The Paradoxical Effect on Pneumonia of Chronic Inhaled Corticosteroids

Abstract

Community-acquired pneumonia (CAP) is the leading infectious cause of death in developed countries. Several studies have shown that the risk of pneumonia is increased in patients with Chronic Obstructive Pulmonary Disease (COPD) who are receiving chronic inhaled corticosteroids (ICS). The impact of ICS On pneumonia prognosis is controversial. Recent studies have shown that COPD patients with prior ICS use have less mortality after developing CAP as compared with patients with COPD without prior ICS use. This review discusses the association of ICS and the risk of CAP and its association with clinical outcomes in patients with COPD and pneumonia.

Association of Inhaled Corticosteroids with Incident Pneumonia and Mortality in COPD Patients; Systematic Review and Meta-Analysis

“…A recently published RCT on the role of systemic corticosteroids among patients hospitalized for community-acquired pneumonia with high inflammatory response has indicated a protective effect of corticosteroids. 47 This paradoxical beneficial effect of corticosteroids that has been earlier suggested 15, 46 might be further supported by the higher adherence among ICS users in RCTs. A sensitivity analysis by PP strategy, which accounted for the imbalance in drop-out rates in RCTs, showed that patients in ICS arms had significantly decreased unadjusted overall mortality compared to patients in non-ICS arms.…”

“…Also, similar to previous reports, 45 in our meta-analysis this risk was more prominent for fluticasone, which has higher corticosteroid receptor affinity compared to budesonide. 46 Although the subgroup analysis showed that the risk of pneumonia was higher in trials where corticosteroids were used in the run-in period, none of the differences among subgroups were statistically significant. A proposed rationale for the observed increased risk of pneumonia with ICS use is combination of immunosuppressive effect of corticosteroids superimposed on an exposed COPD patient with chronically obstructed airways frequently colonized with bacteria.…”

“…A proposed rationale for the observed increased risk of pneumonia with ICS use is combination of immunosuppressive effect of corticosteroids superimposed on an exposed COPD patient with chronically obstructed airways frequently colonized with bacteria. 46 Of note, this risk is not uniform for all patients and is likely dependent on the host characteristics (age, COPD severity, functional status etc.) and medication effects (dose, duration and potency of ICS compounds).…”

“…In view of a recently suggested “double-effect” of ICS, 46, 48 we also analyzed the risk of pneumonia case-fatality between ICS and non-ICS groups. In meta-analyses of both RCTs and observational studies, the estimated risks of pneumonia fatality were in the opposite direction from the observed increased risk for pneumonia, although patients who use ICS tend to be older 9 with more severe disease.…”

Incident Pneumonia and Mortality in Patients with Chronic Obstructive Pulmonary Disease. A Double Effect of Inhaled Corticosteroids?

“…The rationale for the increased risk of pneumonia among patients with COPD using ICS may include a combination of immunosuppressive effect plus the effect of obstruction of airways that are colonized with bacteria (35). It has been shown that ICS can achieve locally high concentrations in the lung (36) and that their potency was directly proportional with the increased risk of pneumonia (9).…”