Recalcitrant Chronic Rhinosinusitis. Nathan Chen, M.D. Dana King, M.D. Jan 2, 2013

Transcription

1 Recalcitrant Chronic Rhinosinusitis Nathan Chen, M.D. Dana King, M.D. Jan 2, 2013

2 Outline Chronic rhinosinusitis Background Pathophysiology Diagnosis Treatment (medical and surgical) Workup and management of recalcitrant disease

3 Background Inflammatory process that involves the paranasal sinuses and persists for 12 weeks or longer Almost always accompanied by concurrent nasal airway inflammation and is often preceded by rhinitis symptoms; thus, the term chronic rhinosinusitis Chronic rhinosinusitis is thought to affect between 5% and 15% of the population 5 th most common disease treated with antibiotics Melen I. Chronic Sinusitis: Clinical and pathophysiological aspects. Acta Otolaryngolgica 1994;515:45 8.

4 Background Most cases of chronic sinusitis are continuation of unresolved acute sinusitis CRS may be noninfectious and related to allergy, cystic fibrosis, gastroesophageal reflux, or exposure to environmental pollutants Risk factors: Allergic rhinitis Nonallergic rhinitis (eg, vasomotor rhinitis, rhinitis medicamentosa, cocaine abuse) Intubation / NG Smoking Immunologic disorders Anatomic obstruction in the ostiomeatal complex American Academy of Pediatrics - Subcommittee on Management of Sinusitis and Committee on Quality Management. Clinical practice guideline: management of sinusitis. Pediatrics. Sep 2001;108(3): Slavin RG, Spector SL, Bernstein IL, et al. The diagnosis and management of sinusitis: a practice parameter update. J Allergy Clin Immunol. Dec 2005;116(6 Suppl):S13-47.

5 What s the hold up?

6 Concha Bullosa

7 What s the hold up?

8 Septal deviation

9 What s the hold up?

10 Agger Nasi

11 What s the hold up?

12 Haller Cells

13 What s the hold up?

14 Paradoxical Middle Turbinate

15

16 Pathophysiology Inflammation Stasis of secretions Secondary bacterial infection (usu. aerobic (ie, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) Persistence of the infection, mixed flora, anaerobic organisms Anaerobic bacteria of oral flora origin often eventually predominating Brook I, Frazier EH, Foote PA. Microbiology of the transition from acute to chronic maxillary sinusitis. J Med Microbiol. Nov 1996;45(5):372-5.

17 Pathophysiology* Multifactorial inflammatory disease: Allergy and other immunologic disorders Superantigens Colonizing fungi that induce and sustain eosinophilic inflammation Persistent infection (including biofilms and osteitis) Metabolic abnormalities such as aspirin sensitivity Ciliary dysfunction

18 Symptoms Nasal stuffiness Nasal discharge (of any character from thin to thick and from clear to purulent) Postnasal drip Facial fullness Malaise Chronic unproductive cough Hyposmia Sore throat Fetid breath Malaise Easy fatigability Anorexia Exacerbation of asthma Dental pain Visual disturbances Sneezing Stuffy ears Unpleasant taste Fever of unknown origin

19 SNOT-22 Patient-reported measure of outcome developed for use in CRS. The SNOT contains 22 individual questions and is a modification of the 31-question Rhinosinusitis Outcome Measure (RSOM-31) The SNOT covers a broad range of health and healthrelated quality of life problems including physical problems, functional limitations and emotional consequences It has been validated to distinguish between diseaseaffected patient groups and those without rhinosinusitis, demonstrate a worse score if the condition gets worse and show an appropriateness of items and scales in the questionnaire Morley AD, Sharp HR.A review of sinonasal outcome scoring systems - which is best?clin Otolaryngol Apr;31(2):103-9.

20 Diagnosis* In 1996, the American Academy of Otolaryngology-Head & Neck Surgery multidisciplinary Rhinosinusitis Task Force (RTF) defined adult rhinosinusitis diagnostic criteria In 2003, the RTF s definition amended to require confirmatory radiographic or nasal endoscopic or physical examination findings in addition to suggestive history Major symptoms and signs Nasal obstruction (81-95%) Facial congestion/pressure/fullness (70-85%) Nasal discharge/purulence (51-83%) Hyposmia/anosmia (61-69%) Minor symptoms and signs Headache Fever Fatigue Dental pain Cough Ear pain/pressure/fullness Overall, the combination of symptoms and endoscopy findings had a sensitivity of 47% and a specificity of 84% for CRS Report of the Rhinosinusitis Task Force Committee Meeting. Alexandria, Virginia, August 17, Otolaryngol Head Neck Surg. Sep 1997;117(3 Pt 2):S1-68. Benninger MS, Ferguson BJ, Hadley JA, et al. Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology. Otolaryngol Head Neck Surg. Sep 2003;129(3 Suppl):S1-32.

