Bronchial epithelium energetic metabolism and functionality under exacerbation in childhood asthma - 09/05/26

Asthma is the most common chronic inflammatory disease in children. Viral infection of the bronchial epithelium (BE) is the main trigger of asthma exacerbations. Rhinoviruses (RV) are detected in 85% of these events, with RV-C accounting for 67.5% in children and linked to severe forms. In adults, BE from asthmatics shifts its energy metabolism from mitochondrial oxidative phosphorylation to glycolysis [1 JACI 2021; 148:1236-1248.

Haga clic aquí para ir a la sección de Referencias] . In healthy BE, viral infection promotes a metabolic switch toward glycolysis, impacting muco-ciliary clearance [2 Nat Commun 2021; 12:3669.

Haga clic aquí para ir a la sección de Referencias] . We hypothesize that RV infection enhances glycolytic metabolism in BE, impairing its function in childhood asthma. We analyzed energy metabolism and BE functions under RV infection in BE from asthmatic and non-asthmatic children.

Cell culture: BE cells were obtained from bronchial brushing of children. In total, 100 000 cells were seeded on ALI transwells (0.4 μm pores, Corning Incorporated Transwell, Costar) with ALI medium (StemCell) at the basal pole.

RV infection: BE were infected with RV-C at MOI 0.1. After 1 h, the mix was removed, and experiments performed 24 h later.

Cellular Oxygen Consumption Rate (OCR): OCR was measured on intact cells (2.5 × 10 ⁵ cells/mL/run) at 37 °C using an Oroboros O ₂ k chamber (Oroboros Instruments).

Ciliary beating frequency: frequency was assessed using a Leica DMi8 videomicroscope (Leica Microsystems) and sCMOS Flash 4.0 high-speed camera (Hamamatsu) at the Bordeaux Imaging Center. A MATLAB program with Fourier transform identified the most represented beat frequency.

Under basal condition, BE from asthmatic children showed distinct metabolic profiles compared to non-asthmatics. Proteomics, OCR, and glycolytic enzyme expression indicated increased glycolysis over mitochondrial metabolism. RV infection exacerbated the shift toward glycolysis especially in non-asthmatic BE. Related to the energetic rewiring, ciliary beating frequency and efficiency were impaired in asthmatic BE compared to non-asthmatic children BE under basal condition an RV infection.

BE from asthmatic and non-asthmatic children differ metabolically at baseline and after RV infection. Also, one of the most important BE barrier function (ciliary beating) appears less efficient in asthmatic children BE. We will further investigate the downstream signalling mechanisms explaining the relationship between RV infection induced energetic metabolism shift and impaired BE barrier functions.