The glucocorticoid dose-mortality nexus in pneumonia patients: unveiling the threshold effect

Abstract

Background: The impact of glucocorticoid use on mortality risk in pneumonia patients remains unclear. This study aimed to investigate the relationship between the accumulated dose of glucocorticoids (ADG) and secondary pneumonia mortality risk among patients receiving oral or intravenous glucocorticoids.

Methods: Data from the DRYAD database were analyzed, covering pneumonia patients from six academic hospitals over a 5-year period who had been administered oral or intravenous glucocorticoids. Piecewise linear regression and multivariate regression analysis were utilized to assess the association between ADG and mortality risk in pneumonia patients, while adjusting for potential confounders.

Results: Among the 628 pneumonia patients included, the 30-day mortality rate was 23.1% and the 90-day mortality rate was 26.4%. In the high-dose glucocorticoid group (≥24 mg/day of methylprednisolone or an equivalent glucocorticoid within 30 days before admission), the 30-day and 90-day mortality rates were 31.2% and 35.9%, respectively. Piecewise linear regression analysis demonstrated a non-linear relationship between ADG and mortality risk in pneumonia patients. Multivariate regression analysis revealed a significantly lower mortality risk in patients receiving an ADG of 20-39 g methylprednisolone compared to those receiving lower (<20 g) or higher doses (≥40 g), after adjusting for potential confounding factors. Additionally, in the high-dose glucocorticoid group, surpassing the inflection point of 20 g of methylprednisolone raised the 30-day and 90-day mortality risks (adjusted odds ratio, 95% confidence interval: 1.16, 1.03-1.30 and 1.23, 1.07-1.42, respectively). Notably, this threshold effect was observed exclusively in male patients.

Conclusion: This study provides evidence supporting a potential threshold effect between ADG and mortality risk in oral or intravenous glucocorticoid users with secondary pneumonia. Specifically, male patients receiving high-dose glucocorticoids should undergo close monitoring when the ADG of methylprednisolone exceeds 20 g, as it may be associated with an elevated risk of mortality.

Keywords: gender; glucocorticoids; mortality; pneumonia; threshold effect.

FIGURE 1

Study flow chart.

FIGURE 2

Smooth fitting curve illustrating the association between ADG (methylprednisolone) and the mortality risk among patients receiving glucocorticoid with secondary pneumonia. (A) The risk of 30-day death and (B) The risk of 90-day death. The ADG and risk of pneumonia death in the presence of (C) ILD, (D) Nephrotic syndrome, (E) IIP, (F) Cerebrovascular disease, (G) CTD, (H) Diabetes mellitus, (I) COPD, and (J) CAP. Adjustments were made for age, etiology, other immunosuppressants, neutrophils, COPD, CTD, ALT, BUN, CVVH, respiratory failure, and solid organ transplantation, except where the variable was analyzed. ADG, accumulated dose of glucocorticoids; ILD, interstitial lung disease; IIP, interstitial lung disease; CTD, connective tissue disease; COPD, chronic obstructive pulmonary disease; CAP, community-acquired pneumonia; ALT, alanine aminotransferase; BUN, blood urea nitrogen; CVVH, continuous venovenous hemofiltration.

FIGURE 3

Kaplan-Meier analysis and comparison of mortality between high- and low-dose glucocorticoid groups. (A) 30-day survival curve analysis. (B) Comparison of 30-day mortality. (C) 90-day survival curve analysis. (D) Comparison of 90-day mortality. GC, glucocorticoid. ***P < 0.001.

FIGURE 4

Smooth fitting curves depict a U-shaped correlation between ADG (methylprednisolone) and the mortality risk among pneumonia patients in the high-dose glucocorticoid population (depicted by the blue dotted line) for (A) 30-day mortality risk and (B) 90-day mortality risk. Notably, this U-shaped correlation pattern is exclusively observed in male patients (illustrated by the red line) for (C) 30-day mortality and (D) 90-day mortality. Adjustments were made for age, etiology, other immunosuppressants, neutrophils, COPD, CTD, ALT, BUN, CVVH, respiratory failure, and solid organ transplantation. ADG, accumulated dose of glucocorticoids; COPD, chronic obstructive pulmonary disease; CTD, connective tissue disease; ALT, alanine aminotransferase; BUN, blood urea nitrogen; CVVH, continuous venovenous hemofiltration.