Inhaled corticosteroids and risk of lower respiratory tract infection with Moraxella catarrhalis in patients with chronic obstructive pulmonary disease

Rikke Helin Johnsen; Christian Kjer Heerfordt; Jonas Bredtoft Boel; Ram Benny Dessau; Christian Ostergaard; Pradeesh Sivapalan; Josefin Eklöf; Jens-Ulrik Stæhr Jensen

doi:10.1136/bmjresp-2023-001726

Inhaled corticosteroids and risk of lower respiratory tract infection with Moraxella catarrhalis in patients with chronic obstructive pulmonary disease

Rikke Helin Johnsen, Christian Kjer Heerfordt, Jonas Bredtoft Boel, Ram Benny Dessau, Christian Ostergaard, Pradeesh Sivapalan, Josefin Eklöf, Jens-Ulrik Stæhr Jensen^*

^*Corresponding author for this work

12 Citations (Scopus)

Abstract

BACKGROUND: Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia. Moraxella catarrhalis is one of the most common bacterial causes of infectious exacerbation in COPD. Currently, to our knowledge, no studies have investigated if ICS increases the risk of lower respiratory tract infection with M. catarrhalis in patients with COPD.

OBJECTIVE: To investigate if accumulated ICS use in patients with COPD, is associated with a dose-dependent risk of infection with M. catarrhalis.

METHODS: This observational cohort study included 18 870 persons with COPD who were registered in The Danish Register of COPD. Linkage to several nationwide registries was performed.Exposure to ICS was determined by identifying all prescriptions for ICS, redeemed within 365 days prior to study entry. Main outcome was a lower respiratory tract sample positive for M. catarrhalis. For the main analysis, a Cox multivariate regression model was used.We defined clinical infection as admission to hospital and/or a redeemed prescription for a relevant antibiotic, within 7 days prior to 14 days after the sample was obtained.

RESULTS: We found an increased, dose-dependent, risk of a lower respiratory tract sample with M. catarrhalis among patients who used ICS, compared with non-users. For low and moderate doses of ICS HR was 1.65 (95% CI 1.19 to 2.30, p=0.003) and 1.82 (95% CI 1.32 to 2.51, p=0.0002), respectively. In the group of patients with highest ICS exposure, the HR of M. catarrhalis was 2.80 (95% CI 2.06 to 3.82, p<0.0001). Results remained stable in sensitivity analyses. 87% of patients fulfilled the criteria for clinical infection, and results remained unchanged in this population.

CONCLUSION: Our study shows a dose-dependent increased risk of infection with M. catarrhalis associated to ICS exposure.

Original language	English
Article number	e001726
Journal	BMJ Open Respiratory Research
Volume	10
Issue number	1
ISSN	2052-4439
DOIs	https://doi.org/10.1136/bmjresp-2023-001726
Publication status	Published - Aug 2023

Keywords

COPD epidemiology
COPD Exacerbations
COPD Pharmacology
Respiratory Infection

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10.1136/bmjresp-2023-001726Licence: CC BY-NC

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Johnsen, R. H., Heerfordt, C. K., Boel, J. B., Dessau, R. B., Ostergaard, C., Sivapalan, P., Eklöf, J., & Jensen, J.-U. S. (2023). Inhaled corticosteroids and risk of lower respiratory tract infection with Moraxella catarrhalis in patients with chronic obstructive pulmonary disease. BMJ Open Respiratory Research, 10(1), Article e001726. https://doi.org/10.1136/bmjresp-2023-001726

Inhaled corticosteroids and risk of lower respiratory tract infection with Moraxella catarrhalis in patients with chronic obstructive pulmonary disease. / Johnsen, Rikke Helin; Heerfordt, Christian Kjer ; Boel, Jonas Bredtoft et al.
In: BMJ Open Respiratory Research, Vol. 10, No. 1, e001726, 08.2023.

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

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title = "Inhaled corticosteroids and risk of lower respiratory tract infection with Moraxella catarrhalis in patients with chronic obstructive pulmonary disease",

abstract = "BACKGROUND: Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia. Moraxella catarrhalis is one of the most common bacterial causes of infectious exacerbation in COPD. Currently, to our knowledge, no studies have investigated if ICS increases the risk of lower respiratory tract infection with M. catarrhalis in patients with COPD.OBJECTIVE: To investigate if accumulated ICS use in patients with COPD, is associated with a dose-dependent risk of infection with M. catarrhalis.METHODS: This observational cohort study included 18 870 persons with COPD who were registered in The Danish Register of COPD. Linkage to several nationwide registries was performed.Exposure to ICS was determined by identifying all prescriptions for ICS, redeemed within 365 days prior to study entry. Main outcome was a lower respiratory tract sample positive for M. catarrhalis. For the main analysis, a Cox multivariate regression model was used.We defined clinical infection as admission to hospital and/or a redeemed prescription for a relevant antibiotic, within 7 days prior to 14 days after the sample was obtained.RESULTS: We found an increased, dose-dependent, risk of a lower respiratory tract sample with M. catarrhalis among patients who used ICS, compared with non-users. For low and moderate doses of ICS HR was 1.65 (95\% CI 1.19 to 2.30, p=0.003) and 1.82 (95\% CI 1.32 to 2.51, p=0.0002), respectively. In the group of patients with highest ICS exposure, the HR of M. catarrhalis was 2.80 (95\% CI 2.06 to 3.82, p<0.0001). Results remained stable in sensitivity analyses. 87\% of patients fulfilled the criteria for clinical infection, and results remained unchanged in this population.CONCLUSION: Our study shows a dose-dependent increased risk of infection with M. catarrhalis associated to ICS exposure.",

