Adrenomedullin independently predicts exertional hypoxemia in COPD - Results of European PROMISE COPD study

Background The prevalence of exertional hypoxemia (EH) in unselected COPD patients is unknown. Hypoxia leads to adrenomedullin (ADM) upregulation through the HIF-1 pathway. We hypothesize that ADM might be associated with EH in COPD. Adding ADM to clinical variables might improve EH prediction Methods 1233 6MWTs from 574 patients with clinically stable COPD II - IV enrolled in an investigator initiated, multinational, prospective, longitudinal, observational cohort were analyzed. EH was defined as an arterial SaO 2 ≤ 88% measured during 6MWT Findings EH was observed in 27.3%, 28.5% and 28.4% at baseline, 1 and 2 years FU. EH was common in GOLD IV (54%) but not infrequent in III (38.8%) and II (15.1%). Patients presenting EH had a longer duration of the disease, more dyspnoea, poorer health-related QoL, shorter 6 MWD, higher HR, and increased ADM. EH was associated with greater deterioration of the health-related QoL (SGRQ activity score ,p=0.038) and SF-36 (physical function, p=0.034), higher severe exacerbation (p=0.006) and death (p=0.02) annual rates. In the UV analysis, MMRC, 6MWD, FEV1% pred, and ADM but not age and Charlson score were associated with EH. In the MV analysis, besides FEV1%pred (p<0.001) and MMRC (p=0.01), only ADM (p=0.004) remained a significant predictor of EH. Relative to using only FEV1% pred, adding ADM improved the predictive properties for EH ( X 2 11.97, p=0.0005), NRI 95% CI (7.4%, p=0.015). Conclusion: Exertional desaturation is common and associated with poorer clinical outcomes in stable COPD. ADM improves prediction of exertional desaturation.