@article {MacDonald00198-2021, author = {Martin I. MacDonald and Christian R. Osadnik and Lauren Bulfin and Elizabeth Leahy and Paul Leong and Eskandarain Shafuddin and Kais Hamza and Paul T. King and Philip G. Bardin}, title = {MULTI-PHACET - MULTIdimensional clinical phenotyping of hospitalised acute COPD ExacerbaTions}, elocation-id = {00198-2021}, year = {2021}, doi = {10.1183/23120541.00198-2021}, publisher = {European Respiratory Society}, abstract = {Background The generic term {\textquotedblleft}exacerbation{\textquotedblright} 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=Coinfection, 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{\textpm}5.6 versus 6.0{\textpm}3.9 days, p=0.03) despite fewer {\textquotedblleft}frequent exacerbators{\textquotedblright} (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 {\textquotedblleft}frequent exacerbators{\textquotedblright} (44\% versus 18.4\%, p=0.001). Eosinophilic exacerbations (28\%) were associated with lower pH (7.32{\textpm}0.06 versus 7.36{\textpm}0.09, p=0.04), higher PvCO2 (53.7{\textpm}10.5 versus 48.8{\textpm}12.8, p=0.04), greater NIV usage (34.1\% versus 18.1\%) but shorter hospitalisation (4[3{\textendash}5] versus 6[4{\textendash}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.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr Martin MacDonald reports financial support for this study from GlaxoSmithKline: Payments made to support this project via an unrestricted educational grant. GlaxoSmithKline had no involvement in study design, patient recruitment, data analysis or manuscript preparation. No further disclosures provided.Conflict of interest: Christian Osadnik has nothing to disclose.Conflict of interest: Lauren J Bulfin reports financial support for this study from GlaxoSmithKline: Payments made to support this project via an unrestricted educational grant. GlaxoSmithKline had no involvement in study design, patient recruitment, data analysis or manuscript preparation. No further disclosures provided.Conflict of interest: Ms Elizabeth Leahy reports financial support for this study from GlaxoSmithKline: Payments made to support this project via an unrestricted educational grant. GlaxoSmithKline had no involvement in study design, patient recruitment, data analysis or manuscript preparation. No further disclosures provided.Conflict of interest: Paul Leong reports financial support for this study from GlaxoSmithKline: Payments made to support this project via an unrestricted educational grant. GlaxoSmithKline had no involvement in study design, patient recruitment, data analysis or manuscript preparation. No further disclosures provided.Conflict of interest: ESKANDARAIN SHAFUDDIN reports financial support for this study from GlaxoSmithKline: Payments made to support this project via an unrestricted educational grant. GlaxoSmithKline had no involvement in study design, patient recruitment, data analysis or manuscript preparation. No further disclosures provided.Conflict of interest: Kais Hamza has nothing to disclose.Conflict of interest: Paul King reports financial support for this study from GlaxoSmithKline: Payments made to support this project via an unrestricted educational grant. GlaxoSmithKline had no involvement in study design, patient recruitment, data analysis or manuscript preparation. No further disclosures provided.Conflict of interest: Philip Bardin reports financial support for this study from GlaxoSmithKline: Payments made to support this project via an unrestricted educational grant. GlaxoSmithKline had no involvement in study design, patient recruitment, data analysis or manuscript preparation. No further disclosures provided.}, URL = {https://openres.ersjournals.com/content/early/2021/04/29/23120541.00198-2021}, eprint = {https://openres.ersjournals.com/content/early/2021/04/29/23120541.00198-2021.full.pdf}, journal = {ERJ Open Research} }