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BackgroundIt is unclear whether patients with asthma benefit from stepping up to high-dose inhaled corticosteroids (ICSs).ObjectiveTo determine the effectiveness of stepping up to high-dose ICSs.MethodsA historic cohort study of patients with asthma (≥13 years old), identified from 2 large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICSs were compared with those who stepped up from medium- to high-dose ICSs, whereas patients who stepped up from low- to medium-dose ICSs were compared with those who stepped up from low- to high-dose ICSs. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and the number of exacerbations and antibiotics courses was analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding.ResultsThe mean follow-up time to first exacerbation was 2.7 ± 2.7 years for those who remained on stable medium-dose ICSs and 2.0 ± 2.2 years for those who stepped up from medium- to high-dose ICSs. A similar pattern was noted for those who stepped up from low- to medium-dose ICSs (2.6 ± 2.5 years) and from low- to high-dose ICSs (2.3 ± 2.5 years). Patients who stepped up from medium- to high-dose ICSs (n = 6879) had a higher risk of exacerbations during follow-up compared with those who remained on medium-dose ICSs (n = 51,737; hazard ratio, 1.17; 95% CI, 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n = 3232) compared with low- to medium-dose (n = 12,659) ICSs (hazard ratio, 1.10; 95% CI, 1.04-1.17). A step-up to high-dose ICSs was also associated with a higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts.ConclusionsWe found no evidence that a step-up to high-dose ICSs is effective in preventing future asthma exacerbations.

Original publication




Journal article


The journal of allergy and clinical immunology. In practice

Publication Date





532 - 543


Respiratory Medicine Unit and Oxford Respiratory NIHR BRC, Oxford, United Kingdom; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.


Humans, Asthma, Adrenal Cortex Hormones, Anti-Asthmatic Agents, Administration, Inhalation, Proportional Hazards Models, Cohort Studies, Adolescent, United Kingdom