Evaluation of the medical and surgical treatment of chronic rhinosinusitis: a prospective, randomised, controlled trial

OBJECTIVES: To conduct the first prospective, randomized, controlled trial evaluating and comparing the medical and surgical treatment of polypoid and nonpolypoid chronic rhinosinusitis (CRS). MATERIALS AND METHODS: Ninety patients with CRS were equally randomized either to medical or surgical therapy. All patients underwent pre- and posttreatment assessments of visual analogue score (VAS), the Sinonasal Outcome Test-20 (SNOT-20), the Short Form 36 Health Survey (SF-36), nitric oxide (NO), acoustic rhinometry, saccharine clearance time (SCT), and nasal endoscopy. Each patient had three assessments: before starting the treatment, after 6 months, and, finally, after 1 year. RESULTS: Both the medical and surgical treatment of CRS significantly improved almost all the subjective and objective parameters of CRS (P <.01), with no significant difference being found between the medical and surgical groups (P >.05), except for the total nasal volume in CRS (P <.01) and CRS without polyposis (P <.01) groups, in which the surgical treatment demonstrated greater changes. CONCLUSION: CRS should be initially targeted with maximal medical therapy (e.g., a 3 month course of a macrolide antibiotic, douche, and topical steroid), with surgical treatment being reserved for cases refractory to medical therapy. The presence of nasal polyps is not a poor prognostic factor for the efficacy of CRS therapy, either surgical or medical.     

Topical antimicrobials in the management of chronic rhinosinusitis: a systematic review

BACKGROUND: Chronic rhinosinusitis (CRS) is a common disease that can significantly impact health. The mainstay of medical treatment is topical steroids and oral antibiotics, but little is known about the efficacy of topical antibiotics. The purpose of this study was to identify evidence for the use of topical antibiotics in the treatment of CRS and exacerbations of CRS. METHODS: Systematic review of literature with a search of the MEDLINE, EMBASE, and CINAHL databases; Cochrane Central Register of Controlled Trials (Third Quarter 2007); and Cochrane Database of Systemic Reviews (3rd Quarter 2007) databases were performed. The dates of search were from December 1, 1949 to September 30, 2007. RESULTS: Fourteen studies that fulfilled the inclusion criteria were identified: seven were controlled trials and of these, five were double blinded and randomized. Only one of the randomized studies showed a positive outcome. Overall, there was low-level corroborative evidence for the use of antibacterials. No definite conclusions could be made regarding the use of antifungals. Currently, there is evidence for the use of nasal irrigation or nebulization rather than delivery by nasal spray. For the antibacterial studies, the highest level of evidence currently exists for studies that have used postsurgical patients and culture-directed therapy. Both stable and acute exacerbations of CRS appear to benefit from topical antimicrobials. CONCLUSION: Topical antibiotics appear effective in the management of CRS. Given the combination of low-level evidence (level III, with inherent potential confounders of natural progression of disease and placebo effect) and the level IIb evidence being limited to the cystic fibrosis group of patients, topical antibiotics should not be first-line management but may be attempted in patients refractory to the traditional topical steroids and oral antibiotics. Larger and better-designed randomized double-blind placebo-controlled trials are required to more fully evaluate this emerging modality of treatment.     

Baby shampoo nasal irrigations for the symptomatic post-functional endoscopic sinus surgery patient

