International Journal of Scientific & Engineering Research Volume 8, Issue 11, November ISSN

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1 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November Chronic Rhinosinusitis, Updated Review of Treatment Approach Abdulrahman Hassan O Makin, Reem Mohammed Noor Kalakattawi, Yahya Ali A Khubrani, Nassar Mohammed Alqurashi, Sulaiman Ahmed Hussain Darbashi, Wjood Abdullah Altalhi, Muna Mahmod Saleh Sambawah, Mohammed Ahmed H Ageeli Abstract: This review was conducted for the purpose to demonstrate and summarize the most updated various treatments in chronic rhinosinusitis (CRS). Moreover, to discuss the etiology and pathogenesis of CRS. PubMed/Medline, and Embase databases were comprehensively searched for relevant studies concerning chronic rhinosinusitis (CRS) especially current treatment options available for CRS. studies published between 1991 up to date (2017) were included in this review. Treatment of CRS, whether clinical (intranasal corticosteroids, saline waterings) or medical, is targeted at lowering inflammation and obstruction in the sinonasal passages. Antibiotics are the most commonly suggested medicine for CRS, however their duty in administration is not highly supported by high-level studies. Corticosteroids are considered by medical professionals to be amongst the most useful drugs in CRS, only four researches have explored the result of topical yet not systemic corticosteroids in CRS. The outcomes of these studies show up complicated, with 2 researches revealing significant enhancement as compared with placebo, Nasal polyposis has actually been recommended to be a poor prognostic factor for the efficiency of the surgical treatment to manage CRS manifestations.

2 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November Introduction: Rhinosinusitis is an inflammatory disease of the paranasal and also nasal sinus mucosa. chronic rhinosinusitis (CRS) is a chronic disease that includes long-lasting swelling of the paranasal as well as nasal sinus mucosa (1). The term CRS includes all inflammatory disorders of the nose as well as paranasal sinuses with a minimum period of 12 weeks. CRS is a common health issue which significantly influences lifestyle. According to a United States national health interview study of the frequency of chronic conditions, CRS has been estimated to influence 12.5% to 15.5% of the total population, making it the 2nd most usual persistent problem in the United States (2,3). The frequency of doctor-diagnosed CRS is a lot lower; an occurrence of 2% was found utilizing International Statistical Classification of Diseases and Related Health Problems (ICD)-10 codes as an identifier (4). The occurrence price is substantially higher in ladies with a woman: male proportion of 6:4 and increases with age, with a mean of 2.7% and also 6.6% in the age groups of 20 to 29 years and also 50 to 59 years, specifically, and leveling off at 4.7% after 60 years (3,5).

3 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November Analysis requirements include the presence of signs consisting of purulent nasal discharge, nasal blockage, face pain/pressure/fullness, and/or lowered feeling of odor plus either endoscopic findings of inflammation, purulent discharge or edema of the center meatus or ethmoid area, polyps in the middle meatus or the nasal dental caries, and/or radiographic imaging revealing swelling of the paranasal sinuses (6,7). The monitoring of this complicated and also diverse illness is for that reason an obstacle. Much ongoing research study is being guided toward the investigation of therapy approaches, along with establishing standards for detecting the numerous CRS subsets. One of the most simplified classification separates CRS right into those people that have nasal polyps (CRSwNP) as well as those without (CRSsNP) (Figure 1) (8,9). Present treatments for CRS target at targeting different points of the inflammatory pathway. For years, the pillar of therapy of CRSsNPs or CRSwNPs has actually included saline solution irrigations, systemic or intranasal steroids, or intranasal and systemic antimicrobials. Aeroallergen immunotherapy in clients with atopic CRS and also pain killers desensitization in patients with aspirin-exacerbated respiratory system disease with nasal polyposis have been used as adjunctive therapies with variable success (10,11). Clinically, refractory illness commonly demands surgical intervention to help with mucociliary clearance as well as recover patency of sinus drain systems, especially in the case of extreme nasal polyposis. Regardless of developments in surgical strategy and also using intranasal steroids after surgical treatment, people could remain to have reoccurrence of their sinus condition, and, consequently, brand-new rehabs are had to deal with these clinically and/or surgically refractory clients (12).

