Functional endoscopic balloon dilation of sinus ostia for chronic rhinosinusitis (Review)

Transcription

1 Functional endoscopic balloon dilation of sinus ostia for chronic rhinosinusitis (Review) Ahmed J, Pal S, Hopkins C, Jayaraj S This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 7

2 T A B L E O F C O N T E N T S HEADER ABSTRACT PLAIN LANGUAGE SUMMARY BACKGROUND OBJECTIVES METHODS RESULTS DISCUSSION AUTHORS CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES CHARACTERISTICS OF STUDIES DATA AND ANALYSES ADDITIONAL TABLES APPENDICES HISTORY CONTRIBUTIONS OF AUTHORS DECLARATIONS OF INTEREST SOURCES OF SUPPORT INDEX TERMS i

3 [Intervention Review] Functional endoscopic balloon dilation of sinus ostia for chronic rhinosinusitis Jahangir Ahmed 1, Surojit Pal 1, Claire Hopkins 2, Samuel Jayaraj 1 1 ENT Department, Whipps Cross University Hospital, London, UK. 2 ENT Department, Guy s Hospital, London, UK Contact address: Jahangir Ahmed, ENT Department, Whipps Cross University Hospital, London, UK. Jayahmed11@hotmail.com. Editorial group: Cochrane Ear, Nose and Throat Disorders Group. Publication status and date: New, published in Issue 7, Review content assessed as up-to-date: 19 December Citation: Ahmed J, Pal S, Hopkins C, Jayaraj S. Functional endoscopic balloon dilation of sinus ostia for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2011, Issue 7. Art. No.: CD DOI: / CD pub2. Background A B S T R A C T Dilation of sinus ostia using a high-pressure balloon has been introduced as a treatment for chronic rhinosinusitis (CRS) refractory to medical treatment. The efficacy of this technology, however, has not been systematically reviewed. Objectives To assess the effectiveness of balloon sinus ostial dilation as a treatment for patients suffering with CRS refractory to medical treatment. Search methods We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL; PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 20 December Selection criteria Randomised controlled trials in patients of any age with rhinosinusitis lasting longer than 12 weeks who have failed a prolonged course of medical treatment. Studies compared either balloon sinus ostial dilation or a hybrid procedure (balloon dilation in conjunction with functional endoscopic sinus surgery (FESS)) versus conventional surgery (e.g. FESS) or a waiting list control. Data collection and analysis Two authors independently selected studies for inclusion, extracted data and assessed risk of bias. Main results One study (34 patients) met our inclusion criteria although it was not yet a peer reviewed publication. The study randomised patients with chronic frontal sinusitis who had failed a prolonged course of medical treatment into two groups: balloon dilatation of the frontal recess (plus conventional FESS of other involved sinuses) versus conventional FESS (Draf type 1/2a procedures on the frontal sinuses). At 12 months follow up there was no statistically significant difference in radiological resolution of frontal sinuses between the two groups. The percentages of directly observed patent frontal recesses at 12 months were 75% in the balloon dilation group versus 63% in the FESS-only group. The authors state that this was statistically significant but details of the analysis were not presented. Indeed the study as a whole suffers from a bias in the way its outcome measures were reported. No major complications were reported. Three patients in the FESS-only group required further revision frontal sinus surgery compared to one in the balloon dilation group, although synechiae were more common in the latter. 1

4 Authors conclusions At present there is no convincing evidence supporting the use of endoscopic balloon sinus ostial dilation compared to conventional surgical modalities in the management of CRS refractory to medical treatment. With the escalating use of balloon sinuplasty, there is an urgent need for more randomised controlled trials to determine its efficacy over conventional surgical treatment modalities. P L A I N L A N G U A G E S U M M A R Y Balloon dilation of sinus openings for chronic rhinosinusitis Chronic rhinosinusitis is one of the most common ailments in the world, affecting all age groups and causing significant suffering. First-line management of this condition is medical, usually comprising a nasally applied steroid, supplemented with a combination of antihistamines, antibiotics and/or oral steroids. Surgical intervention usually becomes necessary if there is failure of a prolonged course of medical treatment. In adults, functional endoscopic sinus surgery (FESS) has become established as the main surgical strategy in these circumstances. Recently a new technology, balloon dilation of sinus ostia (sinus opening), has been introduced. This is designed to open up the drainage pathways of the sinuses by the inflation of a high-pressure balloon in the sinus opening. We sought evidence in the literature evaluating the effectiveness of balloon dilation of sinus ostia compared to conventional surgical methods in the surgical management of patients of all ages suffering with chronic rhinosinusitis. One unpublished trial met our inclusion criteria. This randomised 34 patients with chronic frontal sinusitis into two groups: in one group balloon dilation was used to open up the drainage pathways of the frontal sinuses; in the other group conventional endoscopic sinus surgery was used to do the same. For both groups all other sinuses were treated using conventional functional endoscopic sinus surgery. Balloon dilation did not show an improvement in the resolution of frontal sinusitis as demonstrated by imaging studies, however the technique was associated with an increased likelihood that someone observing a frontal sinus opening would find this open. However, it is not clear whether this was a statistically significant result. The study report appeared to be biased in the way it reported its outcome measures. At present, therefore, we cannot recommend the use of balloon dilation of sinus ostia over conventional surgical treatment modalities in this setting. B A C K G R O U N D Description of the condition Rhinosinusitis is defined as inflammation of the nose and paranasal sinuses. Chronic rhinosinusitis (CRS) is one of the most prevalent chronic ailments in the Western world, affecting up to 16% of the adult population (Adams 1999; Blackwell 2002). Although benign it poses significant personal and societal pressures; impacting on quality of life, schooling and work and leading to immense economic costs. Indeed in the USA, CRS has been estimated to generate annual health-related costs of more than $5 billion (Gross 2001). The pseudostratified, ciliated, columnar epithelial mucosa of the nasal cavities and paranasal sinuses are contiguous through the sinus ostia. Cilia beat the overlying mucus, which traps foreign material and microbes, carrying them out of the sinuses through these narrow openings onto the lateral nasal wall and from there into the nasopharynx. Mucociliary clearance follows well-defined pathways in healthy individuals. A key anatomical area in this mechanism is the osteomeatal complex, a common confluent drainage outflow tract for the frontal, maxillary and anterior ethmoid sinuses. Anatomically it comprises the uncinate process which guards the laterally placed three-dimensional ethmoid infundibulum, into which the majority of these sinuses drain. According to the European Position Paper on Rhinosinusitis and Nasal Polyposis (EPOS) (Fokkens 2007), rhinosinusitis is clinically defined by two or more symptoms, one of which must be nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip). Accompanying cardinal symptoms may include facial pressure/pain and alteration in smell. Chronicity is differentiated by the duration of symptoms. Acute symptoms last less than 12 weeks with complete resolution; chronic symptoms persist for more than 12 weeks. Symptoms should be supplemented by either endoscopic or computed tomographic (CT) evidence of sinusitis. The pathogenesis of CRS remains unclear, but is likely to be the result of an interplay of multiple factors that may be broadly cate- 2

