Chronic rhinosinusitis: Epidemiology and medical management
2011; Elsevier BV; Volume: 128; Issue: 4 Linguagem: Inglês
10.1016/j.jaci.2011.08.004
ISSN1097-6825
Autores Tópico(s)Asthma and respiratory diseases
ResumoChronic rhinosinusitis (CRS) affects 12.5% of the US population. On epidemiologic grounds, some association has been found between CRS prevalence and air pollution, active cigarette smoking, secondhand smoke exposure, perennial allergic rhinitis, and gastroesophageal reflux. The majority of pediatric and adult patients with CRS are immune competent. Data on genetic associations with CRS are still sparse. Current consensus definitions subclassify CRS into CRS without nasal polyposis (CRSsNP), CRS with nasal polyposis (CRSwNP), and allergic fungal rhinosinusitis (AFRS). Evaluation and medical management of CRS has been the subject of several recent consensus reports. The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics. The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations. Aspirin desensitization is beneficial for patients with aspirin-intolerant CRSwNP. Sinus surgery followed by use of systemic steroids is recommended for AFRS. Other modalities of treatment, such as antibiotics for patients with purulent infection and antifungal drugs for patients with AFRS, are potentially useful despite a lack of evidence from controlled treatment trials. The various modalities of medical treatment are reviewed in the context of recent consensus documents and the author’s personal experience. Chronic rhinosinusitis (CRS) affects 12.5% of the US population. On epidemiologic grounds, some association has been found between CRS prevalence and air pollution, active cigarette smoking, secondhand smoke exposure, perennial allergic rhinitis, and gastroesophageal reflux. The majority of pediatric and adult patients with CRS are immune competent. Data on genetic associations with CRS are still sparse. Current consensus definitions subclassify CRS into CRS without nasal polyposis (CRSsNP), CRS with nasal polyposis (CRSwNP), and allergic fungal rhinosinusitis (AFRS). Evaluation and medical management of CRS has been the subject of several recent consensus reports. The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics. The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations. Aspirin desensitization is beneficial for patients with aspirin-intolerant CRSwNP. Sinus surgery followed by use of systemic steroids is recommended for AFRS. Other modalities of treatment, such as antibiotics for patients with purulent infection and antifungal drugs for patients with AFRS, are potentially useful despite a lack of evidence from controlled treatment trials. The various modalities of medical treatment are reviewed in the context of recent consensus documents and the author’s personal experience. Information for Category 1 CME CreditCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted.Date of Original Release: October 2011. Credit may be obtained for these courses until September 30, 2013.Copyright Statement: Copyright © 2011-2013. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates these educational activities for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Daniel L. Hamilos, MDActivity Objectives1.To know the statistics and epidemiology surrounding chronic rhinosinusitis (CRS) and its risk factors and implications for the patient.2.To know the comprehensive management plan for CRS and nasal polyposis, including initial approach, diagnostics, and appropriate treatment.Recognition of Commercial Support: This CME activity has not received external commercial support.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: D. L. Hamilos has declared that he has no conflict of interest. Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions. Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted. Date of Original Release: October 2011. Credit may be obtained for these courses until September 30, 2013. Copyright Statement: Copyright © 2011-2013. