Objective: Evidences which illustrate symptoms of chronic rhinosinusitis (CRS) had negative effects on society and individuals are growing these days. The aims of this study are to assess the quality of life (QoL) of individuals with CRS and to analyze the relationship between socio-demographic as well as clinical factors and the quality of life of patients.
Methods: A cross-sectional and prevalence-based study was conducted from May to July, 2018. We used The Sinonasal Outcome Test-22 (SNOT-22) questionnaire to evaluate the quality of life of patients with chronic rhinosinusitis. In addition, the univariate logistic regression analysis and logistic regression models were used to calculate the Crude odds ratio (OR), adjusted odds ratio (aOR), and 95% confidence intervals (CIs) for factors. Statistical significance was considered as P-value <0.05.
Results: Among 315 participants, about two fifths of them were diagnosed with CRS. The statistical test illustrated that all factors illustrated significant differences. The main exposure variable, CRS, was significantly associated with poor quality of life, with a 78.02-fold increase in the odds of having a good quality of life score.
Conclusion: Our findings have shown that patients with CRS experience a poorer quality of life than healthy controls. The influencing factors included gender, economic status, exercise and nasal discharge.
Keywords: Chronic Rhinosinusitis, Non-Surgical, Quality of Life, Vietnam. (JPMA 69: S-20 (Suppl. 2); 2019)
There is a rise of evidence which illustrates the effect of chronic rhinosinusitis (CRS) with regards to symptom severity, reduced productivity and absenteeism to work.1,2 CRS was defined as a disorder with at least two of following symptoms such as anterior or posterior nasal discharge, nasal congestion, facial pressure/pain, andreduced sense of smell more than three months. 3 According to endoscopic findings, CRS is divided into two subtypes comprising CRS with nasal polyps (CRSwNPs) and CRS without nasal polyps (CRSsNPs). Their differences were in prevalence and severity, immune response, inflammation, and response to treatment. 3,4 When compared with CRSsNP, patients with CRSwNP may have reduced facial pain and/or pressure and sense of smell. 5,6 Major factors which can affect CRS included nasal congestion, nasal discharge or purulence or discoloured postnasal discharge, hyposmia or anosmia, purulence in the nasal cavity, facial pain/pressure, and fever. 7 The prevalence of chronic rhinosinusitis from epidemiological studies in literature reported in many parts of the world. CRS affects up to 15% of the U.S. population while at least 5% of Canadians suffer from this chronic inflammatory disease. 8-11 A current report of a pilot study in South America showed the prevalence of 16.55% for rhinosinusitis. 12 The European multi-center study found a CRS prevalence of approximately 10.9% in 2011. 13 The prevalence of this disease in the Korean population and Chinese population were about 7% and 8% in 2015 respectively. 14,15 In a previous study, the prevalence of CRSsNP was 2.7% in normal population. The CRSsNP was more frequently seen in patients than in the healthy controls. 16 Health-related quality of life (HRQoL) was assessed to observed the difference between expectations and experience and was determined that it could be changed by treatment. 17 Besides of diagnosis and symptoms, medical research focuses on the evaluation of a patient's QoL or more specifically, HRQoL over the past two decades. 18Informative assessment of QoL for CRS patients illustrates its importance to medical, social and economic fields. The presence of nasal polyps (NP) is positively associated with CRS and considered as a subgroup of CRS. 3 The symptoms of CRS comprise nasal congestion, facial pressure/pain, headache, hyposmia, and anosmia which can be worsened and affect HRQoL considerably. 2 A previous study has shown that CRS may cause decrease in work productivity like other chronic diseases, such as asthma, heart disease and diabetes. 19 The Sinonasal Outcome Test-22 (SNOT-22) has proved to be the highest quality validated patient-reported outcome measure (PROM) among 15 PROMs validated for the evaluation of QoL in CRS adult patients. It was first developed in 1998 with 16 items, later modified to 20 items, and finally to 22 items by adding Two special rhinological symptoms which were nasal congestion and loss of sense of taste and smell. 20The questionnaire, which had proven its high reliability and validity, was strongly correlated with the general QoL as the 36-Item Short Form Survey. 21 Chronic rhinosinusitis reduces the QoL of patients. 22 An important relationship between SNOT-22 scores and anxiety and depression scores in CRS patients was conducted. 23 The prevalence of comorbidities in CRS population ranged from approximately 5% to over 40%.24 Moreover, QoL is a very important aspect of assessing the clinical effects and the healthcare service for CRS patients. 25 In Vietnam, few studies have been conducted regarding CRS. Furthermore, doctors have used different standards for evaluating the degree of symptoms as well as the effectiveness of treatment. Therefore, there is a growing need for a simple, reliable and standardized disease measure to evaluate CRS, taking the patients QoL into account. The main aim of this study focused on the quality of life of individuals with CRS, in terms of the SNOT-22 questionnaire, and to analyze the relationship of social demographic and clinical factors influencing patients with poor QoL.
