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 .