Mechanisms of COPD Exacerbation Recurrence

Introduction: People living with chronic obstructive pulmonary disease (COPD) are susceptible to acute deteriorations in respiratory health termed “exacerbations”. Hospitalisations due to exacerbations of COPD are associated with high global health-care burden and cost. Preventing COPD exacerbations resulting in hospital re-admissions is a major target in COPD care. More work is needed to understand the mechanisms of re-admissions, prevent exacerbation recurrence, and find better approaches to prevent exacerbations. Aims: To identify risk factors and potential novel predictors for 30- and 90-day all-cause readmission following admission due to COPD exacerbation, as well as to systematically collect ‘uncertainties’ and prioritise resulting research questions in exacerbations of COPD. Methods: Firstly, a systematic review was completed to summarise and assess factors associated with 30- and 90-day all-cause readmission following hospitalisation for an exacerbation of COPD. Secondly, we assessed the feasibility and clinical utility of using Forced Oscillation Technique (FOT) in a COPD population admitted to hospital due to exacerbation. We next conducted a prospective cohort study in COPD patients admitted due to an exacerbation of COPD to identify risk factors of all-cause readmission within 30 and 90 days and find potential biomarkers that can be targeted to improve readmission burden, specifically examining FOT. In addition, a follow-up study was conducted to assess changes from discharge to a 30-day follow-up in physical activity, peak inspiratory flow rate (PIFR) and expiratory flow limitation (EFL) and how these changes relate to the recovery time for symptoms. Finally, we completed the first research prioritisation exercise for COPD exacerbations, with an equal voice to patient and clinicians’ preferences using the well-established, robust, and transparent James Lind Alliance (JLA) methodology. Results: Based on current literature, comorbidities, previous exacerbations and hospitalisation, and increased length of stay were significant risk factors for 30- and 90-day all-cause readmission after an index hospitalisation with an exacerbation of COPD. FOT was easily used to detect expiratory EFL during hospitalisation due to a COPD exacerbation and an improvement in EFL was associated with a reduction in breathlessness. Previous exacerbations, higher COPD Assessment Test (CAT) score at discharge, frailty, reduced PIFR and increased length of stay were significantly associated with 30-day readmission. 90-day readmissions were significantly associated with previous exacerbations and hospitalisations, higher CAT score at discharge, frailty, depression, lower PIFR and greater EFL in the supine position. The best predictive variable in multivariate analysis for both 30- and 90-day readmission was PIFR at discharge. A final top-ten list of research questions was identified from a list of 51 important research questions worthy of further study. The most highly related question was to identify better ways to prevent COPD exacerbations. Conclusion: We have identified novel and simple predictors for 30- and 90-day all-cause readmission following a COPD exacerbation that help identify patients at highest risk, and to optimise care prior to discharge. We have found important uncertainties and research priorities in the existing evidence for COPD exacerbations, identifying important areas for future investigations