慢性鼻-鼻窦炎患者上、下气道之间一种新的病理生理联系：痰液骨膜蛋白水平与上气道炎症及嗅觉功能的关联
A novel pathophysiologic link between upper and lower airways in patients with chronic rhinosinusitis: Association of sputum periostin levels with upper airway inflammation and olfactory function.
作者信息
Kanemitsu Yoshihiro, Suzuki Motohiko, Fukumitsu Kensuke, Asano Takamitsu, Takeda Norihisa, Nakamura Yoshihisa, Ozawa Yoshiyuki, Masaki Ayako, Ono Junya, Kurokawa Ryota, Yap Jennifer, Nishiyama Hirono, Fukuda Satoshi, Ohkubo Hirotsugu, Maeno Ken, Ito Yutaka, Oguri Tetsuya, Izuhara Kenji, Takemura Masaya, Niimi Akio
机构信息
Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Otorhinolaryngology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
出版信息
World Allergy Organ J. 2020 Jan 6;13(1):100094. doi: 10.1016/j.waojou.2019.100094. eCollection 2020 Jan.
BACKGROUND
Chronic rhinosinusitis (CRS) and asthma are collectively called unified airway diseases. Periostin has been implicated in the pathophysiologic link of these conditions but only by serum measurements. We sought to investigate sputum levels of periostin and their association with upper airway inflammation and olfactory function in CRS patients.
METHODS
We prospectively recruited 56 CRS patients who underwent endoscopic sinus surgery (20 with and 36 without comorbid asthma), and 28 healthy controls between October 2015 and December 2017. Lower and upper airway indices such as sputum periostin levels and eosinophil and neutrophil counts, exhaled fractional nitric oxide (FeNO) levels, and olfactory function were evaluated in the three groups. Radiological severity of CT images and tissue eosinophilia of surgical specimens were also assessed in the CRS patients.
RESULTS
Sputum periostin levels were highest, and olfactory function was most impaired, in the CRS patients with comorbid asthma, followed by those without asthma and controls in this order. CRS with asthma group showed higher sputum eosinophils and FeNO levels than the other two groups, while CRS patients without asthma showed significantly higher neutrophils in sputum than the other two groups. When confined to CRS patients, olfactory dysfunction was correlated with sputum eosinophil counts. Eosinophil counts of nasal polyps showed a significant positive correlation with sputum periostin and FeNO levels. Radiological severity of CRS was correlated with sputum eosinophil counts and FeNO levels.
CONCLUSIONS
Periostin levels and inflammatory cells such as eosinophils and neutrophils in the lower airways are increased in patients with CRS, suggesting the presence of mutual interactions between upper and lower airways even if asthma does not coexist. Olfactory dysfunction and eosinophilic nasal polyps may be potential indicators of Th2-driven inflammation in the lower airways.
TRIAL REGISTRATION
This study was registered on the UMIN Clinical Trials Registry (Registry ID UMIN000018672).
背景
慢性鼻-鼻窦炎（CRS）和哮喘统称为气道统一性疾病。骨膜蛋白与这些疾病的病理生理联系有关，但此前仅通过血清检测进行研究。我们旨在调查CRS患者痰液中骨膜蛋白水平及其与上气道炎症和嗅觉功能的关系。
方法
我们在2015年10月至2017年12月期间前瞻性招募了56例接受鼻内镜鼻窦手术的CRS患者（其中20例合并哮喘，36例不合并哮喘）以及28名健康对照者。对三组对象评估了痰液骨膜蛋白水平、嗜酸性粒细胞和中性粒细胞计数、呼出一氧化氮分数（FeNO）水平以及嗅觉功能等上下气道指标。还对CRS患者的CT图像放射学严重程度和手术标本组织嗜酸性粒细胞增多情况进行了评估。
结果
合并哮喘的CRS患者痰液骨膜蛋白水平最高，嗅觉功能受损最严重，其次依次为不合并哮喘的CRS患者和健康对照者。合并哮喘的CRS组痰液嗜酸性粒细胞和FeNO水平高于其他两组，而不合并哮喘的CRS患者痰液中性粒细胞显著高于其他两组。仅在CRS患者中，嗅觉功能障碍与痰液嗜酸性粒细胞计数相关。鼻息肉的嗜酸性粒细胞计数与痰液骨膜蛋白和FeNO水平呈显著正相关。CRS的放射学严重程度与痰液嗜酸性粒细胞计数和FeNO水平相关。
结论
CRS患者下气道中的骨膜蛋白水平以及嗜酸性粒细胞和中性粒细胞等炎症细胞增加，提示即使不存在哮喘，上下气道之间也存在相互作用。嗅觉功能障碍和嗜酸性鼻息肉可能是下气道Th2驱动炎症的潜在指标。
试验注册
本研究已在UMIN临床试验注册中心注册（注册号UMIN000018672）。
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