An Alternative Method of Acute Lung Injury Classification for Use in Observational Studies

Abstract

T he diagnoses of acute lung injury (ALI) and its more severe manifestation, ARDS, are based on specifi c clinical and radiographic criteria. 1 The AmericanEuropean Consensus Conference (AECC) standardized these criteria in an effort to improve the systematic identifi cation of patients with this syndrome. This standardization has expedited the recognition of patients with ALI for enrollment into clinical trials and promoted studies on ALI epidemiology by providing a uniform defi nition. [2][3][4][5][6][7] Although the simplicity of the AECC criteria can be advantageous for study inclusion, uncertainties in the fulfi llment of criteria can be especially problematic in epidemiologic studies using ALI as the outcome.High interobserver variability in chest radiograph (CXR) interpretation highlights the uncertainties of ALI classifi cation using the AECC criteria. [8][9][10] Misclassifi cation of subjects with ALI as non-ALI may lead to underestimation of associations between risk factors and ALI. 11 Furthermore, the ALI syndrome may represent a spectrum of injury, and classifi cation of subjects as non-ALI with intermediate forms of lung injury who do not fulfi ll strict ALI criteria may hamper efforts at uncovering novel risk factors, including genetic associations. 12 The purpose of this study was twofold: (1) identify a subset of patients (referred to as equivocal ALI) with diffi cult-to-classify hypoxemic respiratory failure Background: In observational studies using acute lung injury (ALI) as an outcome, a spectrum of lung injury and diffi cult-to-interpret chest radiographs (CXRs) may hamper efforts to uncover risk factor associations. We assessed the impact of excluding patients with diffi cult-to-classify or equivocal ALI diagnosis on clinical and genetic risk factor associations for ALI after trauma. Methods: This study was of a prospective cohort of 280 critically ill trauma patients. The primary outcome was the development of ALI. Patients were classifi ed into one of three groups: (1) definite ALI (patients who fulfi lled the American-European Consensus Conference [AECC] criteria for ALI), (2)equivocal ALI (patients who had diffi cult-to-interpret CXRs), and (3) defi nite non-ALI. We compared clinical and genetic ALI risk factor associations between two classifi cation schemes: AECC classifi cation (defi nite ALI vs rest) and alternative classifi cation (defi nite ALI vs defi nite non-ALI, excluding equivocal ALI). Results: Ninety-three (35%) patients were classifi ed as defi nite ALI, 67 (25%) as equivocal, and 104 (39%) as defi nite non-ALI. Estimates of clinical and genetic ALI risk factor associations were farther from the null using the alternative classifi cation. In a multivariable risk factor model, the C statistic of the alternative classifi cation was signifi cantly higher than that derived from the AECC classifi cation (0.82 vs 0.74; P , .01). Conclusions: The ability to detect ALI risk factors may be improved by excluding patients with equivocal or diffi cult-to-classify ALI. Such analyses m...

Genetic Variation in theFASGene and Associations with Acute Lung Injury

“…We performed this secondary analysis restricting the control group in an effort to minimize misclassification of borderline cases of ALI as control subjects. Our findings suggest that such misclassification bias exists and could lead to false-negative results in gene association studies of ALI, as has recently been argued by Shah and colleagues (44). We also found that a haplotype containing FAS 21541T and FAS 9325A was associated with development of ALI in the SIRS cohort.…”

Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality via acute respiratory distress syndrome

“…Informed consent was obtained from patients or their proxies. ARDS was defined in accordance with the Berlin definition, with the added requirement of invasive mechanical ventilation over the first 6 days of ICU admission to be confident that the ARDS was attributable to the first septic episode (66,67); chest radiographs were interpreted as described previously (42,68). Acute kidney injury was determined by Acute Kidney Injury Network criteria (69).…”

The ABO Histo-Blood Group and AKI in Critically Ill Patients with Trauma or Sepsis

“…To determine independence from our previously reported associations between ABO blood types and ARDS (14), we also conducted analyses stratified by the development of ARDS. ARDS was phenotyped using the Berlin definition and our previously published methods over the first 6 days of ICU admission (37,38). We also conducted analyses within the subgroup of patients who did not receive blood product transfusions during the first 24 hours of enrollment.…”