Impact of comorbidities in COPD clinical control criteria. The CLAVE study
Authors: Almagro Pere , Soler-Cataluña Juan José , Huerta Arturo , González-Segura Diego , Cosío Borja G. ,   on behalf of the CLAVE Study Investigators
Published: January 2024

Abstract
Background
Chronic obstructive pulmonary disease (COPD) frequently coexists with other chronic diseases, namely comorbidities. They negatively impact prognosis, exacerbations and quality of life in COPD patients. However, no studies have been performed to explore the impact of these comorbidities on COPD clinical control criteria.

Research question
Determine the relationship between individualized comorbidities and COPD clinical control criteria.

Study design and methods
Observational, multicenter, cross-sectional study performed in Spain involving 4801 patients with severe COPD (< 50 predicted forced expiratory volume in the first second [FEV1%]). Clinical control criteria were defined by the combination of COPD assessment test (CAT) scores (≤16 vs ≥17) and exacerbations in the previous three months (none vs ≥1). Binary logistic regression adjusted by age and FEV1% was performed to identify comorbidities potentially associated with the lack of control of COPD. Secondary endpoints were the relationship between individualized comorbidities with COPD assessment test and exacerbations within the last three months.

Results
Most frequent comorbidities were arterial hypertension (51.2%), dyslipidemia (36.0%), diabetes (24.9%), obstructive sleep apnea-hypopnea syndrome (14.9%), anxiety (14.1%), heart failure (11.6%), depression (11.8%), atrial fibrillation (11.5%), peripheral arterial vascular disease (10.4%) and ischemic heart disease (10.1%). After age and FEV1% adjustment, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; all p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; all p < 0.001), sleep disorders (p < 0.0001), anemia (p = 0.015) and gastroesophageal reflux (p < 0.0001). These comorbidities were also related to previous exacerbations and COPD assessment test scores.

Interpretation
Comorbidities are frequent in patients with severe COPD, negatively impacting COPD clinical control criteria. They are related to health-related quality of life measured by the COPD assessment test. Our results suggest that comorbidities should be investigated and treated in these patients to improve their clinical control.

Take-home points
Study question: What is the impact of comorbidities on COPD clinical control criteria?
Results: Among 4801 patients with severe COPD (27.5% controlled and 72.5% uncontrolled), after adjustment by age and FEV1%, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; p < 0.001), obstructive sleep apnea-hypopnea syndrome (p < 0.0001), anaemia (p = 0.015) and gastroesophageal reflux (p < 0.0001), which were related to previous exacerbations and COPD assessment test scores.
Interpretation: Comorbidities are related to health-related quality of life measured by the COPD assessment test scores and history of exacerbations in the previous three months.