21 Diagnosis No correlation between nasal flora and culture from the sinuses. Nasal swab cultures have no diagnostic value Endoscopically directed middle meatal cultures had a sensitivity of 80.9% and a specificity of 90.5% Culture of an organism from the middle meatus may be more accurate to determine the bacteria involved in the disease process than maxillary sinus tap Benninger MS, Payne SC, Ferguson BJ, Hadley JA, Ahmad N. Endoscopically directed middle meatal cultures versus maxillary sinus taps in acute bacterial maxillary rhinosinusitis: a meta-analysis. Otolaryngol Head Neck Surg. Jan 2006;134(1):3-9.

22 Medical Therapy for CRS Controlling predisposing factors Treating concomitant infections Reducing edema of sinus tissues Facilitating the drainage of sinus secretions Mainstay therapy: Nasal saline irrigations Intranasal corticosteroids Systemic corticosteroids Antibiotics

23 Medical Therapy for CRS Nasal saline irrigations: Mechanical clearance of mucus Protective coating Anti-inflammatory Improved ciliary function Previous literature conclusions range from no benefit to more benefit than standard medical therapy Cochrane review in RCTs (vs. placebo, vs. no rx, vs. nasal steroid) Although not as effective as nasal steroid Beneficial as stand-along and adjunct Irrigation has shown more benefit than spray Hypertonic possibly superior (more radiologic improvement) * Harvey R, Hannan SA, Badia L, Scadding G. Nasal saline irrigations for the symptoms of chronic rhinosinusitis. Cochrane Database Syst Rev Jul 18;(3):CD Review.

24 Medical Therapy for CRS Intranasal corticosteroids Can be given for longer without significant side effects of oral steroids 2011 Cochrane review 10 studies (590 pts) Improved sino-nasal symptoms Decreased polyp size and recurrence after surgery No significant differences when steroid was administered to patients with and without surgery An ostial diameter of around 4.7mm is the minimum to ensure adequate delivery Sinus (direct cannulation, irrigation post-surgery) delivery superior to nasal (drops, sprays, nebulizer) Most common side-effects: headache and epistaxis Snidvongs K, Kalish L, Sacks R, Craig JC, Harvey RJ. Topical steroid for chronic rhinosinusitis without polyps. Cochrane Database Syst Rev Aug 10;(8):CD doi: / CD Singhal D, Weitzel EK, Lin E, Feldt B, Kriete B, McMains KC, et al.effect of head position and surgical dissection on sinus irrigant penetration in cadavers. Laryngoscope 2010; 120(12):

25 Medical Therapy for CRS Systemic corticosteroids Topical reduces rhinitis symptoms, improves nasal breathing, reduces the size of polyps and the recurrence rate, but has a negligible effect on the sense of smell and on any sinus pathology PO improves all symptoms and pathology, including the sense of smell 2012 Cochrane Review 3 prospective trials (166 pts) Short term benefit of 2-4 week PO steriods vs placebo Reduction of polyp size and sino-nasal symptom improvement No significant adverse effects reported Rajasekaran 2010: Higher rate of osteopenia/osteoporosis among men > 50 and postmenopausal women in a retrospective study Kalish L, Snidvongs K, Sivasubramaniam R, Cope D, Harvey RJ. Topical steroids for nasal polyps. Cochrane Database Syst Rev Dec 12;12:CD doi: / CD Rajasekaran K, Seth R, Abelson A, Batra PS. Prevalence of metabolic bone disease among chronic rhinosinusitis patients treated with oral glucocorticoids. American Journal of Rhinology and Allergy 2010;24(3):215 9.

