Respiratory Rehabilitation Index (R2I): Unsupervised Clustering Approach to Identify COPD Subgroups Associated with Rehabilitation Outcomes

<b>Background/Objectives</b>: Chronic obstructive pulmonary disease (COPD) is a progressive condition whose heterogeneous endotypes, clinical manifestations, and recovery pathways complicate the identification of reliable predictors of rehabilitation outcomes. Several respiratory and functional assessments are available with no consensus on the most predictive ones. While univariate markers may miss multifactorial interactions essential for prognosis, data-driven unsupervised clustering methods can integrate complex information from different sources. This study aimed to apply unsupervised clustering to identify pre-rehabilitation characteristics predictive of discharge outcomes for COPD patients undergoing pulmonary rehabilitation. <b>Methods</b>: A total of 126 COPD patients undergoing pulmonary rehabilitation were included in the analysis. Three assessments were performed at admission, namely the forced oscillation technique, spirometry, and the six-minute walk test (6MWT). The outcome was the change in 6MWT distance between admission and discharge. Unsupervised clustering methods were applied to admission variables to identify subgroups associated with outcomes. <b>Results</b>: Among the clustering algorithms tested, k-means (with N_cl = 2) provided the optimal solution. The resulting respiratory rehabilitation index (R2I) was significantly associated with the outcome dichotomized via the minimal clinically important difference of 30 m. Patients with R2I = 1, indicating severe functional and respiratory impairments, were associated with higher post-rehabilitation functional improvement (<i>p</i> = 0.032). While few functional parameters of 6MWT were statistically different between the groups identified by outcome, nearly all variables in the analysis exhibited significant distribution differences among the R2I clusters. <b>Conclusions</b>: These findings highlight the heterogeneity of COPD and the potential of unsupervised clustering to identify distinct patient subgroups, enabling more personalized rehabilitation strategies.