Patients and Methods
This study was a cross-sectional and prevalence-based study conducted from May to July, 2018, at Ear, Nose, Throat Hospital (ENT Hospital), Ho Chi Minh City (HCMC), Vietnam. ENT Hospital in HCMC is a first-class hospital under the Ho Chi Minh City Department of Health, with a total of 150 inpatient beds. 26We asked patients who were diagnosed with CRS signs and symptoms according to the International Classification of Diseases Code-10 (ICD10) (J32- Chronic sinusitis) to participate in our study. 27 Eligible patients were 18 years or above, had CRS and communicate well in the Vietnamese, were willing to participate and were able to provide written consent. Excluded from the study were pregnant women, people who did not finish the full survey, or if they did not want to fill out the survey form. The control group consisted of healthy people without sinonasal disease. People who recruited in this group were aged above 18 years, not pregnant and no sinonasal disease defined by negative responses on the following questions about getting nasal diseases or taking medications. People who declined to participate were excluded from the study. In order to obtain the exact information from participants, the questionnaire was practically administered through face-to-face interviews by the research assistants. All members of the data collection team were recruited and trained prior to the study, and wereunaware of the correct answers to the survey questions. The study subjects who met the inclusion criteria and were not eliminated by the exclusion criteria stated above were enrolled at the universities, parks, commercial centers, and elsewhere. Before starting the study, participants were given and explained the study aims, risks, and benefits of joining this study. Once approved, the interviewers collected information through a structured interview with the subjects assisted by a validated questionnaire. The completeness, consistency, and accuracy of the data collection were examined by researchers daily. In addition, participants were also self-administered via an internet form. This form's content was similar to the paper form that was used in the face-to-face interviews. A link was shared on social network websites and closed at the same time as the face-to-face interviews ended. The study was based on classification questions and excluded those who were not eligible to participated. All eligible patients from May to July 2018 were interviewed. The number of control group was approximately the same as the number of CRS group. The Psychometric tool used was the SNOT-22 (a disease specific questionnaire) which has been internationally validated and includes both disease specific and general domains.20 Each item is scored by using Likert scale (range between 0 and 5) where higher scores depict worse health problems, from 0 = no problem to 5 = problem as bad as it can be. The higher total scores of the SNOT-22 correspond the worse symptom severity and/or daily activities.28 The questionnaire was translated from English to Vietnamese, and two native Vietnamese pulmonologists fluent in English translated the Vietnamese versions into English independently, and merged the translated questionnaires. Finally, a professional native English translator reviewed the original and the reverse translated English versions of the questionnaires. During a panel meeting, the authors had a discussion on ambiguous terms and evolved the final Vietnamese version of the questionnaire. Pretest of the questionnaire was carried out in 30 CRS patients to affirm that all participants easily understood the questions. The responses of these 30 patients were not collected into final data analysis. Data were collected using a semi-structured questionnaire that included two sections. The first part obtained general information on patients, including age, gender, region, educational level, monthly income, smoking status and exercise. The second part was a QoL assessment using the SNOT-22 tool translated into Vietnamese from the original English version. The average time for completing the questionnaire was approximately 12 minutes. Research nurses assessed CRS patients whether they were eligible or not and invited them to participate in the study. After explaining the study objectives patients were asked to fill in the questionnaire by themselves before receiving drugs from the hospital drugstore. They could ask for help