26 Medical Therapy for CRS Topical antibiotic therapy: Theoretical advantage of higher local concentration and min systemic absorption Increased concentration effective in killing bacteria in biofilm (in vitro study) Systematic review 2008: Irrigation & nebulizer effective, not spray Most apparent benefit in postop pts with culture-directed therapy Strong evidence for use in pts with cystic fibrosis: less need for surgery associated with use of tobramycin saline nasal rinses vs. no therapy Uncertain role of topical antifungals (2011 Cochrane review shows no evidence of benefit) Conclusion: topical abx - potential useful adjunct to topical steroids and PO abx (more studies needed) Lim M, Citardi MJ, Leong JL. Topical antimicrobials in the management of chronic rhinosinusitis: a systematic review. Am J Rhinol Jul-Aug;22(4): doi: /ajr Desrosiers M, Bendouah Z, and Barbeau J. Effectiveness of topical antibiotics on Staphylococcus aureus biofilm in vitro. Am J Rhinol 21: , 2007.

27 Medical Therapy for CRS Oral antibiotics: Micro-organisms are recognized as diseasemodifiers, rather than causative agents Initial choice of the appropriate antimicrobial(s) is usually empiric (including both aerobic and anaerobic pathogens, likely beta-lactamase producing) Adequate antibiotic trial in CRS usually consists of a minimum of 3-4 weeks of treatment In CRS, no randomized placebo-controlled trial has demonstrated efficacy of short courses of oral antibiotics

28 Medical Therapy for CRS Oral antibiotics: Long-term macrolide therapy has been shown to be effective in CRS Anti-inflammatory mechanism in addition to antimicrobial effects Possibly decreases biofilm formation and bacterial virulence Recommended as part of primary therapy for non-atopic patients Antifungal: 2011 Cochrane review 6 studies (380 pts) topical/ systemic vs. placebo Immunocompetent pts w/ CRS (not specific to mycetoma, allergic fungal sinusitis) No evidence for topical or systemic antifungals (sx, radiological, endoscopic) Significant higher adverse events (local irritation) in antifungal group Fokkens WJ, Lund VJ, Mullol J, European Position Paper on Rhinosinusitis and Nasal Polyps group. European Position Paperon Nasal Polyps Rhinology Supplement 2007;45(20): Sacks PL, Harvey RJ, Rimmer J, Gallagher RM, Sacks R. Topical and systemic antifungal therapy for the symptomatic treatment of chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2011, Issue 8. Art. No.: CD DOI: / CD pub2.

29 Medical Therapy for CRS Approach to therapy Mild symptoms Intranasal corticosteroids and nasal saline lavage Reassess after 3 months If no improvement, culture and start long-term macrolide, consider CT Reassess again after 3 months If no improvement, CT and consider sinus surgery Moderate/severe symptoms Intranasal steroids, nasal saline lavage, culture, and macrolide Short course of oral steroids for pts with nasal polyposis Reassess again after 3 months If no response, CT and consider sinus surgery Fokkens WJ, Lund VJ, Mullol J, European Position Paper on Rhinosinusitis and Nasal Polyps group. European Position Paperon Nasal Polyps Rhinology Supplement 2007;45(20):1 136.

30 Surgical Therapy for CRS The goal in surgical treatment is to Reestablish sinus ventilation Correct mucosal opposition in order to restore the mucociliary clearance system. Restore the functional integrity of the inflamed mucosal lining.

31 Surgical Therapy for CRS Functional endoscopic sinus surgery (FESS) In CRS, inflammation from viral, bacterial, and fungal infections and from allergies leads to mucosal edema obstruction of the natural sinus ostia Anatomic abnormalities septal deviation, concha bullosa, paradoxical middle turbinate, Haller cells, agger nasi cells, and nasal polyps can obstruct natural sinus ostia Principles of FESS First maximize medical therapy Restore sinus function by re-establishing the physiologic pattern of ventilation and mucociliary clearance Remove diseased mucosa and bone, preserve normal tissue, and widen natural ostia

32 Surgical Therapy for CRS 2008 Cochrane review 3 RCT (212 pts) FESS not superior to medical treatment in CRS Middle meatal antrostomy not superior to inferior meatal antrostomy (small sample size) Study limitations Disease staging/definition not uniform FESS procedures differ Outcome measures not uniform Limited follow-up, medium 1 year Khalil H,Nunez DA. Functional endoscopic sinus surgery for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD DOI: / CD pub2

