From mild-to-moderate to severe asthma: Risk factors and patient profiles from the NORDSTAR cohort

Abstract Background The progression from mild-to-moderate to severe asthma remains unclear. This study aimed to assess the risk of progression following the first asthma exacerbation in mild-to-moderate asthma and to identify risk factors and high-risk patient profiles. Methods This was an observational cohort study based on Danish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. Adult patients with mild-to-moderate asthma experiencing their first asthma exacerbation were identified between 2000-2018 and followed prospectively for five years for the development of severe asthma according to ERS/ATS guidelines. Baseline risk factors for progression to severe asthma were assessed using multivariable logistic regression models and risk of progression was evaluated across specific patient profiles. Results Among 99,748 patients with mild-to-moderate asthma experiencing the first asthma exacerbation, 4.1% progressed to severe asthma within five years. Risk factors included baseline age 40-49 years odds ratio (OR): 1.62 (95% CI: 1.49, 1.77), experiencing an exacerbation despite medium dose inhaled corticosteroid (ICS) use [OR: 3.72 (3.39, 4.09), high use of short-acting beta agonist OR: 1.76 (1.64, 1.90), ≥2 respiratory infections OR: 1.61 (1.49-1.73), and blood eosinophil counts ≥ 0.6 × 109/L OR: 1.97 (1.47-2.61). A 40-49-year-old patient with late-onset eosinophilic asthma, treated with medium-dose ICS and with recurrent respiratory infections, had a 30.4% five-year risk of progressing to severe asthma. Conclusion In patients with mild-to-moderate asthma experiencing their first asthma exacerbation, few patients (4.1%) overall progressed to severe asthma within five years, but specific high-risk patient profiles faced risks of up to 30%. Whether early recognition can modify this risk warrants further investigation.