BACKGROUND: Symptoms of postnasal drainage and thickened mucus are commonly seen in patients with chronic rhinosinusitis (CRS) recalcitrant to sinus surgery and conventional medical therapies. Chemical surfactants can act as a mucolytic by reducing water surface tension and have the potential to serve as an antimicrobial agent. Baby shampoo is an inexpensive, commercially available solution containing multiple chemical surfactants. This is an in vitro study of its antimicrobial effects on Pseudomonas biofilms with translation to a clinical study for use as an adjuvant nasal wash in patients with CRS who remain symptomatic despite adequate sinus surgery and conventional medical therapies. METHODS: In vitro testing was performed to determine the optimal concentration of baby shampoo that disrupted preformed bacterial biofilms and inhibited biofilm formation. This concentration was then used in a prospective study of symptomatic post-functional endoscopic sinus surgery (FESS) patients who irrigated twice a day for 4 weeks. Validated outcome forms and objective smell testing was performed before and after therapy. RESULTS: One percent baby shampoo in normal saline was the optimal concentration for inhibition of Pseudomonas biofilm formation. Baby shampoo had no effect on the eradication of preformed Pseudomonas biofilms. Eighteen patients with CRS with an average of 2.8 surgeries were studied after irrigating with 1% baby shampoo solution. Two patients discontinued use because of minor nasal and skin irritations; 46.6% of patients experienced an overall improvement in their subjective symptoms, and 60% of patients noted improvement in specific symptoms of thickened mucus and postnasal drainage. CONCLUSION: Baby shampoo nasal irrigation has promise as an inexpensive, tolerable adjuvant to conventional medical therapies for symptomatic patients after FESS. Its greatest benefit may be in improving symptoms of thickened nasal discharge and postnasal drainage.     

慢性鼻窦炎生物靶向药物治疗的研究进展

慢性鼻窦炎(CRS)是一种鼻腔鼻窦的慢性炎症性疾病,根据其发病机制可分为1型、2型和3型炎症内在型。目前CRS的药物治疗及手术治疗方法均存在发生各种不良反应和并发症的风险,其中部分难治性鼻窦炎虽经适当的药物和手术治疗仍不能取得满意效果并极易复发,严重影响患者的生活质量。生物靶向药物的应用和发展为CRS的治疗提供了一种有效和安全的替代方案。本文着重介绍针对CRS三种炎症内在型的相关细胞因子(包括TNF-α、IL-4、IL-5、IL-13、IgE和IL-17等)的生物靶向药物治疗的研究进展。     

儿童慢性鼻-鼻窦炎的药物治疗与手术治疗临床疗效观察

目的:探讨药物和手术治疗儿童慢性鼻-鼻窦炎(CRS)的临床疗效。方法:72例诊断为CRS的儿童随机分为药物治疗组(35例)和手术治疗组(37例),药物治疗采用糠酸莫米松喷鼻、碱性盐水鼻腔冲洗加用低剂量克拉霉素,疗程为12周。手术治疗分别采用:①腺样体切除(19例);②扁桃体加腺样体切除(10例);③内镜鼻窦手术(8例)。采用:①VAS评估其症状;②鼻内镜观察评估鼻腔,时间窗分别安排在治疗前和治疗后1、3、6、12个月;③CT评估,时间窗分别安排在治疗前和治疗后12个月。结果:2组患儿经过1个月治疗后,其症状VAS总分和鼻内镜评分均较治疗前明显下降(P<0.05),但2组间差异无统计学意义(P>0.05);经过治疗3、6个月,2组症状VAS总分和鼻内镜评分均较治疗前和治疗1个月明显下降(P<0.01),2组间差异有统计学意义(P<0.01);治疗后12个月,2组症状VAS总分、鼻内镜评分均较治疗前和治疗1、3、6个月明显下降(P<0.01),CT评分也较治疗前明显下降(P<0.01),2组间疗效差异有统计学意义(P<0.01);将手术治疗组中不同术式比较,结果显示术后1个月VAS总分和鼻内镜评分差异有统计学意义...     

Effects of topical amphotericin B on expression of cytokines in nasal polyps

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-gamma, 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.     

In vitro activity of mupirocin on clinical isolates of Staphylococcus aureus and its potential implications in chronic rhinosinusitis

