amphotericin-b and Nasal-Polyps

Chronic rhinosinusitis (CRS) affects 1-4% of the adult population. The etiology of this multifactorial, chronic disease, which leads to a significant impairment of the quality of life, often accompanied by nasal polyposis, is not fully understood. In the past decade, it was presumed that the disease, which causes characteristic eosinophilic infiltration of the nasal mucosa, is triggered by an enhanced (but not classical allergic IgE-type) immune response against fungal organisms in the nasal mucus. If this supposition is correct, then it appears obvious that the administration of amphotericin B nasal spray in adequate concentration following endoscopic polypectomy should be advantageous for these patients, and might even reduce the number of recurrent cases. To check on this assumption, we conducted a prospective randomized placebo-controlled trial involving 33 patients, 30 of whom remained in the study throughout. Patients with nasal polyposis were operated on with an endoscopic technique between 1 November 2005 and 1 October 2006; group A (14 randomly selected patients) were treated with a nasal spray containing 5 mg/ml amphotericin B, while the placebo group B (16 randomly selected patients) received a nasal spray lacking amphotericin B. We evaluated our results with the aid of a modified Lund-Mackay CT score, the SNAQ-11 test (which assesses changes in the symptoms), a quality of life test and endoscopy. The SPSS 14.0 for Windows program was utilized to process the data of examinations performed preoperatively and 1 year postoperatively. The CT scores of the group A patients 1 year after the operation exhibited wide scattering, without signs of recovery. The CT scores of the group B patients indicated a slight improvement, though this did not prove significant relative to group A. Both the SNAQ-11 test and the quality of life test revealed a significant improvement in each group, but the degrees of change in these tests did not differ significantly between the two groups of patients. The endoscopic findings indicated a slight improvement to the advantage of the amphotericin B-treated group 12 months after the operation. These results lead to the conclusion that the administration of amphotericin B nasal spray to patients operated on for nasal polyposis does not give rise to a significant alteration in either CT score, clinical symptoms, or quality of life. The more favorable clinical aspects observed in the amphotericin B-treated group during the endo

Topics: Administration, Intranasal; Amphotericin B; Antifungal Agents; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Nasal Polyps; Placebos; Prospective Studies; Quality of Life; Recurrence; Rhinitis; Sinusitis; Treatment Outcome

It has been suggested that an exaggerated immune response to fungi is crucial in the pathogenesis of chronic rhinosinusitis (CRS). Based on this rationale, the use of topical antifungals (amphotericin B) has been advocated. Studies on its clinical effectiveness are, however, contradictory.. To examine the effect of nasal antifungal treatment on secreted mediators in samples of nasal lavage fluid from patients with CRS with or without nasal polyps (NP).. Part two of a prospective double-blind, placebo-controlled multicenter clinical trial investigating the effect of 13 weeks of treatment with amphotericin B or placebo on the levels of pro-inflammatory cytokines, chemokines and growth factors (i.e., IL-1beta, IL-1RA, IL-2, IL-2R, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p40/p70 subunits), IL-13, IL-15, IL-17, TNF-alpha, IFN-alpha, IFN-gamma, G-CSF, GM-CSF, MIP-1alpha, MIP-1beta, IP-10, MIG, eotaxin, RANTES, MCP-1, MCP-2, MCP-3, VEGF, EGF, FGF-basic, HGF, Gro-alpha) and albumin via a fluorescent enzyme immunoassay in nasal lavage specimens of CRS patients with or without NP.. Topical amphotericin B had no significant effect on the level of any of the tested pro-inflammatory cytokines, chemokines, and growth factors in CRS nasal lavage samples. Treatment with placebo, however, increased the level of MIP-1alpha and MIP-1beta, which are mediators involved in wound healing.. Topical amphotericin B has no significant effect on activation markers of nasal inflammatory cells in chronic rhinosinusitis with or without nasal polyps.

