Use of high-dose inhaled corticosteroids and risk of corticosteroid related adverse events in asthma -findings from the NORDSTAR cohort

Anna von Bülow; Susanne Hansen; Patrik Sandin; Alexandra Cooper; Olivia Ernstsson; Kirk Geale; Lauri Lehtimäki; Charlotte Ulrik; Bernt Bøgvald Aarli; Pinja Ilmarinen; Sylvia Packham; Ghada Hassan; Asger Sverrild; Helena Backman; Jussi Karjalainen; Vibeke Backer; Alan Altraja; Paula Kauppi; Valentina Yasinska; Maritta Kilpeläinen; Arja Viinanen; Johannes Martin-Schmid; Apostolos Bossios; Celeste Porsbjerg; Hannu Kankaanranta; Christer Janson

doi:10.1016/j.jaip.2025.01.023

Use of high-dose inhaled corticosteroids and risk of corticosteroid related adverse events in asthma -findings from the NORDSTAR cohort

Anna von Bülow^*, Susanne Hansen, Patrik Sandin, Alexandra Cooper, Olivia Ernstsson, Kirk Geale, Lauri Lehtimäki, Charlotte Ulrik, Bernt Bøgvald Aarli, Pinja Ilmarinen, Sylvia Packham, Ghada Hassan, Asger Sverrild, Helena Backman, Jussi Karjalainen, Vibeke Backer, Alan Altraja, Paula Kauppi, Valentina Yasinska, Maritta KilpeläinenArja Viinanen, Johannes Martin-Schmid, Apostolos Bossios, Celeste Porsbjerg, Hannu Kankaanranta, Christer Janson^*

^*Corresponding author for this work

32 Citations (Scopus)

Abstract

BACKGROUND: The link between the use of oral corticosteroids (OCS) and adverse events (AEs) in asthma is well described. In contrast, whether the use of high-dose inhaled corticosteroids (ICS) poses a risk to these is unknown.

OBJECTIVE: To examine the association between ICS exposure and corticosteroid (CS)-related AEs.

METHODS: We conducted an observational cohort study using nationwide Swedish registry data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration. We included patients with asthma aged ≥18 years between 2009 and 2019 and calculated their current ICS exposure and average daily ICS dose (budesonide equivalent) in follow-up. The association between ICS exposure and CS-related AEs was analyzed using Cox proportional hazards models adjusting for age, sex, and OCS dose.

RESULTS: We included 529,203 patients with asthma. Overall, we observed increased hazard ratios (HRs) in those exposed to high-dose (≥800-1599 μg) and very high dose (≥1600 μg) ICS for several AEs, including cardiovascular disease, type 2 diabetes mellitus (T2DM), osteoporosis, and pneumonia compared with those not exposed to ICS. HRs for the current use of high-dose ICS ranged from 1.11 (95% confidence interval [CI]: 1.06-1.16) for T2DM to 1.65 (95% CI: 1.58-1.72) for pneumonia. Likewise, HRs linked to average daily high-dose ICS ranged from 1.16 (95% CI: 1.02-1.33) for pneumonia to 1.70 (95% CI: 1.38-2.08) for osteoporosis. Sensitivity analysis excluding patients using OCS showed that high-dose ICS was still associated with an increased risk of CS-related AEs. Overall, ICS <800 μg per day had no increased risk, except for cataract.

CONCLUSION: High-dose ICS is associated with an increased risk of several CS-related AEs. This highlights the importance of clinicians considering this risk in patients treated with high-dose and very high dose ICS.