4 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November Figure 1: CRS differentiation by inflammatory mediators. o Objectives: This review was conducted for the purpose to demonstrate and summarize the most updated various treatments in chronic rhinosinusitis (CRS). Moreover, to discuss the etiology and pathogenesis of CRS. Methods and Materials: PubMed/Medline, and Embase databases were comprehensively searched for relevant studies concerning chronic rhinosinusitis (CRS) especially current treatment options available

5 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November for CRS. studies published between 1991 up to date (2017) were included in our review, and Restrictions applied to our search to only published studies with English language and human subjects. Furthermore, references of extracted studies were manually searched for more relevant articles to be included. Discussion: Pathogenesis and Causes of CRS: The etiology and also pathogenesis of persistent rhinosinusitis are not plainly recognized. Traditionally, it was believed that the chronic inflammatory process is completion phase of without treatment or partially treated severe rhinosinusitis or severe atopy from nasal polyps. This theory leads to the use of antibiotics and also anti-inflammatory medications, eg, corticosteroids for treating CRS clients. Alternative theories consist of excessive host reaction to fungi, (13,14) aspirin intolerance as a result of problems in the eicosanoid pathway (15,16), staphylococcal superantigen leading to exotoxin effects including cells damage (17,18), worked with mechanical barrier and the inherent immune action of the sinonasal mucosa, problems in the immune obstacle as well as biofilms formation (19,20). CRS has a variety of recommended causes. It is commonly attributed to microbial infection; a variety of cardiovascular (staphylococcus spp., Gram-negative poles) and also anaerobic (prevotella, fusobacterium, peptostreptococcus) germs have been cultured from patients with CRS (21). It is uncertain if bacteria are triggering infection, are revealing the host to superantigens triggering an inflammatory response, or are able to conquer due to pre-existing pathology of the

6 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November sinus mucosa (21). A fairly recent concept in the pathogenesis of CRS is emigration with fungis. As a result of the visibility of fungal spores in the air, fungi is an usual searching for in the top respiratory system tract even of healthy people. There are, nonetheless, professional subentities of CRS that have actually long been associateded with fungal etiology. Sensitive fungal rhinosinusitis (AFRS) is a sort of CRS in which people have an allergic response to the fungus colonizing the mucin in their sinonasal tooth cavities. In contrast, fungus balls are caused by overgrowth of fungus in the nose and also paranasal sinuses, without an inflammatory response (21). The inflammatory reaction in feedback to a fungi round is even more of an irritative swelling, like an international body reaction, ie, large cells, and not an eosinophilic swelling, which is present in CRS. Current studies have associated a much broader function to fungis in CRS. It is postulated that in specific individuals, colonizing fungi provoke a hypersensitivity feedback that is non-immunoglobulin E (IgE)-mediated. Rather than an allergic response, the fungi promote a neighborhood inflammatory feedback with infiltration of eosinophils. This problem has actually been termed eosinophilic fungal rhinosinusitis (EFRS), as well as it has been implicated in the majority of instances of CRS (21). The immune feedback in CRS clients is commonly a partial Th2 lymphocyte action (production of interleukin [IL] -5, IL-13, a percentage of IL-4); this is the immune profile seen also among CRS clients who have a favorable skin reaction to fungal irritants, where one would anticipate increased IL-4, as it is necessary for IgE synthesis (22). In reality, it seems that an universal immune action in CRS is a T-cell action (a mix of Th1 as well as Th2 cells) with IL-5 as the most identified mediator, IL-13, and also little IL-4 (22). Although hay fever can be present as a comorbid problem, the individual with CRS alone displays eosinophilic mucin on histology, without proof for IgE-mediated allergy (23).