Topics: Administration, Intranasal; Administration, Topical; Adult; Amphotericin B; Antifungal Agents; Chemokines; Chi-Square Distribution; Chronic Disease; Cytokines; Double-Blind Method; Female; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Nasal Lavage; Nasal Polyps; Prospective Studies; Rhinitis; Sinusitis; Statistics, Nonparametric; Treatment Outcome

Chronic rhinosinusitis affects 1-4% of the adult population. The aetiology of this multifactorial, chronic disease, which leads to a significant impairment of the quality of life, often accompanied by nasal polyposis, is not fully understood. In the past decade it was presumed that the disease, which causes characteristic eosinophilic infiltration of the nasal mucosa, is triggered by an enhanced (but not classical allergic IgE type) immune response.. If this supposition is correct, then it appears obvious that the administration of amphotericin B nasal spray in adequate concentration following endoscopic polypectomy should be advantageous for these patients, and might even reduce the number of recurrent cases.. To check on this assumption, the authors conducted a prospective randomized placebo-controlled trial involving 33 patients, 30 of whom remained in the study throughout. Patients with nasal polyposis were operated on with an endoscopic technique between 1 November 2005 and 1 October 2006; one group of them (group A, 14 randomly selected patients) was treated with a nasal spray containing 5 mg/ml amphotericin B, while the placebo group (group B, 16 randomly selected patients) received a nasal spray lacking amphotericin B. The results were evaluated with the aid of a modified Lund-Mackay CT score, the SNAQ-11 test (which evaluates changes in the symptoms), the life-quality test and endoscopy. The SPSS 14.0 for Windows program was utilized to process the data of examinations performed preoperatively and one year postoperatively.. The CT scores of the group A patients exhibited wide scattering without signs of recovery one year after the operation. The CT scores of the group B patients indicated a slight improvement, though this did not prove significant in relation to group A. Both the SNAQ-11 test and the life-quality test revealed a significant improvement in each group, but the degrees of change in these tests did not significantly differ between the two groups of patients. The endoscopic findings indicated a slight improvement to the advantage of the amphotericin B-treated group 12 months after the operation.. These results lead to the conclusion that the administration of amphotericin B nasal spray to patients operated on for nasal polyposis does not give rise to a significant alteration in CT scores, clinical symptoms, or quality of life. The more favourable clinical aspects observed in the amphotericin B-treated group during the endoscopic follow-up did not correspond to an improvement in the symptoms. In connection with the conclusions drawn from this study the authors discuss the available data on the fungal theory. They critically analyse the contradictory observations of 7 recent clinical studies.

Topics: Adult; Aerosols; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Chronic Disease; Endoscopy; Female; Humans; Male; Middle Aged; Nasal Polyps; Postoperative Period; Prospective Studies; Quality of Life; Rhinitis; Secondary Prevention; Severity of Illness Index; Sinusitis; Surveys and Questionnaires; Treatment Outcome

Fungal infection may be secondary to nasal polyposis or represent a real etiopathogenic factor in the infection itself.. The aim of this study was to evaluate the effectiveness of a combined treatment with lysine acetylsalicylate (LAS) and amphotericin B in preventing recurrence in patients with nasal polyposis with accompanying mycotic infection in comparison with a control group with nasal polyposis and fungal infection who did not receive antifungal therapy.. A total of 115 patients with nasal polyposis were randomly assigned to 4 different groups and treated as follows: (1) group A, 25 patients were first surgically treated and then treated with LAS; (2) group B, 25 patients received 40 mg of triamcinolone retard intramuscularly 3 times every 10 days (total dose 120 mg) and then they were treated with LAS; (3) group C, 16 patients were surgically treated and then treated with LAS and amphotericin B; (4) group D: 23 patients were treated with a medical polypectomy and steroids (as in the group B) and then with LAS and amphotericin B.. We found no significant differences between groups C and D, groups C and A, or groups B and D. However, the recurrence of nasal polyps in the groups treated with amphotericin B plus LAS (C and D) was significantly lower (P = .018) than in the 2 groups treated only with LAS (A and B).. Our results indicate that long term topical treatment with LAS and amphotericin B may be clinically effective in the treatment of patients with nasal polyposis associated with fungal infection.

