Chronic noninvasive ventilation in COPD: towards the identification of a responder phenotype.

Purpose: Chronic noninvasive ventilation (NIV) is an effective treatment for patients with chronic hypercapnia due to COPD, but the improvement in health-related quality of life (HRQoL) varies significantly among individuals. We conducted a cluster analysis to identify clusters of patients based on their HRQoL response to chronic NIV. Patients and methods: Patients with COPD and an indication for chronic NIV were prospectively followed. Gas exchange, lung function, exercise capacity and HRQoL were measured at baseline and at 6 months. HRQoL was measured with the Severe Respiratory Insufficiency questionnaire (SRI). The cluster analysis was performed using the self-organising map-Ward's method. In addition, we compared patient and disease characteristics, changes in outcomes and survival differences between the clusters. Results: A total of 301 participants were included in the analysis and 214 patients completed the 6-month follow-up. We identified three distinct clusters of patients with equal NIV use but different HRQoL response: a "good responder" phenotype of patients, characterised by a clinically relevant improvement on the SRI, a high number of exacerbations, poor baseline HRQoL and high rates of mood disorders; a "moderate responder" phenotype, characterised by milder gas exchange and lung function impairment, and relatively preserved baseline HRQoL; and a "poor responder" phenotype of patients in whom HRQoL worsened and survival was greatly impaired. This cluster included patients with the most severe lung function and gas exchange impairment and low rates of systemic comorbidities. Conclusion: Our cluster analysis suggests that chronic NIV is most likely beneficial in patients with frequent exacerbations, severely impaired HRQoL and a high incidence of mood disorders. Future randomised controlled trials should investigate whether the different HRQoL responses between the clusters are caused by NIV.