title: Sinonasal inhalation of tobramycin vibrating aerosol in cystic fibrosis patients with upper airway Pseudomonas aeruginosa colonization: results of a randomized, double-blind, placebo-controlled pilot study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF.
authors.affiliation: Cystic Fibrosis Centre, Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Mainz
authors.affiliation: Cystic Fibrosis Centre, Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Schädlich
authors.affiliation: Cystic Fibrosis Centre, Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schien
authors.affiliation: Cystic Fibrosis Centre, Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Michl
authors.affiliation: Otorhinolaryngology Department, Jena University Hospital, Jena, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Schelhorn-Neise
authors.affiliation: Otorhinolaryngology Department, Klinikum Stuttgart, Germany.
authors.forename: Assen
authors.initials: A
authors.lastname: Koitschev
authors.affiliation: Otorhinolaryngology Department, University Hospital, Tübingen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Koitschev
authors.affiliation: Microbiology, Jena University Hospital, Jena, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Keller
authors.affiliation: University Hospital, Pediatric CF-Centre, Tübingen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Riethmüller
authors.affiliation: Technical University, Biometrics, Dresden, Germany.
authors.forename: Baerbel
authors.initials: B
authors.lastname: Wiedemann
authors.affiliation: Cystic Fibrosis Centre, Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: James F
authors.initials: JF
authors.lastname: Beck
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D003550:Cystic Fibrosis / Q000382:microbiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000382:microbiology; D010865:Pilot Projects; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D014031:Tobramycin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D014031:Tobramycin
keywords: PARI Sinus; Pseudomonas aeruginosa; SNOT-20; cystic fibrosis; nasal lavage; sinonasal; upper airways