Mainz Jochen G, Schädlich Katja, Schien Claudia, Michl Ruth, Schelhorn-Neise Petra, Koitschev Assen, Koitschev Christiane, Keller Peter M, Riethmüller Joachim, Wiedemann Baerbel, Beck James F
Cystic Fibrosis Centre, Department of Pediatrics, Jena University Hospital, Jena, Germany.
Otorhinolaryngology Department, Jena University Hospital, Jena, Germany.
Drug Des Devel Ther. 2014 Feb 10;8:209-17. doi: 10.2147/DDDT.S54064. eCollection 2014.
In cystic fibrosis (CF), the paranasal sinuses are sites of first and persistent colonization by pathogens such as Pseudomonas aeruginosa. Pathogens subsequently descend to the lower airways, with P. aeruginosa remaining the primary cause of premature death in patients with the inherited disease. Unlike conventional aerosols, vibrating aerosols applied with the PARI Sinus™ nebulizer deposit drugs into the paranasal sinuses. This trial assessed the effects of vibrating sinonasal inhalation of the antibiotic tobramycin in CF patients positive for P. aeruginosa in nasal lavage.
To evaluate the effects of sinonasal inhalation of tobramycin on P. aeruginosa quantification in nasal lavage; and on patient quality of life, measured with the Sino-Nasal Outcome Test (SNOT-20), and otologic and renal safety and tolerability.
Patients were randomized to inhalation of tobramycin (80 mg/2 mL) or placebo (2 mL isotonic saline) once daily (4 minutes/nostril) with the PARI Sinus™ nebulizer over 28 days, with all patients eligible for a subsequent course of open-label inhalation of tobramycin for 28 days. Nasal lavage was obtained before starting and 2 days after the end of each treatment period by rinsing each nostril with 10 mL of isotonic saline.
Nine patients participated, six initially receiving tobramycin and three placebo. Sinonasal inhalation was well tolerated, with serum tobramycin <0.5 mg/L and stable creatinine. P. aeruginosa quantity decreased in four of six (67%) patients given tobramycin, compared with zero of three given placebo (non-significant). SNOT-20 scores were significantly lower in the tobramycin than in the placebo group (P=0.033).
Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF.
在囊性纤维化（CF）中，鼻窦是铜绿假单胞菌等病原体首次定植并持续存在的部位。病原体随后会下行至下呼吸道，铜绿假单胞菌仍是这种遗传性疾病患者过早死亡的主要原因。与传统气雾剂不同，使用PARI Sinus™雾化器产生的振动气雾剂可将药物沉积到鼻窦中。本试验评估了对鼻腔灌洗中铜绿假单胞菌呈阳性的CF患者进行振动鼻窦吸入抗生素妥布霉素的效果。
评估鼻窦吸入妥布霉素对鼻腔灌洗中铜绿假单胞菌定量的影响；以及对患者生活质量的影响（采用鼻窦结局测试（SNOT-20）进行测量），并评估耳科和肾脏的安全性及耐受性。
患者被随机分为两组，一组每天使用PARI Sinus™雾化器吸入一次妥布霉素（80mg/2mL），另一组吸入安慰剂（2mL等渗盐水），每次4分钟/每侧鼻孔，持续28天，所有患者均有资格在后续进行为期28天的开放标签妥布霉素吸入疗程。在每个治疗期开始前和结束后2天，用10mL等渗盐水冲洗每个鼻孔以获取鼻腔灌洗液。
9名患者参与试验，6名最初接受妥布霉素治疗，3名接受安慰剂治疗。鼻窦吸入耐受性良好，血清妥布霉素<0.5mg/L，肌酐水平稳定。接受妥布霉素治疗的6名患者中有4名（67%）铜绿假单胞菌数量减少，而接受安慰剂治疗的3名患者中这一比例为零（无统计学意义）。妥布霉素组的SNOT-20评分显著低于安慰剂组（P=0.033）。
鼻窦吸入振动抗生素气雾剂对于减少CF患者鼻窦病原体定植和控制症状似乎很有前景。
