***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Chronic rhinosinusitis ( CRS ) is one of the most common chronic diseases . Recently , it has been suggested that an exaggerated immune response to fungi is crucial in the pathogenesis of the disease . On the basis of this hypothesis , intranasal treatment with amphotericin B should benefit patients with CRS . Data from 2 uncontrolled and 2 controlled trials are conflicting , however . OBJECTIVE To clarify the role of intranasal antifungal drugs in the treatment of CRS , we conducted a large , double-blind , placebo-controlled , multicenter study comparing the effectiveness of amphotericin B nasal lavages with placebo . METHODS A total of 116 r and omly selected patients with CRS were instructed to instill 25 mL amphotericin B ( 100 microg/mL ) or placebo to each nostril twice daily for 3 months . Primary outcomes included a reduction in total visual analog scale ( VAS ) score and nasal endoscopy score . Secondary outcome measures included peak nasal inspiratory flow , polyp score , quality of life ( Short Form-36 , Rhinosinusitis Outcome Measure-31 ) , and individual VAS scores . RESULTS Analysis was based on intention to treat and involved all patients r and omly assigned .  Mean VAS scores , Short Form-36 and Rhinosinusitis Outcome Measure-31 data , peak nasal inspiratory flow values , nasal endoscopy scores , and polyp scores were similar in both treatment groups at the time of r and omization , and no significant differences were observed after 13 weeks of treatment . CONCLUSION Amphotericin B nasal lavages in the described dosing and time schedule do not reduce clinical signs and symptoms in patients with CRS . CLINICAL IMPLICATION S Amphotericin B nasal lavages in the described dosing and time schedule are ineffective and therefore not advised in the treatment of patients with CRS BACKGROUND Recently , fungal elements were suspected to be the causative agent of chronic rhinosinusitis , and benefits of topical amphotericin B therapy have been reported . OBJECTIVE The effects of amphotericin B versus control nasal spray on chronic rhinosinusitis were compared in a double-blind , r and omized clinical trial . METHODS 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 st and ard culture techniques . RESULTS 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 . CONCLUSION Nasal amphotericin B spray in the described dosing and time schedule is ineffective and deteriorates patient symptoms OBJECTIVES Conventional management of allergic fungal rhinosinusitis ( AFRS ) after surgery consists of the use of steroids to immunomodulate the body 's response to fungi . However , there are many side effects to prolonged steroid use , and some patients are unresponsive to st and ard treatment . The role of systemic antifungal drugs in AFRS is still largely unknown . This was a pilot study to evaluate the effectiveness of itraconazole , an oral antifungal drug , in the treatment of refractory AFRS . METHOD Thirty-two patients with AFRS who had had surgery and were refractory to prednisone , steroid , and amphotericin B nasal sprays were treated with itraconazole for at least 3 months . They were evaluated with pre- and posttreatment endoscopic examinations , serum immunoglobulin E ( IgE ) , and the 31-Item Rhinosinusitis Outcome Measure ( RSOM-31 ) question naires . Monthly liver function tests were done to monitor for the hepatic side effects of itraconazole . RESULTS Twelve cases had endoscopic improvement . Fifteen had no difference , and five had a worse endoscopic stage after 3 months . One patient had to stop treatment due to abnormal liver function tests . The mean pre- and posttreatment IgE levels were 581 microg/L and 766 microg/L , respectively . Subjectively , 9 patients ( 28 % ) reported a significant improvement , 9 ( 28 % ) had moderate improvements , and 14 ( 44 % ) reported little or no change . There was no correlation between the subjective and the endoscopic changes . CONCLUSION Itraconazole may be useful as an adjunct in the management of AFRS . However , more studies , including a prospect i ve r and omized clinical trial , are required to determine if itraconazole is effective in the management of AFRS BACKGROUND 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 . OBJECTIVES To examine the effect of nasal antifungal treatment on secreted mediators in sample s of nasal lavage fluid from patients with CRS with or without nasal polyps ( NP ) . METHODS Part two of a prospect i ve 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 . RESULTS 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 sample s. Treatment with placebo , however , increased the level of MIP-1alpha and MIP-1beta , which are mediators involved in wound healing . CONCLUSIONS Topical amphotericin B has no significant effect on activation markers of nasal inflammatory cells in chronic rhinosinusitis with or without nasal polyps OBJECTIVE To reevaluate the current criteria for diagnosing  allergic fungal sinusitis ( AFS ) and determine the incidence of AFS in patients with chronic rhinosinusitis ( CRS ) . METHODS This prospect i ve study evaluated the incidence of AFS in 210 consecutive patients with CRS with or without polyposis , of whom 101 were treated surgically . Collecting and culturing fungi from nasal mucus require special h and ling , and novel methods are described . Surgical specimen h and ling emphasizes histologic examination to visualize fungi and eosinophils in the mucin . The value of allergy testing in the diagnosis of AFS is examined . RESULTS Fungal cultures of nasal secretions were positive in 202 ( 96 % ) of 210 consecutive CRS patients .  Allergic mucin was found in 97 ( 96 % ) of 101 consecutive surgical cases of CRS . Allergic fungal sinusitis was diagnosed in 94 ( 93 % ) of 101 consecutive surgical cases with CRS , based on histopathologic findings and culture results . Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of AFS patients . CONCLUSION The data presented indicate that the diagnostic criteria for AFS are present in the majority of patients with CRS with or without polyposis . Since the presence of eosinophils in the allergic mucin , and not a type I hypersensitivity , is likely the common denominator in the pathophysiology of AFS , we propose a change in terminology from AFS to eosinophilic fungal rhinosinusitis Objective Assess  paranasal sinus distribution of topical solutions following  endoscopic sinus surgery ( ESS )  using various delivery devices . Study Design Experimental prospect i ve study . Subjects and Methods Ten cadaver sinus systems were irrigated with Gastroview before surgery , after  ESS  , and after medial maxillectomy .  Delivery was via pressurized spray ( NasaMist ) , neti pot ( NasaFlo ) , and squeeze bottle ( Sinus Rinse ) . Scans were performed before and after each delivery with a portable CT machine ( Xoran xCAT ) , and blinded assessment s were made for distribution to individual sinuses . Results Total sinus distribution was greater post-ESS ( P < 0.001 ) . Additional distribution was gained with medial maxillectomy ( P = 0.02 ) . Influence of delivery device on distribution was significantly higher with neti pot > squeeze bottle > pressurized spray ( P < 0.001 ) . Frontal sinus penetration was greatest after surgery ( P = 0.001 ) . Conclusion ESS greatly enhances the delivery of nasal solutions , regardless of delivery device . Pressurized spray solutions in un-operated sinuses provide little more than nasal cavity distribution . Use of squeeze bottle/neti pot post-ESS offers a greatly enhanced ability to deliver solutions to the paranasal sinuses OBJECTIVE To examine the effect of nasal antifungal treatment on eosinophil cationic protein ( ECP ) and tryptase levels in sample s of nasal lavage fluid from patients with chronic rhinosinusitis and nasal polyps . DESIGN Prospect i ve double-blind placebo-controlled clinical trial . SETTING Tertiary surgical center . PATIENTS 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 . INTERVENTIONS Nasal treatment with amphotericin B or saline control for 8 weeks . MAIN OUTCOME MEASURES 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 . RESULTS 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 sample s. Moreover , successful fungus eradication , defined as fungus detection before but not after treatment , did not influence nasal ECP or tryptase levels ( all P>.40 ) . CONCLUSION 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 Objective —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 . Material and Methods —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-γ , RANTES — protein content of polyp homogenates were determined by means of ELISA . Results —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 . Conclusions —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 OBJECTIVES To evaluate antifungal terbinafine in patients with chronic rhinosinusitis . STUDY DESIGN R and omized , double-blind , placebo-controlled multicenter pilot study . METHODS Fifty-three adults with chronic rhinosinusitis received terbinafine 625 mg/day ( n = 25 ) or placebo ( n = 28 ) once daily for 6 weeks . 
    Output:
    
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 .
Conclusion 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