Fibrosis in ARDS: How Close is the Link between Inflammation and Fibroproliferation?

  • G. J. Bellingan
  • R. J. Marshall
  • G. J. Laurent
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 2000)

Abstract

Acute respiratory distress syndrome (ARDS) is defined as acute severe respiratory failure (PaO2/FiO2 ratio of < 200) and increased permeability pulmonary edema (diffuse shadowing on the chest X-ray) occurring after a recognized predisposing insult in patients with relatively normal cardiac function. Also very well recognized are the deterioration in lung compliance accompanying these changes and the progressive fibrosis that is so typical of the later phases of this condition. There have been many approaches to preventing or treating the inflammatory component of ARDS but prevention or treatment of the fibrosis has been the focus of far less attention especially as this is seen essentially as a consequence of the severe inflammation. Although a significant number of patients with ARDS die either from the initiating insult or later from sepsis and multi-organ failure (MOF), it is clear that progressive fibroproliferation is, directly or indirectly, a significant cause of death [1, 2]. Traditionally ARDS has been divided into three pathological phases with the initial injury leading first to an inflammatory or exudative phase where multiple inflammatory mediator cascades are activated, neutrophils emigrate into the airspaces, and there is an accompanying leak of protein rich fluid and hemorrhage. Associated with this is widespread damage to both the endothelial and epithelial lining. The second stage is a proliferative phase where alveolar type II pneumocytes and myofibroblasts multiply and there is organization of the intraluminal exudate. This can progress into a final fibrotic phase with a marked accumulation of collagen. There is now compelling evidence that the fibroproliferative process begins much earlier than previously believed, raising the question of whether inflammation is an essential prerequisite for fibroproliferation. This distinction is fundamental because, if the two processes can be partially disentangled, it then allows therapeutic interventions for fibrosis and inflammation to be considered independently. This chapter will look at the evidence that fibroproliferation is indeed initiated early and will consider the therapeutic potential of a distinction between inflammatory and fibrotic pathways in ARDS.

Keywords

Placebo Permeability Corticosteroid Pneumonia Interferon 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • G. J. Bellingan
  • R. J. Marshall
  • G. J. Laurent

There are no affiliations available

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