Selroos Olof, Brattsand Ralph
Independent researcher.
Sarcoidosis Vasc Diffuse Lung Dis. 2024 Sep 24;41(3):e2024037. doi: 10.36141/svdld.v41i3.15852.
Results of a few controlled clinical studies have been reported with inhaled corticosteroids (ICS) in patients with pulmonary sarcoidosis. Some evidence of efficacy has been observed, but mainly with the ICS budesonide (BUD). These clinically important and statistically significant results are restricted to maintenance therapy with BUD after induction of treatment with systemic corticosteroids for a few weeks or months. Positive results have also been described in patients with relapses after earlier treatment with oral corticosteroids. A possible explanation for BUD's efficacy in patients with parenchymal lesions could be that inhaled BUD is rapidly absorbed into systemic circulation, creating plasma peaks which result in systemic anti-inflammatory activity in both peripheral airways and lung tissue. At airway level this steroid activity is furthermore prolonged because a BUD fraction is intracellularly, reversibly transformed into lipophilic BUD-oleate. These mechanisms have been proposed to explain the theoretically unexpected similar efficacy of BUD compared with more lipophilic ICSs in patients with asthma and COPD. In this review we summarize the results of clinical studies with ICSs in patients with pulmonary sarcoidosis. It is obvious that current ICSs, including BUD, cannot generally be recommended as such for treatment of sarcoidosis. However, using BUD as a model substance further pharmacologic and kinetic studies could possibly define a kinetic profile giving optimal partitioning between airway and systemic activity with less adverse systemic risks. Such a substance could replace or reduce oral corticosteroids in the treatment of airway and pulmonary parenchymal diseases.
已有一些关于吸入性糖皮质激素（ICS）用于肺结节病患者的对照临床研究结果的报道。已观察到一些疗效证据，但主要是关于ICS布地奈德（BUD）的。这些具有临床重要性且在统计学上有显著意义的结果仅限于在全身用糖皮质激素诱导治疗数周或数月后用BUD进行维持治疗。在早期接受口服糖皮质激素治疗后复发的患者中也描述了阳性结果。BUD对实质性病变患者有效的一个可能解释是，吸入的BUD迅速吸收进入体循环，产生血浆峰浓度，从而在外周气道和肺组织中产生全身抗炎活性。在气道水平，这种类固醇活性进一步延长，因为一部分BUD在细胞内可逆地转化为亲脂性的布地奈德油酸酯。有人提出这些机制来解释在哮喘和慢性阻塞性肺疾病（COPD）患者中，BUD与亲脂性更强的ICS相比在理论上意外的相似疗效。在本综述中，我们总结了ICS用于肺结节病患者的临床研究结果。显然，目前的ICS，包括BUD，通常不能被推荐用于结节病的治疗。然而，以BUD作为模型物质，进一步的药理学和动力学研究可能会确定一种动力学特征，使气道和全身活性之间达到最佳分配，同时降低全身不良风险。这样一种物质可以在气道和肺实质疾病的治疗中替代或减少口服糖皮质激素的使用。
