Study population
We identified all adults aged 18 to 45, who had filled at least two asthma drug prescriptions on different occasions within 12 successive months since the age of 15 during the period 1995-2018 (19, 20). We defined the study period as 1999-2018 to ensure a sufficient run-in period (1995-1998). Inclusion time was the date for the first of the two redeemed prescription with the 18th birthday as the earliest date. The asthma-related drugs of interest included inhalations of selective b2-agonists, inhaled glucocorticoids, fixed combinations of b2-agonists and glucocorticoids, leukotriene receptor antagonists and xanthines.
We excluded individuals with diagnoses of chronic obstructive pulmonary diseases or cystic fibrosis, use of roflumilast, or recent migrations within two years prior of inclusion time. Furthermore, we excluded individuals with other diseases commonly treated OCS, i.e. sarcoidosis, primary adrenocortical insufficiency, pneumonitis, inflammatory bowel disease, inflammatory polyarthropathies, systemic connective tissue disorders, inflammatory and/or malignancy. Individuals with apparent inactive asthma, defined by no redeemed asthma-medication for two consecutive years, were censored but were permitted to re-enter the cohort upon resumed use.
Individuals were followed until the age of 46, death, migration, other disease commonly treated with OCS, or end of study period (31st December 2018).
The study design and study population selection are shown inFigure 1 .