) criteria. RESULTS: Compared to children with normal-weight asthma, those with obesity showed early airflow obstruction, with reductions in forced expiratory volume in 1 s (FEV₁%), the FEV₁/forced vital capacity (FVC) ratio, mid-expiratory flow (MMEF%), and peak expiratory flow (PEF%), but preserved FVC. Multivariable analysis confirmed this obstruction was independently associated with obesity after adjusting for age, sex, and T2-inflammatory status. The obese asthma group also presented elevated neutrophil counts, reduced regulatory T-cell (Treg) percentages, and a lower prevalence of the T2-high phenotype, despite a similarly high burden of clinical atopy and elevated serum total immunoglobulin E (IgE). Furthermore, over half (56%) of the obese group had dyslipidemia at diagnosis. CONCLUSION: At asthma diagnosis, obesity defines a phenotype characterized by early airflow limitation, a T2-low inflammatory tendency, and frequent metabolic dysregulation. Obesity itself is a primary, independent determinant of this lung function impairment. These findings establish a critical phenotypic baseline for future longitudinal studies aimed at enabling personalized management of childhood asthma complicated by obesity. WHAT IS KNOWN: • The association between obesity and asthma in children is recognized as a distinct clinical entity associated with more severe disease and poorer outcomes. Comprehensive baseline data integrating lung function, inflammatory profiles, and metabolic status are scarce for children with obesity related asthma in a treatment-naïve state. WHAT IS NEW: • At asthma diagnosis, treatment-naïve children with obesity present a distinct phenotype characterized by 1) early airflow obstruction, 2) a frequent T2-low inflammatory signature (with elevated neutrophils), and 3) a high prevalence of dyslipidemia-despite a high background of clinical atopy. Obesity itself is a primary, independent determinant of this early lung impairment. These findings establish a critical baseline profile, underscoring the need for multidimensional assessment to stratify risk and guide clinical decision-making in this population.