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The Heterogeneity of BAL Cells and Protein in Patients at Risk for and With ARDS^*

^* From the Harborview Medical Center and Seattle Veterans Affairs Medical Center, University of Washington School of Medicine, Seattle, WA.

Correspondence to: Kenneth Steinberg, MD, FCCP, University of Washington School of Medicine, Harborview Medical Center, 325 Ninth Ave, Seattle, WA 98104-2499

Initially thought to be a diffuse, symmetric process, it is now known that ARDS can be a radiographically and physiologically patchy, heterogeneous process. BAL has been used extensively to evaluate the inflammatory process in the lungs of patients with ARDS and those at risk for the syndrome. Polymorphonuclear leukocytes (PMNs) and total protein (TP) concentration are increased in BAL in virtually all cases of ARDS, especially in the early phases of lung injury. It is not known to what degree the heterogeneity of ARDS affects the results of BAL. We hypothesized that the inflammatory process was a systemic one and, as such, bilateral BAL would result in relatively equivalent differential cell counts and TP concentration despite the observed radiographic heterogeneity.

All adult patients admitted to ICUs at Harborview Medical Center were screened prospectively for the onset of ARDS or two risk factors: severe sepsis and severe trauma. Patients were excluded if safety criteria were not met. After informed consent had been obtained, a fiberoptic bronchoscope was passed through the endotracheal tube and wedged into a subsegment of the right middle lobe. BAL was performed using five 30-ml Aliquots of sterile pyrogen-free 0.9% NaCl at room temperature (150 mL total). BAL fluid was recovered by gentle hand suction. The procedure was repeated in a subsegment of the left lingula. Total and differential cell counts and TP concentrations were obtained from both sides.

Bilateral BAL was performed on 17 at-risk patients and 25 ARDS patients. The mean and median values for PMN percent did not differ (lingula, 39% vs right middle lobe, 41%). This was also true for TP concentration. Analysis by group (at risk vs ARDS and by risk factor among ARDS patients) did not alter these results. However, when individual results were plotted for all 42 BAL pairs, and analyzed using the Bland-Altman technique, significant side-to-side variation existed in some BAL. For PMN percent, 10 (24%) had a side-to-side difference 15% (eg, 45% vs 60%) and 7 (17%) had a difference 20%. For TP, 18 (43%) had twofold or more side-to-side variability, 24% had threefold or more difference, and 19% had fourfold or more difference. Two patients had a 20-fold difference and one patient had a 30-fold difference. Heteroscedasticity was observed for TP but not PMN percent: as the TP concentration increased, there was greater side-to-side variability. Lateral bias was not observed. It was not always true that patients with differences in one measure had differences in the other. A patient with a 47% difference in PMN had equal TP and the patient with the 30-fold difference in TP had similar PMN percent (73% and 64%).

While the majority of patients had equivalent bilateral BAL findings, a substantial proportion exhibited asymmetric findings. The heterogeneity of BAL findings reflects either heterogeneity of the inflammatory response or imprecision in the measurement technique. This should be taken into account in comparing BAL studies in patients at risk for and with ARDS.

Footnotes

Supported by NHLBI SCOR HL30542.

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