5 gorised into infection (e.g. bacterial, including biofilms; viral and fungal), intrinsic mucosal inflammation (e.g. allergy, a predisposition to an eosinophilic inflammatory response) and impaired mucociliary clearance (Sturgess 1979; Zacharek 2003). In an attempt to rationalise the plethora of data on aetiology, Timperley et al proposed an educational model of CRS whereby this triad of factors interact with and, importantly, propagate each other, culminating in a positive feedback spiral of mucosal inflammation (Timperley 2010). Contrary to traditional concepts, it is now widely acknowledged that the underlying anatomy of the sinus drainage pathways at best only plays an exacerbating role in CRS and that longterm reduction in mucosal inflammation is the key to successful resolution (Timperley 2010). Thus, first-line management of CRS is medical and usually involves a prolonged course of topical nasal steroids. Other medical options could include a combination of antibiotics, antihistamines and systemic steroids. There is evidence of benefit from prolonged courses of macrolide antibiotics (Ragab 2004) and saline nasal irrigation (Harvey 2007). In addition, leukotriene receptor antagonists may have a role in the management of patients with an allergic aetiology (Grainger 2006). Indeed for the majority of patients with CRS, first-line optimal medical therapy appears to be as effective as endoscopic sinus surgery (Fokkens 2007; Khalil 2006). The latter is therefore usually reserved for failed medical treatment. Functional endoscopic sinus surgery (FESS) opens up the sinus drainage pathways, enhancing mucosal clearance. The word functional emphasises the preservation of normal mucosal clearance via the natural anatomic drainage pathways (Kennedy 1985; Stammberger 1986). Nowhere is this principle more important than in the frontal recess. Here, preservation of mucosa is paramount to prevent restenosis (recurrence of narrowing) and consequent complex and potentially hazardous revision procedures. The outcome of sinus surgery will be affected by multiple factors. These may broadly be divided into patient factors (including age, anatomy and comorbidity), factors related to disease (presence of polyposis, extent of inflammation, previous surgery) and surgeon experience (Fokkens 2007; Hopkins 2006; Stankiewicz 1989). The Royal College of Surgeons of England conducted a prospective national audit of sinus surgery performed in the UK in 2000 (Hopkins 2006). This included 3128 patients from 87 National Health Service (NHS) hospitals in England and Wales undergoing FESS. Major complications, such as orbital penetration and cerebrospinal fluid leak, occurred in 0.4% whereas minor ones, mostly excessive perioperative bleeding (but also postoperative infection, stenosis and adhesions), occurred in 6.6%. Complication risk was related to disease and patient characteristics as opposed to techniques used or surgeon experience. Description of the intervention The concept of dilating an ostium via a high-pressure balloon was originally developed and promoted in the fields of cardiology, vascular surgery and urology. It has recently been applied to sinus surgery and termed balloon sinuplasty T M (Acclarent Inc., CA, USA). As in these specialties, the Seldinger technique (whereby a catheter is advanced and positioned over a guidewire) is used for balloon placement (Brown 2006). Basic equipment requirements include a sinus guidewire (a stainless steel coated wire with a soft non-penetrating tip), a sinus delivery catheter; a sinus balloon and an inflation device. The delivery catheter, which is specifically designed with regard to its length and angulation for each sinus, is endoscopically positioned at the entrance of the relevant ostium. The guidewire is passed through the catheter into the sinus and the balloon advanced over it, positioned to straddle the ostium. It is then transiently inflated to a high pressure (up to 12 atmospheres). Rather than excising inflamed tissue and adjacent bone, the balloon compresses the mucosa and causes microfracture of the underlying circumferential bone. The aim of this technology is therefore to restore the natural sinus drainage pathways in a minimally invasive way; with the hope of preventing the scarring associated with mucosal stripping. Early devices required fluoroscopic confirmation of correct placement in the sinus, exposing the patient and surgeon to ionising radiation. To avoid this, a guidewire, which houses an optical fibre allowing a high power light to be emitted from the tip has been recently developed. The guidewire position is confirmed by transsinus illumination when correctly positioned in the frontal and maxillary sinuses. Why it is important to do this review The published literature on efficacy has to date predominantly been limited to feasibility and safety profiling (Bolger 2007; Kuhn 2008; Levine 2008; Weiss 2008). The CLinical Evaluation to confirm safety and efficacy of sinuplasty in the paranasal sinuses (CLEAR) study, a multi-centred prospective cohort, included 115 patients (358 sinuses) with CRS that were treated either by balloon sinus ostial dilation alone or a hybrid procedure (Bolger 2007). Ninety-seven percent of the sinuses were successfully cannulated. Endoscopic patency at six months was reported at 80.5%, with a similar figure (85.1%) in those followed up to one year (Kuhn 2008). In the latter study the figure rose to 91.6% if patency was implied by radiological improvement. Parallel sustained improvements in SNOT(sinonasal outcome test)-20 scores over the same time period were also reported. In Levine et al s retrospective review of 1036 patients treated at different centres (Levine 2008), 95.5% of patients reported an improvement at initial follow up that was maintained in 73.8% at a mean follow-up period of 40.2 weeks. Impressively for such a large cohort, there were no major complications. Friedman et al performed a retrospective chart review of a cohort of patients who were given a choice of having either func- 3

