LUNG NEUTROPHILS IN THE ADULT RESPIRATORY-DISTRESS SYNDROME - CLINICAL AND PATHOPHYSIOLOGIC SIGNIFICANCE

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Abstract
Although neutrophils are of pathogenetic importance in various animal models of acute lung injury, their role in the adult respiratory distress syndrome (ARDS) is unclear. To study the significance of lung neutrophils in this disorder, patients with ARDS (n = 11) were evaluated by bronchoalveolar lavage within 24 h of admission to the intensive care unit. Patients with non-ARDS respiratory failure requiring mechanical ventilation (n = 4) and normal volunteers (n = 12) were also studied. Neutrophils constituted 67.6 .+-. 9.8% of recovered lavage cells in patients with ARDS compared with only 4.0 .+-. 2.4% of cells in mechanically ventilated control patients and 0.8 .+-. 0.2% in normal volunteers (p < 0.005, both comparisons). Furthermore, in patients with ARDS (n = 6) evaluated serially by bronchoalveolar lavage at 72-h intervals, neutrophils percentages decreased from 91 .+-. 3.2% (initial lavage) to 42.8 .+-. 12% (final lavage) (p < 0.005). Lung neutrophils also predicted the severity of abnormalities in gas exchange and lung protein permeability. That is, the percentage of neutrophils correlated directly with the alveolar-arterial PO2 difference (r = 0.69, p < 0.01) and lavage fluid total protein concentrations (r = 0.62, p < 0.01). Because large numbers of lung neutrophils were present in these patients, ARDS lavage fluid was assayed for neutrophils mediators relevant to the pathogenesis of acute lung injury. Neutrophil elastase activity was not detected in any ARDS lavages, although elastase was antigenically present in most samples and appeared to be complexed to alpha-1-antitrypsin. In contrast to elastase, neutrophil collagenase was readily detectable in ARDS fluid. ARDS lavage fluid also contained high levels of myeloperoxidase (MPO) activity that appeared to be of neutrophil origin. This MPO was cytotoxic for normal lung parenchymal cells when incubated in the presence of the MPO system cofactors H2O2 and halide anion. Thus, lung neutrophils in ARDS correlate with abnormalities of gas exchange and lung protein permeability, and neutrophil products capable of mediating lung injury can be recovered from the lungs of these patients. These findings suggest a central role for neutrophils in the pathogenesis of ARDS.