Chronic hypoxaemia and gender status modulate adiponectin pathway in severe COPD patients: new endotypic presentation?

Abstract Background: Disease progression in COPD patient is associated to lung function decline, leading to a higher risk of hypoxaemia and associated comorbidities, notably cardiovascular diseases (CV). Gender is also known to influence CV risk. Adiponectin (Ad), a cardio-protective hormone, was suggested as a biomarker for COPD risk management. However, determinants and consequences of Ad pathway modulation in COPD are unknown and gender specificities are poorly understood. We postulated that hypoxaemia and gender could influence Ad pathway and contribute to the appearance of a distinct endotype associated to an altered CV risk.Methods: The Ad plasmatic (Adpl) level and proportion of its different forms were evaluated in hypoxemic and non-hypoxemic COPD men or women. The relationship between these measures and BMI, blood gas analysis (PaO2, PaCO2), or lung function (FEV1, FEV1/FVC, TLCO, TLC, RV) were tested.Results: Despite similar age, BMI and obstruction severity, women had a higher TLC and RV than men. Adpl level was higher in women and negatively associated with hyperinflation and hypercapnia. The proportion of the most active forms of Ad (HMW) is increased in hypoxemic women but not in men. A positive correlation between TLCO and HMW form proportion was observed in hypoxemic men, whereas a negative correlation was detected in non-hypoxemic men.Conclusion: Physiopathology of COPD seems to be gender specific. Hypoxaemia, hypercapnia and hyperinflation are associated to gender-specific Ad pathway alterations. Given CV properties of Ad, the impact of such modulation on co-morbidities development have to be considered in future studies.