33 Surgical Therapy for CRS Balloon Sinuplasty Recently developed US FDA approved dilating balloon catheter introduced in Sept 2005 First clinical outcomes published by Bolger in 2007 Guide catheter positioned near sinus to be dilated under endoscopic guidance Guide wire is passed into sinus cavity Position initially confirmed with fluoroscopy A lighted guide wire now available to confirm position without radiation exposure to the patient Balloon passed over guide wire and inflated while within the sinus ostium Used for maxillary, frontal, and sphenoid sinus Initially confined to the OR, now also being performed in the clinic setting

34 Balloon Sinuplasty 2011 Cochrane review 1 RCT (34 pts) Pts 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) vs. conventional FESS (Draf type 1/2a procedures on the frontal sinuses) No statistically significant difference in radiological resolution of frontal sinuses at 12 months Higher patency rate (endoscopic) in balloon group Ahmed J, Pal S, Hopkins C, Jayaraj S. Functional endoscopic balloon dilation of sinus ostia for chronic rhinosinusitis.cochrane Database Syst Rev Jul 6;(7):CD doi: / CD pub2.

35 AAO-HNS Position statement Sinus ostial dilation (e.g. balloon ostial dilation) is an appropriate therapeutic option for selected patients with sinusitis. This approach may be used alone to dilate a sinus ostium (frontal, maxillary, or sphenoid) or in conjunction with other instruments (eg, microdebrider, forceps). The final decision regarding use of techniques or instrumentation for sinus surgery is the responsibility of the attending surgeon. Revised: 12/6/2010 Adopted: 6/28/2010 Reaffirmed: 12/8/2012

36 Indications of Balloon Sinuplasty Serial dilation of frontal stenosis in the operating room and clinic setting Assistance in finding the natural frontal sinus outflow tract in a more complicated revision case Dilation of a laterally obstructed large supraorbital cell or type III frontal cell causing obstruction beyond the limits of frontal sinus instrumentation Targeted treatment of recurrent, occupationally related baro trauma in otherwise normal sinuses Alexander E. Stewart & Winston C. Vaughan Balloon Sinuplasty Versus Surgical Management of Chronic Rhinosinusitis Curr Allergy Asthma Rep (2010) 10:

37 What happens if nothing works Life after standard medical therapy and FESS Identify and treat underlying etiologic and exacerbating factors Maximize anti-inflammatory therapy Ensure that confounding causes of sinus symptoms are addressed

38 GERD GERD is associated with CRS in several studies Prospective trial: ph probe monitoring, acid reflux into the NP was significantly greater in patients with refractory CRS after surgery than in patients in whom ESS successfully relieved symptoms Pawar 2007: PPIs reduce the frequency of postnasal drainage symptoms in patients with extraesophageal manifestations of GERD DiBaise 2002: Decreased sinonasal symptom scores in patients treated with BID omeprazole for 3 months No RCTs available Passali D, Caruso G, Passali FM. ENT manifestations of gastroesophageal reflux. Curr Allergy Asthma Rep 2008;8: DelGaudio JM. Direct nasopharyngeal reflux of gastric acid is a contributing factor in refractory chronic rhinosinusitis. Laryngoscope 2005;115: Pawar S, Lim HJ, GillM, et al. Treatment of postnasal drip with proton pump inhibitors: a prospective, randomized, placebo-controlled study. Am J Rhinol 2007;21: DiBaise JK, Brand RE, Quigley EM. Endoluminal delivery of radiofrequency energy to the gastroesophageal junction in uncomplicated GERD: efficacy and potential mechanism of action. Am J Gastroenterol 2002;97:

39 Allergy Mucosal changes due to AR can alter mucociliary clearance, which can negatively affect CRS Houser 2008: AR as a predictive factor for decreased quality of life and poorer surgical outcomes in CRS Antihistamines: sneezing, itching, rhinorrhea, and watery eyes, poor decongestants unless given topically Anticholinergic: reduce rhinorrhea (may thicken secretions) Leukotriene antagonists Montelukast: approved for asthma and AR, 1 week trial Zileuton: more potent, approved for asthma only, monitor LFT Cromolyn: effective as prophylaxis, low side-effect profile Immunotherapy: only potential cure for allergy, no RCT on efficacy in CRS Anti-IgE (omalizumab): indicated for moderate to severe asthma with positive skin test not adequately controlled with inhaled steroids Limited evidence Costly ($10-12k per year) Twice monthly Risk of anaphylaxis Houser SM, Keen KJ. The role of allergy and smoking in chronic rhinosinusitis and polyposis. Laryngoscope 2008;118:

