Abstract：
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of surfactants in the alveoli. Most cases are classified as autoimmune PAP (APAP) because they are associated with autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). However, GM-CSF autoantibody levels are unlikely to correlate with the disease severity or prognosis of APAP.
METHODS: We collected clinical records and measured 38 serum cytokine concentrations for consecutive patients with APAP. After exclusion of 21 cytokines because of undetectable levels, 17 cytokine levels were compared between low and high disease severity scores (DSSs). We also compared whole lung lavage (WLL)-free survival with cut-off values defined by receiver operating characteristic (ROC) curves of cytokine levels and WLL administration at 11 months.
RESULTS: Nineteen patients with APAP were enrolled in the study. Five were classified as DSS 1 or 2, while the others were classified as DSS 4 or 5. Comparison between DSS 1-2 and 4-5 revealed that the concentrations of IP-10 and GRO increased in the latter groups (p < 0.05). Fifteen patients underwent WLL. Comparison between those who underwent WLL within 11 months and the others showed that IP-10 and TNF-α were tended to be elevated in the former group (p = 0.082 and 0.057, respectively). The cut-off values of IP-10, 308.8 pg/mL and TNF-α, 19.1 pg/mL, defined by the ROC curves, significantly separated WLL-free survivals with log-rank analyses (p = 0.005).
CONCLUSIONS: The concentrations of IP-10 and GRO may reflect the DSSs of APAP. A combination of IP-10 and TNF-α levels could be a biomarker to predict WLL-free survival.
METHODS: We collected clinical records and measured 38 serum cytokine concentrations for consecutive patients with APAP. After exclusion of 21 cytokines because of undetectable levels, 17 cytokine levels were compared between low and high disease severity scores (DSSs). We also compared whole lung lavage (WLL)-free survival with cut-off values defined by receiver operating characteristic (ROC) curves of cytokine levels and WLL administration at 11 months.
RESULTS: Nineteen patients with APAP were enrolled in the study. Five were classified as DSS 1 or 2, while the others were classified as DSS 4 or 5. Comparison between DSS 1-2 and 4-5 revealed that the concentrations of IP-10 and GRO increased in the latter groups (p < 0.05). Fifteen patients underwent WLL. Comparison between those who underwent WLL within 11 months and the others showed that IP-10 and TNF-α were tended to be elevated in the former group (p = 0.082 and 0.057, respectively). The cut-off values of IP-10, 308.8 pg/mL and TNF-α, 19.1 pg/mL, defined by the ROC curves, significantly separated WLL-free survivals with log-rank analyses (p = 0.005).
CONCLUSIONS: The concentrations of IP-10 and GRO may reflect the DSSs of APAP. A combination of IP-10 and TNF-α levels could be a biomarker to predict WLL-free survival.
摘要：
背景：肺泡蛋白沉积症（PAP）的特征是肺泡中表面活性剂的异常积累。大多数病例被归类为自身免疫性PAP（APAP），因为它们与针对粒细胞-巨噬细胞集落刺激因子（GM-CSF）的自身抗体有关。然而,GM-CSF自身抗体水平不太可能与APAP的疾病严重程度或预后相关。
方法：我们收集临床记录并测量了连续APAP患者的38种血清细胞因子浓度。由于无法检测到的水平，排除了21种细胞因子后，在低和高疾病严重度评分（DSS）之间比较了17种细胞因子水平。我们还比较了11个月时细胞因子水平和WLL给药的受试者操作特征（ROC）曲线定义的无全肺灌洗（WLL）生存率。
结果：本研究纳入了19例APAP患者。五个被分类为DSS1或2，而其他被分类为DSS4或5。DSS1-2和4-5之间的比较表明，后一组中IP-10和GRO的浓度增加（p<0.05）。15例患者接受WLL。在11个月内接受WLL的患者与其他人之间的比较表明，前一组中IP-10和TNF-α趋于升高（分别为p=0.082和0.057）。IP-10、308.8pg/mL和TNF-α的截止值，19.1pg/mL,由ROC曲线定义，通过对数秩分析显着分离无WLL生存（p=0.005）。
结论：IP-10和GRO的浓度可以反映APAP的DSS。IP-10和TNF-α水平的组合可以是预测无WLL存活的生物标志物。
方法：我们收集临床记录并测量了连续APAP患者的38种血清细胞因子浓度。由于无法检测到的水平，排除了21种细胞因子后，在低和高疾病严重度评分（DSS）之间比较了17种细胞因子水平。我们还比较了11个月时细胞因子水平和WLL给药的受试者操作特征（ROC）曲线定义的无全肺灌洗（WLL）生存率。
结果：本研究纳入了19例APAP患者。五个被分类为DSS1或2，而其他被分类为DSS4或5。DSS1-2和4-5之间的比较表明，后一组中IP-10和GRO的浓度增加（p<0.05）。15例患者接受WLL。在11个月内接受WLL的患者与其他人之间的比较表明，前一组中IP-10和TNF-α趋于升高（分别为p=0.082和0.057）。IP-10、308.8pg/mL和TNF-α的截止值，19.1pg/mL,由ROC曲线定义，通过对数秩分析显着分离无WLL生存（p=0.005）。
结论：IP-10和GRO的浓度可以反映APAP的DSS。IP-10和TNF-α水平的组合可以是预测无WLL存活的生物标志物。
