Abstract
Young COPD patients (i.e. before 50 years) experience early onset a disease that develops during lung growth. They carry the worst burden with an established poorest prognosis than regular patients with COPD. Hedgehog interacting protein (HHIP) polymorphisms have been previously associated with reduced lung function and risk of COPD, but their effect on the protein expression remains unknown. COPD patients have lower HHIP protein levels than healthy controls.This study aimed to investigate the association between serum HHIP levels and the age of onset of COPD in a cohort of patients.We performed ELISA assessment in each serum sample of the 380 patients included in the French multicenter COBRA cohort. The sample was divided given the age of onset from medical records into four quartiles. We compared three groups using Kruskal Wallis test: ≤ 55 years; 56 to 69 years; ≥ 70 years.Median predicted %FEV1 was 56 (35; 74) and median age of onset was 62 years (55; 69). Serum HHIP protein appeared lower in young patients with a mean level of 17±15 instead of 20±16 in the middle group and 26±15ng/ml in the late-onset group (p<0.01). Similar results were found after linear regression. A Pearson correlation coefficient of 0.20 indicated that 20% of the protein levels variation could be explained by age of onset.These findings could suggest that lower HHIP levels may be associated with an increased risk of young COPD. These results provide insights into the molecular mechanisms involved in COPD pathogenesis. Further research is warranted to elucidate the causative relationship between Hedgehog pathway and early COPD, paving the way for targeted therapeutic interventions and personalized management strategies.