40 Immune Deficiency 8% to 20% of pts w/ CRS or recurrent acute sinusitis CRS associated with immunodeficiency may be responsive to antibiotic therapy but recurs when antibiotics are withdrawn CVID in 10% of pts w/ refractory CRS IVIG Specific polysaccharide antibody deficiency syndrome is diagnosed by deficient responses to pneumovac comparing the levels before 6 weeks after vaccination Pneumococcal vaccine for recurrent acute infections: theoretically immunize pts to most, but not all, streptococcal pneumonia serotypes Not all immunodeficiencies are treatable Kainulainen L, Suonpaa J, Nikoskelainen J, et al. Bacteria and viruses in maxillary sinuses of patients with primary hypogammaglobulinemia. Arch Otolaryngol Head Neck Surg 2007;133: Ferguson BJ, Otto BA, Pant H. When surgery, antibiotics, and steroids fail to resolve chronic rhinosinusitis.immunol Allergy Clin North Am Nov;29(4): doi: /j.iac

41 Cheaper than a sinus CT Ferguson BJ, Otto BA, Pant H. When surgery, antibiotics, and steroids fail to resolve chronic rhinosinusitis.immunol Allergy Clin North Am Nov;29(4): doi: /j.iac

42 Samter s Triad Nasal polyposis, asthma, and aspirin sensitivity 15% of patients with polyps have aspirin sensitivity 20-70% of patients with polyps have asthma 40-80% of patients with aspirin sensitivity have polyps Symptoms usually develop following a prolonged upper respiratory infection in the 3 rd or 4 th decade of life Initially nasal congestion, rhinorrhea, PND, and hyposmia Within a few years, bronchial asthma and nasal polyposis develop Asthma and rhinitis attacks triggered by ingestion of aspirin and nonselective NSAIDs Asthma is usually severe, with 50% of patient requiring chronic burst or daily oral steroid therapy Course of the disease is not affected by aspirin ingestion

43 Samter s Triad Pathogenesis Not completely elucidated Atopy and IgE do not appear to play a role Peripheral blood and local mucosal eosinophilia Elevated tissue and urine cysteinyl-leukotrienes (cys-lts), concentrations of which increase with aspirin exposure Aspirin inhibits COX 1 & 2, funneling arachidonic acid metabolism toward leukotrienes Several-fold elevation of LTC4 synthase (terminal enzyme in cys-lt production) found in eosinophils of aspirin sensitive patients Polymorphisms in the LTC4 synthase gene suggested as a possible etiology

44 Samter s Triad Diagnosis No validated laboratory testing available Oral aspirin provocation in a controlled setting is the current gold standard in the U.S. Asthma medications are discontinued prior to the testing Aspirin is dosed q3h, with increasing amount of aspirin in each dose Positive test: Decrease in FEV1 by 20% or more from baseline Severe nasal congestion and/or rhinorrhea occur Negative test: Cumulative dose of 1000 mg of aspirin is reached without either of the positive test criteria occuring

45 Samter s Triad Medical Therapy Avoidance of aspirin and non-specific NSAIDs Acetaminophen and celecoxib are tolerated in most patients Treatment of asthma symptoms as per asthma guidelines Leukotriene modifiers Somewhat effective, though no more so than in regular asthma Aspirin desensitization Nearly all can be desensitized Unknown mech: theory IL-4 induced reduction in leukotriene production Needs to continue taking NSAID daily (only ASA prevent polyp recurrence and improve asthma) Can tolerate other NSAIDs CRS improves more than asthma Surgical Therapy FESS necessary in some patients due to burden of nasal polyps and inadequate response to medical treatment Stevenson DD, Hankammer MA, Mathison DA, et al. Aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma: long-term outcomes. J Allergy Clin Immunol 1996;98:751 8.

