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

Jochen G Mainz, Katja Schädlich, Claudia Schien, Ruth Michl, Petra Schelhorn-Neise, Assen Koitschev, Christiane Koitschev, Peter M Keller, Joachim Riethmüller, Baerbel Wiedemann, James F Beck, Jochen G Mainz, Katja Schädlich, Claudia Schien, Ruth Michl, Petra Schelhorn-Neise, Assen Koitschev, Christiane Koitschev, Peter M Keller, Joachim Riethmüller, Baerbel Wiedemann, James F Beck

Abstract

Rationale: 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.

Objectives: 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).

Conclusion: Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF.

Keywords: PARI Sinus; Pseudomonas aeruginosa; SNOT-20; cystic fibrosis; nasal lavage; sinonasal; upper airways.

Figures

Figure 1
Figure 1
Logarithmic changes in Pseudomonas aeruginosa colony count in nasal lavage from day 1 (before first sinonasal inhalation) to day 30 (2 days after last sinonasal inhalation) within the double-blind, placebo-controlled phase (three patients inhaled isotonic saline; and six, tobramycin).
Figure 2
Figure 2
Effects of tobramycin or isotonic saline (placebo) treatment on quality of life assessed by SNOT-20-GAV overall scores. Notes: **Significant changes for tobramycin, compared with isotonic saline; P=0.033. Abbreviation: SNOT-20-GAV, German-adapted version of the Sino-Nasal Outcome Test.

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