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Review
. 2014 Dec;35(4):639-53.
doi: 10.1016/j.ccm.2014.08.004. Epub 2014 Sep 23.

Clinical and biological heterogeneity in acute respiratory distress syndrome: direct versus indirect lung injury

Ciara M Shaver  1 , Julie A Bastarache  2
Affiliations
Review

Clinical and biological heterogeneity in acute respiratory distress syndrome: direct versus indirect lung injury

Ciara M Shaver et al. Clin Chest Med. 2014 Dec.

Abstract

The acute respiratory distress syndrome (ARDS) is a heterogeneous group of illnesses affecting the pulmonary parenchyma with acute onset bilateral inflammatory pulmonary infiltrates with associated hypoxemia. ARDS occurs after 2 major types of pulmonary injury: direct lung injury affecting the lung epithelium or indirect lung injury disrupting the vascular endothelium. Greater understanding of the differences between direct and indirect lung injury may refine the classification of patients with ARDS and lead to development of new therapeutics targeted at specific subpopulations of patients with ARDS.

Keywords: Acute lung injury; Acute respiratory distress syndrome; Direct lung injury; Indirect lung injury.

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Conflict of interest statement

Conflicts of Interest:

Dr. Shaver: none

Dr. Bastarache: none

Figures

Figure 1
Figure 1. Histopathology and immunohistochemistry of direct and indirect ARDS
Hematoxylin and eosin (H&E) staining shows that SP-A positive hyaline membranes (arrows) are thick layers in direct ARDS, but thin and discontinuous layers in indirect ARDS. Direct ARDS shows lack of AE1-AE3 staining, consistent with epithelial injury. In contrast, indirect ARDS shows increased anti-factor VIII staining, consistent with endothelial damage. Adapted from Peres e Serra A, Parra ER, Eher E, Capelozzi VL. Nonhomogeneous immunostaining of hyaline membranes in different manifestations of diffuse alveolar damage. Clinics (Sao Paulo). Dec 2006;61(6):497–502; with permission.
Figure 2
Figure 2. Electron microscopy of experimental direct and indirect ARDS
Direct injury from IT LPS caused destruction of the alveolar epithelium with hyaline deposition and significant neutrophil apoptosis. In contrast, indirect injury from IP LPS caused pulmonary interstitial edema with intact epithelial and endothelial layers. Mφ, macrophage; PI and PII, types I and II pneumocytes; LB, lamellar bodies; ALV, alveolar space; IE, interstitial edema; CAP, capillary From Menezes SL, Bozza PT, Neto HC, et al. Pulmonary and extrapulmonary acute lung injury: inflammatory and ultrastructural analyses. J Appl Physiol (1985). May 2005;98(5):1777–1783.
See this image and copyright information in PMC

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