1 Department of Respiratory Medicine, Allergy and Clinical Immunology.
2 Department of Otorhinolaryngology, and.
Ann Am Thorac Soc. 2017 May;14(5):667-675. doi: 10.1513/AnnalsATS.201609-720OC.
Periostin is a matricellular protein that is involved in the pathophysiology of allergic rhinitis, chronic rhinosinusitis, and asthma. Associations of serum periostin with systemic and airway eosinophilic inflammation and comorbid chronic rhinosinusitis in patients with asthma have been demonstrated. Although serum periostin is positioned as a marker of helper T cell 2 immune responses, its implication regarding the presence of comorbid upper airway diseases in patients with asthma remains unclear.
To investigate the utility of serum periostin as a diagnostic biomarker for upper airway disease in patients with asthma.
We prospectively enrolled 65 patients with stable asthma, 20 without upper airway disease, 22 with rhinitis, and 23 with chronic rhinosinusitis (13 with nasal polyps, 10 without). Serum periostin, eotaxin, total IgE, fractional exhaled nitric oxide, and blood and sputum eosinophil levels were measured and compared between upper airway disease subtypes. We evaluated the utility of each biomarker in detecting upper airway disease, associations among the biomarkers, and severity of upper airway disease as measured by the Lund-Mackay score for sinus computed tomography.
Serum periostin levels were higher in patients with asthma who had chronic rhinosinusitis (109.6 ± 47.4 ng/ml) than in those without upper airway disease (83.2 ± 22.9 ng/ml) (P = 0.04). Serum periostin levels in patients with asthma who had chronic rhinosinusitis and nasal polyps were significantly higher (130.0 ± 46.6 ng/ml) than in those without nasal polyps (87.9 ± 37.7 ng/ml) (P = 0.001). Serum periostin levels were not associated with the presence or the severity of rhinitis. In contrast, receiver operating characteristic curve analyses showed moderate diagnostic accuracy for detecting chronic rhinosinusitis (area under the curve, 0.71; P = 0.01) and high accuracy for chronic rhinosinusitis with nasal polyps (area under the curve, 0.86; P = 0.0002). When we compared patients with asthma who had comorbid chronic rhinosinusitis and nasal polyps with patients with asthma without these comorbidities, we found serum periostin to be the sole biomarker among those tested for detecting the presence of nasal polyps. Serum periostin was also the sole biomarker that significantly correlated with Lund-Mackay score in patients with chronic rhinosinusitis (r = 0.44; P = 0.04).
Serum periostin is useful for detecting chronic rhinosinusitis with nasal polyps and predicting radiological chronic rhinosinusitis severity in patients with asthma. Clinical trial registered with the UMIN Clinical Trials Registry (UMIN000017533).
纤连蛋白是一种细胞外基质蛋白,参与变应性鼻炎、慢性鼻-鼻窦炎和哮喘的病理生理学过程。已有研究表明,血清纤连蛋白与哮喘患者的全身和气道嗜酸性粒细胞炎症以及合并的慢性鼻-鼻窦炎相关。虽然血清纤连蛋白被定位为辅助性 T 细胞 2 免疫反应的标志物,但它与哮喘患者合并上呼吸道疾病的关系尚不清楚。
研究血清纤连蛋白作为哮喘患者上呼吸道疾病的诊断生物标志物的效用。
我们前瞻性纳入 65 例稳定期哮喘患者,其中 20 例无上呼吸道疾病,22 例患有鼻炎,23 例患有慢性鼻-鼻窦炎(13 例伴鼻息肉,10 例无鼻息肉)。测量并比较了各组患者血清纤连蛋白、嗜酸性粒细胞趋化因子、总 IgE、呼出气一氧化氮分数、血液和痰中嗜酸性粒细胞水平,并比较了各生物标志物对上呼吸道疾病的检测能力,以及各生物标志物之间的相关性,以及鼻窦计算机断层扫描 Lund-Mackay 评分评估的上呼吸道疾病严重程度。
与无上呼吸道疾病的哮喘患者(83.2±22.9ng/ml)相比,患有慢性鼻-鼻窦炎的哮喘患者(109.6±47.4ng/ml)血清纤连蛋白水平更高(P=0.04)。患有慢性鼻-鼻窦炎伴鼻息肉的哮喘患者的血清纤连蛋白水平(130.0±46.6ng/ml)明显高于无鼻息肉的患者(87.9±37.7ng/ml)(P=0.001)。血清纤连蛋白水平与鼻炎的存在或严重程度无关。相比之下,受试者工作特征曲线分析显示,血清纤连蛋白对慢性鼻-鼻窦炎的检测具有中等诊断准确性(曲线下面积,0.71;P=0.01),对伴鼻息肉的慢性鼻-鼻窦炎具有较高的准确性(曲线下面积,0.86;P=0.0002)。当我们将患有合并鼻息肉的慢性鼻-鼻窦炎和无这些合并症的哮喘患者进行比较时,我们发现血清纤连蛋白是检测鼻息肉存在的唯一测试生物标志物。在慢性鼻-鼻窦炎患者中,血清纤连蛋白也是唯一与 Lund-Mackay 评分显著相关的生物标志物(r=0.44;P=0.04)。
血清纤连蛋白可用于检测伴鼻息肉的慢性鼻-鼻窦炎,并预测哮喘患者的鼻窦放射学慢性鼻-鼻窦炎严重程度。临床试验已在日本 UMIN 临床试验注册中心(UMIN000017533)注册。