Delivery and Safety of Inhaled Interferon-γ in Idiopathic Pulmonary Fibrosis
Delivery and Safety of Inhaled Interferon-γ in Idiopathic Pulmonary Fibrosis
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DOI：
10.1089/jamp.2011.0919
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发表时间：
2012-04-01
影响因子：
3.4
通讯作者：
Condos, Rany
中科院分区：
文献类型：
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作者：
Diaz, Keith T.;Skaria, Shibu;Condos, Rany
背景：吸入干扰素-γ气雾剂（aINF-γ）可能是治疗特发性肺纤维化（IPF）的有效方法。我们使用I-neb（PhilipsRespironics，帕西帕尼，NJ）在10名IPF患者中评估aIFN-γ（100 μ g，3次/周）的安全性和递送。入组了10例平均年龄为68岁的IPF患者（美国胸科学会/欧洲呼吸学会共识指南）。通过伽马照相机测量体内沉积。雾化器记录患者治疗依从性。在基线时测量肺功能检查[PFT、用力肺活量（FVC）、总肺活量（TLC）、一氧化碳弥散量（DLCO）]和6分钟步行试验，每12-14周测量一次，共80周。在基线和28周时进行中叶支气管肺泡灌洗（BAL）。BAL和血浆样本进行了分析趋化因子和细胞因子，包括INF-γ。结果：所有10例患者耐受80周的吸入IFN-γ以及，没有全身副作用。气雾剂治疗的真实依从性平均为96.7 ± 4.81%（+/- SEM）。体内肺沉积平均为65.4 +/- 4.8 μ g，口咽沉积为12.6 +/- 3.0 μ g。BAL IFN-γ增加60倍，促纤维化细胞因子（FGP-2、Flt-3配体、IL-5）显著降低; IFN-γ血浆水平不变。PFT显示FVC变化极小。事后分析表明，TLC和DLCO的下降斜率在开始治疗后逆转。结论：IFN-γ在IPF中是安全的，并且可以有效地递送到肺实质。PFT在整个试验期间保持稳定。治疗前PFT下降的恢复可能为未来的临床试验定义一个终点。
Background: Inhaled interferon-gamma aerosol (aINF-gamma) may be effective treatment for idiopathic pulmonary fibrosis (IPF). We evaluated safety and delivery of aIFN-gamma (100 mu g 3 times/week) in 10 IPF patients using the I-neb (Philips Respironics, Parsippany, NJ).Methods: IFN-gamma activity in the aerosol was confirmed by viral inhibition. Ten patients with an average age of 68 diagnosed with IPF (American Thoracic Society/European Respiratory Society consensus guidelines) were enrolled. In vivo deposition was measured via a gamma camera. The nebulizer recorded patient adherence to therapy. Pulmonary function tests [PFTs, forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO)] and the 6-min walk test were measured at baseline, and every 12-14 weeks for 80 weeks. Bronchoalveolar lavage (BAL) of the middle lobe was performed at baseline and 28 weeks. BAL and plasma samples were analyzed for chemokines and cytokines, including INF-gamma.Results: All 10 patients tolerated 80 weeks of inhaled IFN-gamma well, with no systemic side effects. True adherence with aerosol treatment averaged 96.7 +/- 4.81% (+/- SEM). In vivo lung deposition averaged 65.4 +/- 4.8 mu g and oropharyngeal deposition 12.6 +/- 3.0 mu g. BAL IFN-gamma increased 60-fold and profibrotic cytokines (FGP-2, Flt-3 ligand, IL-5) were significantly decreased; IFN-gamma plasma levels were unchanged. PFTs showed minimal change in FVC. Post hoc analysis indicated that the slope of decline in TLC and DLCO reversed after beginning therapy. The 6-min walk was unchanged.Conclusions: IFN-gamma is safe in IPF and can be effectively delivered to lung parenchyma. PFTs remained stable throughout the trial. Reversal of pretherapy PFT decline may define an end-point for future clinical trials.