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates these educational activities for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Daniel L. Hamilos, MD Activity Objectives1.To know the statistics and epidemiology surrounding chronic rhinosinusitis (CRS) and its risk factors and implications for the patient.2.To know the comprehensive management plan for CRS and nasal polyposis, including initial approach, diagnostics, and appropriate treatment. Recognition of Commercial Support: This CME activity has not received external commercial support. Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: D. L. Hamilos has declared that he has no conflict of interest. According to the National Health Interview Survey of 1996, chronic sinusitis was the second most prevalent chronic health condition, affecting 12.5% of the US population or approximately 31 million patients each year.1Adams P.F. Hendershot G.E. Marano M.A. Centers for Disease Control and Prevention/National Center for Health Statistics Current estimates from the National Health Interview Survey, 1996.Vital Health Stat. 1999; 10: 1-203Google Scholar, 2Anand V.K. Epidemiology and economic impact of rhinosinusitis.Ann Otol Rhinol Laryngol Suppl. 2004; 193: 3-5Crossref PubMed Google Scholar According to an analysis of the 2008 National Health Interview Survey data, rhinosinusitis affected approximately 1 in 7 adults.3Pleis J.R. Lucas J.W. Ward B.W. Summary health statistics for U.S. adults: National Health Interview Survey, 2008.Vital Health Stat. 2009; 10: 1-157Google Scholar Because chronic rhinosinusitis (CRS) was classified solely on symptomatic criteria, CRS prevalence was likely overestimated in these surveys. A study by Stankiewicz and Chow4Stankiewicz J.A. Chow J.M. Nasal endoscopy and the definition and diagnosis of chronic rhinosinusitis.Otolaryngol Head Neck Surg. 2002; 126: 623-627Crossref PubMed Scopus (90) Google Scholar found a poor correlation of CRS symptoms with objective evidence of sinus disease either by means of nasal endoscopy or sinus computed tomographic (CT) scanning.4Stankiewicz J.A. Chow J.M. Nasal endoscopy and the definition and diagnosis of chronic rhinosinusitis.Otolaryngol Head Neck Surg. 2002; 126: 623-627Crossref PubMed Scopus (90) Google Scholar In 2003, a consensus panel redefined CRS (also known as chronic sinusitis) as an inflammatory disorder of the nose and paranasal sinuses of unknown cause defined on the basis of characteristic symptoms (≥2 of the following: nasal congestion, facial pain/pressure, anterior or posterior nasal drainage, and reduced or absent sense of smell), duration (>12 weeks), and objective evidence of sinus disease by means of direct visualization or imaging studies.5Benninger M.S. Ferguson B.J. Hadley J.A. Hamilos D.L. Jacobs M. Kennedy D.W. et al.Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology.Otolaryngol Head Neck Surg. 2003; 129: S1-S32Crossref PubMed Scopus (10) Google Scholar Regardless of its true prevalence, CRS accounts for substantial health care expenditures in terms of office visits, antibiotic prescriptions filled, lost work days, and missed school days. The number of workdays missed annually because of rhinosinusitis is similar to that reported for acute asthma (5.67 vs 5.79 days, respectively), and patients with rhinosinusitis are more likely to spend greater than $500 per year on health care than people with chronic bronchitis, ulcer disease, asthma, or hay fever.6Bhattacharyya N. Contemporary assessment of the disease burden of sinusitis.Am J Rhinol Allergy. 2009; 23: 392-395Crossref PubMed Scopus (111) Google Scholar Approximately 20% of patients with chronic sinusitis have nasal polyposis (NP).7Settipane G.A. Epidemiology of nasal polyps.Allergy Asthma Proc. 1996; 17: 231-236Crossref PubMed Scopus (187) Google Scholar There were approximately 200,000 sinus surgeries performed in the United States in 1994.8Kaliner M.A. Osguthorpe J.D. Fireman P. Anon J. Georgitis J. Davis M.L. et al.Sinusitis: bench to bedside. Current findings, future directions.J Allergy Clin Immunol. 