6 tional endoscopic dilation of sinus ostia (FEDS) or conventional FESS (Friedman 2008). They compared pre and postintervention SNOT-20 scores in two groups. There were 35 patients in each arm. Preoperatively, the SNOT-20 scores were similar (2.8 versus 2.7 respectively), but at three months postoperatively the FEDS group had a significantly lower score (0.78 versus 1.29, P = 0.006). Ramadan and Terrell reported a non-randomised study comparing balloon sinus ostial dilation and sinus irrigation (with adenoidectomy if enlarged) versus adenoidectomy alone for the surgical management of children aged below 12 with CRS who had failed a prolonged course of medical treatment (Ramadan 2010). Thirty out of 49 children had a balloon sinus dilation procedure. At an average of one-year follow up, 80% of the balloon dilation group, in comparison to 52.6% of the adenoidectomy-only group, reported an improvement in symptoms using the SN-5 scale (Kay 2003). Interestingly 87% (48 of the 55) dilated sinus ostia in the balloon dilation group were maxillary. The author in a different study with a similar patient cohort had reported an 87.5% improvement in patient outcome scores if adenoidectomy was performed in conjunction with maxillary sinus washout mediated by endoscopic insertion of a needle through the natural ostium. This compared favourably to a 60.7% improvement in the adenoidectomy-alone group (Ramadan 2008). It is therefore unclear whether in addition to adenoidectomy, balloon sinus ostial dilation adds any advantage over draining the maxillary sinuses by more simpler means in children with CRS. The United States Food and Drug Administration (FDA) provided clearance for the use of balloon sinuplasty T M in 2005 (US FDA 2005). The UK followed suit in 2008, when the National Institute of Clinical Excellence (NICE) approved use of balloon dilation of paranasal sinus ostia based on the above and other short-term efficacy and safety profiles (NICE 2008). Specific mention was made, however, of the possibility of a revision to their recommendation in the light of longer-term follow-up studies. Despite these encouraging preliminary data, the use of balloon sinus ostial dilation has generated much debate. First, there is doubt about the theoretical premise of its action, i.e. opening the ostia by mucosal and bony compression, as opposed to removing these diseased entities. Indeed in addition to inflamed mucosa, underlying osteitis may occur in up to 53% of surgical candidates (Lee 2006). Concern has thus been expressed that foci of retained pathological mucosa and bone may restimulate inflammation ( Lanza 2006). Proponents of the procedure, however, would argue that to achieve a positive clinical response, it is not necessary nor indeed practical to remove every piece of osteitic bone, which conventional FESS does not do either (Melroy 2008). The high-pressure compression injury inflicted on the respiratory mucosal epithelium should recover due to the brief nature of the application, nevertheless there is a lack of published basic scientific research confirming this or indeed whether the mucociliary action of the draining sinus is functionally restored. Little is also known about the consequences of crushing the underlying bone, especially that surrounding the frontal sinus. Kieff et al report a case series where repneumatisation and bony regrowth of concha bollosae (an enlarged air-filled middle turbinate) occurred following a crushing procedure to alleviate middle meatal obstruction; in some cases up to 15 years after the original procedure (Kieff 2009). The authors relate this observation to balloon dilation of the frontal recess area where the agger nasi and other air cells in the vicinity will inevitably be crushed. It is postulated that there may be similar regrowth and thus restenosis perhaps many years later in this region (Kieff 2009) In the context of recent insights into the underlying, complex aetiology of CRS, the traditional idea that surgery for CRS works by relieving ostial obstruction and thus enhancing ventilation may only be a part of the story. Indeed up to 24% to 28% of patients may still be symptomatic in terms of quality of life outcome measures following FESS (Smith 2010). Where successful, FESS may be so for different reasons. Thus an overall reduction of the total inflammatory mucosal surface area and removal of osteitic bone may create new cavities that are more efficient in mass-transporting the mucous blanket (Timperley 2010). Furthermore, access of topical agents to the sinus mucosa post-surgery may be the key factor in breaking the positive feedback of inflammation. Harvey et al have demonstrated that conventional FESS certainly improves nasal sinus irrigation in a cadaveric model (Harvey 2008). A similar effect has yet to be demonstrated in ostial balloon dilation as a sole procedure. Prominent rhinologists also argue that indications for this technology at present are relatively sparse (Jones 2006). Clearly it cannot be used as a sole procedure in nasal polyposis or indeed in fungal sinusitis and neoplasm where pathological clearance is vital. Possible other indications for this procedure may include recurrent acute sinusitis, patient preference or in at-risk surgical candidates (e.g. from comorbidities or a bleeding predisposition). Most studies have used balloon dilation of sinus ostia as an adjunct to FESS; its use being pertinent to anatomical areas deemed at relatively high risk of iatrogenic stenosis or major complications, the frontal recess for example. It will therefore be difficult, using standardised outcome tools, to separate the additional benefits of balloon dilation (and justify its relatively high additional monetary cost) in comparison studies of FESS versus hybrid procedures. Directly visualising the patency of individual sinuses will help in this regard, but may not necessarily reflect patient well-being. As balloon dilation of sinus ostia is a relatively novel technology, there are likely to be few, high-level comparative studies in the literature. This fact needs to be highlighted with the aim of stimulating research of high methodological quality. O B J E C T I V E S To assess the effectiveness of balloon sinuplasty in the treatment of chronic rhinosinusitis. 4

7 M E T H O D S Criteria for considering studies for this review Search methods for identification of studies We conducted systematic searches for randomised controlled trials. There were no language, publication year or publication status restrictions. The date of the last search was 20 December Types of studies Prospective randomised controlled trials. Types of participants We applied no age restriction. Inclusion criteria Patients with a diagnosis of chronic rhinosinusitis as defined by the EPOS 2007 criteria, i.e. two or more symptoms one of which must be blocked nose or nasal discharge, lasting for longer than 12 weeks with accompanying endoscopic signs and/or CT changes. Patients should have failed a prolonged course of medical treatment and thus be eligible for surgical intervention. Exclusion criteria We excluded patients with granulomatous disease, sinonasal malignancy or who have undergone revision surgery. Types of interventions Studies that include patients who have received balloon sinus ostial dilation either solely or as part of a hybrid (balloon dilation/ FESS) procedure after failure of an appropriate course of medical treatment, versus a control group. The latter could be a waiting list control group or a conventional FESS group. Types of outcome measures Electronic searches We searched the following databases from their inception for published, unpublished and ongoing trials: the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4); PubMed; EMBASE; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; CAB Abstracts; Web of Science; BIOSIS Previews; CNKI; ISRCTN; ClinicalTrials.gov; IC- TRP (International Clinical Trials Registry Platform) and Google. We modelled subject strategies for databases on the search strategy designed for CENTRAL. Where appropriate, we combined subject strategies with adaptations of the highly sensitive search strategy designed by the Cochrane Collaboration for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2, Box 6.4.b. (Handbook 2011)). Search strategies for major databases including CENTRAL are provided in Appendix 1. Searching other resources We scanned the reference lists of identified publications for additional trials and contacted trial authors where necessary. In addition, we searched PubMed, TRIPdatabase, NHS Evidence - ENT & Audiology, and Google to retrieve existing systematic reviews relevant to this systematic review, so that we could scan their reference lists for additional trials. Data collection and analysis Primary outcomes A nasal-specific or quality of life symptom scoring system. Secondary outcomes Changes in nasal endoscopic view and/or CT images (these will be a primary outcome measures in studies comparing hybrid procedures). Documented adverse effects and complications. A reduction in subsequent maintenance/rescue medication. The need for subsequent revision procedures. Selection of studies Two authors (JA and SP) independently assessed all potential studies as identified by the search strategy for eligibility, defined above. We obtained full-text articles if the relevant information to enable inclusion/exclusion was not apparent from the title or abstract. Disagreements were settled by discussion with all authors. Data extraction and management JA and SP independently extracted data onto a standardised proforma. We attempted contact with the corresponding author in trials where data were missing or ambiguous. 5

