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June 1997
Biological markers of acute lung injury: prognostic and pathogenetic significance.
Pittett JP, Mackersie RC, Martin TR, and Matthay MA; American Journal of Respiratory and Critical Care Medicine 1997; 155: 1187-1205.
[no abstract available]
The pathogenetic mechanisms of acute lung injury have focused most recently on the cellular and biochemical mediators of the acute respiratory distress syndrome (ARDS). Searching for sensitive and specific biologic markers of ARDS has become an increasingly compelling matter for three primary reasons. First, these markers may improve the predication of ARDS in high-risk clinical conditions such as sepsis, aspiration of gastric contents, pneumonia, and severe asthma.
Secondly, the biological markers of ARDS may provide new insights into the pathogenesis of this syndrome. Thirdly, these markers may serve to predict a course and outcome of patients diagnosed with ARDS. These authors have provided an excellent review of the current inventory of biological markers of acute lung injury, as well as a critical assessment of the measurements of these entities in plasma or in the distal air spaces of the lung as predictors in either onset or outcome of ARDS.
The authors have compiled their review in three sections. The first section addresses protein measurements in pulmonary edema and bronchoalveolar lavage (BAL). The second section addresses cell-specific markers of acute lung injury, in which the prognostic significance of changes in the number and type of cells in the concentration of cell-specific markers in edema fluid, BAL, or plasma of patients at risk or with acute lung injury is reviewed.
Finally, the third section addresses the value of measuring biologic markers of acute inflammation in pulmonary edema fluid, BAL, or plasma of patients at risk in order to predict the onset of ARDS and its clinical outcome.
The results of this detailed and thoroughly referenced review highlight several important themes for the future. These authors found in their extensive search of clinical studies related to acute lung injury that it is currently difficult to generalize findings related to biological markers because of the lack of uniform definitions for "acute lung injury" and "ARDS."
The inclusion of patients with acute lung injury from multiple causes (sepsis, trauma, aspiration, and pneumonia), in addition to major differences in study design, further precluded useful generalities. One point that seems clear from this review is that it is unlikely that one biologic marker will be useful to predict the development of acute lung injury, while providing new insights into the pathogenesis of this syndrome and, further, help to predict outcome.
That is to say that some combination of biologic markers of acute lung injury most likely will be required in order to address these important issues in further understanding and treating acute lung injury.
The authors summarized the results of their extensive critical review of the literature. "The measurement of biological markers of acute lung injury in patients has provided major new insights into the pathogenesis of ARDS. For example, it is clear that the release of proximal cytokines in the lung, such as TNF-a, IL-8 constitutes a critical part of the early inflammatory response in most patients with ARDS, although several other inflammatory pathways are also involved, including the activation of fibroblasts to produce collagen.
Some of these inflammatory markers, such as IL-8 or PCP-3, have prognostic value for identifying patients with ARDS who are likely to die. Measurements of anti-inflammatory cytokines (IL-10) or growth factors may be of prognostic value as well, however, to improve understanding of the pathogenesis of ARDS and the ability to predict the development of this syndrome in patients at risk for ARDS, future studies should integrate measurement of markers of acute inflammation and cell specific injury, as well as physiologic variables in well defined patient populations classified by the clinical causes of ARDS (non-pulmonary sepsis, aspiration, trauma, pneumonia)."
Clearly, the best predictors and diagnostic tools for ARDS are yet to be identified. However, important relationships are beginning to be established for the first time, bringing us much closer to the worthwhile goals in improving the outcomes of patients with ARDS.
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