7 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November o Effective treatment strategies for CRS: Therapy methods differ based upon divergent etiologies of the numerous CRS subdivisions. Both topical and also systemic representatives are used. These treatments differ in CRS with nasal polyposis (CRSwNP), CRS without nasal polyposis (CRSsNP) as well as specific circumstances such as allergic fungal rhinosinusitis or aspirin-exacerbated respiratory condition. Intranasal saline for topical therapy of CRS: Intranasal saline has been shown to be beneficial in both unoperated and postoperative patients. High volume, low pressure irrigation devices have demonstrated superiority over other methods of delivery. Pynnonen et al. (24) evaluated the efficacy of large volume, low-pressure saline irrigation versus saline spray in non-postoperative patients in an RCT. The irrigation group had improved symptoms over the spray group as measured by the Sino-Nasal Outcome Test (SNOT- 20) (24). Liang et al. (25) performed a randomized trial of large-volume saline irrigation in CRS patients post-ess and found significant benefit in symptoms and endoscopy scores in patients with mild CRS. However, there was no significant difference in those with severe CRS (25). Other studies evaluating the effect of intranasal saline on endoscopic appearance in CRS have been performed. A single-blinded RCT in which patients post-ess performed unilateral nasal douching demonstrated improved discharge and edema at 3 weeks, but no difference in adhesions or crusting. There were no differences in nasal endoscopy noted at 3 months (26). (Table 1) shows ten RCTs evaluating the impact of intranasal saline on clinical outcomes in CRS patients, with type of saline (hypertonic versus isotonic), delivery method, and outcomes noted. Both pre-surgical and post-ess studies were included. All seven pre-surgical RCTs (24, 27,28,29,30,31,32) demonstrated improved symptoms and health-related quality of life, although the study by Heatley et al. (29) showed no difference between reflexology as placebo and saline irrigation groups. Of the three post-ess studies, two RCTs showed improved outcomes with intranasal saline (25,26), while the third showed no difference in patient symptom scores between normal saline, hypertonic saline, and no irrigation groups (33). Overall, saline nasal irrigations are well tolerated. Side effects are uncommon, but include nasal discomfort, drainage, epistaxis, headache, and otalgia (34). Table 1: Randomized controlled trials evaluating intranasal saline in CRS Author Year Outcome measures Treatment groups Delivery method Shoseyov et al (27) 1998 Symptom and radiological scores in children 3.5% HTS versus ITS 1 ml nasal drops Results Improved cough score in HTS group; other scores similar Bachmann et 2000 Symptom, HTS versus ITS 200 ml Improved symptom scores

8 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November al (28) Author Year Outcome measures Treatment groups Delivery method Heatley et al (29) Rabago et al (30) Cordray et al (31) endoscopic, mucociliary clearance, rhinometry and olfactometry scores 2001 SNOT-20 and RSOM31 scores 2002 QoL, RSDI, and SIA scores 2.7% HTS via bulb syringe versus irrigation pot versus reflexology placebo 2% HTS versus control 2005 QoL scores HTS versus triamcinolone versus ITS Pinto et al (33) 2006 Symptoms post-ess ITS versus HTS versus control Hauptmanand 2007 Acoustic rhinometry, Ryan (32) saccharine clearance times, symptoms Pynnonen et al (24) irrigator Bulb syringe versus irrigator 300 ml nasal cup Nasal spray Nasal spray Results in both groups; no difference between groups Improved scores in all groups, with no difference between groups and placebo Improved RSDI and SIA in saline group versus controls Improvements in steroid and HTS groups No symptom improvement in ITS or HTS group over control. More pain in HTS group ITS versus HTS Nasal spray ITS and HTS improved saccharine clearance times and symptoms of nasal stuffiness. ITS improved nasal patency 2007 SNOT-20 score, ITS via large volume Large Improved SNOT-20 score symptom frequency, irrigation versus volume and symptom frequency in and medication usage spray irrigation irrigation over spray group versus spray Liang et al (25) 2008 Symptom and endoscopy scores post-ess Freeman et al (26) 2008 Endoscopy scores post-ess Buffered ITS + medical treatment versus medical treatment ITS + medical treatment versus medical treatment 500 ml pulsatile irrigator 2 ml atomized Improved endoscopy and symptom scores in irrigation group with mild CRS only Improved endoscopic appearance at 3 weeks; no difference at 3 months Topical steroids Topical corticosteroids make up first-line treatment in the medical management of CRS. Longlasting treatment with topical nasal steroid sprays has been revealed to lower sinus swelling and nasal polyp size and boost symptoms related to CRS (35,36,37). Short courses of oral steroids are utilized in the treatment of CRS with nasal polyps however could additionally be used in cases of

