Kandhare Amit D, Mukherjee Anwesha, Ghosh Pinaki, Bodhankar Subhash L
Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Paud Road, Pune-411 038, India.
EXCLI J. 2016 Nov 7;15:636-651. doi: 10.17179/excli2016-619. eCollection 2016.
Idiopathic pulmonary fibrosis (IPF) is a chronic oxido-inflammatory disorder of the lung. Oxidative stress is widely recognized as a central feature of IPF. Antioxidant therapy has been proposed as an effective treatment for IPF. An array of clinical trials describing the therapeutic impact of these drugs have been reporting albeit with conflicting evidence points. We performed a meta-analysis of trials in which efficacy of antioxidant therapy was compared with control in IPF. Systematic literature search was conducted in PubMed, EMBASE, the Cochrane Library, CPCI-S (Conference Proceedings Citation Index-Science), ICTRP (International Clinical Trials Registry Platform), and Google Scholar till June 2016 by two independent researchers. Various outcomes such as changes in pulmonary function tests (change in vital capacity [ΔVC], change in forced vital capacity [ΔFVC], change in percentage of predicted vital capacity [Δ%VC], and change in percentage of predicted carbon monoxide diffusing capacity [Δ%DLco]), changes in 6 minutes walking test distance (Δ6MWT), rates of adverse events, and rates of death, were included. All statistical analyses were performed using RevMan V.5.3. Twelve studies (n = 1062) were identified that used antioxidants (N-acetylcysteine and lecithinized superoxide dismutase) as a treatment for IPF. Overall, there was no association of antioxidant therapy with ΔFVC (SMD = 0.27, 95% CI:-0.07 to 0.61; P = 0.12), ΔFVC (%) (SMD = -0.10, 95% CI:-0.56 to 0.36; P = 0.66) and 6MWT (SMD = -0.04, 95% CI:-0.11 to 0.20; P = 0.59) in IPF patients. However, combined antioxidant therapy was found to be associated with %VC (SMD = 0.37, 95% CI: 0.09 to 0.64; P = 0.008) and Δ%DLco (SMD = 0.15, 95% CI: 0.00 to 0.29; P = 0.05) in IPF patients. Strong evidence was obtained that the antioxidants increased adverse effects adverse events (OR = 1.56, 95% CI: 0.75 to 3.24; P = 0.23) but it did not associate mortality (OR = 0.96, 95% CI: 0.44 to 2.11; P = 0.92). The use of significant clinical heterogeneity, low statistical power, high dropout rates, duration of follow-ups, and dosing regimens of antioxidant agents. Combined antioxidant therapy seems to be a safe and effective therapy for IPF patients which provides a more beneficial effect in terms of VC, and DLco rather than monotherapy. Further randomized controlled trials with homogeneous outcome measures are needed.
特发性肺纤维化（IPF）是一种肺部慢性氧化炎症性疾病。氧化应激被广泛认为是IPF的一个核心特征。抗氧化治疗已被提议作为IPF的一种有效治疗方法。尽管有相互矛盾的证据点，但一系列描述这些药物治疗效果的临床试验一直在进行报告。我们对将抗氧化治疗在IPF中的疗效与对照组进行比较的试验进行了荟萃分析。由两名独立研究人员在截至2016年6月的PubMed、EMBASE、Cochrane图书馆、CPCI-S（会议论文引文索引 - 科学版）、ICTRP（国际临床试验注册平台）和谷歌学术中进行了系统的文献检索。纳入了各种结局指标，如肺功能测试的变化（肺活量变化[ΔVC]、用力肺活量变化[ΔFVC]、预测肺活量百分比变化[Δ%VC]以及预测一氧化碳弥散量百分比变化[Δ%DLco]）、6分钟步行试验距离变化（Δ6MWT）、不良事件发生率和死亡率。所有统计分析均使用RevMan V.5.3进行。共确定了12项研究（n = 1062），这些研究使用抗氧化剂（N - 乙酰半胱氨酸和卵磷脂化超氧化物歧化酶）治疗IPF。总体而言，在IPF患者中，抗氧化治疗与ΔFVC（标准化均数差[SMD] = 0.27，95%置信区间：-0.07至0.61；P = 0.12）、ΔFVC（%）（SMD = -0.10，95%置信区间：-0.56至0.36；P = 0.66）和6MWT（SMD = -0.04，95%置信区间：-0.11至0.20；P = 0.59）均无关联。然而，发现联合抗氧化治疗与IPF患者的%VC（SMD = 0.37，95%置信区间：0.09至0.64；P = 0.008）和Δ%DLco（SMD = 0.15，95%置信区间：0.00至0.29；P = 0.05）有关联。有强有力的证据表明抗氧化剂增加了不良事件（比值比[OR] = 1.56，95%置信区间：0.75至3.24；P = 0.23），但与死亡率无关（OR = 0.96, 95%置信区间：0.44至2.11；P = 0.92）。存在显著的临床异质性、低统计效能、高失访率、随访持续时间以及抗氧化剂的给药方案等问题。联合抗氧化治疗似乎是IPF患者的一种安全有效的治疗方法，在肺活量和一氧化碳弥散量方面比单一疗法提供了更有益的效果。需要进一步开展具有同质结局指标的随机对照试验。
