Akesson A, Scheja A, Lundin A, Wollheim F A
Department of Rheumatology, Lund University Hospital, Sweden.
Arthritis Rheum. 1994 May;37(5):729-35. doi: 10.1002/art.1780370518.
Pulmonary fibrosis is a common feature of systemic sclerosis (SSc) and a major cause of morbidity and mortality. Since alveolitis may be an essential step in the development of pulmonary fibrosis, we investigated the use of immunosuppressive drug therapy to improve pulmonary function in patients with SSc.
Eighteen patients with progressive pulmonary dysfunction, diminished vital capacity (VC), and/or decreased static lung compliance (Cst) were treated with cyclophosphamide and corticosteroids for 1 year. Eight patients had diffuse cutaneous SSc and 10 had limited cutaneous SSc. The median disease duration was 2.5 years (range 0.5-17 years).
VC increased in 14 of 18 patients and the median VC rose from 74% to 80% of predicted. Cst improved in 8 of 12 patients and the median Cst increased from 59% to 66% of predicted. Pulmonary nonfibrotic opacities disappeared in 9 of 12 patients. The erythrocyte sedimentation rate (ESR) and serum concentrations of orosomucoid, C-reactive protein, and aminopropeptide type III collagen all improved. The patients were divided into 2 groups based on the presence or absence of elevations in acute-phase protein levels and ESR before therapy. Among the 12 patients with biochemical signs of inflammation, VC increased in 11, and Cst improved or was unchanged in 7 of the 8 who were tested. The median VC in this subgroup increased from 73% to 80% of predicted and the median Cst increased from 57% to 60% of predicted. In the group of 18 patients overall, the skin score decreased, while esophageal and renal function remained stable.
Cyclophosphamide may have a beneficial effect on pulmonary fibrosis in patients with SSc and elevated levels of acute-phase proteins. Controlled trials of cyclophosphamide in pulmonary SSc should be performed and should focus on such patients.
肺纤维化是系统性硬化症（SSc）的常见特征，也是发病和死亡的主要原因。由于肺泡炎可能是肺纤维化发展的关键步骤，我们研究了使用免疫抑制药物治疗来改善SSc患者的肺功能。
18例进行性肺功能障碍、肺活量（VC）降低和/或静态肺顺应性（Cst）下降的患者接受环磷酰胺和皮质类固醇治疗1年。8例为弥漫性皮肤型SSc，10例为局限性皮肤型SSc。疾病中位病程为2.5年（范围0.5 - 17年）。
18例患者中有14例VC增加，VC中位数从预测值的74%升至80%。12例患者中有8例Cst改善，Cst中位数从预测值的59%增至66%。12例患者中有9例肺部非纤维化混浊消失。红细胞沉降率（ESR）以及血清类黏蛋白、C反应蛋白和III型前胶原氨基端肽浓度均有所改善。根据治疗前急性期蛋白水平和ESR是否升高将患者分为两组。在12例有炎症生化指标的患者中，11例VC增加，8例接受测试的患者中有7例Cst改善或未改变。该亚组的VC中位数从预测值的73%升至80%，Cst中位数从预测值的57%增至60%。在18例患者总体中，皮肤评分下降，而食管和肾功能保持稳定。
环磷酰胺可能对急性期蛋白水平升高的SSc患者的肺纤维化有有益作用。应进行环磷酰胺治疗肺部SSc的对照试验，且应关注此类患者。