1997; 99: S829-S848Google Scholar CRS with nasal polyposis (CRSwNP) is one of the most common indications for sinus surgery. Of patients participating in our nasal polyp research studies, 69% have had previous surgery, attesting to the high frequency of recurrent disease in these patients. Certain anatomic variants, such as septal deviation, Haller cells, paradoxical curvature of the middle turbinate, and agger nasi cells, have been suggested to predispose to obstruction of the ostiomeatal unit, development of CRS, or both. However, there is currently little evidence that these play a role in most cases of chronic sinusitis.9Lusk R.P. McAlister B. el Fouley A. Anatomic variation in pediatric chronic sinusitis: a CT study.Otolaryngol Clin North Am. 1996; 29: 75-91Google Scholar, 10Bolger W.E. Butzin C.A. Parsons D.S. Paranasal sinus bony anatomic variations and mucosal abnormalities: CT analysis for endoscopic sinus surgery.Laryngoscope. 1991; 101: 56-64Crossref PubMed Google Scholar, 11Jones N.S. Strobl A. Holland I. A study of the CT findings in 100 patients with rhinosinusitis and 100 controls.Clin Otolaryngol Allied Sci. 1997; 22: 47-51Crossref Scopus (133) Google Scholar, 12Danese M. Duvoisin B. Agrifoglio A. Cherpillod J. Krayenbuhl M. Influence of naso-sinusal anatomic variants on recurrent, persistent or chronic sinusitis. X-ray computed tomographic evaluation in 112 patients.J Radiol. 1997; 78: 651-657PubMed Google Scholar Furthermore, a recent study in a pediatric population found no correlation between anatomic abnormalities and the extent of CRS on sinus CT scanning.13Al-Qudah M. The relationship between anatomical variations of the sino-nasal region and chronic sinusitis extension in children.Int J Pediatr Otorhinolaryngol. 2008; 72: 817-821Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar There have been relatively few studies examining the relationship between air pollutants and CRS incidence or prevalence. Bhattacharyya6Bhattacharyya N. Contemporary assessment of the disease burden of sinusitis.Am J Rhinol Allergy. 2009; 23: 392-395Crossref PubMed Scopus (111) Google Scholar performed a cross-sectional analysis to examine the relationship between the prevalence of “hay fever” and “sinusitis” and US-wide air quality measurements during the period 1997-2006. Using the National Health Interview Survey and pollutant level data from the US Environmental Protection Agency, a direct relationship was found between the prevalence of both hay fever and sinusitis and pollutant levels of carbon monoxide, nitrous dioxide, sulfur dioxide, and particulate matter. In contrast, the control condition kidney failure/weakening showed only a very weak relationship with these parameters. This study did not examine regional differences in hay fever, sinusitis, and pollutant levels, such as rural versus urban areas. Heinrich et al14Heinrich J. Hoelscher B. Frye C. Meyer I. Wjst M. Wichmann H.E. Trends in prevalence of atopic diseases and allergic sensitization in children in Eastern Germany.Eur Respir J. 2002; 19: 1040-1046Crossref PubMed Scopus (113) Google Scholar examined the relationship between decreasing ambient total suspended particles and sulfur dioxide levels in 3 study areas of East Germany after German reunification in 1990 and the prevalence of bronchitis, sinusitis, and colds in 7632 children aged 5 to 14 years of age. Data were collected in 3 phases: 1992-1993, 1995-1996, and 1998-1999. An association was found between total suspended particles and sulfur dioxide levels and for bronchitis (adjusted odds ratio [OR], 3.0; 95% CI, 1.7-5.3), sinusitis (adjusted OR. 2.6; 95% CI, 1.0-6.6), and frequent colds (adjusted OR, 1.9; 95% CI, 1.2-3.1). No relation was found between these conditions and nucleation-mode particles (10-30 