ORAL CYCLOPHOSPHAMIDE VS ORAL PLACEBO IN SYSTEMIC SCLEROSIS PULMONARY ALVEOLITIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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，肺纤维化发生在SSc病程早期，通常在炎症发生之前，可以通过检查支气管肺泡灌洗（BAL）获得的细胞来检测。非对照研究表明，环磷酰胺（CYC）可以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、平行组、双盲、随机对照研究，比较口服CYC （1- 2mg /kg/天）与安慰剂对163例早期SSc患者（临床发病5年内）稳定或改善FVC病程（预期百分比）的疗效，这些患者已经出现呼吸困难，GVC <预测值的85%，并表现出活动性肺泡炎，定义为BAL液中有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（马勒过渡呼吸困难指数）和一氧化碳弥散能力（DLCO）的影响。研究者在之前的硬皮病对照研究中采用了经过验证的时间数据分析方法，将用于评估口服CYC （1-2mg/kg/天）在改善或预防FVC恶化、改善或预防生活质量、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.