Simvastatin to modify neutrophil function in older patients with septic pneumonia (SNOOPI): study protocol for a randomised placebo-controlled trial

Simvastatin to modify neutrophil function in older patients with septic pneumonia (SNOOPI): study protocol for a randomised placebo-controlled trial

Trials, August 2014

25146127

Hannah Greenwood, Jaimin Patel, Rahul Mahida, Qian Wang, Dhruv Parekh, Rachel CA Dancer, Heena Khiroya, Elizabeth Sapey, David R Thickett

Community-acquired pneumonia (CAP) is considered the leading cause of death from infectious disease in developed countries, while complications of CAP - sepsis being the most common and challenging - increase the risk of mortality. During the progression of sepsis, a state of neutrophil 'paralysis' develops resulting in the impairment of neutrophil anti-microbial functions including: chemotaxis, production of reactive oxygen species, and formation of neutrophil extracellular traps (NETs). Mechanisms underlying defective neutrophil function remain elusive although NET formation has been implicated in the immunosuppression and increased rates of sepsis observed in neonates. There is, however, increasing evidence that statins are able to modulate neutrophil function in sepsis as several systematic reviews have concluded that statins have a role in improving infection-related outcomes and mortality while, in vitro, statins have also been shown to boost NET formation in healthy individuals.