Topics: Administration, Intranasal; Amphotericin B; Antifungal Agents; Aspirin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fungi; Humans; Kaplan-Meier Estimate; Lysine; Mycoses; Nasal Polyps; Treatment Outcome

To examine the effect of nasal antifungal treatment on eosinophil cationic protein (ECP) and tryptase levels in samples of nasal lavage fluid from patients with chronic rhinosinusitis and nasal polyps.. Prospective double-blind placebo-controlled clinical trial.. Tertiary surgical center.. Subjects with severe chronic rhinosinusitis and nasal polyps. Of 120 screened patients, 76 were eligible. Six patients withdrew because of minor adverse events, and 10 dropped out for other reasons. In total, 60 patients completed the study according to the study protocol.. Nasal treatment with amphotericin B or saline control for 8 weeks.. Nasal lavages were performed before and after treatment. Fungal elements were assessed by culture and with different polymerase chain reaction assays. Levels of ECP and tryptase were determined by fluorescent enzyme immunoassay.. No correlation between cell activation markers and fungus detection was observed before treatment (all P>.20). Nasal amphotericin B treatment had no effect on levels of ECP (P = .17) or tryptase (P = .09) in nasal lavage samples. Moreover, successful fungus eradication, defined as fungus detection before but not after treatment, did not influence nasal ECP or tryptase levels (all P>.40).. Neither topical amphotericin B therapy nor fungal state before and after treatment had any significant influence on activation markers of nasal inflammatory cells in chronic rhinosinusitis.

Topics: Administration, Intranasal; Adult; Aged; Amphotericin B; Antifungal Agents; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Nasal Mucosa; Nasal Polyps; Prospective Studies; Rhinitis; Sinusitis; Tomography, X-Ray Computed; Treatment Outcome

Nasal polyps and chronic rhinosinusitis are the products of an inflammatory process. Recently, fungal involvement has been thought to stimulate the development of polyps, and administration of antifungal agents was therefore considered a potential treatment. Several studies have been published indicating amphotericin B as an effective treatment for nasal polyps and chronic rhinosinusitis. The aim of our investigation was to evaluate the efficacy of intranasal applied amphotericin B on the growth of nasal polyps in a three-month, prospective, open trial. Our results show that nasal amphotericin B spray is not effective for nasal polyps and may even cause deterioration.

Topics: Administration, Intranasal; Adult; Aged; Amphotericin B; Antifungal Agents; Female; Humans; Male; Middle Aged; Nasal Polyps; Prospective Studies; Rhinitis; Treatment Failure

Recently, fungal elements were suspected to be the causative agent of chronic rhinosinusitis, and benefits of topical amphotericin B therapy have been reported.. The effects of amphotericin B versus control nasal spray on chronic rhinosinusitis were compared in a double-blind, randomized clinical trial.. Patients with chronic rhinosinusitis were administered 200 microL per nostril amphotericin B (3 mg/mL) or saline nasal spray 4 times daily over a period of 8 weeks. The response rate, defined as a 50% reduction of pretreatment computed tomography score, was the primary outcome variable. Additional outcome variables included a symptom score, a quality of life score, and an endoscopy score. Before and after treatment, nasal lavages were pretreated with dithiothreitol and examined for fungal elements by PCR and standard culture techniques.. Seventy-eight patients were included, and 60 patients finished the study per protocol. In the control group, no positive response (0 of 32) was observed, and 2 of 28 patients responded in the amphotericin B group (P>.2). The symptom scores were distinctly worse after amphotericin B therapy (P <.005). The other parameters investigated did not differ remarkably between the treatment groups.. Nasal amphotericin B spray in the described dosing and time schedule is ineffective and deteriorates patient symptoms.

Topics: Administration, Topical; Adult; Aged; Amphotericin B; Antifungal Agents; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Nasal Polyps; Prospective Studies; Rhinitis; Sinusitis; Tomography, X-Ray Computed

Although chronic rhinosinusitis (CRS) is one of the most frequently reported chronic diseases its etiology is not well understood. Recently, fungi have been proposed to influence the chronicity of rhinosinusitis. If fungi do play an important role then topical antifungal treatment may improve the inflammatory process of CRS. Therefore, in this study we measured inflammatory cytokine levels in nasal polyps after intranasal antifungal irrigation.. Nasal polyps were collected before and 4 weeks after treatment with 100 mg/l topical amphotericin B (n = 16), 50 mg/l topical amphotericin B (n = 14) or normal saline (n = 11). The cytokine--IL-5, IL-8, interferon-gamma, RANTES--protein content of polyp homogenates were determined by means of ELISA.. Nasal polyps were found to contain large amounts of cytokines (IL-5, IL-8 and RANTES) compared with normal inferior turbinates. After 4 weeks of treatment with topical agents, IL-5 levels tended to decrease in comparison with those of the other cytokines, but this difference was not statistically significant.. Topical amphotericin B treatment and nasal saline irrigation both influence the expression of nasal polyp cytokines. Topical nasal irrigation may influence the inflammatory process of CRS.