from researcher assistants if they did not understand clearly any question. Data was analysed by SPSS for Windows, version 22.0(SPSS Inc., Chicago, USA). For the demographical and clinical characteristics of study participants, descriptive analysis was undertaken with the number and percentage for categorical variables while a Chi-square test was calculated to make comparisons. Each domain and total scores were calculated for a single participant. The total score of the SNOT-22 of below or equal 7 was considered as good QoL and a score of above 7 as bad QoL. 29 The percentage of patients with good QoL in each category of CRS was measured. To make comparisons between patients with good QoL scores in the CRS and non-CRS due to each category, the Chi-square test was used, while independent samples t-test was used to compare the difference between the mean SNOT-22 scores and each domain score of individuals with and without CRS. To determine the factors associated with poor quality of life, univariate logistic regression analysis and logistic regression models were conducted to measure the crude odds ratio and adjusted odds ratio (aOR) as well as 95% confidence intervals (CIs) for factors. Statistical significance was considered as P <0.05. Ethical approval was given by ENT Hospital HCMC. Participants were informed of their right to give up the survey at any time without any adverse effect on their access to healthcare. Written informed consent was obtained from all participants before the questionnaire survey. The data collection was only used for research purposes.
Of the 315 participants, about two fifths of them were diagnosed with CRS. Most of the participants lived in urban areas. More than half of them were female and had monthly income above $250. One-fourth were current smokers and had received 12 years of education. Nearly half of them were in the 36-59 age group and exercised three times a week. There was no important difference related to the distribution of age and exercise. The two groups of patients differed in distribution in many demographical characteristics, such as gender, education, monthly income and smoking criteria. Participants without CRS had a trend to have higher income compared to those with CRS (Table-1).
In clinical characteristics, the two groups of patients illustrated only one similar pattern: most of them had not had nasal surgery. Only 4 CRS patients reported on SNOT- 22 that they had good quality of life compared with 139 of non-CRS. There were 115 (93.5%) patients diagnosed with CRS having more than one symptom while 125 (65.1%) non-CRS patients had no symptoms. The statistical test showed that all factors illustrated significant differences between the two groups (Table-2).
Univariate logistic regression and logistic regression models were applied to explore which factor related poor QoL due to CRS. Only monthly income did not affect quality of life. Women were more likely to have poor QoL than men. Patients with below $250 monthly income showed a trend of having a 1.51-fold increase in the odds of poor QoL when compared to those that had monthly income above $250. Other variables related to increased poor QoL were region, nasal discharge, andexercise. The main variable, CRS, was highly associated with poor QoL, with a 78.02-fold increase in the odds, compared to a good quality of life score. After adjustment for confounders, there was a significant risk of poor QoL for patients with CRS (46.36-fold increase in the odds) compared to those without CRS. The risk of poor QoL increased significantly with gender and smoking status. Participants who were currently nonsmokers had 0.13-fold increase in the adjusted odds of poor QoL in comparison with smokers or ex-smokers (Table-3).
Overall, the SNOT-22 and each domain scores of patients with CRS were higher than those without CRS, indicating the poorer QoL among these patients. The mean SNOT-22 score of CRS patients was 42.9 } 18.2 while that of patients without CRS was 6.2 } 3.1. The domains of nasal symptoms gaining the highest mean scores were (14.1 } 6.1) among CRS patients, while the highest among those without CRS was psychological symptoms (3.1 } 1.7). The domain gaining the lowest mean scores for patients with CRS was extra nasal symptoms (7.8 } 3.4), whereas ear/face symptoms were lowest among the domains in the non-CRS group. The p values calculated from statistic tests were all significant (p<0.01)(Table-4).
