10 Chapter 1 Pneumonia Lower respiratory tract infections are the leading infectious cause of death worldwide and the fifth-leading cause of death overall [1]. Pneumonia is an acute lower respiratory tract infection which arises when a pathogen successfully crosses the mucosal barrier, escapes the host defence system, and manages to multiply to ensure its survival [2]. Pneumonia is mostly seen in children younger than 5 years and in older adults with chronic comorbidities. Most often, pneumonia is caused by bacteria or viruses – less often by other pathogens. However, development of the disease is more driven by the immune response of the patient than by characteristics of the invading pathogen [3]. The diagnosis of pneumonia is based on a combination of acute signs and symptoms of a lower respiratory tract infection (such as cough, fever, breathlessness and expectoration) and a new pulmonary infiltrate on chest imaging [2,4,5]. In the absence of a clear viral aetiology, the treatment of pneumonia consists of rapid administration of empiric antibiotics. In most outpatients, diagnostic testing for bacteria is not necessary - testing for influenza and SARS-CoV-2 can be considered [2]. In hospitalized patients, comprehensive microbiologic testing is recommended to determine the appropriate pathogen-specific therapy [2,5]. Supportive care (such as fluids and oxygen) is administered if necessary [5,6]. Pneumonia can be further specified as communityacquired pneumonia and hospital-acquired pneumonia (which includes Intensive Care Unit (ICU)-acquired pneumonia and ventilator-associated pneumonia)[4,7], based on the location where the infection was acquired. Sepsis With insufficient control, pneumonia can deteriorate into sepsis. At the turn of the century, sepsis was predominantly understood as a consequence of an overwhelming inflammatory response following pathogen invasion [8]. Current consensus recognises two seemingly opposing host reactions in severe infections, characterized by both proinflammatory and anti-inflammatory features. Sepsis is a characterized by dysregulation of the immune response to infection with a failure to return to homeostasis, resulting in a life-threatening condition which often requires organ support in the ICU. Nearly a fifth of all global deaths are sepsis-related with an especially high health-related burden in Sub-Saharan Africa [9]. If ICU admission for sepsis is necessary, the sepsis syndrome is fatal for approximately one out of every four patients [10]. Pneumonia is the most common cause of sepsis [11,12]. Decades of research and many failed therapeutic sepsis trials have accentuated the high variability of this syndrome at the individual patient level [13,14]. The critical care community now seeks to utilize clinical and biologic features to identify subgroups that are more homogeneous within the heterogenous population of sepsis patients [15].
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