Maternal and early-life obesity is associated with pediatric asthma phenotype in children and with a shift of the epithelial cell methylome towards premature epithelial aging

Hintergrund Obesity early in life often affects the clinical course of asthma. While maternal obesity has been identified as a risk factor for childhood obesity, the impact of early-life obesity on asthma phenotype and the underlying mechanisms are unclear. Therefore, we now investigated (i) the influence of maternal and childhood obesity on the onset, severity and triggers of asthma symptoms in children and (ii) analysed the epigenetic profile of nasal epithelial cells of asthmatics using the methylome as an indicator of obesity-related premature aging of lung epithelial cells in asthma.

Methoden 221 patients with diagnosed asthma or wheeze and 33 healthy controls from two sites of the pediatric arm of the longitudinal All-Age Asthma Cohort (ALLIANCE) study were investigated. Maternal [weight and BMI during pregnancy] as well as children’s parameters [birthweight; BMI at Baseline Visit and Body-Fat Fraction (BFF)] were correlated with FEV1 at Baseline Visit, GINA symptom control, hospital admissions per year, onset of symptoms, baseline IgE and triggers for wheezing. In 120 additional patients and controls, methylome-derived “DNAge” (mDNAge) was estimated in human nasal epithelial cells using an epigenetic clock model by Horvath.

Ergebnisse Maternal BMI during pregnancy was higher in the asthma cohort than in healthy controls (Mean: 24,68 kg/m2 vs. 22,30 kg/m², p = 0,0075). Furthermore, maternal BMI was higher in children with increased asthma-related hospital treatments per year (p = 0,046). In addition, birth weight was higher in children who developed wheezing in the first 6 months of life (3544g vs. 3375g, p = 0,0099). Similarly, higher BFF at baseline visit was linked to an early onset of symptoms (27,78% vs. 21,90%, p = 0,03) and was also associated with worse GINA symptom control and FEV1. Higher BMI in patients was associated with higher Baseline IgE (p=0,036) and specific wheezing triggers e.g. physical activity, pollen and dust exposition. Higher BMI was positively associated with higher mDNAge of nasal epithelial cells (p= 0,0539) and obese asthmatics showed higher mDNAge than non-obese asthmatics (p=0,0008).

Schlussfolgerung Our results highlight the clinical impact of perinatal obesity on asthma triggers, onset and severity in childhood. In addition, they suggest that obesity-driven premature aging of respiratory epithelial cells could be the mechanism underlying a possible epithelial dysfunction triggering obesity-related asthma in children.

Publication History

Article published online:
22 February 2024