Comorbidities and mortality in relation to asthma severity and exacerbations.

<bold>Background:</bold> Severe asthma patients have a significant disease burden, however, comorbidities and mortality by disease severity are not fully known. <bold>Aims and objectives:</bold> Explore comorbidity and mortality in bionaïve asthmatics by severity and exacerbations. <bold>Methods:</bold> Observational, registry-based, cohort study in all Finnish patients with physician-diagnosed asthma and a collection of obstructive airways drugs from Jan 2015 – Dec 2016 (followed until Dec 2020). Severe asthma was defined by treatment intensity (fluticasone propionate ≥ 800 μg/day + 2nd controller). Frequent exacerbations were defined as either two emergency visits/one hospitalization or baseline prednisolone >600 mg/year. Four cohorts were created based on severity (severe vs non-severe) and exacerbations (frequent vs non-frequent), matched on age, sex and district (n=5125/cohort). <bold>Results and conclusions:</bold> Cardiovascular and respiratory comorbidities were more common in asthmatics with frequent exacerbations, independent of severity. In patients with frequent exacerbations at baseline, cumulative no. of exacerbations was higher in severe vs. non-severe disease (mean 5.14 vs. 0.86 at 48 months). Compared to non-severe asthma with infrequent exacerbations, patients with severe asthma and frequent exacerbations had higher respiratory-, cardiovascular- and overall mortality (rate ratio 1.93, 8.17 and 1.9, respectively, p<0.001). Patients with severe asthma and frequent exacerbations have significant comorbidity and increased mortality. There is a need for effective therapies to reduce exacerbations in bionaïve patients uncontrolled by high intensity treatment. Impact of better treatment on comorbidities/mortality needs to be elucidated.