糖皮质激素是慢性鼻窦炎鼻息肉（CRSwNP）药物治疗中最重要的药物，激素抵抗是影响疗效的关键因素，关于CRSwNP激素抵抗的机制研究鲜见报道。我们基于前期在慢性鼻窦炎鼻息肉病理免疫分型、经鼻雾化吸入糖皮质激素治疗、微生物组学、遗传学等领域的系列研究工作，提出假说：激素敏感型和激素抵抗型CRSwNP存在不同的免疫机制，微生物组和遗传因素可能通过影响鼻黏膜的免疫应答而影响CRSwNP患者对激素治疗的敏感性。联合使用维生素D与糖皮质激素治疗，可能提高CRSwNP激素治疗的疗效。本研究将入选激素抵抗型和激素敏感型CRSwNP患者，采集外周血、鼻息肉组织和鼻分泌物标本，采用流式细胞术、Luminex、16S rDNA检测等方法，从组织、细胞及分子水平，系统阐述激素抵抗型CRSwNP的发病机制及相关影响因素，探索激素联合维生素D治疗激素抵抗型CRSwNP的免疫干预机制，有助于解决激素抵抗的临床难题。

Corticosteroids are regarded as the mainstay of medical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). However, a subset of patients with CRSwNP are resistant to oral corticosteroids. To date, limited knowledge about mechanisms of corticosteroid resistance in CRSwNP is available. In previous studies, we identified cellular phenotypes of CRSwNP, proposed corticosteroid transnasal nebulization in eosinophilic CRSwNP, and explored microbiota profiling and micro RNA expression in this condition. Accordingly, we hypothesized that immunologic mechanisms of corticosteroid response are distinguished in CRSwNP patients with corticosteroid resistance and corticosteroid sensitivity. Furthermore, microbiota and micro RNA play roles on corticosteroid responses in CRSwNP, potentially influencing the efficacy of corticosteroid treatment. Combination therapy of corticosteroids and vitamin D might restore corticosteroid sensitivity. The proposed study will recruit CRSwNP patients with corticosteroid resistance and corticosteroid sensitivity, respectively, and collect peripheral blood, nasal polyps and nasal secretion samples. FACS, Luminex, 16S rDNA and cell culture in vitro will be performed to explore the underlying immunologic mechanisms of corticosteroid resistance in CRSwNP and its corresponding influence factors. We anticipate this study will provide improvements of corticosteroid efficacy in CRSwNP.