MULTI-PHACET: multidimensional clinical phenotyping of hospitalised acute COPD exacerbations

MacDonald, Martin I.; Osadnik, Christian R.; Bulfin, Lauren; Leahy, Elizabeth; Leong, Paul; Shafuddin, Eskandarain; Hamza, Kais; King, Paul T.; Bardin, Philip G.

BACKGROUND: The generic term “exacerbation” does not reflect the heterogeneity of acute exacerbations of COPD (AECOPD). We utilised a novel algorithmic strategy to profile exacerbation phenotypes based on underlying aetiologies. METHODS: Patients hospitalised for AECOPD (n=146) were investigated for aetiological contributors summarised in a mnemonic acronym ABCDEFGX (A: airway virus; B: bacterial; C: co-infection; D: depression/anxiety; E: eosinophils; F: failure (cardiac); G: general environment; X: unknown). Results from clinical investigations were combined to construct AECOPD phenotypes. Relationships to clinical outcomes were examined for both composite phenotypes and their specific aetiological components. Aetiologies identified at exacerbation were reassessed at outpatient follow-up. RESULTS: Hospitalised AECOPDs were remarkably diverse, with 26 distinct phenotypes identified. Multiple aetiologies were common (70%) and unidentifiable aetiology rare (4.1%). If viruses were detected (29.5%), patients had longer hospitalisation (7.7±5.6 versus 6.0±3.9 days, p=0.03) despite fewer “frequent exacerbators” (9.3% versus 37%, p=0.001) and lower mortality at 1 year (p=0.03). If bacterial infection was found (40.4%), patients were commonly “frequent exacerbators” (44% versus 18.4%, p=0.001). Eosinophilic exacerbations (28%) were associated with lower pH (7.32±0.06 versus 7.36±0.09, p=0.04), higher venous carbon dioxide tension (P(vCO(2))) (53.7±10.5 versus 48.8±12.8, p=0.04), greater noninvasive ventilation (NIV) usage (34.1% versus 18.1%) but shorter hospitalisation (4 (3–5) versus 6 (4–9) days, p<0.001) and lower infection rates (41.4% versus 80.9%, p<0.0001). Cardiac dysfunction and severe anxiety/depression were common in both infective and non-infective exacerbations. Characteristics identified at exacerbation often persisted after recovery. CONCLUSIONS: Hospitalised AECOPDs have numerous causes, often in combination, that converge in complex, multi-faceted phenotypes. Clinically important differences in outcomes suggest that a phenotyping strategy based on aetiologies can enhance AECOPD management.