8 Assessment of risk of bias in included studies JA and SP individually assessed the risk of bias for each potentially suitable study. We utilised the tool recommended by The Cochrane Collaboration (Handbook 2011). In summary this involved assessing each study with respect to six domains, namely: sequence generation, allocation concealment, blinding, incomplete data, selective outcome reporting and other issues. For each of these domains we documented a) a description (verbatim if possible) of the relevant event and b) an overall judgement of the risk of bias (low, high or unclear risk of bias). Thus, we obtained a six by two table for each study. As more studies emerge in future, we may use RevMan 5.1 to generate an overall Risk of bias graph and summary figure (Higgins 2011; RevMan 2011). Data synthesis We aimed to calculate risk ratio (RR) for studies reporting binary outcomes and standardised mean difference (SMD) for those reporting continuous outcomes. The latter takes into account the use of different outcome scales between studies. Subgroup analysis and investigation of heterogeneity In subsequent updates we will assess the impact of heterogeneity on any meta-analyses we perform using the I 2 statistic. As described in the current Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011), we will use a fixed-effect model in the absence of significant heterogeneity. Should there be significant heterogeneity, this will be explored and if necessary we will reconsider pooling the data and simply report individual trial outcomes. Where possible, we will perform subgroup analysis, in the first instance based on the following patient characteristics: chronic rhinosinusitis with or without nasal polyposis. R E S U L T S Description of studies See: Characteristics of included studies; Characteristics of excluded studies. See Characteristics of included studies and Characteristics of excluded studies. Results of the search We retrieved a total of 75 references from the electronic searches: 40 of these were removed at first-level screening (i.e. duplicates and clearly irrelevant items), leaving 35 references for further consideration. Eleven published references were deemed to be relevant and we retrieved full-text versions of these. Following examination of the full text, we excluded all 11 studies (see Excluded studies). We also identified one as yet unpublished trial which was presented as a poster at the American Academy of Otolaryngology, Head and Neck Surgery annual meeting, Boston, September 2010 (Plaza 2010). The corresponding author kindly provided us with a manuscript detailing the study, but not the raw data. This study met the inclusion criteria for the review. Included studies The study by Plaza et al was a prospective randomised controlled trial that aimed to evaluate the effectiveness and safety of balloon dilation of the frontal recess in the management of CRS of the frontal sinuses. Patients were aged over 18, had CRS including nasal polyposis as dictated by EPOS criteria (Fokkens 2007) with radiological involvement of their frontal sinuses and had failed an eight-week course of medical therapy. They were randomly allocated to the following surgical treatment arms: 1) balloon dilation of the frontal recess with conventional FESS for the remaining paranasal sinuses as required (i.e. a hybrid procedure); or 2) conventional FESS for frontal and other paranasal sinuses as required. In the latter arm, dissection was performed until the surgeon was able to completely visualise the frontal sinus ostium, which in all cases was achieved with Draf type 1 or 2a procedures (see Table 1 for the Draf classification). Postoperative care was the same for both groups and patients were followed up for 12 months. Patients were excluded if pregnant or lactating, if they had concurrent asthma, severe systemic illness (e.g. diabetes) or had previous nasal surgery. Smokers who smoked more than 20 cigarettes per day were also excluded. The primary outcome measures were radiological grading of the frontal sinuses using the Lund-Mackay staging system and office endoscopic assessment of the patency of the frontal recesses. They also recorded a pre and postoperative score on non-validated visual analogue scales of common rhinosinusitis symptoms as well as corresponding scores on a Spanish adaptation of the Rhinosinusitis Disability Index (RSDI). Thirty-four patients were randomised, resulting in 17 in each group. Excluded studies All 11 of the retrieved published studies were excluded (see sections Characteristics of excluded studies table and Why it is important to do this review for further details). In adults, all published studies that collected clinical or radiological outcome data prospectively were limited to uncontrolled, nonrandomised case series (Bolger 2007; Brown 2006; Catalano 2009; Friedman 2008; Levine 2008; Luong 2008; Weiss 2008). The CLEAR study, reported over the course of three papers is the most 6

9 cited of these. It followed a cohort of 115 patients from multiple centres. In the face of a 43% loss to follow up (50 of 115 patients), stable improvements in ostial patency and SNOT 20 scores were maintained at two years of follow up (Weiss 2008; see also section: Why it is important to do this review). Catalano et al (Catalano 2009) focused on specifically treating different severities of frontal sinus disease with balloon dilation of the frontal recess, using CT changes as the primary outcome measure. This study was also excluded for not having a control group but, in addition, 13 of 20 patients had previously had prior endoscopic sinus surgery. We excluded Levine et al s multicentre review of 1036 patients as it was a retrospective uncontrolled review (Levine 2008) The only published comparative study in adults was that of Friedman et al (Friedman 2008). We excluded this study because it was a retrospective chart review, in which selected patients were given a choice of interventions and were thus not randomised. Similarly in children, the comparative study by Ramadan and Terrell (Ramadan 2010), although carried out prospectively, lacked randomisation and was thus also excluded. Risk of bias in included studies See the Risk of bias table in Characteristics of included studies. The included study (Plaza 2010) was a prospective, randomised controlled trial. Randomisation was by a computer-generated sequence of numbers. However, from the manuscript provided, it was unclear whether patient allocation was adequately concealed, i.e. whether the allocator used a pre-drawn list of random numbers. The patient and the outcome assessor were blinded to the intervention arm. No formal calculation was made to determine the sample size to adequately power the study, although the authors state: sample size was estimated considering previous papers on sinuplasty. A type II statistical error therefore remains a possibility. One patient from each group was lost to follow up. Statistical analysis was based on intention-to-treat. In the poster and manuscript provided, the authors state an improvement in visual analogue scale (VAS) and Rhinosinusitis Disability Index (RSDI) scores at 12 months follow up compared to preoperatively, although no confirmatory statistics were documented. Furthermore, a comparison between the two treatment groups in this regard was not made. Despite these being secondary outcome measures, the poster (and manuscript in its current unpublished form) therefore suffers from a selective reporting bias. Indeed, although there was mention of significance or non-significance at P < 0.05 with reference to comparison of the main outcome variables, the exact figures including confidence intervals were not disclosed (see Effects of interventions). Unfortunately the authors did not provide us with the raw data to enable us to perform further analysis. We appreciate that these documents may not reflect the final version and any changes will be highlighted in the next update of this review. Effects of interventions On the basis of the only included study (Plaza 2010), we may only comment in this regard on balloon dilation of the frontal recess. Thirty-four patients were randomised to the treatment groups: hybrid versus functional endoscopic sinus surgery (FESS)-only (Draf I/2a), resulting in 17 patients in each group. The overall median age of enrolled patients was (range 20 to 65). The corresponding age figures were not available per group. Primary outcome measures Nasal-specific or quality of life symptom scoring system The authors state that there were no significant differences in visual analogue scale (VAS)/Rhinosinusitis Disability Index (RSDI) scores, measured olfactory thresholds or severity of nasal polyposis between the groups but no figures were provided. Sixteen patients in each group were available for follow up at 12 months. Changes in nasal endoscopic view and/or computed tomography (CT) images in studies comparing hybrid procedures As this study effectively compared a hybrid procedure with conventional FESS, Plaza et al s main outcome measures were radiological and endoscopic appearance of sinus ostia in the followup clinic. To this effect, Lund-Mackay scores of the frontal sinuses fell from a preoperative mean of 1.9 to 0.5 at 12 months in the hybrid group, with similar figures in the FESS-only group (2 to 0.4). These falls in scores were statistically significant, with P quoted as < 0.05, but exact figures or confidence intervals were not documented. A between-group frontal Lund-Mackay score analysis was not performed, although the authors state that the percentage CT resolution of frontal sinus disease at 12 months (80.95% in the hybrid procedure versus 75% in the FESS-only group) was not statistically significant. Endoscopic patency at 12 months was quoted as statistically more frequent after balloon treatment (75% versus 63%; P < 0.05). Unfortunately no other data or analysis were provided. Due to lack of raw data, no subgroup analysis was possible. Secondary outcome measures Documented adverse effects and complications No major complications were reported. Synechiae were reportedly more common in the hybrid group but not statistically. No further details of complications were available. 7

