Deterioration of oxygenation and abnormal lung microvascular permeability during resolution of leukopenia in patients...

To determine whether circulating leukocytes contribute to gas exchange abnormalities in diffuse lung injury, we retrospectively examined oxygenation 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. Four of the 6 patients 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 oxygen tension difference increased between leukocyte counts. The mean value for the alveolar to arterial oxygen tension difference for the group doubled during this period (148 +/- 37 mmHg 3 days prior to resolution; 290 +/- 37 mmHg 1 day after resolution; p less than 0.05). As an index of lung capillary permeability, we measured the lung permeability-surface area product for urea (PSu) for an additional patient with oxygen 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. We conclude that 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 provide a clinical parallel to several leukocyte-depletion studies reported in animal models of increased permeability pulmonary edema that implicate white blood cells in the pathogenesis of hypoxemia and lung edema.