The results illustrate a significant difference in the QoL between patients with CRS and the healthy people without this disease, which illustrate the important impact of CRS on the QoL of these patients. These results also explored the relationship between health-related QoL and related factors by collecting information on QoL from CRS and control populations. It may lead to a conclusion that CRS patients had similar and substantially impaired QoL compared to the control population. The SNOT-22 scores can show a clear difference between the patients with sinus diseases and those without one. 30 This study used the SNOT-22 questionnaire to access the differences between two groups by comparing the mean SNOT-22 scores of 123 CRS patients and those of 192 non- CRS subjects. The results showed that there was a statistically significant difference between CRS patients (42.9 } 18.2) with those of normal ones (6.2 } 3.1) (p<0.001, Table-4). Gillett et al.29 defined the "normal" SNOT-22 score by the median score of 7 in a group of 116 healthy participants. In this study, the median score of CRS patients was 42.9, and the figure for the control group as 6.2, slightly below the value in the study of Gillett et al. 29 This bias might depend on the geographical area of study and the criteria of the control group. Generally, individuals with CRS experience poorer QoL compared to healthy ones. 31-33 The results from this study also illustrate the same that HRQoL of patients with CRS is poorer, than that of the normal group. The nasal domain dominated the mean score among CRS patients, followed by psychological symptoms. Browne et al. found the highest mean score in CRS patients to be in the nasal symptom domain, followed by the mean psychological score, similar to our study and a study conducted in Uganda. 20,34Non-CRS group had highest scores in the psychological domain while another two domains, nasal symptoms and sleep symptoms, were also greatly affected. Mean scores and trends in the SNOT-22 domains for non-CRS individuals varied from study to study because the non-CRS groups were from diverse backgrounds. 20,34,35
Factors Related to CRS Patients
A strong relationship between smoking status and poor QoL in CRS patients was illustrated in the results of this study. The relationship between smoking status and the prevalence of sinusitis was also observed from a study conducted in Europe (OR:1.91; 95% CI: 1.77-1.05).13 This association could be also discovered in Canada for female (OR: 1.57; 95% CI: 1.24-1.99), whereas the risk is likely to increase in active smokers (OR: 1.67; 95% CI: 1.18-2.37) and in former smokers (OR: 1.20; 95% CI: 0.90-1.60). Although this negative effect could not be found in Brazil and in male in Canada (adjusted OR: 1.24; 95% CI: 0.9- 1.7%), the majority of the investigations showed that the smoking behaviour is a risk factor of CRS. 12,36However, the relationship between smoking status and endoscopic sinus surgery (ESS) patients have been less measurable. 37 In a previous study, continuing to smoke after ESS did not influence the QoL indexes; however, higher smoking volume may be associated with worsening postoperative endoscopic scores at more than six months follow-up. 38 Another study with 2 to 9-year period indicated that smoking did not influence the preoperative symptoms, but could lead to a higher rate of revision surgery (20% smokers vs 7% non-smokers). 39 In a post-surgical study of accessing QoL, there was less improvement in smokers after ESS in a dose-dependent manner. 40 The findings of these studies suggest that smoking behaviour could have a negative effect on patients after ESS. Possible mechanisms affecting QoL may potentially derive from the microbial alteration and tobacco-mediated stimulation of sinonasal microbial biofilms. 41,42 Smoking can be an immunosuppressive factor by changing toll-like receptors and inhibiting IL-8 and human B-defensin, which promote clearance of gram-negative and gram positive bacteria. 