46 References Melen I. Chronic Sinusitis: Clinical and pathophysiological aspects. Acta Otolaryngolgica 1994;515:45 8. American Academy of Pediatrics - Subcommittee on Management of Sinusitis and Committee on Quality Management. Clinical practice guideline: management of sinusitis. Pediatrics. Sep 2001;108(3): Slavin RG, Spector SL, Bernstein IL, et al. The diagnosis and management of sinusitis: a practice parameter update. J Allergy Clin Immunol. Dec 2005;116(6 Suppl):S Brook I, Frazier EH, Foote PA. Microbiology of the transition from acute to chronic maxillary sinusitis. J Med Microbiol. Nov 1996;45(5): Report of the Rhinosinusitis Task Force Committee Meeting. Alexandria, Virginia, August 17, Otolaryngol Head Neck Surg. Sep 1997;117(3 Pt 2):S1-68. Benninger MS, Ferguson BJ, Hadley JA, et al. Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology. Otolaryngol Head Neck Surg. Sep 2003;129(3 Suppl):S1-32. Harvey R, Hannan SA, Badia L, Scadding G. Nasal saline irrigations for the symptoms of chronic rhinosinusitis. Cochrane Database Syst Rev Jul 18;(3):CD Review. Snidvongs K, Kalish L, Sacks R, Craig JC, Harvey RJ. Topical steroid for chronic rhinosinusitis without polyps. Cochrane Database Syst Rev Aug 10;(8):CD doi: / CD Singhal D, Weitzel EK, Lin E, Feldt B, Kriete B, McMains KC, et al.effect of head position and surgical dissection on sinus irrigant penetration in cadavers. Laryngoscope 2010; 120(12): Kalish L, Snidvongs K, Sivasubramaniam R, Cope D, Harvey RJ. Topical steroids for nasal polyps. Cochrane Database Syst Rev Dec 12;12:CD doi: / CD Rajasekaran K, Seth R, Abelson A, Batra PS. Prevalence of metabolic bone disease among chronic rhinosinusitis patients treated with oral glucocorticoids. American Journal of Rhinology and Allergy 2010;24(3): Lim M, Citardi MJ, Leong JL. Topical antimicrobials in the management of chronic rhinosinusitis: a systematic review. Am J Rhinol Jul-Aug;22(4): doi: /ajr Desrosiers M, Bendouah Z, and Barbeau J. Effectiveness of topical antibiotics on Staphylococcus aureus biofilm in vitro. Am J Rhinol 21: , Fokkens WJ, Lund VJ, Mullol J, European Position Paper on Rhinosinusitis and Nasal Polyps group. European Position Paperon Nasal Polyps Rhinology Supplement 2007;45(20): Sacks PL, Harvey RJ, Rimmer J, Gallagher RM, Sacks R. Topical and systemic antifungal therapy for the symptomatic treatment of chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2011, Issue 8. Art. No.: CD DOI: / CD pub2. Khalil H,Nunez DA. Functional endoscopic sinus surgery for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD DOI: / CD pub2 Ahmed J, Pal S, Hopkins C, Jayaraj S. Functional endoscopic balloon dilation of sinus ostia for chronic rhinosinusitis.cochrane Database Syst Rev Jul 6;(7):CD doi: / CD pub2. Alexander E. Stewart & Winston C. Vaughan Balloon Sinuplasty Versus Surgical Management of Chronic Rhinosinusitis Curr Allergy Asthma Rep (2010) 10: Passali D, Caruso G, Passali FM. ENT manifestations of gastroesophageal reflux. Curr Allergy Asthma Rep 2008;8: DelGaudio JM. Direct nasopharyngeal reflux of gastric acid is a contributing factor in refractory chronic rhinosinusitis. Laryngoscope 2005;115: Pawar S, Lim HJ, GillM, et al. Treatment of postnasal drip with proton pump inhibitors: a prospective, randomized, placebo-controlled study. Am J Rhinol 2007;21: DiBaise JK, Brand RE, Quigley EM. Endoluminal delivery of radiofrequency energy to the gastroesophageal junction in uncomplicated GERD: efficacy and potential mechanism of action. Am J Gastroenterol 2002;97: Houser SM, Keen KJ. The role of allergy and smoking in chronic rhinosinusitis and polyposis. Laryngoscope 2008;118: Kainulainen L, Suonpaa J, Nikoskelainen J, et al. Bacteria and viruses in maxillary sinuses of patients with primary hypogammaglobulinemia. Arch Otolaryngol Head Neck Surg 2007;133: Ferguson BJ, Otto BA, Pant H. When surgery, antibiotics, and steroids fail to resolve chronic rhinosinusitis.immunol Allergy Clin North Am Nov;29(4): doi: /j.iac Stevenson DD, Hankammer MA, Mathison DA, et al. Aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma: long-term outcomes. J Allergy Clin Immunol 1996;98:751 8.