Topics: Administration, Intranasal; Administration, Topical; Adult; Amphotericin B; Antifungal Agents; Chemokine CCL5; Cytokines; Female; Humans; Interferon-gamma; Interleukin-5; Interleukin-8; Male; Mycoses; Nasal Polyps; Sodium Chloride; Therapeutic Irrigation

To determine the effect of topical antifungal irrigation fluid containing amphotericin B on nasal polyp and their recurrence pattern, and to study the association of serum IgE in predicting the presence of fungus along with the nasal polyps.. An interventional study.. Dow University Hospital, Dow International Medical College, DUHS, Karachi, from June 2015 to June 2017.. All adult patients having nasal polyps, who had not undergone any previous nasal surgery, were included in the study. Patients aged under 18 years, history of granulomatous diseases, immunosuppression, invasive fungal sinusitis, and pregnant ladies were excluded from the study. The ratio was kept as 1:2; one receiving irrigation with amphotericin B and the other only saline nasal irrigation without the medicine. After surgery, the patients were divided into two groups; 58 patients were in the placebo group and 29 in the amphotericin group. Serum IgE levels were documented before and one month postoperative treatment. Serum IgE level of more than 250 ng/ml was taken as a high value. All the patients were followed for six months. Recurrence was defined as the recurrence of nasal symptoms and recurrence of mucosal thickening based on repeat CT scan. Frequency tables and cross tabulations using Chi-square test were performed with p-values of 0.05 taken as significant were performed on different variables.. A total of 87 patients were inducted. Overall 22 (25.3%) patients had recurrence of symptoms at six-month followup visit. Twelve (13.7%) of these were in the placebo group and 10 (11.5%) were in the amphotericin B nasal irrigation group. Serum IgE level preoperatively ranged between 52 - 9344 ng/dl; postoperatively it ranged from 13-1050 ng/dl. When pre and postoperative serum IgE level were compared with each other and CT scan scores, using Chi-square test, the difference was significant (p<0.001).. Amphotericin B improved the CT scan score of the patients. The nasal irrigation of amphotericin B did not show significant change in the recurrence pattern of chronic sinuses with polyps. Serum IgE can be used as marker for the presence and response to treatment for non-invasive fungal sinusitis.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Biomarkers; Chronic Disease; Endoscopy; Female; Humans; Immunoglobulin E; Male; Middle Aged; Nasal Lavage; Nasal Polyps; Recurrence; Rhinitis; Sinusitis; Tomography, X-Ray Computed

Sinonasal polyposis is considered to be the end-result of a chronic inflammatory process in the sinonasal mucosa. Its underlying mechanisms are still unclear, but the involvement of fungi has been suggested for many years. In the present study, we retrospectively evaluated the clinical and mycological profile of 161 patients with chronic rhinosinusitis (CRS) and nasal polyps who were undergoing surgery at our tertiary care facility during 2002 to 2010. CT scan findings and per-operative presence of allergic mucin were provisionally suggestive of fungal rhinosinusitis (FRS) in all the patients. Total serum IgE and peripheral eosinophilia were noted. Histological examination of polyp tissue showed eosinophilic mucin in 100% of the cases and the incidence of allergic fungal rhinosinusitis (AFRS) was 83.9% in the patient population. KOH and/or culture were positive for fungal hyphae or yeast in 93% (150/161) of the patients. Aspergillus spp. were the most commonly recovered isolates (70%). MICs of all A. flavus and A. fumigatus isolates were within the susceptible zone for itraconazole, voriconazole, and amphoterecin B. In conclusion, allergic fungal rhinosinusitis (FRS) is a common disorder in patients with sinonasal polyposis and due to its recurrent and intractable nature, a high degree of clinical suspicion for the presence of FRS in nasal polyposis should be considered.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Chronic Disease; Female; Fungi; Humans; Immunoglobulin E; Incidence; India; Itraconazole; Male; Middle Aged; Mucins; Mycoses; Nasal Polyps; Pyrimidines; Retrospective Studies; Rhinitis, Allergic, Perennial; Sinusitis; Tertiary Healthcare; Tomography, X-Ray Computed; Triazoles; Voriconazole

