O'Driscoll B R, Hasleton P S, Taylor P M, Poulter L W, Gattameneni H R, Woodcock A A
Northwest Regional Cardiothoracic Unit, Wythenshawe Hospital, Manchester, United Kingdom.
N Engl J Med. 1990 Aug 9;323(6):378-82. doi: 10.1056/NEJM199008093230604.
Carmustine (BCNU) is an anticancer drug known to produce pulmonary fibrosis as a side effect within three years of treatment. It is not known whether pulmonary fibrosis can appear later.
To investigate the clinical range of this side effect, we studied the survivors among 31 children treated with carmustine for brain tumors between 1972 and 1976. Fourteen had died of their tumor; of the remaining 17, 6 had died of lung fibrosis--2 within 3 years of treatment and 4 from 8 to 13 years after treatment. This report focuses primarily on the 11 survivors, 8 of whom were available for detailed study 13 to 17 years (mean, 14) after treatment.
Of the eight survivors studied, six had abnormal chest radiographs showing predominantly upper-zone fibrotic changes. These patients also had abnormal CT scans, showing a previously undescribed pattern of upper-zone fibrosis. All the survivors studied had restrictive spirometric defects (mean [+/- SD] vital capacity, 54 +/- 19 percent of the predicted value). Bronchoalveolar-lavage fluid contained abnormal proportions of specific macrophage subgroups. Light and electron microscopy in six patients revealed interstitial fibrosis and elastosis with damage to epithelial and endothelial cells. Four patients had symptoms (shortness of breath, cough, or both).
Carmustine chemotherapy in childhood causes lung fibrosis that may remain asymptomatic for many years or become symptomatic at any time.
卡莫司汀（BCNU）是一种抗癌药物，已知在治疗后三年内会产生肺纤维化这一侧效应。尚不清楚肺纤维化是否会在更晚的时候出现。
为了研究这种副作用的临床范围，我们对1972年至1976年间接受卡莫司汀治疗脑肿瘤的31名儿童中的幸存者进行了研究。14名儿童死于肿瘤；在其余17名中，6名死于肺纤维化——2名在治疗后3年内死亡，4名在治疗后8至13年死亡。本报告主要关注11名幸存者，其中8名在治疗后13至17年（平均14年）可进行详细研究。
在研究的8名幸存者中，6名胸部X光片异常，主要表现为上叶纤维化改变。这些患者的CT扫描也异常，显示出一种以前未描述过的上叶纤维化模式。所有接受研究的幸存者肺功能检查均有限制性缺陷（平均[±标准差]肺活量为预测值的54±19%）。支气管肺泡灌洗液中特定巨噬细胞亚群的比例异常。6名患者的光镜和电镜检查显示间质纤维化和弹性组织变性，伴有上皮细胞和内皮细胞损伤。4名患者有症状（呼吸急促、咳嗽或两者皆有）。
儿童期使用卡莫司汀化疗会导致肺纤维化，这种纤维化可能多年无症状，也可能随时出现症状。
