Inflammatory Markers in CAP Influenced by Time From Symptom Onset to Presentation

There may be significant differences in serum inflammatory marker levels in adults who present within the first 48 hours of symptom onset of community-acquired pneumonia (CAP) compared with individuals who present ≥3 days after symptom onset, according to a study published in the American Journal of Respiratory and Critical Care Medicine.

Researchers performed a secondary analysis of 2 prospective longitudinal cohorts of hospitalized patients at 2 tertiary care university hospitals in Spain (a derivation cohort [n=541] and a validation cohort [n=422]) to determine the influence of time since symptom onset on inflammatory cytokines and biomarker levels in individuals diagnosed with CAP.

Biomarkers were obtained from individuals via blood sample within 24 hours of hospital admission for CAP. Individuals were placed into 2 different groups (early presenters and nonearly presenters), depending on the length of time between onset of symptoms and presentation at the hospital. The study also evaluated hospital length of stay and mortality rates both during hospitalization and during a 30-day follow-up period.

Study results found a significant difference in inflammatory cytokines and biomarker levels in both the derivation cohort and the validation cohort. C-reactive protein (CRP) levels were 38.2% higher in patients with ≥3 days of symptoms compared with patients with <3 days of symptoms, and 36.4% in the derivation cohort. Meanwhile, procalcitonin (PCT) levels were 40% lower in patients with ≥3 days of symptoms compared with patients with <3 days of symptoms in the derivation cohort and 56% in the validation cohort.

There were no differences between cohorts in inflammatory markers with regard to previous antibiotic treatment before presenting to the emergency department. There was a longer length of stay for individuals who presented early in the derivation cohort, but this was not observed in the validation cohort.

Individuals diagnosed with sepsis had higher levels of CRP than those without sepsis; however, regardless of sepsis, the CRP levels were still lower in individuals with <3 days of symptoms compared with ≥3 days of symptoms in both cohorts, but did not reach statistical significance for individuals in the validation cohort (P =.092). Of note, PCT levels were found to be higher in individuals with sepsis in the derivation cohort who presented early when compared with those without sepsis (P <.05), but this did not reach statistical significance in the validation cohort (P =.100)

Researchers concluded that time from the onset of symptoms directly influences the inflammatory response at the time of presentation and CAP diagnosis, as CRP levels were found to be lower in individuals with <3 days since onset of symptoms, whereas PCT, interleukin 6, and interleukin 8 were elevated, which researchers suggested is a reflection of a robust early response to infection.

Conversely, after 3 days of symptoms, PCT, interleukin 6, and interleukin 8 were found to have declined, whereas CRP levels were elevated. Researchers recommended clinicians use PCT, interleukin 6, or interleukin 8 to assess disease severity in individuals who present with ≤48 hours since onset of symptoms, and CRP in individuals presenting ≥3 days since onset of symptoms. Clinicians should take these findings into consideration when designing and conducting clinical trials.

Reference

Méndez R, Menéndez R, Cillóniz C, et al. Initial inflammatory profile in community-acquired pneumonia depends on time since onset of symptoms [published online March 6, 2018]. Am J Respir Crit Care Med. doi:10.1164/rccm.201709-1908OC