Pathophysiology of Acute Respiratory Distress Syndrome
Important advances have been made in our understanding of acute respiratory distress syndrome (ARDS) pathophysiology, largely as the result of mechanistic studies about the most important cells involved in this condition, such as alveolar macrophages, neu
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Pathophysiology of Acute Respiratory Distress Syndrome Pedro Leme Silva and Patricia R.M. Rocco
2.1
Introduction
The acute respiratory distress syndrome (ARDS) is a form of hypoxemic respiratory failure characterized by severe inflammatory damage to the alveolar–capillary barrier. This damage can be triggered by primary injury to the epithelium (pulmonary ARDS), as in cases of pneumonia or bronchial aspiration, or to the endothelium (extrapulmonary ARDS), as in cases of nonpulmonary sepsis [37, 51, 54]. Recently, evidence has emerged showing differences in molecular phenotypes between these two etiologies [8]. In addition, patients who develop ARDS after trauma (trauma- associated lung injury) may exhibit distinct clinical features and biomarker profiles compared to other forms of ARDS [7]. Not only the distinction in severity among ARDS patients seems important, but also discrimination among different ARDS phenotypes and etiologies, i.e., whether associated to trauma, transfusion, cancer, and septic events. Novel therapies targeted specifically at these entities may benefit from this separation by pathophysiology.
2.2
athophysiology of Acute Respiratory Distress P Syndrome: The Actors
The innate immune response plays a profound role in the pathophysiology of ARDS. Multiple immune processes involving macrophages, neutrophils, and epithelial and endothelial cells are implicated in mediating tissue injury.
P.L. Silva • P.R.M. Rocco, MD, PhD (*) Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Bloco G1-014, Ilha do Fundão, 21941-902 Rio de Janeiro, Brazil e-mail: [email protected] © Springer International Publishing Switzerland 2017 D. Chiumello (ed.), Acute Respiratory Distress Syndrome (ARDS), DOI 10.1007/978-3-319-41852-0_2
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P.L. Silva and P.R.M. Rocco
2.2.1 Alveolar Macrophages Alveolar macrophages form the first line of defense against airborne particles and microorganisms and use a variety of pattern recognition mechanisms and receptors to sense and phagocytose pathogens [2]. During lung inflammation, two main states of differentiation exist, characterized by classically activated macrophages (CAMs) and alternatively activated macrophages (AAMs). CAMs display the M1 macrophage phenotype and produce high levels of proinflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-12, and inducible nitric oxide synthase (iNOS), in response to paracrine signaling from the T helper 1 (Th1) cytokine interferon (IFN)-γ and in response to autocrine signaling by IFN-β [28, 62]. AAMs display the M2 macrophage phenotype and produce the anti- inflammatory cytokines IL-10 and IL-1Ra in response to signaling from the Th2 cytokines IL-4 and IL-13. Most studies on detection of macrophage phenotype have been experimental, and, although few studies have been conducted in humans, these investigations are noteworthy. In a comparison of bronchoalveolar lavage fluid (BALF) from pati
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