9 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November extreme CRS when quick symptomatic enhancement is needed (36, 38). Systemic and also topical steroids lower mucosal eosinophil chemotaxis as well as boost eosinophil apoptosis. Corticosteroids also lower leukocyte movement, manufacturing of inflammatory arbitrators, antibody manufacturing, histamine release, and also swelling via a range of devices (39). The daily use topical nasal steroids seem related to marginal dangers; nevertheless, long-lasting systemic steroid usage is connected with considerable adverse effects (37, 38). Fokkens et al. (40) executed a recent methodical review of RCTs for evidence of advantage in dealing with CRSsNP with topical corticosteroids, which included eleven researches. Of these, data from five research studies could be merged for meta-analysis, showing substantial advantage in the topical steroid team when compared with placebo. When the medical state of the people was evaluated on subgroup evaluation, just people with prior surgery for CRSsNP had signs and symptom enhancement. There was no renovation for patients without surgical treatment (40). Topical steroids are also efficient in CRSwNP. Fokkens et al. (40) did a separate methodical review of RCTs for CRSwNP treated with topical corticosteroids, which generated 38 research studies. Meta-analysis revealed intranasal steroids, when compared with placebo, enhanced signs, polyp dimension, polyp recurrence, and nasal airflow. In the subgroup evaluation, patients with sinus surgical procedure responded to topical steroids more than individuals without sinus surgical procedure in polyp size decrease (40). Topical antibiotics & Oral antibiotics The goal of topical antibiotic treatment is to deliver high concentrations of anti-biotics straight to the website of infection with low systemic absorption and also adverse effects (41). Pseudomonas or methicillin-resistant Staphylococcus aureus (MRSA) exacerbation of CRS after endoscopic

10 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November sinus surgery can be seen in up to 30% of endoscopically led societies (4142). These infections are notoriously difficult to treat and can bring about persistent mucosal swelling, altered sinonasal ciliary feature, and nasal polyp formation. Topical treatment with prescription antibiotics such as gentamicin or tobramycin for individuals with CRS can be effective in minimizing discomfort, mucosal edema, secretions, and postnasal drip, specifically after endoscopic sinus surgical treatment (43,44). Vaughan and Carvalho (44) utilized 3-week programs of culture-directed antibiotics via nebulizer as well as demonstrated improvements in sinus endoscopic evaluations, posterior nasal discharge, facial pain/pressure, as well as had much longer infection-free durations. Jervis-Bardy et al. (46) just recently released a double-blinded, placebo-controlled RCT examining topical mupirocin irrigations versus saline on microbial societies, signs and symptoms, and also endoscopy ratings in post-ess clients with a pre-treatment S. aureus favorable culture. They located 0% versus 88.9% S. aureus-negative sinonasal culture at 1 month in the saline versus mupirocin teams, respectively. Endoscopy scores at 1 month were significantly improved in the mupirocin team compared to the saline team; nonetheless, there were no significant distinctions in symptoms in between teams (46). Current investigations of topical prescription antibiotics in CRS have been directed toward biofilms. The topical application of mupirocin, ciprofloxacin, and vancomycin on well-known in-vitro biofilms of S. aureusisolated from people with CRS was reviewed by Ha et al. (47) Their research revealed mupirocin was capable of reducing biofilm mass by more than 90% at safe focus. Ciprofloxacin and also vancomycin were largely inadequate at concentrations within riskfree dosage arrays (47).

11 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November No antibiotic has been authorized by the U.S. Food and also Drug Administration for the treatment of CRS. Many recommendations on antibiotic use have actually been based mostly on historic method rather than degrees of proof (48). Most professionals concur that antimicrobials for treatment of CRS must give broadspectrum protection. Commonly made use of agents consist of amoxicillinclavulanate, clindamycin, levofloxacin, and sulfamethoxazole/trimethoprim or ciprofloxacin. Antibiotics contribute in the administration of CRS to reduce microbial lots as well as to treat acute bacterial worsenings of CRS. Intense worsenings of CRS stand for unexpected getting worse or brand-new symptoms in a person with CRS as well as are generally connected with purulence draining pipes from the sinuses envisioned on nasal endoscopy (49). Oral anti-biotics are one of the most typically recommended medicine for CRS and also continue to be a mainstay of treatment. In spite of this, there is a surprising scarceness of top quality information pertaining to efficiency. There is level 2 evidence for temporary therapy of CRSsNP in worsening with a positive society based upon two RCTs (50,51), though no placebo-controlled research studies have been carried out. As a whole, first-line antibiotics for CRS exacerbations include amoxicillin-clavulanate and 2nd- or third-generation cephalosporins. The respiratory quinolones are practical second-line representatives for refractory cases (Figure 2) (52).

