Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease and Risk of Acquiring Streptococcus pneumoniae Infection. A Multiregional Epidemiological Study

Abstract

Background

Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users.

Methods

The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010–2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses.

Findings

 A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample with S. pneumoniae during follow-up. In the multivariable analysis ICS-use was associated with a dose-dependent risk of S. pneumoniae as follows: low ICS dose: HR 1.11, 95% CI 0.84 to 1.45, p = 0.5; moderate ICS dose: HR 1.47, 95% CI 1.13 to 1.90, p = 0.004; high ICS dose: HR 1.77, 95% CI 1.38 to 2.29, p < 0.0001, compared to no ICS use. Sensitivity analyses confirmed these results.

Interpretation

Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiring S. pneumoniae, but only for moderate and high dose. Caution should be taken when administering high dose of ICS to patients with COPD. Low dose of ICS seemed not to carry this risk.

Keywords:

• COPD
• inhaled corticosteroids
• Streptococcus pneumoniae
• clinical epidemiology

Ethical Statement

This study was approved by the Danish Data Protection Agency. The Committee on Health Research Ethics, Capital Region of Denmark confirmed specifically that this study could be initiated without further ethical approval since retrospective use of register data does not require ethical approval or patient consent in Denmark. Data were only available on closed servers via the Danish Health Data Authority.

Acknowledgment

The abstract was published prior to submission due to presentation at the Nordic Lung Congress 2022.²⁶

Disclosure

The authors declare that there are no conflicts of interest regarding this article. However, to ensure full transparency, we disclose the following potential conflicts of interest: PS received payment for lectures by Boehringer Ingelheim AstraZeneca, and GSK. TBS received grants from Sanofi Pasteur, Novo Nordisk Foundation, and Lundbeck foundation, received Consulting fees from Sanofi Pasteur, and Amgen, and received payment for lectures by Sanofi Pasteur, and GSK. TBS participates on Data Safety Monitoring Board or Advisory Board for Sanofi Pasteur and Amgen. ZBH received support for meetings and/or travel by Phizer. AKB received support for meetings and/or travel by PulmonX and reports non-financial support from GSK, during the conduct of the study. AGM received grants from Boehringer Ingelheim and is associated with the startup “Healthy network” producing automated e-stethoscopes. JRH received consulting fees from AstraZeneca, received payment for lectures by Boehringer Ingelheim, and Takeda, and received support to meetings and/or travel by AstraZeneca, and participates in AstraZeneca’s Advisory board and British Thoracic Society. MP received grants from Roche, received consulting fees from Takeda, Therakos, Zambon, and received payment for lectures by Mallinckrodt, PulmonX, and Glaxo-smith Kline, received support for meetings and/or travel by Boehringer-Ingelheim and is Chair of Danish transplant Society, and associated with The ERS group for transplantation. All other authors declare no competing interests in this work.

Additional information

Funding

The study was financed by grants from Novo Nordisk Fonden (No. NNF20OC0060657). The funding sources had no influence on study design, data collection, analysis or reporting of data.