BACKGROUND: It has been postulated that bacterial biofilms are involved in the pathogenesis of chronic rhinosinusitis (CRS). Biofilms present on sinus mucosa are difficult to eradicate with conventional antibiotic therapy and are thought to provide a nidus for recurrent infection. Topical delivery of antibiotics via nasal irrigation may present a way of delivering high concentrations of antibiofilm agents with potentially low systemic absorption and side effects. This study investigates the effectiveness of mupirocin and two other antibiotics, ciprofloxacin and vancomycin, on established in vitro biofilms of Staphylococcus aureus isolated from patients with CRS. METHODS: S. aureus American Type Culture Collection 25923 and 12 clinical isolates were investigated for their ability to form biofilms in an in vitro setting using a 96 well microtiter crystal violet (CV) plate assay and confocal scanning laser microscopy (CSLM). Antimicrobial susceptibility tests to determine minimum inhibitory concentrations were performed on planktonic and biofilm forming strains. In addition, established biofilms were subjected to the antimicrobial agents at a twofold dilution series. A CV analysis of biofilm mass was performed after 1 and 24 hours of treatment, and minimum biofilm inhibition concentrations at 50% (MIB50) and 90% (MIB90) biofilm inhibition were recorded. RESULTS: With use of a 96-well microtiter plate CV assay, 8 of the 12 clinical isolates formed mature biofilms after 8 days of culture. These results correlated with findings from CSLM analysis of in vitro biofilms grown on Permanox chamber slides. Increased antimicrobial resistance was observed in the biofilm isolates when compared with planktonic counterparts. Mupirocin was capable of reducing biofilm mass by greater than 90% at concentrations of 125 mug/mL or less in all S. aureus isolates. Ciprofloxacin and vancomycin were largely ineffective in attaining MIB90 concentrations within safe dosage ranges. CONCLUSIONS: The topical application of mupirocin via nasal irrigation may be useful in eliminating S. aureus biofilms present on the sinus mucosa of patients with CRS and may offer an additional treatment to patients with recalcitrant sinusitis.     

Medical management and diagnosis of chronic rhinosinusitis: A survey of treatment patterns by United States otolaryngologists

BACKGROUND: This study was performed to identify current patterns of diagnostic criteria and medical treatment for chronic rhinosinusitis (CRS) by otolaryngologists in the United States. METHODS: A 15-item survey was mailed to a random sample of 200 members of the American Academy of Otolaryngology-Head and Neck Surgery; statistical analysis was performed. RESULTS: The overall response rate was 40.0%. Of respondents, 73% defined CRS as lasting >12 weeks. Seventy-three percent also believed radiological imaging was necessary for definitive diagnosis, but only 30% believed nasal endoscopy was necessary. Regarding treatment, respondents reported use of oral antibiotics (94%) and nasal corticosteroids (94%) as part of maximum medical management; oral decongestants, oral mucoevacuants, and allergy testing were used only by about one-half of the respondents, and less frequently topical decongestants (38%), oral corticosteroids (36%), and oral antihistamines (27%) were used. Oral corticosteroids were more likely to be used by specialists that self-classified as rhinologists than by other otolaryngologists (p = 0.005), but rhinologists were less likely to use radiological imaging (p = 0.04) as a diagnostic criterion. Pediatric otolaryngologists used allergy testing in medical management more frequently than other otolaryngologists (p < 0.001). Overall, the basis for choice of maximal medical management was personal clinical experience (74%), rather than clinical research results or expert recommendations. CONCLUSION: We had a fairly small sample of returned surveys; therefore, our findings may not be generalizable to the entire population of U.S. otolaryngologists. Nevertheless, in our survey, U.S. otolaryngologists agree on the use of oral antibiotics and nasal corticosteroids as part of maximal medical management for CRS but do not agree on other adjuvant therapies or on the use of endoscopy as a diagnostic criterion.     

Intracellular residency is frequently associated with recurrent Staphylococcus aureus rhinosinusitis

AIM: The prevalence of intracellular Staphylococcus aureus organisms in the nasal mucosa of patients with recurrent infectious rhinosinusitis episodes was studied. METHOD: Twenty-seven consecutive adult patients who failed medical management of chronic rhinosinusitis (CRS) of multiple origins, associated or not with nasal polyposis, were consecutively enrolled for endonasal sinus surgery (including partial middle turbinectomy, middle antrostomy, ethmoidectomy, sphenoidotomy) and followed for a 12-month post-operative period. RESULTS: Seventeen of these patients showed the presence of intracellular S. aureus as detected by confocal laser scan immunofluorescence microscopy in epithelial cells of surgical intranasal biopsy specimens. Nine of the patients with and two without intracellular bacteria yielded S. aureus in endoscopically guided cultures of middle meatus secretions, despite the recent administration of prophylactic antibiotics. Eleven of the 17 patients with intracellular S. aureus relapsed for rhinosinusitis within the 12-month follow-up period. Molecular typing of sequential S. aureus isolates demonstrated the persistence of unique patient-specific S. aureus clonotypes in nine of the patients with intracellular bacteria during the 12-month follow-up. CONCLUSION: The presence of intracellular S. aureus in epithelial cells of the nasal mucosa is a significant risk factor for recurrent episodes of rhinosinusitis due to persistent bacterial clonotypes, which appear refractory to antimicrobial and surgical therapy.     

