14 Chapter 1 Chapter 3 we describe the role of biomarkers in sepsis. Chapter 4 studies the incidence and pathophysiological implications of hyperferritinemia in patients with communityacquired pneumonia, and in Chapter 5 we analyse plasma protein biomarkers reflective of the host response in patients developing ICU-acquired pneumonia. Part II of this thesis is a brief intermezzo on the relation between the microbiome, sepsis and pulmonary immunity. Chapter 6 presents an overview of current knowledge of the effect of the most common empiric antibiotics utilized during sepsis on the composition of the gut microbiota, and the effects of sepsis itself on gut microbiota. In Chapter 7 we describe the outcomes of a human proof-of-concept intervention trial modulating the gut microbiome by antibiotics in patients with adult asthma. Part III of this thesis moves towards improvement of diagnosis and clinical care of patients with pneumonia. In Chapter 8 we address the challenge of proper classification of diagnoses in large (randomized) cohorts of study participants suspected of nontraumatic pulmonary disease, and we present a structured, efficient, and validated approach for diagnostic classification. Chapter 9 contains outcomes of a RCT aimed to study the value of ultra-low-dose chest CT in clinical management of patients suspected of non-traumatic pulmonary disease at the Emergency Department. Chapter 10 specifically aims to address the value of ultra-low-dose chest CT in patients suspected of pneumonia. Part IV can be considered the epilogue of this thesis and consists of a position paper regarding future perspectives on precision medicine in sepsis in Chapter 11, a general discussion of the work in this thesis in Chapter 12, and a summary of the main results of this thesis, both in English and Dutch, in Chapter 13 and Chapter 14.
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