nm), which increased after reunification (see www.newmediastudio.org/DataDiscovery/Aero_Ed_Center/Charact/A.what_are_aerosols.html for explanation of nucleation mode particles). Irritants in air pollution, including sulfur dioxide,15Kienast K. Riechelmann H. Knorst M. Haffner B. Muller-Quernheim J. Schellenberg J. et al.Combined exposures of human ciliated cells to different concentrations of sulfur dioxide and nitrogen dioxide.Eur J Med Res. 1996; 1: 533-536Google Scholar, 16Spektor D.M. Yen B.M. Lippmann M. Effect of concentration and cumulative exposure of inhaled sulfuric acid on tracheobronchial particle clearance in healthy humans.Environ Health Perspect. 1989; 79: 167-172Crossref Scopus (44) Google Scholar ozone,17Christian D.L. Chen L.L. Scannell C.H. Ferrando R.E. Welch B.S. Balmes J.R. Ozone-induced inflammation is attenuated with multiday exposure.Am J Respir Crit Care Med. 1998; 158: 532-537Crossref Scopus (61) Google Scholar and formaldehyde (indoor pollutant),18Schafer D. Brommer C. Riechelmann H. Mann J.W. In vivo and in vitro effect of ozone and formaldehyde on human nasal mucociliary transport system.Rhinology. 1999; 37: 56-60Google Scholar but not diesel exhaust particles,19Wolff R.K. Effects of airborne pollutants on mucociliary clearance.Environ Health Perspect. 1986; 66: 223-237Crossref Scopus (51) Google Scholar have been reported to adversely affect mucociliary clearance. Although some studies of health effects associated with self-reported exposure to indoor dampness or mold have found an increase in sinusitis,20Koskinen O.M. Husman T.M. Meklin T.M. Nevalainen A.I. The relationship between moisture or mould observations in houses and the state of health of their occupants.Eur Respir J. 1999; 14: 1363-1367Crossref PubMed Scopus (106) Google Scholar an Institute of Medicine report (Damp Indoor Spaces and Health, www.nap.edu/catalog/11011.html) concluded that there is little evidence associating sinusitis with either indoor dampness or moldy indoor spaces. Active cigarette smoking is associated with a decrease in mucociliary clearance measured based on saccharine transit time21Karaman M. Tek A. Deleterious effect of smoking and nasal septal deviation on mucociliary clearance and improvement after septoplasty.Am J Rhinol Allergy. 2009; 23: 2-7Crossref PubMed Scopus (24) Google Scholar and has been shown to have a negative effect on mucosal recovery after endoscopic sinus surgery in adults and children.22Sopori M. Effects of cigarette smoke on the immune system.Nat Rev Immunol. 2002; 2: 372-377Crossref PubMed Scopus (729) Google Scholar, 23Ramadan H.H. Hinerman R.A. Smoke exposure and outcome of endoscopic sinus surgery in children.Otolaryngol Head Neck Surg. 2002; 127: 546-548Crossref Scopus (30) Google Scholar, 24Sobol S.E. Wright E.D. Frenkiel S. One-year outcome analysis of functional endoscopic sinus surgery for chronic sinusitis.J Otolaryngol. 1998; 27: 252-257Google Scholar, 25Briggs R.D. Wright S.T. Cordes S. Calhoun K.H. Smoking in chronic rhinosinusitis: a predictor of poor long-term outcome after endoscopic sinus surgery.Laryngoscope. 2004; 114: 126-128Crossref PubMed Scopus (74) Google Scholar In a study using the Third National Health and Nutrition Examination Survey (1988-1994) of 33,994 persons, Lieu and Feinstein26Lieu J.E. Feinstein A.R. Confirmations and surprises in the association of tobacco use with sinusitis.Arch Otolaryngol Head Neck Surg. 2000; 126: 940-946Crossref PubMed Scopus (82) Google Scholar examined the relationship between chronic sinusitis, active cigarette smoking, and secondhand smoke (SHS) exposure. Active cigarette smoking was associated with an increased risk of sinus disease (relative risk, 1.22; 95% CI, 1.05-1.39); however, no increased risk was found in association with SHS exposure. A concern about this study is the fact that serum cotinine levels of less than 28.4 nmol/mL (<5 ng/mL) were regarded as indicative of nonsmokers without SHS exposure, and