43 The results from this study also illustrate that there is a more significant risk of poor quality of life for female patients with CRS as compared to male patients. A study conducted in the UK reported that women had higher scores than men in two types of CRS. Nasal domain was the most significant factor affecting male and female patients while that for female patients was this domain, which followed by the emotional domain in both genders. 44 Other studies from North America and England also illustrated that men increased positively with the prevalence of CRSwNP, whereas women have higher rates of CRS without NP. 45-47 Similarly, another study conducted in a 10-year period cohort of primary care patients found that men accounted for up to 54% of patients with CRSwNP. 48 In contrast, other studies conducted in Europe, Korea, and Taiwan showed there was no difference in the prevalence of CRS by gender. 13,15,49,50 Clinical characteristics as symptoms of chronic sinusitis may illustrate high risk of poor QoL. From the multivariate analysis result, poor HRQoL was found to be significantly associated with demographical factors such as gender and smoking status. CRS patients had 46 times poorer QoL compared to those without the disease. The results agree with the outcome of other studies using SNOT-22 among CRS patients.31-34
Some limitations of the present study must be considered. First, by including ICD-10 code J32, there could be a possibility that several cases with otherwise unspecified rhinosinusitis were also included but may not be considered as the true nature of CRS. This could mean that the impact of CRS among patients might differ greatly. Second, because the SNOT-22 questionnaire was not validated in Vietnam, a professional translator was used, meaning that language may have a minimal effect on the results obtained in the Quality of life assessment. Third, due to lack of treatment information, the analysis could not calculate other potential covariates and confounders, such as body mass index, years of taking CRS medications and other possible risk factors for CRS as well as comorbidities. The relationship between CRS patients and healthy individuals should be analysed deeper in future studies. There is a rising need to further clarify the concept of factors that affect QoL of people suffering from CRS.
Our study has shown that those with CRS experience poorer quality of life than healthy controls. Additionally, some demographic factors such as gender, monthly income, exercise and nasal discharge were strictly associated with poor QoL of patients. Based on the quality of life assessment outcome proper treatment strategies should be built up in low-to-middle income countries like Vietnam.
Acknowledgment: The authors would like to acknowledge supports by the Director of ENT Hospital HCMC for study recruitment and data collection.
Disclaimer: None to declare.
Conflict of Interest: None to declare.
Funding Disclosure: None to declare.
1. Anand VK.Epidemiology and economic impact of rhinosinusitis. Ann Otol Rhinol Laryngol Suppl 2004; 193:3-5.
2. Rudmik L, Smith TL. Quality of life in patients with chronic rhinosinusitis. Curr Allergy Asthma Rep 2011; 11:247-52.
3. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology 2012; 50:1-12.
4. Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM, et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 2013;131:1479-90.
5. Bhattacharyya N. Assessing the additional disease burden of polyps in chronic rhinosinusitis. Ann OtolRhinolLaryngol 2009;118:185-9.
6. Eweiss AZ, Lund VJ, Barlow J, Rose G. Do patients with chronic rhinosinusitis with nasal polyps suffer with facial pain? Rhinology 2013;51:231-5.
7. Brook I. What are the diagnostic criteria for chronic rhinosinusitis (CRS)? [Online] 2018 [Cited 2018 August 23]. Available from URL: https://www.medscape.com/answers/232791-42201/2051401-overview
8. Bhattacharyya N. Contemporary assessment of the disease burden of sinusitis. Am J Rhinol Allergy 2009;23:392-5.
9. Bhattacharyya N. Incremental health care utilization and expenditures for chronic rhinosinusitis in the United States. Ann OtolRhinolLaryngol 2011;120:423-7
10. Luu K, Sutherland J, Crump T, Liu G, Janjua A. The impact of chronic airway disease on symptom severity and global suffering in Canadian rhinosinusitis patients. J Otolaryngol Head Neck Surg 2018;47:40.
