Rinaldo J E, Borovetz H
Am Rev Respir Dis. 1985 Apr;131(4):579-83. doi: 10.1164/arrd.1985.131.4.579.
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.
为了确定循环白细胞是否会导致弥漫性肺损伤中的气体交换异常，我们回顾性研究了6例符合以下3条标准患者的氧合情况：因骨髓性白血病缓解诱导化疗导致的骨髓发育不全引起的白细胞减少、白细胞减少的最终缓解，以及临床上诊断为通透性增加型肺水肿并发的急性呼吸衰竭。6例患者中有4例在周围白细胞减少缓解前的96小时内突然出现明显的肺功能障碍临床证据。在所有6例患者中，白细胞计数期间肺泡-动脉氧分压差均增加。该组患者肺泡-动脉氧分压差的平均值在此期间增加了一倍（缓解前3天为148±37 mmHg；缓解后1天为290±37 mmHg；p<0.05）。作为肺毛细血管通透性的指标，我们对另一名因氧中毒和药物性白细胞减少导致白细胞减少缓解前低氧血症立即加重的患者测量了尿素的肺通透性-表面积乘积（PSu）。该患者的PSu较高，处于先前报道的对致命结局的通透性增加型肺水肿具有高度特异性的范围内。我们得出结论，这种类似于成人呼吸窘迫综合征的弥漫性肺损伤可发生于白细胞减少的患者中，但此类患者白细胞减少的缓解可能与氧合恶化及肺微血管通透性异常升高有关。这些观察结果并未证明因果关系，但与通透性增加型肺水肿动物模型中报道的几项白细胞耗竭研究提供了临床平行关系，这些研究表明白细胞在低氧血症和肺水肿的发病机制中起作用。
