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.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Cystic Fibrosis/microbiology , Pseudomonas aeruginosa/drug effects , Tobramycin/administration & dosage , Administration, Inhalation , Adolescent , Adult , Aerosols , Anti-Bacterial Agents/adverse effects , Child , Double-Blind Method , Female , Humans , Male , Nasal Mucosa/microbiology , Pilot Projects , Tobramycin/adverse effectsABSTRACT
In the rehabilitation of cleft palate patients the quality of spoken language represents one of the most important aspects of successful social integration. It is therefore necessary to direct special attention to phoniatric care and speech therapy following operative reconstruction. One of the main problems is the comparison of subjective and objective measures of the degree and type of nasal disorder. In an interdisciplinary project at the University of Jena nasometry was assessed. Due to a lack of norm values for German a representative sample for the calibration of cleft palate patients and normal subjects was collected. Speech was elicited using standardized and phonetically validated reading materials. Nasalance measurements were compared with judgements made by a group of trained listeners who were asked to assess voice quality (RBH) and nasality. A database containing nasalance values and acoustic signals from 120 subjects was built up. The results generally exhibited highly significant correlations between instrumental measurements and auditory judgements. Profiles of norm values for a phonetically and statistically reliable standard for German were obtained, which in turn can be used as a comparative basis for further studies.