keywords = "COPD epidemiology, COPD Exacerbations, COPD Pharmacology, Respiratory Infection",

author = "Johnsen, \{Rikke Helin\} and Heerfordt, \{Christian Kjer\} and Boel, \{Jonas Bredtoft\} and Dessau, \{Ram Benny\} and Christian Ostergaard and Pradeesh Sivapalan and Josefin Ekl{\"o}f and Jensen, \{Jens-Ulrik St{\ae}hr\}",

note = "{\textcopyright} Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2023",

month = aug,

doi = "10.1136/bmjresp-2023-001726",

language = "English",

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T1 - Inhaled corticosteroids and risk of lower respiratory tract infection with Moraxella catarrhalis in patients with chronic obstructive pulmonary disease

AU - Johnsen, Rikke Helin

AU - Heerfordt, Christian Kjer

AU - Boel, Jonas Bredtoft

AU - Dessau, Ram Benny

AU - Ostergaard, Christian

AU - Sivapalan, Pradeesh

AU - Eklöf, Josefin

AU - Jensen, Jens-Ulrik Stæhr

PY - 2023/8

Y1 - 2023/8

N2 - BACKGROUND: Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia. Moraxella catarrhalis is one of the most common bacterial causes of infectious exacerbation in COPD. Currently, to our knowledge, no studies have investigated if ICS increases the risk of lower respiratory tract infection with M. catarrhalis in patients with COPD.OBJECTIVE: To investigate if accumulated ICS use in patients with COPD, is associated with a dose-dependent risk of infection with M. catarrhalis.METHODS: This observational cohort study included 18 870 persons with COPD who were registered in The Danish Register of COPD. Linkage to several nationwide registries was performed.Exposure to ICS was determined by identifying all prescriptions for ICS, redeemed within 365 days prior to study entry. Main outcome was a lower respiratory tract sample positive for M. catarrhalis. For the main analysis, a Cox multivariate regression model was used.We defined clinical infection as admission to hospital and/or a redeemed prescription for a relevant antibiotic, within 7 days prior to 14 days after the sample was obtained.RESULTS: We found an increased, dose-dependent, risk of a lower respiratory tract sample with M. catarrhalis among patients who used ICS, compared with non-users. For low and moderate doses of ICS HR was 1.65 (95% CI 1.19 to 2.30, p=0.003) and 1.82 (95% CI 1.32 to 2.51, p=0.0002), respectively. In the group of patients with highest ICS exposure, the HR of M. catarrhalis was 2.80 (95% CI 2.06 to 3.82, p<0.0001). Results remained stable in sensitivity analyses. 87% of patients fulfilled the criteria for clinical infection, and results remained unchanged in this population.CONCLUSION: Our study shows a dose-dependent increased risk of infection with M. catarrhalis associated to ICS exposure.

AB - BACKGROUND: Use of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of pneumonia. Moraxella catarrhalis is one of the most common bacterial causes of infectious exacerbation in COPD. Currently, to our knowledge, no studies have investigated if ICS increases the risk of lower respiratory tract infection with M. catarrhalis in patients with COPD.OBJECTIVE: To investigate if accumulated ICS use in patients with COPD, is associated with a dose-dependent risk of infection with M. catarrhalis.METHODS: This observational cohort study included 18 870 persons with COPD who were registered in The Danish Register of COPD. Linkage to several nationwide registries was performed.Exposure to ICS was determined by identifying all prescriptions for ICS, redeemed within 365 days prior to study entry. Main outcome was a lower respiratory tract sample positive for M. catarrhalis. For the main analysis, a Cox multivariate regression model was used.We defined clinical infection as admission to hospital and/or a redeemed prescription for a relevant antibiotic, within 7 days prior to 14 days after the sample was obtained.RESULTS: We found an increased, dose-dependent, risk of a lower respiratory tract sample with M. catarrhalis among patients who used ICS, compared with non-users. For low and moderate doses of ICS HR was 1.65 (95% CI 1.19 to 2.30, p=0.003) and 1.82 (95% CI 1.32 to 2.51, p=0.0002), respectively. In the group of patients with highest ICS exposure, the HR of M. catarrhalis was 2.80 (95% CI 2.06 to 3.82, p<0.0001). Results remained stable in sensitivity analyses. 87% of patients fulfilled the criteria for clinical infection, and results remained unchanged in this population.CONCLUSION: Our study shows a dose-dependent increased risk of infection with M. catarrhalis associated to ICS exposure.

KW - COPD epidemiology

KW - COPD Exacerbations

KW - COPD Pharmacology

KW - Respiratory Infection

UR - https://www.scopus.com/pages/publications/85168365074

U2 - 10.1136/bmjresp-2023-001726

DO - 10.1136/bmjresp-2023-001726

M3 - Journal article

C2 - 37597970

SN - 2052-4439

VL - 10

JO - BMJ Open Respiratory Research

JF - BMJ Open Respiratory Research

IS - 1

M1 - e001726

ER -

Inhaled corticosteroids and risk of lower respiratory tract infection with Moraxella catarrhalis in patients with chronic obstructive pulmonary disease

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