Deterioration of Oxygenation and Abnormal Lung Microvascular Permeability during Resolution of Leukopenia in Patients with Diffuse Lung Injury

Abstract

To determine whether circulating leukocytes contribute to gas exchange abnormalities in diffuse lung injury, oxygenation was examined in 6 patients who met 3 criteria: leukopenia caused by marrow aplasia from remission-inducing chemotherapy for myelogenous leukemia, the eventual resolution of leukopenia, and concurrent acute respiratory failure diagnosed clinically as increased permeability pulmonary edema. Of the 6 patients, 4 abruptly developed overt clinical evidence of pulmonary dysfunction within the 96 h preceding the resolution of the peripheral leukopenia. In all 6 patients, the alveolar to arterial O2 tension difference increased between 72 h before and 24 h after the rise in peripheral leukocyte counts. The mean value for the alveolar to arterial O2 tension difference for the group doubled during this period (148 .+-. 37 mm Hg 3 days prior to resolution; 290 .+-. 37 mm Hg 1 day after resolution; P < 0.05). As an index of lung capillary permeability, the lung permeability-surface area product for urea (PSu) was measured for an additional patient with O2 toxicity and drug-induced leukopenia, whose hypoxemia increased immediately before the resolution of leukopenia. The PSu in this patient was high, in the range previously reported as being highly specific for increased permeability pulmonary edema with a fatal outcome. Such diffuse lung injury resembling the adult respiratory distress syndrome can occur in leukopenic patients, but the resolution of leukopenia in such patients may be associated with worsening oxygenation and with abnormally high pulmonary microvascular permeability. These observations do not prove a causal relationship, but they provide a clinical parallel to several leukocyte depletion studies reported in animal models of increased permeability pulmonary edema that implicate white white blood cells in the pathogenesis of hypoxemia and lung edema.