Respiratory Distress Syndrome: Underrecognition by Clinicians
Objective: To determine and compare the diagnostic accuracy of three clinical definitions of acute respiratory distress syndrome (ARDS): (1) the American-European consensus conference definition; (2) the lung injury score; and (3) a recently developed Delphi definition. A second objective was to determine the accuracy of clinical diagnoses of ARDS made in daily practice.
Design: Independent comparison of autopsy findings with the daily status of clinical definitions, constructed with data abstracted retrospectively from medical records.
Setting: Tertiary intensive care unit.
Patients: One hundred thirty-eight patients from the period 1995 through 2001 who were autopsied after being mechanically ventilated.
Interventions: Clinical ARDS diagnoses were determined daily without knowledge of autopsy Results. Charts were reviewed for any mention of ARDS in the clinical notes. Autopsies were reviewed independently by two pathologists for the presence of diffuse alveolar damage. The sensitivity and specificity of the definitions were determined with use of diffuse alveolar damage at autopsy as the reference standard.
Measurements and Main Results: Diffuse alveolar damage at autopsy was documented in 42 of 138 cases (30.4%). Only 20 of these 42 patients (47.6%) had any mention of ARDS in their chart. Sensitivities and specificities (95% confidence intervals) were as follows: American-European definition, 0.83 (0.72-0.95), 0.51 (0.41-0.61); lung injury score, 0.74 (0.61-0.87), 0.77 (0.69-0.86); and Delphi definition, 0.69 (0.55-0.83), 0.82 (0.75-0.90). Specificity was significantly higher for both the lung injury score and Delphi definition than for the American-European definition (p < .001 for both), whereas comparisons of sensitivity, which was higher for the American-European definition, were not significantly different (p = .34 and p = .07, respectively).
Conclusions: Acute respiratory distress syndrome appears underrecognized by clinicians in patients who die with this syndrome. In this population, the specificities of existing clinical definitions vary considerably, which may be problematic for clinical trials.

The manner in which a population is defined for any clinical trial is critically important, because it not only affects the study generalizability and the ability to draw comparisons across studies but also can have a direct effect on the study Results. Studies that inadvertently include patients who do not have the disease of interest or who for other reasons have a low chance of responding to the experimental treatment are prone to false-negative Results. In the case of acute respiratory distress syndrome (ARDS), two clinical definitions are commonly employed to define this population for studies: the lung injury score and the American-European consensus conference definition (henceforth abbreviated as the American-European definition) ( Table 1 ). How clinicians make a diagnosis of ARDS in usual practice outside of research settings is not well described.

The diagnostic test properties of the lung injury score have never been studied. Moreover, the American-European definition has performed poorly in limited reliability testing, and the agreement between these two definitions has been shown to be only moderate. We previously developed another clinical definition of ARDS, using the Delphi technique. This consensus result then underwent sensibility testing, with feedback subsequently incorporated into the definition ( Table 1 ).

Recognition of the importance of accurate diagnostic criteria, along with a succession of negative trials in this area, have led to calls for a reevaluation of ARDS definitions. We recently compared the American-European definition to autopsy findings of diffuse alveolar damage (DAD) in a series of 382 patients and found the sensitivity and specificity to be only moderate in this setting. In the current study we examined a subset of these patients in order to compare the sensitivity and specificity of the lung injury score and Delphi definitions ( Table 1 ) with those of the American-European definition, when all definitions were applied on a strict daily basis without benefit of knowledge regarding a patient's disease evolution. In addition, we sought to determine how accurately clinicians were diagnosing ARDS in clinical practice.