Original language	English
Journal	The journal of allergy and clinical immunology. In practice
Volume	13
Issue number	7
Pages (from-to)	1609-1619.e5
ISSN	2213-2198
DOIs	https://doi.org/10.1016/j.jaip.2025.01.023
Publication status	Published - Jul 2025

Keywords

Administration, Inhalation
Adolescent
Adrenal Cortex Hormones/adverse effects
Adult
Aged
Anti-Asthmatic Agents/adverse effects
Asthma/drug therapy
Cardiovascular Diseases/epidemiology
Cohort Studies
Diabetes Mellitus, Type 2/epidemiology
Female
Humans
Male
Middle Aged
Osteoporosis/epidemiology
Pneumonia/epidemiology
Proportional Hazards Models
Registries
Sweden/epidemiology
Young Adult
Cardiovascular disease
Type 2 diabetes mellitus
Osteoporosis
Adverse events
Severe asthma
Asthma management
Cataract
Inhaled corticosteroids
Oral corticosteroids
Asthma

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10.1016/j.jaip.2025.01.023

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von Bülow, A., Hansen, S., Sandin, P., Cooper, A., Ernstsson, O., Geale, K., Lehtimäki, L., Ulrik, C., Bøgvald Aarli, B., Ilmarinen, P., Packham, S., Hassan, G., Sverrild, A., Backman, H., Karjalainen, J., Backer, V., Altraja, A., Kauppi, P., Yasinska, V., ... Janson, C. (2025). Use of high-dose inhaled corticosteroids and risk of corticosteroid related adverse events in asthma -findings from the NORDSTAR cohort. The journal of allergy and clinical immunology. In practice, 13(7), 1609-1619.e5. https://doi.org/10.1016/j.jaip.2025.01.023

Use of high-dose inhaled corticosteroids and risk of corticosteroid related adverse events in asthma -findings from the NORDSTAR cohort. / von Bülow, Anna; Hansen, Susanne; Sandin, Patrik et al.
In: The journal of allergy and clinical immunology. In practice, Vol. 13, No. 7, 07.2025, p. 1609-1619.e5.

Research output: Contribution to journal › Journal article › Research › peer-review

von Bülow, A, Hansen, S, Sandin, P, Cooper, A, Ernstsson, O, Geale, K, Lehtimäki, L, Ulrik, C, Bøgvald Aarli, B, Ilmarinen, P, Packham, S, Hassan, G, Sverrild, A, Backman, H, Karjalainen, J, Backer, V, Altraja, A, Kauppi, P, Yasinska, V, Kilpeläinen, M, Viinanen, A, Martin-Schmid, J, Bossios, A, Porsbjerg, C, Kankaanranta, H & Janson, C 2025, 'Use of high-dose inhaled corticosteroids and risk of corticosteroid related adverse events in asthma -findings from the NORDSTAR cohort', The journal of allergy and clinical immunology. In practice, vol. 13, no. 7, pp. 1609-1619.e5. https://doi.org/10.1016/j.jaip.2025.01.023

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title = "Use of high-dose inhaled corticosteroids and risk of corticosteroid related adverse events in asthma -findings from the NORDSTAR cohort",

abstract = "BACKGROUND: The link between the use of oral corticosteroids (OCS) and adverse events (AEs) in asthma is well described. In contrast, whether the use of high-dose inhaled corticosteroids (ICS) poses a risk to these is unknown.OBJECTIVE: To examine the association between ICS exposure and corticosteroid (CS)-related AEs.METHODS: We conducted an observational cohort study using nationwide Swedish registry data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration. We included patients with asthma aged ≥18 years between 2009 and 2019 and calculated their current ICS exposure and average daily ICS dose (budesonide equivalent) in follow-up. The association between ICS exposure and CS-related AEs was analyzed using Cox proportional hazards models adjusting for age, sex, and OCS dose.RESULTS: We included 529,203 patients with asthma. Overall, we observed increased hazard ratios (HRs) in those exposed to high-dose (≥800-1599 μg) and very high dose (≥1600 μg) ICS for several AEs, including cardiovascular disease, type 2 diabetes mellitus (T2DM), osteoporosis, and pneumonia compared with those not exposed to ICS. HRs for the current use of high-dose ICS ranged from 1.11 (95\% confidence interval [CI]: 1.06-1.16) for T2DM to 1.65 (95\% CI: 1.58-1.72) for pneumonia. Likewise, HRs linked to average daily high-dose ICS ranged from 1.16 (95\% CI: 1.02-1.33) for pneumonia to 1.70 (95\% CI: 1.38-2.08) for osteoporosis. Sensitivity analysis excluding patients using OCS showed that high-dose ICS was still associated with an increased risk of CS-related AEs. Overall, ICS <800 μg per day had no increased risk, except for cataract.CONCLUSION: High-dose ICS is associated with an increased risk of several CS-related AEs. This highlights the importance of clinicians considering this risk in patients treated with high-dose and very high dose ICS.",

