Multifactorial Determinants of Refractory Breathlessness in COPD: Development of the Refractory Breathlessness Score for Risk Stratification.

PURPOSE: Despite optimized dual-bronchodilator therapy, many chronic obstructive pulmonary disease (COPD) patients continue to experience refractory breathlessness. This study aimed to identify the factors contributing to refractory breathlessness in patients with COPD, and to construct a clinically useful risk stratification tool, the Refractory Breathlessness Score (RB-Score).

PATIENTS AND

METHODS

In this retrospective cohort study conducted at a single teaching hospital between January 2014 and December 2023, patients with COPD who maintained the same type of dual-bronchodilator therapy, with or without inhaled corticosteroids, for one year were included. Refractory breathlessness was defined as the absence of at least a 1-point improvement in the mMRC dyspnea score at 12 months following treatment initiation. Independent predictors for refractory breathlessness were identified, and weighted points were assigned based on adjusted odds ratios (aORs) to develop the RB-Score.

RESULTS

Among 405 eligible patients, 244 (60.2%) had refractory breathlessness. Significant contributors included exacerbation events during treatment, comorbidities (severe anemia, cardiovascular disease, depression/anxiety, pulmonary hypertension), structural abnormalities (giant bulla, endobronchial stenosis), and inhaler-related factors (poor adherence, improper technique, multiple device use). In adjusted restricted cubic spline curve, RB-Score <1.92 was associated with a decreased risk of refractory breathlessness (aOR=0.77, 95% CI=0.59-1.00), while RB-Score >3.51 indicated increased risk (aOR=1.53, 95% CI=1.00-2.35). The RB-Score achieved good predictive performance (AUROC=0.854 [95% CI=0.818-0.891], AUPRC=0.899 [95% CI=0.865-0.928]).

CONCLUSION

Refractory breathlessness in COPD results from multiple factors, including pulmonary, comorbid, and inhaler-related issues. The RB-Score may facilitate risk stratification and guide individualized interventions though external validation is required.