FUNCTIONAL CHARACTERISATION, DISEASE BURDEN AND PREDICTORS OF MORTALITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: PRELIMINARY RESULTS FROM THE ITALIAN COPD REGISTRY

Background Chronic Obstructive Pulmonary Disease (COPD) is a complex and heterogeneous disease characterized by variable respiratory symptoms and by different degrees of small airways dysfunction and emphysema. Patients with COPD are at increased risk of exacerbations, hospitalizations and mortality, but although over the years numerous severity classification systems have been proposed, they often revealed to be poorly associated with clinical outcomes. The degree of disease burden, the role of lung function, comorbidities and pharmacological therapy in real life is still poorly understood. Aim of the study The co-primary outcomes of the study were 1) to evaluate the informativeness of different severity classification systems based on lung function characteristics, clinical phenotypes and serum eosinophils and 2) to evaluate the burden of COPD in terms of exacerbations, exacerbation rate and mortality within the Italian COPD registry. Methods This was a retrospective, multicenter study based on the preliminary analysis of the data from the novel Italian COPD registry. Patients were retrospectively enrolled from 2014 until 2016 and variables regarding anthropometric, clinical and functional characteristics of patients with a confirmed diagnosis of COPD were reviewed and collected for a cross-sectional analysis. Risk subgroups were based on exacerbation history during the year before entering the study were followed for the incidence of moderate and severe exacerbation during each year of follow up, up to 3 consecutive years. Survival state was assessed at the end of follow up. Results In total, 1360 patients (73.4% males) were enrolled in the registry and analyzed. Overall, 37% had very severe airflow obstruction. Inspiratory capacity, diffusion lung capacity for carbon monoxide (DLCO) and the prevalence of emphysema were reflected by the functional Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification only. The proportion of patients with > 200 eosinophils/μl was higher in GOLD 4 III-IV stages compared with GOLD I-II (P=0.008). For the longitudinal analysis 1111 patients were included (73% males); 41.5% had a history of exacerbations. The proportion of patients experiencing ≥1 exacerbation during follow-up increased according to pre-defined study risk categories. Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% severe), and 13% died. Compared with survivors, patients that died were older, had worse airflow obstruction and hyperinflation. Severe exacerbations were more frequent in patients that died (23%, vs 10%; P=0.002). Chronic heart failure and ischemic heart disease were independent risk factors for mortality (OR (95%CI: 2.2 (1.4-3.6), P=0.001 and 1.9 (1.2-2.9), P=0.007). Conclusions COPD classifications excluding lung function might miss relevant patients’ clinical characteristics such as hyperinflation, DLCO impairment and clinical phenotypes, which have a significant impact on outcomes and disease severity. Patients at low exacerbation risk are at significant risk of future moderate or severe events. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.