the prevalence of chronic sinusitis in this population served as the reference point for comparison with subjects with higher levels of SHS exposure. However, the mean serum cotinine level of nonsmokers at the time of the Third National Health and Nutrition Examination Survey study was only 0.20 ng/mL, and this level has been steadily decreasing to a level of 0.05 in 2001-2002 (www.cdc.gov/mmwr/preview/mmwrhtml/mm5541a7.htm), indicating that a significant degree of SHS exposure was present in the “unexposed” subjects in this study. With the high background SHS exposure of healthy unexposed adults in this study, it is possible that an effect of SHS on chronic sinusitis was missed. Tammemagi et al27Tammemagi C.M. Davis R.M. Benninger M.S. Holm A.L. Krajenta R. Secondhand smoke as a potential cause of chronic rhinosinusitis: a case-control study.Arch Otolaryngol Head Neck Surg. 2010; 136: 327-334Crossref PubMed Scopus (30) Google Scholar performed a matched case-controlled study to assess the association of SHS and CRS. In this study a questionnaire was used to quantify SHS exposure in the home, workplace, public places, and private social functions outside the home in 306 nonsmoking patients with CRS and 306 age-matched, sex-matched, and race/ethnicity-matched nonsmoking control subjects over a 5-year period before the diagnosis of CRS. Using conditional logistic regression ORs, the authors reported higher levels of exposure to SHS in patients with CRS than control subjects in the home (9.1% vs 13.4%), work (6.9% vs 18.6%), public places (84.3% vs 90.2%), and private social functions (27.8% vs 51.3%). This study has potential for confounding because of recall bias and ascertainment bias on the part of CRS-affected patients. Reh et al28Reh D.D. Lin S.Y. Clipp S.L. Irani L. Alberg A.J. Navas-Acien A. Secondhand tobacco smoke exposure and chronic rhinosinusitis: a population-based case-control study.Am J Rhinol Allergy. 2009; 23: 562-567Crossref Scopus (40) Google Scholar performed a case-controlled study of 100 adult patients with CRS and 100 control subjects matched for age, sex, and smoking status by using a validated questionnaire to quantify both current and past SHS exposure. Using an OR computed based on comparison with those who reported no SHS exposure, they reported that current or childhood SHS exposure was associated with a higher risk of CRS (OR, 2.33; 95% CI, 1.02-5.34; P = .05). Although the method used for computing ORs in this study can be criticized, the authors also found that patients with CRS exposed to SHS had higher symptom scores for nasal obstruction/blockage, nasal discharge, headaches, and cough. SHS exposure was not quantified in this study. The prevalence of IgE-mediated allergy to environmental allergens in patients with CRS (both with and without NP) is estimated at 60% compared with 30% to 40% for the general population.29Berrettini S. Carabelli A. Sellari-Franceschini S. Bruschini L. Abruzzese A. Quartieri F. et al.Perennial allergic rhinitis and chronic sinusitis: correlation with rhinologic risk factors.Allergy. 1999; 54: 242-248Crossref PubMed Scopus (106) Google Scholar Patients with CRS are typically sensitized to perennial rather than seasonal (ie, pollen) allergens.30Asero R. Bottazzi G. Nasal polyposis: a study of its association with airborne allergen hypersensitivity.Ann Allergy Asthma Immunol. 2001; 86: 283-285Abstract Full Text PDF Scopus (42) Google Scholar Important perennial allergens include house dust mites, fungal spores from indoor and/or outdoor sources, animal danders, cockroaches, and sometimes feathers. Perennial allergens are generally present at higher levels for longer periods of time compared with pollen allergens. Fungal spores can germinate in sinus mucus, thereby increasing the allergenic stimulus. Histopathologic studies of ethmoidal tissue and nasal polyp tissue have demonstrated that allergic patients with CRS have chronic allergic inflammation, with local T-cell infiltration and production of classic TH2 cytokines, including IL-4, IL-5, and IL-13.31al Ghamdi K. Ghaffar O. Small P. Frenkiel S. Hamid Q. IL-4 and IL-13 expression in chronic sinusitis: relationship with cellular infiltrate and effect of topical corticosteroid treatment.J Otolaryngol. 