keywords = "Administration, Inhalation, Adolescent, Adrenal Cortex Hormones/adverse effects, Adult, Aged, Anti-Asthmatic Agents/adverse effects, Asthma/drug therapy, Cardiovascular Diseases/epidemiology, Cohort Studies, Diabetes Mellitus, Type 2/epidemiology, Female, Humans, Male, Middle Aged, Osteoporosis/epidemiology, Pneumonia/epidemiology, Proportional Hazards Models, Registries, Sweden/epidemiology, Young Adult, Cardiovascular disease, Type 2 diabetes mellitus, Osteoporosis, Adverse events, Severe asthma, Asthma management, Cataract, Inhaled corticosteroids, Oral corticosteroids, Asthma",

author = "\{von B{\"u}low\}, Anna and Susanne Hansen and Patrik Sandin and Alexandra Cooper and Olivia Ernstsson and Kirk Geale and Lauri Lehtim{\"a}ki and Charlotte Ulrik and \{B{\o}gvald Aarli\}, Bernt and Pinja Ilmarinen and Sylvia Packham and Ghada Hassan and Asger Sverrild and Helena Backman and Jussi Karjalainen and Vibeke Backer and Alan Altraja and Paula Kauppi and Valentina Yasinska and Maritta Kilpel{\"a}inen and Arja Viinanen and Johannes Martin-Schmid and Apostolos Bossios and Celeste Porsbjerg and Hannu Kankaanranta and Christer Janson",

note = "Copyright {\textcopyright} 2025. Published by Elsevier Inc.",

year = "2025",

month = jul,

doi = "10.1016/j.jaip.2025.01.023",

language = "English",

volume = "13",

pages = "1609--1619.e5",

journal = "The journal of allergy and clinical immunology. In practice",

issn = "2213-2198",

publisher = "American Academy of Allergy, Asthma and Immunology",

number = "7",

}

TY - JOUR

T1 - Use of high-dose inhaled corticosteroids and risk of corticosteroid related adverse events in asthma -findings from the NORDSTAR cohort

