Ventilation and aerosolized drug delivery to the paranasal sinuses using pulsating airflow aeuro" a preliminary study

Moeller, Winfried; Schuschnig, Uwe; Meyer, Gabriele; Häußinger, K.; Keller, Manfred; Junge-Hülsing, B.; Mentzel, Heribert

doi:10.4193/rhin08.180

Cited by 48 publications

(96 citation statements)

References 28 publications

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“…Due to the small dimensions of the ostium, drainage in the nasal cavity is impaired in CF, and chronic sinusitis is therefore found in nearly all patients. It has been shown that microaerophilic conditions are encountered (Aanaes et al, 2011), that fewer PMNs are present surrounding the bacteria and that lower antibiotic concentrations are achieved in the sinus compared to the lung, since the nebulized antibiotics do not reach the paranasal sinuses (Moeller et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

Diversity of metabolic profiles of cystic fibrosis Pseudomonas aeruginosa during the early stages of lung infection

et al. 2015

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Pseudomonas aeruginosa is the dominant pathogen infecting the airways of cystic fibrosis (CF) patients. During the intermittent colonization phase, P. aeruginosa resembles environmental strains but later evolves to the chronic adapted phenotype characterized by resistance to antibiotics and mutations in the global regulator genes mucA, lasR and rpoN. Our aim was to understand the metabolic changes occurring over time and between niches of the CF airways. By applying Phenotype MicroArrays, we investigated changes in the carbon and nitrogen catabolism of subsequently clonally related mucoid and non-mucoid (NM) lung and sinus P. aeruginosa isolates from 10 CF patients (five intermittently colonized/five chronically infected). We found the most pronounced catabolic changes for the early/late NM isolate comparisons, with respiratory reduction seen for all chronically infecting isolates and two intermittently colonizing isolates. Fewer differences were observed between sinus and lung isolates, showing a higher degree of isolate similarity between these two niches. Modest respiratory changes were seen for the early isolate/PAO1 comparisons, indicating colonization with environmental isolates. Assignment of metabolic pathways via the KEGG database showed a prevalence of substrates involved in the metabolism of Ala, Asp and Glu, D-Ala, and Arg and Pro. In conclusion, extensive heterogeneity in the metabolic profiles of the P. aeruginosa isolates was observed from the initial stages of the infection, showing a rapid diversification of the bacteria in the heterogeneous environment of the lung. Metabolic reduction seems to be a common trait and therefore an adaptive phenotype, though it can be reached via multiple metabolic pathways.

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Section: Discussionmentioning

confidence: 99%

Diversity of metabolic profiles of cystic fibrosis Pseudomonas aeruginosa during the early stages of lung infection

et al. 2015

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“…Based on previous studies (Maniscalco, 2006;Möller et al, 2008Möller et al, , 2009Durand et al, 2001;Valentine et al, 2008), specific nasal jet nebulizers using sound effects are currently the best option for targeting antibiotic aerosols to the site of infection in case of chronic rhinosinusitis. This study demonstrates that aerosols produced by these specific nasal sonic jet nebulizers using sound effect are deposited in the anatomical targets to treat sinusitis.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, based on the (Möller et al, 2008) method using 81m Kr gas, we used a specific nasal sonic jet nebulizer with sound effect that enables gas to penetrate the maxillary sinuses and hence allows anatomical regions to be determined. With the nasal sonic jet nebulizer with sound effect, aerosol deposited in volunteers' lungs was similar to results obtained from Pari jet nebulizer without sound effect (Djupesland et al, 2004) (27 ± 10% vs 22 ± 8.1%), demonstrating that the sound effect has no significant effect on lung deposition.…”

Section: Discussionmentioning

confidence: 99%

“…The 81m Kr generator was connected to an AOHBOX ® box compressor generating a 100 Hz sound to image maxillary sinuses (Möller et al, 2009). Images were acquired without and later with additional sound during 2 min of gas administration.…”

Section: M Kr Gas Inhalationmentioning

confidence: 99%

“…The sound generates a positive pressure from the ostium to the maxillary sinuses allowing the gas exchange with the maxillary sinuses: it can be considered as a Helmholtz resonator (Maniscalco, 2006). In vitro and in vivo studies have demonstrated the benefit of applying this sound for maxillary sinus ventilation and deposition Möller et al, 2008;Durand et al, 2001;Valentine et al, 2008) increasing the aerosol deposition into maxillary sinuses by a factor two (Möller et al, 2009). Specific nasal sonic jet nebulizers using sound effect are therefore the best option for targeting antibiotic aerosols to the site of infection in the case of chronic rhinosinusitis.…”

Section: Introductionmentioning

confidence: 98%

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Deposition of aerosols delivered by nasal route with jet and mesh nebulizers

Vecellio

Gersem

Guellec

et al. 2011

International Journal of Pharmaceutics

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Phase 1 clinical study to assess the safety of a novel drug delivery system providing long‐term topical steroid therapy for chronic rhinosinusitis

Douglas

Psaltis

Rimmer

et al. 2019

Int Forum Allergy Rhinol

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Background Chronic rhinosinusitis (CRS) patients who fail medical management have few treatment options other than endoscopic sinus surgery (ESS). A novel biodegradable mometasone furoate drug delivery system (LYR‐210) providing continuous topical steroid therapy to sinonasal mucosa over 24 weeks was developed to treat unoperated CRS patients who have failed medical management prior to ESS. LYR‐210 was designed to slowly expand in the middle meatus, ensuring efficient drug delivery as mucosal swelling reduces. Methods A prospective, multicenter, open‐label study was conducted in 20 CRS subjects who were determined to be candidates for ESS. Under endoscopic guidance and topical anesthesia, LYR‐210 was placed in both middle meatuses. The primary endpoint was product‐related serious adverse events (SAEs) at 4 weeks. Additional assessments included plasma drug concentration, morning serum cortisol levels, intraocular pressures (IOPs), and Sino‐Nasal Outcome Test (SNOT‐22) scores. Results LYR‐210 was successfully placed bilaterally in 20 subjects (12 without nasal polyps and 8 with polyps) in an office setting. There were no product‐related SAEs through 24 weeks, at which point 86% of LYR‐210 depots were still retained in the middle meatus. Serum cortisol, IOP, and plasma drug concentrations supported systemic safety at all time points tested. Subjects experienced significant reductions in their SNOT‐22 scores as early as week 1, and this reduction persisted through week 24 (p < 0.01). Significant symptom improvement was achieved in the SNOT‐22 rhinologic, extranasal rhinologic, ear‐facial, psychological, and sleep dysfunction subdomains at 24 weeks (p < 0.05). Conclusion LYR‐210 is safe and well‐tolerated in ESS‐naive CRS patients and leads to sustained symptom improvement in patients.

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Ventilation and aerosolized drug delivery to the paranasal sinuses using pulsating airflow aeuro" a preliminary study

Abstract: The study demonstrates the high efficiency of a pulsating airflow in paranasal sinus ventilation and aerosolized drug delivery. This proves that topical drug delivery to the paranasal sinuses in relevant quantities is possible and indicates further clinical studies are necessary.

Cited by 48 publications

References 28 publications

Diversity of metabolic profiles of cystic fibrosis Pseudomonas aeruginosa during the early stages of lung infection

Diversity of metabolic profiles of cystic fibrosis Pseudomonas aeruginosa during the early stages of lung infection

Deposition of aerosols delivered by nasal route with jet and mesh nebulizers

Phase 1 clinical study to assess the safety of a novel drug delivery system providing long‐term topical steroid therapy for chronic rhinosinusitis

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