Comorbidities and their association with exacerbations in single inhaler triple therapy COPD patients

BACKGROUND: It is known that comorbidities associated with chronic obstructive pulmonary disease (COPD) can influence its course. However, according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, it is not clear which can affect the disease exacerbations in group E patients being regularly treated with single inhaler triple therapy (SITT).METHODS: We retrospectively extracted from our database SITT individuals treated with fluticasone furoate/vilanterol/umeclidinium (FF/UMEC/VI) or beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/GLI) for 1 year. Only patients who were prescribed more than 7 triple-therapy packages/year were considered. At least 3 oral corticosteroid (OC) packages prescribed during the triple treatment were used to identify COPD exacerbations.RESULTS: The number of patients enrolled on SITT therapy for 1 year was 5107 (1844-36.1%/females; 3263-63.9%/males; mean age: 74.9±9.3). SITT treatment adherence, i.e., triple therapy packages/year, was 10.8±2.9. The most common comorbidities associated to COPD were cardiovascular diseases (CVD - 73.4%), hypertension HYP (71.8%), and gastroesophageal reflux/dyspepsia (GER/D - 63.1%) and then all the others. Comorbidities increasing the risk of having ≥3 OC packages/year were: CVD (OR: 1.242 [95% CI: 1.033-1.494]; P=0.021), GER/G (OR: 3.164 [95% CI: 2.702-3.717]; P=0.0001), psychiatric disorders (OR: 1.751 [95% CI: 1.508-2.036]; P=0.0001), oncological diseases (OR: 2.227 [95% CI: 1.890-2.617]; P=0.0001), anemia (OR: 1.283 [95% CI: 1.046-1.577]; P=0.017), osteoporosis (OP) (OR: 1.631 [95% CI: 1.261-2.114]; P=0.0001), autoimmune diseases (OR: 1.748 [95% CI: 1.251-2.444]; P=0.001) and chronic kidney diseases (OR: 2.247 [95% CI: 1.453-3.412]; P=0.0001). Conversely, the association of COPD and HYP (OR: 0.788 [95% CI: 0.671-0.926]; P=0.004) and dyslipidemia (DYS) (OR: 0.753 [95% CI: 0.646-0.877]; P=0.0001) significantly reduced the exacerbation risk.CONCLUSIONS: In conclusion, in GOLD-Group E, many comorbidities are associated with increased risk of COPD exacerbations despite SITT. GER/D was the disease leading to a greater exacerbation risk. Conversely, HYP/DYS associations were protective against them. In higher risk patients, treatment increases for both COPD and comorbidities should be considered.