10 A reduction in subsequent maintenance/rescue medication The study made no reference to this outcome. The need for subsequent revision procedures Three patients in the FESS-only group required further revision frontal sinus surgery compared to one in the hybrid group. D I S C U S S I O N Summary of main results We felt that although the study by Plaza et al (Plaza 2010) is yet to be peer reviewed and published and despite the lack of available raw data it was important to include it in this review. This is the first prospective, double-blind, randomised controlled trial assessing the efficacy of balloon sinus ostial dilation, in this case for the management of chronic frontal sinusitis refractory to medical therapy. With regard to the FESS-only treatment arm, the philosophy of their approach in dealing with this difficult anatomical area is a widely accepted one, i.e. to perform the least invasive procedure that enables restoration of physiological drainage (Kuhn 2006), with more complex procedures reserved for failure of simpler ones (Kuhn 2006; Lee 2010). In some large case series over 80% of patients have been successfully managed by endoscopic frontal sinusotomy (equivalent to Draf type 1/2 procedures) as the primary surgical intervention, although they were performed in tertiary referral centres with a high level of expertise (Chan 2009; Chandra 2004; Philpott 2010). Indeed in one series of 717 frontal sinus procedures, 92% of patients were effectively managed by a Draf 2a procedure (Hahn 2009). By comparison, in the CLEAR study (Kuhn 2008) the patency of frontal sinuses treated by balloon dilation was 85% (63/74) at a follow-up period of one year. The strengths of the current study are independence from corporate sponsorship, a high-quality methodology, a relatively long follow up and a low attrition rate. In terms of radiological resolution of frontal sinusitis at 12 months postoperatively, there was no significant difference between a hybrid procedure as compared to conventional FESS. There was a stated significant difference in endoscopic patency at this time interval, but the treatment effect appears to be relatively small (75% versus 63%). However, the overall quality of the trial does suffer, mainly due to a selective reporting bias, with a conspicuous absence of comparisons of symptom scores between the groups and a lack of much of the numerical data and statistical analysis. Furthermore, the group sizes were possibly not large enough to detect a true difference in frontal sinus radiological scores (i.e. the trial was not adequately powered). Pre-trial sample size calculations should always be performed where relevant statistical data are available from the literature. A minimum effect size or minimum clinically important difference (MCID) will need to be defined and the study adequately powered (usually at 80%) to detect this minimum difference. With regards to quality of life outcome scores, validation across many quality of life instruments consistently appears to place the MCID at 0.5 times the standard deviation (SD); assuming normality of the distribution of the measured outcome parameter (Norman 2003). As an example, in one multicentred cohort of patients with chronic rhinosinusitis (CRS), the standard deviation (SD) of the RSDI scores in untreated patients was 20.7, giving a MCID of (0.5 x 20.7) (Smith 2010; Soler 2010). A total of 128 patients (64 in each arm) will be required in a study with a power of 80% to detect an MCID of 0.5 times the SD of the measured outcome parameter (calculated using one of the many statistical packages freely available on the internet (Dupont 1990)). This number is relatively large and may require co-operation between multiple centres to achieve. The distribution of the total Lund-Mackay scores of patients with CRS is also normally distributed and can thus be described with a mean and SD score. In the UK National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis (Hopkins 2007) the mean and SD of pre-operative Lund-Mackay scores of 1840 patients were 11 and 6.5. The MCID for radiological scoring has not been validated and quality of life symptom scores only weakly correlate with radiology (Hopkins 2007), nevertheless 0.5 x SD is a statistically acknowledged moderate size effect that is a useful guide in designing an adequately powered study. All other prospective studies in adults lacked a control arm and thus by their very nature can only confirm safety and feasibility. The only other comparative study in adults was retrospective and non-randomised. Likewise in the paediatric population, a study comparing adenoidectomy with or without balloon sinuplasty suffered from being non-randomised. A U T H O R S C O N C L U S I O N S Implications for practice The only completed randomised controlled trial to date which has assessed the efficacy of balloon dilation of sinus ostia was the study by Plaza et al (Plaza 2010). The study revealed no significant difference in radiological resolution of a balloon dilation/hybrid (with FESS) procedure compared to conventional functional endoscopic sinus surgery (FESS-only) in the management of chronic frontal sinusitis refractory to medical treatment. The authors do report a statistically significant improvement in endoscopic patency, but as mentioned the study in its currently presented form suffers from a significant risk of bias, particularly in the reporting of outcome measures and statistical analyses. Bearing in mind that 8

