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Association between biomarkers and house dust mite sublingual immunotherapy in allergic asthma.

生物标志物与过敏性哮喘屋尘螨舌下免疫治疗的相关性。

  • 影响因子:4.19
  • DOI:10.1111/cea.13686
  • 作者列表:"Hoshino M","Akitsu K","Kubota K","Ohtawa J
  • 发表时间:2020-06-17
Abstract

BACKGROUND:House dust mite (HDM) sublingual immunotherapy (SLIT) has demonstrated efficacy in clinical trials of patients with asthma. Airway inflammation is a characteristics of respiratory allergy, but its relationship to SLIT remain unclear. OBJECTIVE:We evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SLIT (UMIN-Number 000022390). METHODS:One hundred twelve patients with asthma sensitized to HDM were randomized to add-on 6 standardized quality (SQ)-HDM SLIT to pharmacotherapy or pharmacotherapy alone for 48 weeks. At baseline and end of study, biomarkers, blood eosinophils, serum IgE, serum periostin, fractional exhaled nitric oxide (FeNO), and spirometry and clinical symptoms were measured. Association between biomarkers and an increase in FEV1 of 120 ml or greater were analyzed. RESULTS:SLIT demonstrated a significant reduction of serum periostin (P < 0.001), FeNO (P < 0.01), and increase in HDM specific IgE (P < 0.05), FEV1 (P < 0.001) and improvement of clinical symptom scores, when compared to pharmacotherapy. The change in FEV1 correlated with the changes in serum periostin (r = 0.696, P < 0.001) and the changes in FeNO (r = 0.682, P < 0.001). The independent predictor of improvement in airflow limitation were change in serum periostin (r2 = 0.753, P = 0.013) and FeNO (P = 0.038). Based on cutoff values derived by receiver operating characteristic analysis (periostin 30.9 ng/mL, FeNO 28.0 ppb), patients were distinguished responders from non-responders, but with no predictive value for blood eosinophils or total IgE. The proportion of patients with both high periostin and FeNO levels was significantly higher in responder than in non-responder (P = 0.026). CONCLUSIONS AND CLINICAL RELEVANCE:Adding HDM SLIT to pharmacotherapy resulted in reduced serum periostin and FeNO, and improved pulmonary function. Serum periostin and FeNO may be useful biomarkers for prediction of SLIT.

摘要

背景: 屋尘螨 (HDM) 舌下免疫疗法 (SLIT) 已在哮喘患者的临床试验中证明有效。气道炎症是呼吸道过敏的特征,但其与 SLIT 的关系仍不清楚。 目的: 我们评价 HDM SLIT (UMIN-Number 000022390) 前后临床结局与肺功能和生物标志物之间的相关性。 方法: 将 112 例 HDM 致敏的哮喘患者随机分为两组,分别加入 6 个标准化质量 (SQ)-HDM SLIT 进行药物治疗或单用药物治疗 48 周。在基线和研究结束时,测量生物标志物、血嗜酸性粒细胞、血清 IgE 、血清 periostin 、呼出气一氧化氮 (FeNO) 、肺活量测定和临床症状。分析了生物标志物与 FEV1 增加 120毫升或更大的相关性。 结果: SLIT 可显著降低血清骨膜蛋白 (P < 0.001) 、 FeNO (P < 0.01) 和 HDM 特异性 IgE (P <0.05)。与药物治疗相比,FEV1 (P < 0.001) 和临床症状评分的改善。FEV1 的变化与血清骨膜蛋白的变化 (r = 0.696,P <0.001) 和 FeNO 的变化 (r = 0.682,P <0.001) 相关。气流受限改善的独立预测因子是血清骨膜蛋白 (r2 = 0.753,P = 0.013) 和 FeNO (P = 0.038) 的变化。根据受试者工作特征分析得出的截断值 (periostin 30.9 ng/mL,FeNO 28.0 ppb),将患者与非应答者区分开来,但对血嗜酸性粒细胞或总 IgE 无预测价值。应答者同时具有高骨膜蛋白和 FeNO 水平的患者比例显著高于无应答者 (P = 0.026)。 结论和临床相关性: 在药物治疗的基础上加用 HDM SLIT 可降低血清 periostin 和 FeNO,改善肺功能。血清骨膜蛋白和 FeNO 可能是预测 SLIT 的有用生物标志物。

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DOI:10.1111/bph.14861
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影响因子:3.94
发表时间:2020-01-15
DOI:10.1016/j.taap.2019.114847
作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

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DOI:10.1042/BST20191010
作者列表:["Zaragosi LE","Deprez M","Barbry P"]

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