A quantitative analysis of the intranasal delivery of topical nasal drugs to the middle meatus: spray versus drop administration

The delivery of nasal drugs specifically to the middle meatus is of critical importance in the medical treatment of rhinosinusitis. In this respect, topical nasal drug administration by drops has generally been perceived to be superior to nasal sprays, although there is a lack of evidence to support this notion. This study aims to compare the intranasal delivery of nasal sprays and drops to the middle meatus in vivo, using a novel quantitative method. A surgical patty was placed in the middle meatus. Radio-labelled topical nasal drops and aqueous sprays were administered in a standardized fashion in normal volunteers (10 nasal cavities). The subsequent absorption of administered radio-labelled saline on the patty was measured using a gamma counter. A randomized prospective crossover design was used for the study. The mean percentage (range) of absorbed administered saline on the swab was 8.7 (0.3-39.5) and 9.7 (0.03-20.4) for the spray and drop administration techniques respectively (p = 0.8). Thus, there is wide variation in the delivery of topical nasal drugs and the perceived superiority of nasal drop administration, in terms of delivery to the middle meatus, may be incorrect.     

Tolerability of N-chlorotaurine in chronic rhinosinusitis applied via yamik catheter

OBJECTIVES: A rational approach in the treatment of chronic rhinosinusitis (CRS) is the intranasal application of antiseptic agents, due to the pathogenetic role of bacteria and fungi. N-Chlorotaurine (NCT), a mild endogenous oxidant with broad-spectrum antimicrobial activity, has been tested for the first time in CRS. METHODS: This one-arm phase IIa clinical study is the first step in the clinical development of this promising substance for local therapy of CRS. The nasal and paranasal cavities of 12 patients were rinsed with 10-20 ml of 1% aqueous NCT solution, applied via a novel catheter system (YAMIK). Treatment consisted of three lavages per week for 4 weeks. RESULTS: NCT caused neither alterations of the mucosa nor burning pain during application. Nevertheless, the insertion of the catheter, the insufflation of the posterior cuff and the overpressure inside the sinuses after infiltration led to moderate pain in some patients. Mucosal swelling decreased in all subjects, nasal breathing could be improved in nine patients and impaired olfaction in seven. Polyps did not disappear within the 1-month period of the study. CONCLUSIONS: The good tolerability and possible beneficial effects of NCT encourage its further investigation in CRS. Despite some limitations the YAMIK catheter proved to be a convenient and safe device for rinsing the nasal and paranasal sinuses.     

Do patients with chronic rhinosinusitis benefit from consultation with an ENT-doctor?

Conclusion: By consulting an ENT-doctor, patients with chronic rhinosinusitis (CRS), in the general population, receive disease information and adjustment of treatment which can improve disease-specific Quality-of-Life and may improve objective measurements. Objectives: This study aims to follow persons with clinical diagnosed CRS from the general population, to evaluate their benefit from consultation with an ENT-doctor in terms of severity of symptoms and Quality-of-Life. Methods: As part of a trans-European study, selected respondents to a survey questionnaire were invited for a clinical visit. Based on the European Position Paper on Rhinosinusitis and Nasal Polyps, persons were diagnosed with CRS and followed for 2 years. Quality-of-Life was measured using the Sino Nasal Outcome Test 22 and European Quality-of-Life – 5 Dimensions. Clinical examination included rhinoscopy, acoustic rhinometry, peak nasal inspiratory flow, smell test, and skin prick test. Results: Out of 91 persons with CRS, only 42% had previously consulted an ENT-doctor, and 51% were in current treatment for CRS. Most patients were advised medical treatment and 20% underwent surgery. Disease-specific Quality-of-Life, peak nasal inspiratory flow, olfactory function, and the nasal volume significantly increased over the 2-year period.     

