PMID: 10667541

Issn Print: 0090-3493

Publication Date: 2000/01/01


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Leukotriene B4, acute respiratory distress syndrome, and outcomes

David L. Bowton

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Excerpt

Acute respiratory distress syndrome (ARDS) remains a vexing clinical entity with a high mortality rate and few well-validated guidelines to support therapeutic decision-making. A number of animal models of ARDS have been used to study both the pathophysiology and the efficacy of a variety of treatment options. These models, and bronchoalveolar sampling in clinical ARDS, have implicated leukotriene B4 (LTB4), along with other leukotrienes and chemokines, in the pathogenesis of lung injury (1-4). Neutrophils seem to play a major role in the tissue injury seen in ARDS, and LTB4 is a powerful promoter of neutrophil chemotaxis (5-7). Dr. Amat and colleagues (8) demonstrate in this issue of Critical Care Medicine that concentrations of LTB4 are elevated in the serum of patients with ARDS compared with matched patients without ARDS, but with one or more risk factors for development of the condition. These data complement the studies of bronchoalveolar lavage fluid in similar populations and, as the authors suggest, provide a much more readily obtainable sample for study of the interrelationships among leukotrienes and interleukins (IL) on the genesis and outcome of ARDS. Whether the LTB4 in serum is a "spillover" from the lung or is reflective of processes in other organ systems is not known. The lower concentrations in serum compared with bronchoalveolar lavage fluid and the lower concentrations in subjects who have similar underlying diseases but do not have ARDS (at-risk patients) suggest that the former is likely.
Dr. Amat and colleagues (8) suggest that measurement of LTB4 and/or IL-8 may have diagnostic or prognostic utility in patients at risk or with ARDS. Furthermore, they suggest that measurement of serum LTB4 concentrations may be useful as a prognostic or diagnostic tool. Although their data are consistent with these positions, the number of patients is far too small to conclude that LTB4 will be a useful prognostic marker for the development of ARDS in those at risk. Only three of their 14 at-risk patients had high LTB4 concentrations, and only one of these patients developed ARDS. Furthermore, they use a concentration of 14 pmol/mL to define an elevated concentration and to stratify risk. This concentration was determined from receiver operator characteristic curves derived from patients in the study. Therefore, the utility of this concentration as a predictor of risk or outcome must now be confirmed in another population of patients before any statements about its predictive or prognostic value can be made. Importantly, the intergroup differences in LTB4 and IL-8 were significant only at specific time points (days 1 and 5, respectively). Position in the time course of ARDS or sepsis is an important determinant of measured responses. The time of admission to the intensive care unit or intubation may not reflect the time of onset of the ARDS-triggering event or process (such as sepsis). Therefore, the use of time of admission to the intensive care unit as the "clock trigger" imposes an additional uncontrolled variable on data analysis that may be especially important when statistically significant differences are only found at specific time points.
The use of LTB4 as a diagnostic tool, on the other hand, begs the issue of whether ARDS is a disease or a syndrome. As its name implies, the acute respiratory distress syndrome, as defined by internationally accepted criteria, is a syndrome (9). LTB4 concentrations are currently not a defining parameter of this definition. The incorporation of LTB4 levels into the definition of ARDS without widespread consensus would only lead to further variability and uncertainty in determining patient populations for study.

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