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

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.