12 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November Figure 2: Efficacy of antibiotics in CRS. Surgical treatment of CRS: The choice to continue to surgical procedure was mostly based upon the people' point of view that their feedback to medical therapy was not ample. It is extremely challenging to externalize the basis of this choice, and also it is at risk to person as well as cosmetic surgeon predispositions. Various huge, well organized possible researches have shown endoscopic sinus surgical procedure (ESS) to be secure as well as efficient in managing both patients suffering from CRS with nasal polyposis (CRSwNP), CRS without nasal polyposis (CRSsNP) who have actually fallen short ample control with clinical therapy (53,54). The goals of ESS consist of elimination of inflammatory tissue and osteitis, execution of ample water drainage as well as ventilation paths, remediation of mucociliary feature, production of access for topical medication, decrease of severe worsenings and systemic medicine usage, and lifestyle

13 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November improvement. A testimonial of 21 research studies including 2070 individuals with CRS discovered all signs were improved after a mean period of 13 months following ESS, with nasal obstruction enhancing the most, facial pain as well as postnasal discharge demonstrating modest renovations, and also migraine improving the least (55). Improvements in generic and diseasespecific quality of life with surgery have actually also been shown (53). ESS significantly reduces antibiotic usage in CRSwNP and also CRSsNP (56). In a possible multi-institutional research contrasting medical and surgical treatment for CRS, clients electing ESS experienced dramatically higher degrees of renovation based upon two verified disease-specific quality-oflife tools (57). Roughly 15%-- 20% of people need alteration sinus surgical procedure. Previous alteration surgery, comprehensive polyps, bronchial asthma, aspirin intolerance, and also cystic fibrosis are predictors of patients that might need modification surgical procedure (54). Conclusion: Treatment of CRS, whether clinical (intranasal corticosteroids, saline waterings) or medical, is targeted at lowering inflammation and obstruction in the sinonasal passages. Antibiotics are the most commonly suggested medicine for CRS, however their duty in administration is not highly supported by high-level studies. Corticosteroids are considered by medical professionals to be amongst the most useful drugs in CRS, only four researches have explored the result of topical yet not systemic corticosteroids in CRS. The outcomes of these studies show up complicated, with 2 researches revealing significant enhancement as compared with placebo, Nasal polyposis has actually been recommended to be a poor prognostic factor for the efficiency of the surgical treatment to manage CRS manifestations.

14 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November References: 1. Benninger MS, Ferguson BJ, Hadley JA, et al. Adult chronic rhinosinusitis: def initions, diagnosis, epidemiology, and pathophysiology. Otolaryngol Head Neck Surg. 2003;129(3 Suppl):S Adams PF, Hendershot GE, Marano MA, Centers for Disease Control and Prevention/National Center for Health Statistics Current estimates from the National Health Interview Survey, Vital Health Stat ;200: Collins JG. Prevalence of selected chronic conditions: United States, Vital Health Stat. 1997;10(194): Shashy RG, Moore EJ, Weaver A. Prevalence of the chronic sinusitis diagnosis in Olmsted County, Minnesota. Arch Otolaryngol Head Neck Surg. 2004;130(3): Bonfils P, Halimi P, Le Bihan C, Norès JM, Avan P, Landais P. Correlation between nasosinusal symptoms and topographic diagnosis in chronic rhinosinusitis. Ann Otol Rhinol Laryngol. 2005;114(1 Pt 1): Fokkens W, Lund V, Mullol J, European Position Paper on Rhinosinusitis and Nasal Polyps group European position paper on rhinosinusitis and nasal polyps Rhinol Suppl. 2007;(20): Rosenfeld RM, Andes D, Bhattacharyya N, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg. 2007;137(Suppl 3):S1 S Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps A summary for otorhinolaryngologists. Rhinology. 2012;50(1): Van Zele T, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy.2006;61: Lee JY, Simon RA, Stevenson DD. Selection of aspirin dosages for aspirin desensitization treatment in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 119: , 2007.

