The acute respiratory distress syndrome (ARDS), first identified by Ashbaugh et al in 1967, described a constellation of findings in 12 patients who had experienced acute onset of tachypnea, hypoxemia, loss of lung compliance, cyanosis refractory to oxygen therapy, and diffuse alveolar infiltration on chest x-ray. Pathologic examination from seven of these patients found atelectasis, vascular congestion with hemorrhage, hyaline membranes, and pulmonary edema.1
Decades later, in an effort to better define the syndrome using specific and measurable criteria, Murray et al developed a lung injury scoring system. The components of the score quantified alveolar consolidation measured by chest x-ray, hypoxemia measured by Pao2/FiO2 ratios, levels of required positive end-expiratory pressure (PEEP), and pulmonary compliance.2
In 1994 the American–European Consensus Committee (AECC) on ARDS implemented new criteria, identifying two different levels of severity of lung injury. It allowed for those with less severe hypoxemia to be classified as having acute lung injury (ALI) and those with more severe hypoxemia to be defined as having ARDS.3
The AECC defined ALI as the acute onset of respiratory distress with Pao2/FiO2 <300 mm Hg, bilateral, patchy infiltrates on chest radiograph, and a pulmonary artery occlusion pressure (PAOP) <18 mm or absent clinical evidence of left atrial hypertension (indicating presumptive noncardiac etiology of pulmonary edema). ARDS was given similar diagnostic criteria, but with Pao2/FiO2 <200 mm Hg.
Achieving diagnostic accuracy using clinical definitions is imperative so as not to underdiagnose or overdiagnose the pathology and to assure that clinical trials are in fact targeting the correct disease process. However, the subjective nature of describing chest x-ray morphology, the limitations of PAOP to evaluate cardiac dysfunction, and the impact of mechanically delivered airway pressures on oxygenation are just a few of the limitations of the standard ARDS definitions.4
Pathologic examination is perhaps the gold standard for ALI/ARDS diagnosis with the key lesion identified being diffuse alveolar damage (DAD).5 While not typically performed to diagnose ARDS, one retrospective study concluded that open lung biopsy may be safely done for the diagnosis of ALI/ARDS and that in many cases (60% in their series) it produced alternative diagnoses such as pneumonia, pulmonary hemorrhage, and interstitial fibrosis, among others.6
Several studies have attempted to clarify the diagnostic accuracy of the arguably subjective clinical definitions. One such study by Ferguson et al compared the accuracy of the three different commonly used clinical definitions (Table 9-1) with autopsy results and with each other, in 138 subjects.7 They found that clinicians diagnosed ARDS in only 48% of autopsy-confirmed disease and their clinical diagnoses were 91% specific. Agreement between the Delphi and lung injury score definitions was good. Both showed significant disagreement with the AECC definition. The AECC definitions had the highest sensitivity (83%) and lowest specificity (51%), while the Delphi definition had the lowest sensitivity (69%) and highest specificity (82%). Lung injury scores had a 74% sensitivity and 77% specificity. These limited diagnostic accuracies which have been corroborated in several studies, have important implications for clinical practice, and may be problematic for subject recruitment into clinical trials.