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

RationaleIn 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.ObjectivesTo 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.MethodsPatients 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.ResultsNine 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).ConclusionSinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF.

Optical coherence tomography detects structural abnormalitiesof the nasal mucosa in patients with cystic fibrosis

“…So far, it has not been possible to determine effects of novel therapies on inflammation and remodeling of the airway mucosa in patients with CF. Based on the present study results and considering ongoing developments in OCT technology with improved spatial resolution, our results suggest further development of OCT imaging as a potential minimal-invasive quantitative endpoint of mucosal alterations in CF clinical trials testing novel treatment modalities including systemic causal treatment with recently introduced CFTR modulators ivacaftor and lumacaftor [8,9,[18][19][20] or topical anti-inflammatory and antibiotic treatment with pulsed nasal nebulizers [7,21,22]. In this context, OCT imaging of the nasal mucosa was reproducible and easy to apply in the clinical setting.…”

“…This is of particular interest as new treatment modalities including nebulized nasal antibiotics and anti-inflammatories as well as systemic CFTR-targeted pharmacotherapy become available [7][8][9]. At present, non-invasive imaging of the upper airways relies on nasal endoscopy and radiological imaging techniques such as CT and MRI.…”

Paediatric nasal polyps in cystic fibrosis

“…Meanwhile, nasal sprays deliver large size droplets without any aerosol effect to the sinuses that tend to deposit on the anterior portion of the nose 22. Thus, these factors (figure 9) need to be addressed to allow effective drug delivery into the sinuses 21 23 24…”

Inhaled Antibiotics for Gram-Negative Respiratory Infections

“…The Pari Sinus vibrating-mesh nebulizer has successfully been used in this fashion to effectively reduce the quantity of P. aeruginosa bacteria and increase quality of life while maintaining undetectable serum concentrations in patients with CF (82).…”