Community-acquired pneumonia. Monitoring and modulation of the host response

PhD ceremony: Mr. D. Snijders, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Community-acquired pneumonia. Monitoring and modulation of the host response

Promotor(s): prof. T.S. van der Werf

Faculty: Medical Sciences

This thesis reports several studies investigating the host response induced by a community-acquired pneumonia. The host response consists of several aspects, including a general inflammatory response and activation of the anticoagulation system. Changes in various haematologic parameters are also observed. This response can elicit an exaggerated inflammation which supersedes the amount of response needed for dealing with the offending pathogens and can cause excess damage. In this thesis the hypothesis is tested whether adjunctive corticosteroids, anti-inflammatory agents, are beneficial in patients with a community-acquired pneumonia. In a randomised clinical trial involving 213 patients, adjunctive corticosteroids did not lead to improved clinical outcome. The use of corticosteroids was associated with an increase in late failure, which required additional treatment. Furthermore, the use of D-dimers, fibrin-degradation products, as marker for community-acquired pneumonia are investigated. D-dimers as standalone markers, or combined with the CURB-65 score, did not improve the severity scoring in patients with community-acquired pneumonia. The haematological changes due to community-acquired pneumonia are caused by a diminished incorporation of iron in red blood cells. This effect is likely caused by hepcidin, a regulatory protein. The findings of this thesis provide insight in the host response occurring in community-acquired pneumonia, and points out issues for further research of the host response and treatment of community-acquired pneumonia.