Fifty Years of Research in ARDS.Is Acute Respiratory Distress Syndrome a Preventable Disease?

Abstract

Despite significant advances in our understanding and management of patients with acute respiratory distress syndrome (ARDS), the morbidity and mortality from ARDS remains high. Given the limited number of effective treatments for established ARDS, the strategic focus of ARDS research has shifted toward identifying patients with or at high risk of ARDS early in the course of the underlying illness, when strategies to reduce the development and progression of ARDS and associated organ failures can be systematically evaluated. In this review, we summarize the rationale, current evidence, and future directions in ARDS prevention.

Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

“…Platelets were not examined in this study. Hyperoxia induces pulmonary platelet sequestration and platelet-fibrin thrombi formation, is a classic cause of DAD, and may accelerate the progression of ARDS (72,73,163). Nevertheless, platelet depletion did not markedly alter lung injury resulting from exposure of hybrid (CBAxC57BL/10) mice to 100% oxygen for various time periods, yielding the conclusion that platelets are not requisite for oxygen toxicity (166).…”

“…Platelets contribute to comorbid conditions that frequently affect patients with ARDS, regardless of the frequency of the underlying cause (reviewed in [16,162]). In addition, inappropriate measures of systemic or respiratory support, including ventilation with excessive VT and high concentrations of inspired oxygen, are potential causes of morbidity and mortality in patients with ARDS (62,163). Platelets may also contribute to these iatrogenic complications (14).…”

“…In addition to high-VT ventilation and excessive inspired oxygen, excessive fluid administration resulting in increased lung microvascular pressure can worsen extravasation of fluid and protein across the leaky alveolar-capillary membrane and may drive progression of ALI to ARDS (61,163). In earlier studies of alveolar responses to hydrostatic stresses, increased pressure in venular capillaries in isolated, blood-perfused rat lungs induced surface P-selectin expression on endothelial cell-(167) and P-selectin-dependent leukocyte accumulation in lung postcapillary venules (168).…”

Pharmacological modulation of C‐X‐C motif chemokine receptor 4 influences development of acute respiratory distress syndrome after lung ischaemia–reperfusion injury

“…While several independent risk factors for development of ARDS have been identified, such as pneumonia, non‐pulmonary‐sepsis or severe injuries, the molecular events leading to ARDS remain poorly understood . Thus, therapeutic options are currently limited to lung‐protective ventilation strategies . Pharmacological interventions that may attenuate progression of mild ARDS to moderate or severe ARDS are currently not available, but urgently needed.…”

Platelet biology of the rapidly failing lung

“…ARDS is distinguished as a clinical entity by specific criteria: rapid onset (within seven days of initial insult); diffuse bilateral lung infiltrates consistent with pulmonary oedema and not fully explained by other pulmonary pathologies such as effusions, lobar/lung collapse or consolidation; respiratory failure not explained by heart failure or volume overload; and a decreased ratio of arterial pressure to inspired oxygen ( P a O 2 / F i O 2 ) with a positive end‐expiratory pressure (PEEP) or a continuous positive airway pressure (CPAP) ≥ 5 cm H 2 O while receiving supplemental oxygen (Force et al , ). For a comprehensive review on ARDS, we recommend any of several very good reviews on ARDS in the literature (Ware & Matthay, ; Yadav et al , ; Middleton et al , ),…”