11. Orlandi RR, Kingdom TT, Hwang PH, Smith TL, Alt JA, Baroody FM, et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol 2016;6(Suppl 1):S22-209.
12. Pilan RR, Pinna FR, Bezerra TF, Mori RL, Padua FG, Bento RF, et al. Prevalence of chronic rhinosinusitis in Sao Paulo. Rhinology 2012;50:129-38.
13. Hastan D1, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, et al. Chronic rhinosinusitis in Europe—an underestimated disease. A GA2LEN study. Allergy 2011;66:1216-23.
14. Shi JB, Fu QL, Zhang H, Cheng L, Wang YJ, Zhu DD, et al. Epidemiology of chronic rhinosinusitis: results from a crosssectional survey in seven Chinese cities. Allergy 2015;70:533-9.
15. Kim YS, Kim NH, Seong SY, Kim KR, Lee GB, Kim KS. Prevalence and risk factors of chronic rhinosinusitis in Korea. Am J Rhinol Allergy 2011;25:117-21.
16. Verim A, Cebeci F, Ba?er E, Calim OF, Kadio?lu D, Kocagoz GD. Prevalence of chronic rhinosinusitis in the setting of Behcet disease. J Craniofac Surg 2015;26:186-90.
17. Calman KC. Quality of life in cancer patients--an hypothesis. J Med Ethics 1984;10:124-7.
18. Metson RB, Gliklich RE. Clinical outcomes in patients with chronic sinusitis. Laryngoscope 2000;110:24-8.
19. Rudmik L, Smith TL, Schlosser RJ, Hwang PH, Mace JC, Soler ZM. Productivity costs in patients with refractory chronic rhinosinusitis. Laryngoscope 2014;124:2007-12.
20. Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol 2009;34:447-54.
21. Anderson ER, Murphy MP, Weymuller EA Jr. Clinimetric evaluation of the Sinonasal Outcome Test-16. Student Research Award 1998. Otolaryngol Head Neck Surg 1999;121:702-7.
22. Marambaia PP, Lima MG, Santos KP, Gomes Ade M, de Sousa MM, Marques ME. Evaluation of the quality of life of patients with chronic rhinosinusitis by means of the SNOT-22 questionnaire. Braz J Otorhinolaryngol 2013;79:54-8.
23. Nanayakkara JP, Igwe C, Roberts D, Hopkins C. The impact of mental health on chronic rhinosinusitis symptom scores. Eur Arch Otorhinolaryngol 2013;270:1361-4.
24. Hoehle LP, Phillips KM, Caradonna DS, Gray ST, Sedaghat AR. A contemporary analysis of clinical and demographic factors of chronic rhinosinusitis patients and their association with disease severity. Ir J Med Sci 2018;187:215-21.
25. Gliklich RE, Metson R. Effect of sinus surgery on quality of life. Otolaryngol Head Neck Surg 1997;117:12-7.
26. Ear Nose Throat Hospital (ENT Hospital). Ho Chi Minh city (HCMc). [Online] 2017 [Cited 2018 August 25]. Available from URL: http://taimuihongtphcm.vn/lich-su-phat-trien-benh-vien-taimui-hong/
27. World Health Organization. International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10)-WHO Version. [Online] 2016 [Cited 2018 August 31]. Available from URL: http://apps.who.int/classifications/icd10/browse/2016/en#/J30-J39
28. DeConde AS, Bodner TE, Mace JC, Smith TL. Response shift in quality of life after endoscopic sinus surgery for chronic rhinosinusitis. JAMA Otolaryngol Head Neck Surg 2014;140:712-9.
29. Gillett S, Hopkins C, Slack R, Browne JP. A pilot study of the SNOT 22 score in adults with no sinonasal disease. Clin Otolaryngol 2009;34:467-9.