Topics: Administration, Intranasal; Air Microbiology; Amphotericin B; Antifungal Agents; Chronic Disease; Double-Blind Method; Fungi; Humans; Mycoses; Nasal Polyps; Prospective Studies; Randomized Controlled Trials as Topic; Sinusitis

Intranasal application of the antimycotic agent amphotericin B (AmphoB) has been proposed as an effective treatment of chronic rhinosinusitis (CRS) with polyps. AmphoB is a sterol-binding agent known to modify cell membrane structure. The cytotoxic effects of AmphoB were studied on primary human nasal epithelial cells in vitro.. Human epithelial cells were isolated from nasal polyps and middle turbinates of patients suffering from CRS, and grown on collagen-coated polycarbonate filters with an air liquid-interface. After 15 days of culture, cells were exposed apically to 50 microM AmphoB during 4 h daily for 5 days. Some cells were treated during 4 weeks. The bioelectric properties of cells were then studied in Ussing chambers. Integrity of the cell monolayers was assessed by measurement of the transepithelial resistance (R) and immunofluorescent localization of the tight junction protein occludin.. Disruption of the epithelial monolayer integrity was observed in all of the nasal polyps cell cultures, as demonstrated by a 60% drop in R. Immunofluorescence microscopy showed significant loss in cell number and disruption in the distribution of occludin. Turbinate cell cultures elicited no change in R and expression of occludin after AmphoB treatment. However, the transepithelial potential, the basal short-circuit current and the amiloride-sensitive current were reduced by 70%.. AmphoB was cytotoxic for nasal polyp epithelial cells with disruption of the epithelium integrity and loss of tight junctions. In contrast, integrity of turbinate epithelial cells was conserved despite alterations in transepithelial ion transport. These observations may explain the beneficial effect of intranasal application of AmphoB on CRS observed in clinical trials.

Topics: Amphotericin B; Anti-Bacterial Agents; Cell Membrane Permeability; Cells, Cultured; Chronic Disease; Electrophysiology; Epithelial Cells; Female; Fluorescent Antibody Technique; Humans; In Vitro Techniques; Ion Channels; Male; Membrane Proteins; Nasal Polyps; Occludin; Rhinitis; Sinusitis; Tight Junctions; Turbinates

Recent studies have suggested that allergic fungal rhino-sinusitis could be involved in the development of nasal polyposis. The aim of this study was to evaluate the response of anti-fungal nasal lavages. Patients performed nasal lavage with 20 ml of a one per one thousand amphotericin B suspension in each nostril, twice a day, for four weeks. In addition, all patients continued their saline nasal lavage and their conventional topical corticosteroid spray. This study included 74 patients, with a mean age of 46 years (range from 19 to 73). Before anti-fungal treatment, the distribution of nasal polyposis, according to Malm, was: 13 patients in stage I (17.5 per cent), 48 patients in stage II (65 per cent) and 13 patients in stage III (17.5 per cent). After anti-fungal nasal lavages, the total disappearance of nasal polyposis was observed in 29 patients (39 per cent). Eight patients were stage I, 21 stage II, and none stage III. In patients who have had previous endoscopic polypectomy and functional endoscopic sinus surgery, total disappearance of nasal polyposis was seen in 24 patients (47 per cent). Hyper-reactivity to fungal organisms could be one of the mechanisms underlying the development of nasal polyposis. A direct effect of amphotericin B suspension on the integrity of the cell membrane of the polyps' epithelium could not be excluded.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Chi-Square Distribution; Humans; Middle Aged; Nasal Mucosa; Nasal Polyps; Prospective Studies; Therapeutic Irrigation; Treatment Outcome

Topics: Adult; Amphotericin B; Female; Fungi; Humans; Male; Nasal Polyps; Radiography; Rhinitis; Tomography