Fungal DNA is present in tissue specimens of patients with chronic rhinosinusitis

BACKGROUND: It has been postulated that fungal organisms might represent the immunologic target initiating and maintaining the disease process in patients with chronic rhinosinusitis (CRS). The presence of fungi in nasal mucus has been established by different groups, but so far it has not been shown how the immune system could even recognize such extramucosal--extracorporal--fungal targets. The aim of this study was to determine whether fungal DNA is present in tissue specimens taken from patients with polypoid CRS. METHODS: Twenty-seven surgical specimens were collected from patients suffering from CRS. Fifteen surgical specimens from healthy ethmoidal mucosa served as controls. A second set of controls consisted of five surgical specimens of acoustic neuroma, which were included to rule out contamination within the protocol. All paranasal tissue samples were treated and rinsed carefully with a solution of Dithiothreitol to digest any nasal mucus and ensure that only tissue was examined. A highly sensitive two-step polymerase chain reaction (PCR) was applied to detect fungal DNA, using one universal primer for unspecific detection of fungal DNA and a second primer pair specific for Alternaria. RESULTS: Fungal DNA was detected in all 27 CRS specimens equally with both PCR primers. Controls from healthy paranasal mucosa were positive using the panfungal primers in 10 of 15 cases but were all negative for Alternaria DNA. PCR was negative for fungal DNA in all five neuroma specimens. CONCLUSIONS: Fungal DNA can be detected within sinonasal tissue specimens of patients suffering from CRS. These findings need to be discussed with respect to the proposed hypothesis of the immune system recognizing extramucosal organisms and initiating an immune response in sensitized patients.     

The risk of development of antimicrobial resistance in individual patients with chronic rhinosinusitis

OBJECTIVE: To determine if individual patients with chronic rhinosinusitis (CRS) demonstrate an increasing prevalence of antimicrobial resistance over time. PATIENTS: A prospectively maintained database of microbiologic culture results for adult patients with CRS was sequentially analyzed, extracting patients who underwent multiple serial sinus cultures over time. Antimicrobial resistance patterns were identified and quantified for each bacterium. Sequential culture results were compared for individual patients to determine if increasing overall bacterial resistance, gram-positive resistance, gram-negative resistance, or a shift toward gram-negative organisms was manifested within individual patients. RESULTS: During a 7-year period, 90 adult patients were identified with 224 serial cultures (mean, 2.5 cultures per patient) obtained, with a median time between cultures of 157 days. Four hundred twenty-nine organisms were isolated from these serial cultures, consisting of 255 gram-positive organisms, 120 gram-negative organisms, 48 anaerobes, and 6 fungi. Pairwise analysis of sequential cultures revealed no significant trend toward increasing bacterial resistance within individual patients (P = .57, runs test). Similarly, no significant trend toward increasing gram-positive or gram-negative resistance was demonstrated. There was no shift toward gram-negative organisms (P>.15 for all). CONCLUSIONS: Individual patients with CRS do not necessarily develop increasing levels of bacterial resistance over time. The use of culture-directed antimicrobial therapy may "protect" against the development of sequentially increasing antimicrobial resistance for patients with CRS.     

Treatment alternatives for chronic rhinosinusitis persisting after ESS: what to do when antibiotics, steroids and surgery fail

