ORAL CYCLOPHOSPHAMIDE VS ORAL PLACEBO IN SYSTEMIC SCLEROSIS PULMONARY ALVEOLITIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目前的证据表明，在SSC发病的10年内，肺纤维化的发生率为40-45%。目前的证据表明，SSC病程早期发生的肺纤维化通常先于炎症，而炎症可以通过对支气管肺泡灌洗(BAL)获得的细胞进行检查来发现。非对照系列研究表明，环磷酰胺(CyC)可稳定或改善伴有活动性肺泡炎的SSc患者的肺功能。我们建议进行一项为期5年、13个中心、平行分组、双盲、随机对照研究，比较口服环磷酰胺(1-2 mg/kg/天)和安慰剂，以评估环磷酰胺在稳定或改善FVC病程(如预测的百分比)方面的有效性，163名早期SSC患者(临床发病5年内)已经呼吸困难，GVC&lt；85%的预测和表现为活动性肺泡炎，定义为BAL液中3%的中性粒细胞或2%的嗜酸性粒细胞。其次，我们将评估CyC对这些患者的生活质量(SF36)、功能活动(SSC健康评估问卷)、呼吸困难(Mahler过渡性呼吸困难指数)和一氧化碳弥散能力(DLCO)的影响。研究人员在以前的硬皮病对照研究中使用了经过验证的以时间为导向的数据分析方法，将用于评估口服环磷酰胺(1-2 mg/kg/天)在改善或防止FVC恶化以及在改善或防止生活质量、功能能力、呼吸困难和DLCO恶化方面是否优于安慰剂。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Present evidence suggests that pulmonary fibrosis is 40-45% within 10 years of SSc onset. Present evidence suggests that pulmonary fibrosis, which occurs early in the course of SSc, is usually preceded by inflammation which can be detected by examination of cells obtained by bronchoalveolar lavage (BAL). Uncontrolled series suggest that cyclophosphamide (CYC) may stabilize or improve lung function in SSc patients with active alveolitis. We propose to conduct a five-year, 13-center, parallel-group, double-blind, randomized controlled study of oral CYC (1-2 mg/kg/day) versus placebo to assess the efficacy of CYC in stabilizing or improving the course of FVC (as % predicted) in 163 patients with early SSc (within 5 years of clinical disease onset) who are already dyspneic, have a GVC <85% of predicted and exhibit active alveolitis defined as 3% neutrophils or 2% eosinophils in BAL fluid. Secondarily, we will assess the impact of CYC on quality of life (SF36), functional activity (SSc Health Assessment Questionnaire), dyspnea (Mahler Transition Dyspnea Index) and diffusing capacity for carbon monoxide (DLCO) in these patients. Proven methods for analyzing time-oriented data employed by the investigators in previous controlled studies of scleroderma will be used to evaluate whether oral CYC (1-2mg/kg/day) is better than placebo in improving or preventing worsening of FVC and in improving or preventing worsening of quality of life, functional ability, breathlessness and DLCO.