11 the raw data were not made available and the potential limitation in sample size and thus power of the study, it is difficult to draw firm conclusions. Therefore, at present, there is no evidence to support the use of endoscopic balloon dilation of sinus ostia over and above conventional surgical modalities in the management of CRS refractory to medical treatment. Surgical management of children with CRS has been primarily with adenoidectomy due to its technical simplicity and safety. In failures, additional drainage and washout of maxillary and other sinuses has been advocated by either needle drainage or FESS. It should be noted, however, that the vast majority of children with CRS do improve with medical management. Again there is no evidence to support the use of balloon dilation of sinus ostia in children with CRS over the use of conventional surgical treatment. Implications for research With the escalating use of balloon sinus ostial dilation, there is an urgent need for randomised controlled trials to determine its efficacy over conventional surgical treatment methods. In order to reduce heterogenous outcome data and thus enable meta-analyses, trials should ideally utilise outcome measures similar to those that formed the basis of this review. A C K N O W L E D G E M E N T S We would like to thank Jenny Bellorini, Gemma Sandberg and the review panel of the Cochrane Ear, Nose and Throat Disorders Group for their helpful comments. R E F E R E N C E S References to studies included in this review Plaza 2010 {unpublished data only} Plaza G, Eisenberg G, Montojo J, Onrubia T, Urbasos M. Balloon dilatation of the frontal recess: a randomised study. American Academy of Otolaryngology, Head and Neck Surgery annual meeting, Boston, September :Poster SP503. References to studies excluded from this review Bolger 2007 {published data only} Bolger WE, Brown CL, Church CA, Goldberg AN, Karanfilov B, Kuhn FA, et al.safety and outcomes of balloon catheter sinusotomy: a multicenter 24-week analysis in 115 patients. Otolaryngology - Head and Neck Surgery 2007;137 (1): Brown 2006 {published data only} Brown CL, Bolger WE. Safety and feasibility of balloon catheter dilation of paranasal sinus ostia: a preliminary investigation. Annals of Otology, Rhinology and Laryngology 2006;115(4): Catalano 2009 {published data only} Catalano PJ, Payne SC. Balloon dilation of the frontal recess in patients with chronic frontal sinusitis and advanced sinus disease: an initial report. Annals of Otology, Rhinology and Laryngology 2009;118(2): [PUBMED: ] Friedman 2008 {published data only} Friedman M, Schalch P, Lin HC, Mazloom N, Neidich M, Joseph NJ. Functional endoscopic dilatation of the sinuses: patient satisfaction, postoperative pain, and cost. American Journal of Rhinology 2008;22(2): [PUBMED: ] Kuhn 2008 {published data only} Kuhn FA, Church CA, Goldberg AN, Levine HL, Sillers MJ, Vaughan WC, et al.balloon catheter sinusotomy: oneyear follow-up - outcomes and role in functional endoscopic sinus surgery. Otolaryngology - Head and Neck Surgery 2008; 139(3 (Suppl 3)):S Levine 2008 {published data only} Levine HL, Sertich AP, Hoisington DR, Weiss RL, Pritikin J. Multicenter registry of balloon catheter sinusotomy outcomes for 1,036 patients. Annals of Otology, Rhinology and Laryngology 2008;117(4): Luong 2008 {published data only} Luong A, Batra PS, Fakhri S, Citardi MJ. Balloon catheter dilatation for frontal sinus ostium stenosis in the office setting. American Journal of Rhinology 2008;22(6): [PUBMED: ] Ramadan 2009 {published data only} Ramadan HH. Safety and feasibility of balloon sinuplasty for treatment of chronic rhinosinusitis in children. Annals of Otology, Rhinology and Laryngology 2009;118(3): [PUBMED: ] Ramadan 2010 {published data only} Ramadan HH, Terrell AM. Balloon catheter sinuplasty and adenoidectomy in children with chronic rhinosinusitis. Annals of Otology, Rhinology and Laryngology 2010;119(9): [PUBMED: ] Weiss 2008 {published data only} Weiss RL, Church CA, Kuhn FA, Levine HL, Sillers MJ, Vaughan WC. Long-term outcome analysis of balloon catheter sinusotomy: two-year follow-up. Otolaryngology - Head and Neck Surgery 2008;139(3 (Suppl 3)):S Additional references Adams 1999 Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, Vital and Health Statistics ;200:

12 Blackwell 2002 Blackwell DL, Collins JG, Coles R. Summary health statistics for U.S. adults: National Health Interview Survey, Vital and Health Statistics ;205: Chan 2009 Chan Y, Melroy CT, Kuhn CA, Kuhn FL, Daniel WT, Kuhn FA. Long-term frontal sinus patency after endoscopic frontal sinusotomy. Laryngoscope 2009;119(6): [PUBMED: ] Chandra 2004 Chandra RK, Palmer JN, Tangsujarittham T, Kennedy DW. Factors associated with failure of frontal sinusotomy in the early follow-up period. Otolaryngology - Head and Neck Surgery 2004;131(4): [PUBMED: ] Draf 1991 Draf W. Endonasal micro-endoscopic frontal sinus surgery: the fulda concept. Operative Techniques in Otolaryngology - Head and Neck Surgery 1991;2(4): Dupont 1990 Dupont WD, Plummer WD Jr. Power and sample size calculations. A review and computer program. Controlled Clinical Trials 1990;11(2): [PUBMED: ] Fokkens 2007 Fokkens W, Lund V, Mullol J. European position paper on rhinosinusitis and nasal polyps Rhinology. Supplement 2007;20: Grainger 2006 Grainger J, Drake-Lee A. Montelukast in allergic rhinitis: a systematic review and meta-analysis. Clinical Otolaryngology 2006;31(5): Gross 2001 Gross CW, Schlosser RJ. Prevalence and economic impact of rhinosinusitis. Current Opinion in Otolaryngology & Head and Neck Surgery 2001;9(1):8 10. Hahn 2009 Hahn S, Palmer JN, Purkey MT, Kennedy DW, Chiu AG. Indications for external frontal sinus procedures for inflammatory sinus disease. American Journal of Rhinology & Allergy 2009;23(3): [PUBMED: ] Handbook 2011 Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions [updated March 2011]. The Cochrane Collaboration, Available from Harvey 2007 Harvey R, Hannan SA, Badia L, Scadding G. Nasal saline irrigations for the symptoms of chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2007, Issue 3. [DOI: / CD pub2] Harvey 2008 Harvey RJ, Goddard JC, Wise SK, Schlosser RJ. Effects of endoscopic sinus surgery and delivery device on cadaver sinus irrigation. Otolaryngology - Head and Neck Surgery 2008;139(1): [PUBMED: ] Higgins 2011 Higgins JPT, Altman DG. Chapter 8: Assessing the risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version (updated March 2011). The Cochrane Collaboration, Available from Hopkins 2006 Hopkins C, Browne JP, Slack R, Lund VJ, Topham J, Reeves BC, et al.complications of surgery for nasal polyposis and chronic rhinosinusitis: the results of a national audit in England and Wales. Laryngoscope 2006;116(8): Hopkins 2007 Hopkins C, Browne JP, Slack R, Lund V, Brown P. The Lund-Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict?. Otolaryngology - Head and Neck Surgery 2007;137(4): [PUBMED: ] Jones 2006 Jones N. Commentary on Safety and feasibility of ballooncatheter dilation of paranasal sinus ostia: a preliminary investigation. Annals of Otology, Rhinology and Laryngology 2006;115: Kay 2003 Kay DJ, Rosenfeld RM. Quality of life for children with persistent sinonasal symptoms. Otolaryngology - Head and Neck Surgery 2003;128(1): [PUBMED: ] Kennedy 1985 Kennedy DW, Zinreich SJ, Rosenbaum AE, Johns ME. Functional endoscopic sinus surgery. Theory and diagnostic evaluation. Archives of Otolaryngology 1985;111(9): Khalil 2006 Khalil HS, Nunez DA. Functional endoscopic sinus surgery for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: / CD pub2] Kieff 2009 Kieff DA, Busaba NY. Reformation of concha bullosa following treatment by crushing surgical technique: implication for balloon sinuplasty. Laryngoscope 2009;119 (12): [PUBMED: ] Kuhn 2006 Kuhn FA. An integrated approach to frontal sinus surgery. Otolaryngologic Clinics of North America 2006;39(3):437-61, viii. [PUBMED: ] Lanza 2006 Lanza DC, Kennedy DW. Balloon sinuplasty: not ready for prime time. Annals of Otology, Rhinology and Laryngology 2006;115(10): Lee 2006 Lee JT, Kennedy DW, Palmer JN, Feldman M, Chiu AG. The incidence of concurrent osteitis in patients with chronic rhinosinusitis: a clinicopathological study. American Journal of Rhinology 2006;20(3): [PUBMED: ] 10