15 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November Ta V, Simon R. State of art: Medical treatment of aspirin exacerbated respiratory disease (AERD). Am J Rhinol Allergy 29:41 43, Li N, Peters AT. Chronic rhinosinusitis management beyond intranasal steroids and saline solution irrigations. Allergy and Asthma Proceedings. 2015;36(5): doi: /aap Ponikau JU, Sherris DA, Kern EB, et al. The diagnosis and incidence of allergic fungal sinusitis. Mayo Clin Proc. 1999;74(9): Sasama J, Sherris DA, Shin SH, Kephart GM, Kern EB, Ponikau JU. New paradigm for the roles of fungi and eosinophils in chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg. 2005;13(1): Van Crombruggen K, Zhang N, Gevaert P, Tomassen P, Bachert C. Pathogenesis of chronic rhinosinusitis: inflammation. J Allergy Clin Immunol. 2011;128(4): Roca-Ferrer J, Garcia-Garcia FJ, Pereda J, et al. Reduced expression of COXs and production of prostaglandin E(2) in patients with nasal polyps with or without aspirin-intolerant asthma. J Allergy Clin Immunol. 2011;128(1): e Bachert C, Gevaert P, Holtappels G, Johansson SG, van Cauwenberge P. Total and specific IgE in nasal polyps is related to local eosinophilic inflammation. J Allergy Clin Immunol. 2001;107(4): Bachert C, Zhang N, Patou J, van Zele T, Gevaert P. Role of staphylococcal superantigens in upper airway disease. Curr Opin Allergy Clin Immunol. 2008;8(1): Kern RC, Conley DB, Walsh W, et al. Perspectives on the etiology of chronic rhinosinusitis: an immune barrier hypothesis. Am J Rhinol. 2008;22(6): Foreman A, Holtappels G, Psaltis AJ, et al. Adaptive immune responses in Staphylococcus aureus biofilm-associated chronic rhinosinusitis. Allergy. 2011;66(11): Meltzer EO, Hamilos DL, Hadley JA, et al. Rhinosinusitis: establishing definitions for clinical research and patient care. J Allergy Clin Immunol. 2004;114(6 Suppl): Hamilos DL, Lund VJ. Etiology of chronic rhinosinusitis: the role of fungus. Ann Otol Rhinol Laryngol Suppl. 2004;193: Sasama J, Sherris DA, Shin SH, et al. New paradigm for the roles of fungi and eosinophils in chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg. 2005;13:2 8.

16 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November Pynnonen MA, Mukerji SS, Kim HM, Adams ME, Terrell JE. Nasal saline for chronic sinonasal symptoms: a randomized controlled trial. Arch Otolaryngol Head Neck Surg. 2007;133(11): Liang KL, Su MC, Tseng HC, Jiang RS. Impact of pulsatile nasal irrigation on the prognosis of functional endoscopic sinus surgery. J Otolaryngol Head Neck Surg. 2008;37(2): Freeman S?R, Sivayoham ES, Jepson K, de Carpentier J. A preliminary randomized controlled trial evaluating the efficacy of saline douching following endoscopic sinus surgery. Clin Otolaryngol. 2008;33(5): Shoseyov D, Bibi H, Shai P, Shoseyov N, Shazberg G, Hurvitz H. Treatment with hypertonic saline versus normal saline nasal wash of pediatric chronic sinusitis. J Allergy Clin Immunol. 1998;101(5): Bachmann G, Hommel G, Michel O. Effect of irrigation of the nose with isotonic salt solution on adult patients with chronic paranasal sinus disease. Eur Arch Otorhinolaryngol. 2000;257(10): Heatley DG, McConnell KE, Kille TL, Leverson GE. Nasal irrigation for the alleviation of sinonasal symptoms. Otolaryngol Head Neck Surg. 2001;125(1): Rabago D, Zgierska A, Mundt M, Barrett B, Bobula J, Maberry R. Efficacy of daily hypertonic saline nasal irrigation among patients with sinusitis: a randomized controlled trial. J Fam Pract. 2002;51(12): Cordray S, Harjo JB, Miner L. Comparison of intranasal hypertonic dead sea saline spray and intranasal aqueous triamcinolone spray in seasonal allergic rhinitis. Ear Nose Throat J. 2005;84(7): Hauptman G, Ryan MW. The effect of saline solutions on nasal patency and mucociliary clearance in rhinosinusitis patients. Otolaryngol Head Neck Surg. 2007;137(5): Pinto JM, Elwany S, Baroody FM, Nacierio RM. Effects of saline sprays on symptoms after endoscopic sinus surgery. Am J Rhinol. 2006;20(2): Harvey R, Hannan SA, Badia L, Scadding G. Nasal saline irrigations for the symptoms of chronic rhinosinusitis. Cochrane Database Syst Rev. 2007;3:CD Benninger MS, Anon J, Mabry RL. The medical management of rhinosinusitis. Otolaryngol Head Neck Surg 1997;117:S41 S49.

