307 Summary in English In Chapter 6, the thesis reviews the impact of antibiotics and sepsis on the gut microbiota. While antibiotics are life-saving interventions, they can disrupt the microbiome, with long-term consequences for immune function. This chapter emphasizes the need for a balanced approach to antibiotic use, minimizing unnecessary exposure while ensuring effective treatment of infections. The concept of the “gut-lung axis” is also explored, hypothesizing a link between gut microbiota composition and pulmonary immunity. However, human data on this interaction remains limited. Chapter 7 presents a proof-of-concept human trial that investigates whether gut microbiome modulation through antibiotics affects lung inflammation in patients with allergic asthma. The results indicate that shortterm disruption of the gut microbiome due to antibiotics does not impact pulmonary inflammation and argue against the presence of a gut-lung axis in humans. However, many questions about the potential negative effects of antibiotics on pulmonary inflammation in sepsis management remain unresolved. Part III addresses the challenges of diagnosing pneumonia, particularly in the Emergency Department (ED) and ICU. Accurate diagnosis is essential for effective treatment, but the sometimes-nonspecific symptoms of pneumonia can make it difficult to distinguish infection from other respiratory conditions. Chapter 8 introduces a structured approach for classifying the diagnosis of study participants in large-scale clinical trials. The method described in this thesis uses a carefully developed reference standard combined with a classification system that uses assessors with increasing levels of medical experience. It proved to be a valid and efficient way to classify the diagnosis of patients suspected of pulmonary disease at the ED. The thesis presents findings from the OPTIMACT trial in Chapter 9, which compared the use of ultra-low-dose chest CT scans with conventional chest X-rays. Short-term functional health outcomes were similar between patients who had an ultra-low-dose chest CT and those who had conventional chest X-rays, as were hospital admissions, length of stay, and mortality rates. These findings do not justify the routine use of ultralow-dose chest CT for evaluating patients with suspected non-traumatic pulmonary disease in the ED. Chapter 10 further investigates the diagnostic value of ultra-low-dose chest CT in patients specifically suspected of having community-acquired pneumonia. The clinical management and outcomes, including mortality and length of hospital stay, remained comparable between patients who underwent ultra-low-dose chest CT scans and patients who underwent conventional chest X-rays. An exploratory analysis suggests a value of ultra-low-dose chest CT among patients whose clinical presentation is not straightforward, such as patients who are elderly or afebrile. Future studies should aim to identify patients in the ED who would benefit from the increased sensitivity of ultra-low-dose chest CT and determine when it should be the preferred imaging method. In Chapter 11, the thesis looks to the future, emphasizing the potential of precision medicine to revolutionize the treatment of pneumonia and sepsis. Biomarkers are 13
RkJQdWJsaXNoZXIy MTk4NDMw