13 Lee 2010 Lee JM, Chiu AG. Role of maximal endoscopic sinus surgery techniques in chronic rhinosinusitis. Otolaryngologic Clinics of North America 2010;43(3):579-89, ix. [PUBMED: ] Melroy 2008 Melroy CT. The balloon dilating catheter as an instrument in sinus surgery. Otolaryngology - Head and Neck Surgery 2008;139(3 (Suppl 3)):S23 6. [PUBMED: ] NICE 2008 National Institute for Health and Clinical Excellence. Balloon catheter dilation of paranasal sinus ostia for chronic sinusitis. IPG273guidance.pdf 2008 (accessed 13 April 2010). Norman 2003 Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Medical Care 2003; 41(5): [PUBMED: ] Philpott 2010 Philpott CM, Thamboo A, Lai L, Park J, Javer AR. Endoscopic frontal sinusotomy - preventing recurrence or a route to revision?. Laryngoscope 2010;120(8): [PUBMED: ] Ragab 2004 Ragab SM, Lund VJ, Scadding G. Evaluation of the medical and surgical treatment of chronic rhinosinusitis: a prospective, randomised, controlled trial. Laryngoscope 2004;114(5): Ramadan 2008 Ramadan HH, Cost JL. Outcome of adenoidectomy versus adenoidectomy with maxillary sinus wash for chronic rhinosinusitis in children. Laryngoscope 2008;118(5): [PUBMED: ] RevMan 2011 The Cochrane Collaboration. Review Manager (RevMan) Copenhagen: The Nordic Cochrane Centre: The Cochrane Collaboration, Smith 2010 Smith TL, Litvack JR, Hwang PH, Loehrl TA, Mace JC, Fong KJ, et al.determinants of outcomes of sinus surgery: a multi-institutional prospective cohort study. Otolaryngology - Head and Neck Surgery 2010;142(1): [PUBMED: ] Soler 2010 Soler ZM, Smith TL. Quality of life outcomes after functional endoscopic sinus surgery. Otolaryngologic Clinics of North America 2010;43(3):605-12, x. [PUBMED: ] Stammberger 1986 Stammberger H. Endoscopic endonasal surgery - concepts in treatment of recurring rhinosinusitis. Part II. Surgical technique. Otolaryngology - Head and Neck Surgery 1986;94 (2): Stankiewicz 1989 Stankiewicz JA. Complications in endoscopic intranasal ethmoidectomy: an update. Laryngoscope 1989;99(7 Pt 1): Sturgess 1979 Sturgess JM, Chao J, Wong J, Aspin N, Turner JA. Cilia with defective radial spokes: a cause of human respiratory disease. New England Journal of Medicine 1979;300(2): Timperley 2010 Timperley D, Schlosser RJ, Harvey RJ. Chronic rhinosinusitis: an education and treatment model. Otolaryngology - Head and Neck Surgery 2010;143(5 (Suppl 3)):S3 8. [PUBMED: ] US FDA 2005 US Food, Drug Administration. Medical Devices. April 2005 Clearances. MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/510kClearances/ ucm htm 2005 (accessed 13 April 2010). Zacharek 2003 Zacharek MA, Krouse JH. The role of allergy in chronic rhinosinusitis. Current Opinion in Otolaryngology & Head and Neck Surgery 2003;11(3): Indicates the major publication for the study 11

14 C H A R A C T E R I S T I C S O F S T U D I E S Characteristics of included studies [ordered by study ID] Plaza 2010 Methods Participants Interventions Outcomes Randomised controlled trial Setting: University Hospital Country: Spain Median age: years (range 20 to 65) Percentage male: 63% Clinical diagnosis: CRS including nasal polyposis Number randomised: month follow up Balloon sinuplasty of the frontal sinuses plus FESS for the remaining paranasal sinuses (hybrid) versus FESS (including Draf type 1/2a for frontal sinus drainage) Endoscopic visualisation of frontal recess CT scores of frontal sinuses (Lund-Mackay score) Symptom score (VAS/modified RSDI) Notes - Risk of bias Bias Authors judgement Support for judgement Adequate sequence generation? Low risk randomisation was achieved using a sequence of random numbers from a computer generated sequence Allocation concealment? Unclear risk randomisation was achieved using a sequence of random numbers from a computer generated sequence. Unclear whether this was an open list of random numbers, thus providing the allocator with prior knowledge of which intervention a participant was to receive Blinding? Hybrid Low risk Patient and outcome assessor blinded to intervention Blinding? FESS only Low risk Patient and outcome assessor blinded to intervention Incomplete outcome data addressed? Hybrid Low risk One patient lost to follow up (moved away) Incomplete outcome data addressed? FESS only Low risk One patient stopped follow up after suffering myocardial ischaemia 12

