Topical and systemic antifungal therapy for chronic rhinosinusitis.
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ABSTRACT:
SUBMITTER: Head K
PROVIDER: S-EPMC6513454 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC8763400 | biostudies-literature
Project description:Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Because fungi were postulated as a potential cause of CRS in the late 1990s, contrasting articles have advocated and refuted the use of antifungal agents in its management. Although good research shows an interaction of the immune system with fungus in CRS, e.g., allergic fungal sinusitis (AFS), this does not imply that fungi are the cause of CRS or that antifungals will be effective in management. This study was designed to assess the potential advantage of either topical or systemic antifungal therapy in the symptomatic treatment of CRS to aid physicians in making informed decisions about treating patients with CRS.A systematic review of the literature was performed with meta-analysis. All studies obtained from searches were reviewed and trials meeting the eligibility criteria were selected. CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps or American Academy of Otolaryngology-Head and Neck Surgery criteria. Authors were contacted and original data were used for data analysis.Five studies investigating topical antifungals and one investigating systemic antifungals met the inclusion criteria. All trials were double blinded and randomized. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo. Symptoms scores statistically favored the placebo group for this outcome. Adverse event reporting was higher in the antifungal group.Reported side-effects of antifungal therapies may outweigh any potential benefits of treatment based on this meta-analysis and the authors therefore do not advocate the use antifungal treatment in the management of CRS.
| S-EPMC3906505 | biostudies-other
Project description:Research in immunology has brought great progress in knowledge of inflammatory processes in the last 2 decades, which also has an impact on the upper airways. Our understanding of the pathophysiology of chronic rhinosinusitis developed from a rather mechanistic point of view with a focus on narrow clefts and mucociliary clearance to the appreciation of a complex network of immunological pathways forming the basis of disease. We today differentiate various forms of inflammation, we start to understand complex immune-regulatory networks and the reasons for their failure, and have already developed innovative approaches for therapy for the most severely ill subjects. Due to this new knowledge in inflammation and remodeling processes within mucosal tissue, specifically on the key driving factors, new diagnostic tools and therapeutic approaches for chronic rhinosinusitis have developed; the differentiation of endotypes based on pathophysiological principles will be crucial for the use of innovative therapies, mostly humanized monoclonal antibodies. Several hundred of those antibodies are currently developed for various indications and will impact our specialty as well as pneumology to a great extent.
| S-EPMC4702058 | biostudies-literature
Project description:IntroductionThe pathophysiology and temporal dynamics of affected tissues in chronic rhinosinusitis (CRS) remain poorly understood. Here, we present a multiomics-based time-series assessment of nasal polyp biopsies from three patients with CRS, assessing natural variability over time and local response to systemic corticosteroid therapy.MethodsPolyp tissue biopsies were collected at three time points over two consecutive weeks. Patients were prescribed prednisone (30 mg daily) for 1 week between Collections 2 and 3. Polyp transcriptome, proteome, and microbiota were assessed via RNAseq, SWATH mass spectrometry, and 16S ribosomal RNA and ITS2 amplicon sequencing. Baseline interpatient variability, natural intrapatient variability over time, and local response to systemic corticosteroids, were investigated.ResultsOverall, the highly abundant transcripts and proteins were associated with pathways involved in inflammation, FAS, cadherin, integrin, Wnt, apoptosis, and cytoskeletal signaling, as well as coagulation and B- and T-cell activation. Transcripts and proteins that naturally varied over time included those involved with inflammation- and epithelial-mesenchymal transition-related pathways, and a number of common candidate target biomarkers of CRS. Ten transcripts responded significantly to corticosteroid therapy, including downregulation of TNF, CCL20, and GSDMA, and upregulation of OVGP1, and PCDHGB1. Members of the bacterial genus Streptococcus positively correlated with immunoglobulin proteins IGKC and IGHG1.ConclusionsUnderstanding natural dynamics of CRS-associated tissues is essential to provide baseline context for all studies on putative biomarkers, mechanisms, and subtypes of CRS. These data further our understanding of the natural dynamics within nasal polypoid tissue, as well as local changes in response to systemic corticosteroid therapy.
| S-EPMC7860613 | biostudies-literature
Project description:Bacterial microbiota of the sinuses in CRS.
| PRJEB20232 | ENA
Project description:Recalcitrant chronic rhinosinusitis without polyposis (CRSsP) is a challenging condition to manage as traditional medical therapies and surgery fail to provide satisfactory clinical improvements. Colloidal silver (CS), a widely used naturopathic agent, has recently shown anti-biofilm properties both in vitro and within a rhinosinusitis animal model. To date, no trials involving humans have been published in world literature. The purpose of this study was to assess the efficacy of CS as a topical nasal spray in patients with refractory CRSsP.A prospective cohort study was conducted using a convenience sample of 20 randomized patients with crossover methodology, comparing nasal sprays with CS versus saline. Patients sprayed twice daily for six weeks with the first intervention and then switched to the second for the next six weeks, with measurements made at baseline and each time point. Primary outcomes were changes in SNOT-22 and Lund-Kennedy (LK) endoscopic scores. All analysis was non-parametric and was conducted using STATA 14.Twenty-two patients were enrolled in the study with 20 completing the entire protocol. Mean 6-week change in SNOT-22 scores were -2.8 and 1.0 for saline and CS, respectively (p?=?0.373). Similarly, mean 6-week change in LK scores were -1.4 and -1.1 for saline and CS, respectively (p?=?0.794). Significant period effects were observed with the SNOT-22 score between the randomized groups. No participants experienced negative health effects directly attributable to the administration of intranasal CS.Commercially available CS nasal spray did not demonstrate any meaningful subjective or objective improvements in patients with recalcitrant CRSsP.NCT02403479 . Registered on March 1, 2015.