BACKGROUND: It is estimated that over 500,000 individuals in the United States currently suffer from chronic rhinosinusitis (CRS), which has persisted or recurred despite maximal medical therapy and endoscopic sinus surgery (ESS). Management of these individuals remains uncertain, as recent published guidelines on CRS do not extend to this population. OBJECTIVE: Our objective is to provide a framework for the management of patients who fail standard therapy for CRS while providing recommendations based on the strength of the evidence for alternative medical therapies that can be used for the treatment of recurrent CRS. This guideline targets ENT physicians and allergists managing this increasingly frequent clinical situation and attempts to assist them in selecting from the increasing array of potential therapies available. To this end, factors contributing to the pathophysiology of post-ESS CRS are reviewed to identify method of action of existing and potential therapies and recommendations are made for their use. RESULTS: Given the accessibility of the sinus cavities after ESS, topical therapies are privileged. Saline spray or irrigation is recommended for all patients. Corticosteroids in oral or topical forms are recommended for controlling the inflammatory component, while the use of a short term course of oral or topical antibiotics are recommended mainly for the treatment of exacerbations. Long-term therapy with oral macrolides is also recommended as an alternative therapy. Desensitization with acetylsalicylic acid (ASA) for individuals with documented ASA sensitivity is recommended where available, while revision surgery, anti-leukotriene agents and intravenous immunoglobulins are options in management in selected patients. Antifungal therapy is not recommended. No recommendations for potentially experimental strategies are made in the absence of published experience and safety data in human subjects.     

American Rhinologic Society member survey on "maximal medical therapy" for chronic rhinosinusitis

BACKGROUND: "Maximal medical therapy" is the standard of care for chronic rhinosinusitis (CRS) treatment before the recommendation for surgery. However, this therapy is not consistent. Therefore, as a first step in determining the role of the disparate "maximal medical" treatments for CRS, American Rhinologic Society (ARS) members were surveyed. METHODS: A survey was mailed to all nonresident members of the ARS (n=723). Focusing on the time period before surgical intervention is first considered for CRS patients, the survey assessed types of therapies, frequency of use, details on antibiotic and steroid usage, use of computed tomography (CT), and demographic data of respondents. All responses were anonymous. RESULTS: Three hundred eight surveys were returned (43%). A majority of respondents used oral antibiotics and nasal steroids "almost always (>90%)". Oral antibiotics, oral steroids, nasal steroids, saline irrigation, and allergy testing were most commonly used at least "usually (50-90%)". The median antibiotic length was 3.1-4 weeks. The mean peak prednisone dose was 51.7 mg when oral steroids were used. Therapies that were rarely or never used by the majority included oral antifungals, antifungal spray, antibiotic spray, antibiotic nebulizer, steroid nebulizer, and i.v. antibiotics. CONCLUSION: Oral antibiotics (median, 3.1-4 weeks) and nasal steroids are used >90% of the time by a majority of ARS members for maximal medical treatment of CRS.     

Functional endoscopic sinus surgery in children using a limited approach

OBJECTIVES: To evaluate the efficacy of the limited approach of functional endoscopic sinus surgery (FESS) in pediatric patients with chronic rhinosinusitis (CRS) and to interpret the indications for second-look endoscopy. DESIGN: A retrospective review of medical records of patients who received pediatric FESS between January 1995 and September 2002 and a comprehensive parental questionnaire were used to assess postoperative symptom improvement at a mean postoperative follow-up of 27.2 months after surgery. SETTING: A university-affiliated medical center. PATIENTS: We studied 101 patients who received treatment of pediatric CRS refractory to optimal medical treatment. MAIN OUTCOME MEASURES: We analyzed preoperative and postoperative nasal obstruction, purulent rhinorrhea, postnasal drip, headache, hyposmia, and chronic cough. INTERVENTIONS: Patients underwent a limited surgical approach of FESS, basically a drainage rather than an extirpation procedure, for the treatment of pediatric CRS refractory to optimal medical treatment. Additionally, 29 patients (28%) underwent second-look endoscopy. RESULTS: The proportions of patients whose symptoms improved were as follows: nasal obstruction, 91%; purulent rhinorrhea, 90%; postnasal drip, 90%; headache, 97%; hyposmia, 89%; and chronic cough, 96%. Of the 101 patients, parents of 87 (86%) were satisfied with the surgery. CONCLUSIONS: Our literature review did not reveal any other large series in the Asian population. The limited approach to FESS was effective in treating medically recalcitrant CRS in the children we studied. Second-look endoscopy was indicated for selected cases to ensure the extirpation of residual disease and the patency of ostiomeatal complex and sinus ostia.