15 Plaza 2010 (Continued) Free of selective reporting? High risk Symptom scores not compared between groups postintervention. Individual data and exact statistical results, including confidence intervals, not presented CRS: chronic rhinosinusitis FESS: functional endoscopic sinus surgery RSDI: Rhinosinusitis Disability Index VAS: visual analogue scale Characteristics of excluded studies [ordered by study ID] Study Bolger 2007 Brown 2006 Catalano 2009 Friedman 2008 Kuhn 2008 Levine 2008 Luong 2008 Ramadan 2009 Ramadan 2010 Weiss 2008 Reason for exclusion No control group (same cohort as Kuhn 2008 and Weiss 2008) Feasibility study, no control group Included revisions, no control group Non-randomised retrospective study No control group (same cohort as Bolger 2007 and Weiss 2008) Retrospective chart review, no control group Feasibility study, balloon sinus ostial dilation performed under local anaesthetic, no control group Feasibility study, no control group Non-randomised No control group (same cohort as Bolger 2007 and Kuhn 2008) 13

16 D A T A A N D A N A L Y S E S This review has no analyses. A D D I T I O N A L T A B L E S Table 1. Endonasal frontal sinus drainage procedures as outlined by Draf (1991) Classification Description of procedure 1 Anterior ethmoidectomy including septa in the frontal recess, but the mucosa of the frontal sinus outflow tract is not touched 2 Removal of the floor of the frontal sinus to establish an opening between the lamina papyracea laterally and the medially placed: 2a 2b middle turbinate; or nasal septum anterior to the ventral margin of the olfactory fossa 3 Bilateral type 2 drainage procedures connected by the removal of the upper nasal septum and the lower frontal sinus septum Reference: Draf A P P E N D I C E S Appendix 1. Search strategies CENTRAL PubMed EMBASE (Ovid) CINAHL (EBSCO) #1 MeSH descriptor Paranasal Sinus Diseases explode all trees #2 MeSH descriptor Rhinitis explode all trees #3 MeSH descriptor Paranasal Sinuses explode all trees #4 rhinosin* OR rhinit* OR sinusit* OR nasosinusit* OR pansinusit* OR ethmoiditis OR antritis OR sphenoiditis OR inflamm* NEAR sinus* #5 (#1 OR #2 OR #3 OR #4) #1 Paranasal Sinus Diseases [Mesh] OR Rhinitis [Mesh] OR Paranasal Sinuses [Mesh] OR rhinosin* [tiab] OR rhinit* [tiab] OR sinusit* [tiab] OR nasosinusit* [tiab] OR pansinusit* [tiab] OR ethmoiditis [tiab] OR antritis [tiab] OR sphenoiditis [tiab] OR (inflamm* [tiab] AND sinus* [tiab]) #2 Balloon Dilatation [Mesh] 1 exp paranasal sinus/ 2 exp paranasal sinus disease/ 3 exp rhinitis/ 4 (rhinosin* or rhinit* or sinusit* or nasosinusit* or pansinusit* or ethmoiditis or antritis or sphenoiditis or (inflamm* and sinus*)).tw. 5 exp balloon dilatation/ 6 (balloon and (sinuplasty or dilat* or dilatation or inflat* or S1 (MH Paranasal Sinuses+ ) or (MH Paranasal Sinus Diseases+ ) S2 (MH Rhinitis+ ) S3 TX (rhinosin* or rhinit* or sinusit* or nasosinusit* or pansinusit* or ethmoiditis or antritis or sphenoiditis or (inflamm* and sinus*)) S4 S1 or S2 or S3 S5 (MH Balloon 14

17 (Continued) #6 MeSH descriptor Balloon Dilatation explode all trees #7 balloon AND (sinuplasty OR dilat* OR dilatation OR inflat* OR catheter* OR tamponade*) #8 (#6 OR #7) #9 (#5 AND #8) OR (balloon [tiab] AND (sinuplasty [tiab] OR dilat* [tiab] OR dilatation [tiab] OR inflat* [tiab] OR catheter* [tiab] OR tamponade* [tiab])) #3 #1 AND #2 catheter* or tamponade*)).tw. 7 1 or 2 or 3 or or 6 Dilatation+ ) S6 TX (balloon and (sinuplasty or dilat* or dilatation or inflat* or catheter* or tamponade*)) S7 S5 or S6 S8 S4 and S7 Web of Science/BIOSIS Previews (Web of Knowledge) Cochrane Ear Nose and Throat Group Trials Register (ProCite) CAB Abstracts (Ovid) ISRCTN #1 TS=(rhinosin* or rhinit* or sinusit* or nasosinusit* or pansinusit* or ethmoiditis or antritis or sphenoiditis or (inflamm* and sinus*)) #2 TS=(balloon and (sinuplasty or dilat* or dilatation or inflat* or catheter* or tamponade*)) #3 #1 AND #2 balloon 1 exp paranasal sinus/ 2 exp rhinitis/ 3 (rhinosin* or rhinit* or sinusit* or nasosinusit* or pansinusit* or ethmoiditis or antritis or sphenoiditis or (inflamm* and sinus*)).tw. 4 1 OR 2 OR 3 5 (balloon and (sinuplasty or dilat* or dilatation or inflat* or catheter* or tamponade*)).tw. 6 4 AND 5 (rhinosinusitis or rhinitis or sinusitis or nasosinusitis or pansinusitis or ethmoiditis or antritis or sphenoiditis) AND balloon H I S T O R Y Protocol first published: Issue 5, 2010 Review first published: Issue 7, 2011 C O N T R I B U T I O N S O F A U T H O R S Jahangir Ahmed searched, interpreted the literature and wrote the manuscript. Surojit Pal searched, interpreted the literature and helped in developing the protocol. Claire Hopkins provided valuable editorial support at all stages of manuscript development. Samuel Jayaraj provided valuable editorial support at all stages of manuscript development. 15

18 D E C L A R A T I O N S O F I N T E R E S T None known. The authors have no affiliation to Acclarent or any other manufacturer of similar surgical devices. S O U R C E S O F S U P P O R T Internal sources None, Not specified. External sources None, Not specified. I N D E X T E R M S Medical Subject Headings (MeSH) Catheterization [ methods]; Endoscopy [methods]; Frontal Sinus; Frontal Sinusitis [ therapy]; Randomized Controlled Trials as Topic; Rhinitis [ therapy] MeSH check words Humans 16