| S-EPMC5702207 | biostudies-literature
Project description:ObjectivesChronic rhinosinusitis (CRS) is a common chronic disease of the upper airways and has considerable impact on quality of life. Topical delivery of drugs to the paranasal sinuses is challenging, therefore the rate of surgery is high. This study investigates the delivery efficiency of a pulsating aerosol in comparison to a nasal pump spray to the sinuses and the nose in healthy volunteers and in CRS patients before and after sinus surgery.Methods(99m)Tc-DTPA pulsating aerosols were applied in eleven CRSsNP patients without nasal polyps before and after sinus surgery. In addition, pulsating aerosols were studied in comparison to nasal pump sprays in eleven healthy volunteers. Total nasal and frontal, maxillary and sphenoidal sinus aerosol deposition and lung penetration were assessed by anterior and lateral planar gamma camera imaging.ResultsIn healthy volunteers nasal pump sprays resulted in 100% nasal, non-significant sinus and lung deposition, while pulsating aerosols resulted 61.3+/-8.6% nasal deposition and 38.7% exit the other nostril. 9.7+/-2.0 % of the nasal dose penetrated into maxillary and sphenoidal sinuses. In CRS patients, total nasal deposition was 56.7+/-13.3% and 46.7+/-12.7% before and after sinus surgery, respectively (p<0.01). Accordingly, maxillary and sphenoidal sinus deposition was 4.8+/-2.2% and 8.2+/-3.8% of the nasal dose (p<0.01). Neither in healthy volunteers nor in CRS patients there was significant dose in the frontal sinuses.ConclusionIn contrast to nasal pump sprays, pulsating aerosols can deliver significant doses into posterior nasal spaces and paranasal sinuses, providing alternative therapy options before and after sinus surgery. Patients with chronic lung diseases based on clearance dysfunction may also benefit from pulsating aerosols, since these diseases also manifest in the upper airways.
| S-EPMC3770586 | biostudies-literature
Project description:Invasive pulmonary Aspergillosis is a leading cause of morbidity and mortality in immunosuppressed patients and treatment outcomes using oral antifungal triazoles remain suboptimal. Here we show that combining topical treatment using PC945, a novel inhaled triazole, with systemic treatment using known triazoles demonstrated synergistic antifungal effects against Aspergillus fumigatus (AF) in an in vitro human alveolus bilayer model and in the lungs of neutropenic immunocompromised mice. Combination treatment with apical PC945 and either basolateral posaconazole or voriconazole resulted in a synergistic interaction with potency improved over either compound as a monotherapy against both azole-susceptible and resistant AF invasion in vitro. Surprisingly there was little, or no synergistic interaction observed when apical and basolateral posaconazole or voriconazole were combined. In addition, repeated prophylactic treatment with PC945, but not posaconazole or voriconazole, showed superior effects to single prophylactic dose, suggesting tissue retention and/or accumulation of PC945. Furthermore, in mice infected with AF intranasally, 83% of animals treated with a combination of intranasal PC945 and oral posaconazole survived until day 7, while little protective effects were observed by either compound alone. Thus, the combination of a highly optimised topical triazole with oral triazoles potentially induces synergistic effects against AF infection.
| S-EPMC6603190 | biostudies-literature
Project description:Fungal mycoses have become an important health and environmental concern due to the numerous deleterious side effects on the well-being of plants and humans. Antifungal therapy is limited, expensive, and unspecific (causes toxic effects), thus, more efficient alternatives need to be developed. In this work, Copper (I) Iodide (CuI) nanomaterials (NMs) were synthesized and fully characterized, aiming to develop efficient antifungal agents. The bioactivity of CuI NMs was evaluated using Sporothrix schenckii and Candida albicans as model organisms. CuI NMs were prepared as powders and as colloidal suspensions by a two-step reaction: first, the CuI2 controlled precipitation, followed by hydrazine reduction. Biopolymers (Arabic gum and chitosan) were used as surfactants to control the size of the CuI materials and to enhance its antifungal activity. The materials (powders and colloids) were characterized by SEM-EDX and AFM. The materials exhibit a hierarchical 3D shell morphology composed of ordered nanostructures. Excellent antifungal activity is shown by the NMs against pathogenic fungal strains, due to the simultaneous and multiple mechanisms of the composites to combat fungi. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of CuI-AG and CuI-Chitosan are below 50 ?g/mL (with 5 h of exposition). Optical and Atomic Force Microscopy (AFM) analyses demonstrate the capability of the materials to disrupt biofilm formation. AFM also demonstrates the ability of the materials to adhere and penetrate fungal cells, followed by their lysis and death. Following the concept of safe by design, the biocompatibility of the materials was tested. The hemolytic activity of the materials was evaluated using red blood cells. Our results indicate that the materials show an excellent antifungal activity at lower doses of hemolytic disruption.
| S-EPMC7926374 | biostudies-literature
Project description:Increasing evidence suggests that CRS is a heterogeneous group of sinus disorders involving overlapping but distinct disease entities.The factors leading to different CRS phenotypes remain enigmatic. The role of miRNAs in the regulation of immunological and inflammatory processes is beginning to emerge.Thus, we examined microRNAs expression profiles in eosinophilic CRSwNP adn CRSsNP. Compared with controls, 31 differentially expressed miRNAs (30 downregulated and 1 upregulated miRNAs) in eosinophilic CRSwNP and 4 differentially expressed miRNAs (2 downregulated and 2 upregulated miRNAs) in CRSsNP were indentified. Real time RT-PCR was subsequently performed to verify the miRNA microarray result.
2011-12-08 | GSE32300 | GEO