Inhaled corticosteroid (ICS) exposure is associated with a dose-dependent increased risk of lower respiratory tract infection with Moraxella catarrhalis in patients with chronic obstructive pulmonary disease (COPD), according to study findings published in BMJ Open Respiratory Research.

Investigators in Denmark assessed whether accumulated ICS use in patients with COPD is linked to a dose-dependent risk for M. catarrhalis (Gram-negative aerobic diplococcus) infection. The primary study endpoint was a lower respiratory tract sample positive for M. catarrhalis, which is both a significant cause of upper and lower respiratory tract infections and a common cause of bacterial exacerbation in COPD.

The observational cohort study included almost 19,000 individuals with COPD (median age, 69.6 years; 54% female) registered in The Danish Register of COPD, a registry that is linked with multiple nationwide registries. All participants had attended an outpatient clinic visit from January 2010 through October 2017.

Prescriptions for ICS redeemed within 365 days prior to study entry were used to determine ICS exposure. Investigators defined the timepoint for study entry as the first outpatient clinic visit. Clinical infection was defined as hospital admission and/or redemption of a relevant prescribed antibiotic within 7 days prior to/14 days after a positive culture with M. catarrhalis.

[O]ur findings support that ICS, especially high doses must be prescribed with care in patients with COPD.

Patients with the highest ICS exposure (n=4362) vs those with no ICS exposure or low or medium ICS exposure tended to be older, female, had formerly smoked, and were more likely to use long-acting beta-2-agonists or long-acting muscarinic antagonists. Patients with no ICS exposure (n=5687) tended to be younger, male, and were currently smoking.

In comparing patients who used ICS with those who did not, the investigators found the ICS group had an increased, dose-dependent risk for having a lower respiratory tract sample with M. catarrhalis. The hazard ratio (HR) of M. catarrhalis for low dose ICS was 1.65 (95% CI, 1.19-2.30; P =.003). The HR for moderate dose ICS was 1.82 (95% CI, 1.32-2.51; P =.0002). Among patients with the highest ICS exposure, the HR of M. catarrhalis was 2.80 (95% CI, 2.06-3.82; P <.0001). Results were consistent through sensitivity analysis.

A total of 521 patients had a positive culture for M. catarrhalis; of those, 455 patients (87%) had clinical M. catarrhalis infection. Overall, 309 patients were admitted to the hospital within 7 days before/14 days after obtaining the positive sample. Prescription for a relevant antibiotic was redeemed by 258 patients within 7 days before/14 days after the positive culture.

Study limitations include limited knowledge of the clinical circumstance in which the samples were obtained and using prescription redemption as proxy for adherence.

As the study authors concluded, “Our study shows a dose-dependent increased risk of infection with M. catarrhalis associated to ICS exposure.” They added, “[O]ur findings support that ICS, especially high doses must be prescribed with care in patients with COPD.”

Disclosure: This research was supported by Novo Nordisk. One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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