17 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November Lund VJ. Maximal medical therapy for chronic rhinosinusitis. Otolaryngol Clin North Am 2005;38: Grzincich G, Capra L, Cammarata MG, Spaggiari C, Pisi G. Effectiveness of intranasal corticosteroids. Acta Biomed. 2004;75: Gillespie MB, Osguthorpe JD. Pharmacologic management of chronic rhinosinusitis, alone or with nasal polyposis. Curr Allergy Asthma Rep 2004;4: Derendorf H, Meltzer EO. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications. Allergy 2008;63: Fokkens WJ, Lund VJ, Mullol J, et al. European position paper on rhinosinusitis and nasal polyps Rhinol Suppl. 2012;23: Leonard DW, Bolger WE. Topical antibiotic therapy for recalcitrant sinusitis. Laryngoscope 1999;109: Araujo E, Palombini BC, Cantarelli V, Pereira A, Mariante A. Microbiology of middle meatus in chronic rhinosinusitis. Am J Rhinol 2003;17: Chiu AG, Antunes MB, Palmer JN, Cohen NA. Evaluation of the in vivo efficacy of topical tobramycin against Pseudomonas sinonasal biofilms. J Antimicrob Chemother 2007;59: Whatley WS, Chandra RK, MacDonald CB. Systemic absorption of gentacmicin nasal irrigations. Am J Rhinol 2006;20: Vaughan WC, Carvalho G. Use of nebulized antibiotics for acute infections in chronic sinusitis. Otolaryngol Head Neck Surg 2002;127: Jervis-Bardy J, Boase S, Psaltis A, Foreman A, Wormald PJ. A randomized trial of mupirocin sinonasal rinses versus saline in surgically recalcitrant staphylococcal chronic rhinosinusitis. Laryngoscope. 2012;122(10): Ha KR, Psaltis AJ, Butcher AR, Wormald PJ, Tan LW. In vitro activity of mupirocin on clinical isolates of Staphylococcus aureus and its potential implications in chronic rhinosinusitis. Laryngoscope. 2008;118(3): Bhattacharyya N. Antimicrobial therapy in chronic rhinosinusitis. Curr Allergy Asthma Rep 2009;9:

18 International Journal of Scientific & Engineering Research Volume 8, Issue 11, November Lanza DC, Kennedy DW. Adult rhinosinusitis defined. Otolaryngol Head Neck Surg 1997;117:S1 S Legent F, Bordure P, Beauvillain C, Berche P. A double-blind comparison of ciprofloxacin and amoxycillin/clavulanic acid in the treatment of chronic sinusitis. Chemotherapy. 1994;40( Suppl 1): Namyslowski G, Misiolek M, Czecior E, et al. Comparison of the efficacy and tolerability of amoxycillin/clavulanic acid 875 mg bid with cefuroxime 500 mg bid in the treatment of chronic and acute exacerbation of chronic sinusitis in adults. J Chemother. 2002;14(5): Anon JB, Jacobs MR, Poole MD, et al. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg. 2004;130(Suppl 1): Smith TL, Batra PS, Seiden AM, Hannley M. Evidence supporting endoscopic sinus surgery in the management of adult chronic rhinosinusitis: a systematic review. Am J Rhinol. 2005;19(6): Hopkins C, Browne J P, Slack R, et al. The national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis. Clin Otolaryngol. 2006;31(5): Chester AC, Antisdel JL, Sindwani R. Symptom-specific outcomes of endoscopic sinus surgery: a systematic review. Otolaryngol Head Neck Surg. 2009;140(5): Bhandarkar ND, Mace JC, Smith TL. Endoscopic sinus surgery reduces antibiotic utilization in rhinosinusitis. Int Forum Allergy Rhinol. 2011;1(1): Smith TL, Kern RC, Palmer JN, et al. Medical therapy vs surgery for chronic rhinosinusitis: a prospective, multi-institutional study. Int Forum Allergy Rhinol. 2011;1(4):