1997; 26: 160-166PubMed Google Scholar, 32Hamilos D.L. Leung D.Y. Wood R. Cunningham L. Bean D.K. Yasruel Z. et al.Evidence for distinct cytokine expression in allergic versus nonallergic chronic sinusitis.J Allergy Clin Immunol. 1995; 96: 537-544Abstract Full Text Full Text PDF PubMed Scopus (309) Google Scholar These cytokines promote local IgE production and eosinophil infiltration and prolong the survival of eosinophils in the tissues, leading to sustained allergic inflammation. Despite these associations, the intensity of eosinophilic inflammation in patients with CRS without nasal polyposis (CRSsNP) and those with CRSwNP is independent of the presence of underlying systemic allergy.33Demoly P. Crampette L. Mondain M. Campbell A.M. Lequeux N. Enander I. et al.Assessment of inflammation in noninfectious chronic maxillary sinusitis.J Allergy Clin Immunol. 1994; 94: 95-108Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 34Hamilos D.L. Leung D.Y. Huston D.P. Kamil A. Wood R. Hamid Q. G.M.-C.S.F. IL-5 and RANTES immunoreactivity and mRNA expression in chronic hyperplastic sinusitis with nasal polyposis (NP).Clin Exp Allergy. 1998; 28: 1145-1152Crossref PubMed Scopus (160) Google Scholar, 35Hamilos D.L. Leung D.Y. Wood R. Meyers A. Stephens J.K. Barkans J. et al.Chronic hyperplastic sinusitis: association of tissue eosinophilia with mRNA expression of granulocyte-macrophage colony-stimulating factor and interleukin-3.J Allergy Clin Immunol. 1993; 92: 39-48Abstract Full Text PDF PubMed Scopus (162) Google Scholar Similarly, Robinson et al36Robinson S. Douglas R. Wormald P.J. The relationship between atopy and chronic rhinosinusitis.Am J Rhinol. 2006; 20: 625-628Crossref PubMed Scopus (66) Google Scholar found no relationship between the presence of atopy (defined as a positive in vitro IgE CAP RAST test result) and sinusitis disease severity or the rate of revision sinus surgery in a population of 193 patients with CRS. Allergic fungal rhinosinusitis (AFRS) is distinct among the CRS subtypes in having a significant geographic distribution of disease. Ferguson et al37Ferguson B.J. Barnes L. Bernstein J.M. Brown D. Clark 3rd, C.E. Cook P.R. et al.Geographic variation in allergic fungal rhinosinusitis.Otolaryngol Clin North Am. 2000; 33: 441-449Abstract Full Text PDF PubMed Scopus (119) Google Scholar surveyed 20 otolaryngologic practices in the United States and confirmed that areas such as Memphis, Tennessee, and other southern locations reported prevalences of AFRS relative to endoscopic sinus procedures of 10% to 23%, whereas other northern locations reported frequencies ranging from 0% to 4%. In one of the areas of high AFRS prevalence (South Carolina), Wise et al38Wise S.K. Ghegan M.D. Gorham E. Schlosser R.J. Socioeconomic factors in the diagnosis of allergic fungal rhinosinusitis.Otolaryngol Head Neck Surg. 2008; 138: 38-42Crossref Scopus (42) Google Scholar performed a retrospective review to examine socioeconomic and demographic factors that might differentiate AFRS from other forms of CRS, including CRSsNP and CRSwNP. They found that patients with AFRS were younger, more likely to be African American, more likely to be uninsured or Medicaid patients, and more likely to live in areas of high poverty or lower median income in comparison with patients with either CRSsNP or CRSwNP. The reason for these differences is not obvious. In contrast, the same authors did not find the same socioeconomic factor associations with bone erosion in patients with AFRS.39Ghegan M.D. Wise S.K. Gorham E. Schlosser R.J. Socioeconomic factors in allergic fungal rhinosinusitis with bone erosion.Am J Rhinol. 