AU - von Bülow, Anna

AU - Hansen, Susanne

AU - Sandin, Patrik

AU - Cooper, Alexandra

AU - Ernstsson, Olivia

AU - Geale, Kirk

AU - Lehtimäki, Lauri

AU - Ulrik, Charlotte

AU - Bøgvald Aarli, Bernt

AU - Ilmarinen, Pinja

AU - Packham, Sylvia

AU - Hassan, Ghada

AU - Sverrild, Asger

AU - Backman, Helena

AU - Karjalainen, Jussi

AU - Backer, Vibeke

AU - Altraja, Alan

AU - Kauppi, Paula

AU - Yasinska, Valentina

AU - Kilpeläinen, Maritta

AU - Viinanen, Arja

AU - Martin-Schmid, Johannes

AU - Bossios, Apostolos

AU - Porsbjerg, Celeste

AU - Kankaanranta, Hannu

AU - Janson, Christer

PY - 2025/7

Y1 - 2025/7

N2 - BACKGROUND: The link between the use of oral corticosteroids (OCS) and adverse events (AEs) in asthma is well described. In contrast, whether the use of high-dose inhaled corticosteroids (ICS) poses a risk to these is unknown.OBJECTIVE: To examine the association between ICS exposure and corticosteroid (CS)-related AEs.METHODS: We conducted an observational cohort study using nationwide Swedish registry data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration. We included patients with asthma aged ≥18 years between 2009 and 2019 and calculated their current ICS exposure and average daily ICS dose (budesonide equivalent) in follow-up. The association between ICS exposure and CS-related AEs was analyzed using Cox proportional hazards models adjusting for age, sex, and OCS dose.RESULTS: We included 529,203 patients with asthma. Overall, we observed increased hazard ratios (HRs) in those exposed to high-dose (≥800-1599 μg) and very high dose (≥1600 μg) ICS for several AEs, including cardiovascular disease, type 2 diabetes mellitus (T2DM), osteoporosis, and pneumonia compared with those not exposed to ICS. HRs for the current use of high-dose ICS ranged from 1.11 (95% confidence interval [CI]: 1.06-1.16) for T2DM to 1.65 (95% CI: 1.58-1.72) for pneumonia. Likewise, HRs linked to average daily high-dose ICS ranged from 1.16 (95% CI: 1.02-1.33) for pneumonia to 1.70 (95% CI: 1.38-2.08) for osteoporosis. Sensitivity analysis excluding patients using OCS showed that high-dose ICS was still associated with an increased risk of CS-related AEs. Overall, ICS <800 μg per day had no increased risk, except for cataract.CONCLUSION: High-dose ICS is associated with an increased risk of several CS-related AEs. This highlights the importance of clinicians considering this risk in patients treated with high-dose and very high dose ICS.

AB - BACKGROUND: The link between the use of oral corticosteroids (OCS) and adverse events (AEs) in asthma is well described. In contrast, whether the use of high-dose inhaled corticosteroids (ICS) poses a risk to these is unknown.OBJECTIVE: To examine the association between ICS exposure and corticosteroid (CS)-related AEs.METHODS: We conducted an observational cohort study using nationwide Swedish registry data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration. We included patients with asthma aged ≥18 years between 2009 and 2019 and calculated their current ICS exposure and average daily ICS dose (budesonide equivalent) in follow-up. The association between ICS exposure and CS-related AEs was analyzed using Cox proportional hazards models adjusting for age, sex, and OCS dose.RESULTS: We included 529,203 patients with asthma. Overall, we observed increased hazard ratios (HRs) in those exposed to high-dose (≥800-1599 μg) and very high dose (≥1600 μg) ICS for several AEs, including cardiovascular disease, type 2 diabetes mellitus (T2DM), osteoporosis, and pneumonia compared with those not exposed to ICS. HRs for the current use of high-dose ICS ranged from 1.11 (95% confidence interval [CI]: 1.06-1.16) for T2DM to 1.65 (95% CI: 1.58-1.72) for pneumonia. Likewise, HRs linked to average daily high-dose ICS ranged from 1.16 (95% CI: 1.02-1.33) for pneumonia to 1.70 (95% CI: 1.38-2.08) for osteoporosis. Sensitivity analysis excluding patients using OCS showed that high-dose ICS was still associated with an increased risk of CS-related AEs. Overall, ICS <800 μg per day had no increased risk, except for cataract.CONCLUSION: High-dose ICS is associated with an increased risk of several CS-related AEs. This highlights the importance of clinicians considering this risk in patients treated with high-dose and very high dose ICS.

KW - Administration, Inhalation

KW - Adolescent

KW - Adrenal Cortex Hormones/adverse effects

KW - Adult

KW - Aged

KW - Anti-Asthmatic Agents/adverse effects

KW - Asthma/drug therapy

KW - Cardiovascular Diseases/epidemiology

KW - Cohort Studies

KW - Diabetes Mellitus, Type 2/epidemiology

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Osteoporosis/epidemiology

KW - Pneumonia/epidemiology

KW - Proportional Hazards Models

KW - Registries

KW - Sweden/epidemiology

KW - Young Adult

KW - Cardiovascular disease

KW - Type 2 diabetes mellitus

KW - Osteoporosis

KW - Adverse events

KW - Severe asthma

KW - Asthma management

KW - Cataract

KW - Inhaled corticosteroids

KW - Oral corticosteroids

KW - Asthma

UR - https://www.scopus.com/pages/publications/85219042895

U2 - 10.1016/j.jaip.2025.01.023

DO - 10.1016/j.jaip.2025.01.023

M3 - Journal article

C2 - 39900241

SN - 2213-2198

VL - 13

SP - 1609-1619.e5

JO - The journal of allergy and clinical immunology. In practice

JF - The journal of allergy and clinical immunology. In practice

IS - 7

ER -

Use of high-dose inhaled corticosteroids and risk of corticosteroid related adverse events in asthma -findings from the NORDSTAR cohort

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