Worse Outcomes in Community-Acquired Pneumonia Linked to Higher FGF21 Levels

Pneumonia, microbe
Pneumonia, microbe
Patients diagnosed with community-acquired pneumonia with higher levels of fibroblast growth factor-21 may have higher mortality rates and longer hospitalizations.

A secondary analysis of 2 clinical trials found that patients with moderate-to-severe community-acquired pneumonia (CAP) have an increased risk for clinical instability, prolonged hospitalization, and 30-day all-cause mortality if they have higher levels of fibroblast growth factor-21 (FGF21) at hospital admission. Findings from the study were published in the European Respiratory Journal.

Consecutive patients with CAP who were receiving care at emergency departments or medical wards of tertiary care hospitals in Switzerland were enrolled (n=509). Investigators analyzed patients from the Procalcitonin-Guided Reduction of the Duration of Antibiotic Therapy in Community-Acquired Pneumonia trial (ProCAP), all of whom were randomly assigned to procalcitonin-guided antibiotic treatment or usual care. Additionally, researchers analyzed data from patients who received either prednisone 50 mg/d or placebo for a total of 7 days as adjunct treatment in the Corticosteroid Treatment for Community-Acquired Pneumonia trial (STEP; ClinicalTrials.gov Identifier: NCT00973154).

The researchers systematically gathered data to analyze outcomes, including time to effective hospital discharge, 30-day all-cause mortality, duration of intravenous and overall antibiotic treatment, time to clinical stability (, ie, the time to stabilization of vital signs at 2 consecutive measurements ≥12 hours apart), intensive care unit (ICU) admission, and complications (eg, recurrence, acute respiratory distress syndrome, empyema, nosocomial infections until day 30, severe adverse events possibly related to CAP, ICU admission, and hospital readmission).

Compared with elderly healthy controls, serum FGF21 levels were higher at baseline in patients with CAP (456.5 pg/mL; interquartile range [IQR], 181.2-1127.9 vs 140.2 pg/mL; IQR, 81.1-161.8; respectively; P <.001). FGF21 levels were approximately 10-fold higher in patients with CAP vs young healthy controls (50.4 pg/mL; IQR 13.7-113.3; P <.001).

Patients with higher FGF21 levels were less likely to survive at 30 days (adjusted odds ratio, 1.61; 95% CI, 1.21-2.14; P =.001). Additionally, patients had longer median length of hospital stay if they were in the highest FGF21 tertile vs the lower 2 FGF21 tertile levels (10.0 days; IQR, 7.0-16.0 vs 8.0 days; IQR, 5.0-14.0, respectively; adjusted hazard ratio, 0.93; 95% CI, 0.87-0.99; P =.03).

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“Further studies are required to characterize the role of FGF21 in the regulation of immunometabolism during the progression and remission of septic conditions and to elucidate whether targeting this pathway would be of therapeutic benefit,” the researchers concluded.


Ebrahimi F, Wolffenbuttel C, Blum CA, et al. Fibroblast growth factor-21 predicts outcome in community-acquired pneumonia secondary analysis of two randomized controlled trials [published online December 21, 2018]. Eur Respir J. doi:10.1183/13993003.00973-2018