2007; 21: 560-563Crossref PubMed Scopus (20) Google Scholar Data on genetic associations with CRS are still sparse. However, Wang et al40Wang X. Kim J. McWilliams R. Cutting G.R. Increased prevalence of chronic rhinosinusitis in carriers of a cystic fibrosis mutation.Arch Otolaryngol Head Neck Surg. 2005; 131: 237-240Crossref PubMed Scopus (90) Google Scholar found that the prevalence of CRS in an unselected group of obligate cystic fibrosis (CF) carriers was 36%, clearly much higher than the prevalence of chronic sinusitis (approximately 12.5% in the United States). Furthermore, the prevalence of CF carrier status in an unselected group of patients with CRS was found to be 7% or statistically higher than the 2% CF carrier status in the control population.41Wang X. Moylan B. Leopold D.A. Kim J. Rubenstein R.C. Togias A. et al.Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population.JAMA. 2000; 284: 1814-1819Crossref PubMed Scopus (201) Google Scholar CF is a well-recognized cause of NP in children. Primary ciliary dyskinesia is a rare recognized cause of CRS. It has been shown to be a risk factor for CRSsNP but not CRSwNP,42Rollin M. Seymour K. Hariri M. Harcourt J. Rhinosinusitis, symptomatology and absence of polyposis in children with primary ciliary dyskinesia.Rhinology. 2009; 47: 75-78Google Scholar which distinguishes primary ciliary dyskinesia from CF. Humoral or innate immune deficiency should be considered as an underlying factor in patients with CRS with a pattern of recurrent purulent infection. In a pediatric population Shapiro et al43Shapiro G.G. Virant F.S. Furukawa C.T. Pierson W.E. Bierman C.W. Immunologic defects in patients with refractory sinusitis.Pediatrics. 1991; 87: 311-316PubMed Google Scholar found that 34 of 61 children with refractory sinusitis had abnormal results on immune studies, with decreased IgG3 levels and poor response to pneumococcal antigen being the most common abnormalities found. In adult patients with CRS, a much lower prevalence of decreased humoral immunity has been found. Vanlerberghe et al44Vanlerberghe L. Joniau S. Jorissen M. The prevalence of humoral immunodeficiency in refractory rhinosinusitis: a retrospective analysis.B-ENT. 2006; 2: 161-166Google Scholar found that IgG2, IgG3, or a combined defect of major and/or minor IgG subclasses occurred in 22.8% of patients with refractory CRS. Hamilos45Hamilos D.L. Chronic rhinosinusitis patterns of illness.Clin Allergy Immunol. 2007; 20: 1-13Google Scholar found a prevalence of any type of low immunoglobulin or poor response to vaccination of 12.7% in patients with CRSsNP and only 2.2% of patients with CRSwNP. Innate immune deficiency is difficult to diagnose because of limited testing capabilities. Mannose-binding lectin deficiency is one of the most prevalent innate immune deficiencies, but there is little evidence for an increased prevalence of mannose-binding lectin deficiency in children or adults with CRS.46Dahl M. Tybjaerg-Hansen A. Schnohr P. Nordestgaard B.G. A population-based study of morbidity and mortality in mannose-binding lectin deficiency.J Exp Med. 2004; 199: 1391-1399Crossref Scopus (125) Google Scholar Gastroesophageal reflux, specifically laryngopharyngeal reflux (LPR), has been proposed as a contributive factor to CRS. The mechanism for this is believed to be due to direct effects of refluxate on nasal/sinus mucosa, although no consistent effect of LPR on nasal mucociliary clearance has been demonstrated.47Durmus R. Naiboglu B. Tek A. Sezikli M. Cetinkaya Z.A. Toros S.Z. et al.Does reflux have an effect on nasal mucociliary transport?.Acta Otolaryngol. 2010; 130: 1053-1057Crossref Scopus (8) Google Scholar One study found that patients with LPR had higher scores on the Sinonasal Outcome Test (SNOT-20), even in the absence of a diagnosis of CRS,48Katle E.J. Hart H. Kjaergaard T. Kvaloy J.T. Steinsvag S.K. Nose- and sinus-related quality o
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