30. Vaitkus S, Padervinskis E, Balsevicius T, Siupsinskiene N, Staikuniene J, Ryskiene S, et al. Translation, cross-cultural adaptation, and validation of the sino-nasal outcome test (SNOT)- 22 for Lithuanian patients. Eur Arch Otorhinolaryngol 2013;270:1843-8.
31. Kosugi EM, Chen VG, Fonseca VM, Cursino MM, Mendes Neto JA, Gregorio LC. Translation, cross-cultural adaptation and validation of SinoNasal Outcome Test (SNOT): 22 to Brazilian Portuguese. Braz J Otorhinolaryngol 2011;77:663-9.
32. Browne JP, Hopkins C, Slack R, Cano SJ. The Sino-Nasal Outcome Test (SNOT): can we make it more clinically meaningful? Otolaryngol Head Neck Surg 2007;136:736-41.
33. Lange B, Holst R, Thilsing T, Baelum J, Kjeldsen A. Quality of life and associated factors in persons with chronic
rhinosinusitis in the general population: a prospective questionnaire and clinical cross-sectional study. Clin Otolaryngol 2013;38:474-80.
34. Nyaiteera V, Nakku D, Nakasagga E, Llovet E, Kakande E, Nakalema G, et al. The burden of chronic rhinosinusitis and its effect on quality of life among patients re-attending an otolaryngology clinic in south western Uganda. BMC Ear Nose Throat Disord 2018;18:10.
35. Jalessi M, Farhadi M, Kamrava SK, Amintehran E, Asghari A, Rezaei Hemami M, et al. The reliability and validity of the persian version of sinonasal outcome test 22 (snot 22) questionnaires. Iran Red Crescent Med J 2013;15:404-8.
36. Chen Y, Dales R, Lin M. The epidemiology of chronic rhinosinusitis in Canadians. Laryngoscope 2003;113:1199-205.
37. Uhliarova B, Adamkov M, Svec M, Calkovska A. The effect of smoking on CT score, bacterial colonization and distribution of inflammatory cells in the upper airways of patients with chronic rhinosinusitis. InhalToxicol 2014;26:419-25.
38. Rudmik L, Mace JC, Smith TL. Smoking and endoscopic sinus surgery: does smoking volume contribute to clinical outcome. Int Forum Allergy Rhinol 2011;1:145-52.
39. Krzeski A, Galewicz A, Chmielewski R, Kisiel M. Influence of cigarette smoking on endoscopic sinus surgery long-term outcomes. Rhinology 2011;49:577-82.
40. Katotomichelakis M, Simopoulos E, Tripsianis G, Zhang N, Danielides G, Gouma P, et al. The effects of smoking on quality of life recovery after surgery for chronic rhinosinusitis. Rhinology 2014;52:341-7.
41. Goldstein-Daruech N, Cope EK, Zhao KQ, Vukovic K, Kofonow JM, Doghramji L, et al. Tobacco smoke mediated induction of sinonasal microbial biofilms. PLoS One 2011;6:e15700.
42. Ramakrishnan VR, Frank DN. Impact of cigarette smoking on the middle meatus microbiome in health and chronic rhinosinusitis.Int Forum Allergy Rhinol 2015;5:981-9.
43. Reh DD, Higgins TS, Smith TL. Impact of tobacco smoke on chronic rhinosinusitis: a review of the literature.Int Forum Allergy Rhinol 2012;2:362-9.
44. Erskine S, Hopkins C, Kumar N, Wilson J, Clark A, Robertson A, et al. A cross sectional analysis of a case-control study about quality of life in CRS in the UK; a comparison between CRS subtypes. Rhinology 2016;54:311-15.
45. Bernstein JM, Anon JB, Rontal M, Conroy J, Wang C, Sucheston L. Genetic polymorphisms in chronic hyperplastic sinusitis with nasal polyposis. Laryngoscope 2009;119:1258-64. 46. Busaba NY, Sin HJ, Salman SD. Impact of gender on clinical presentation of chronic rhinosinusitis with and without polyposis. J LaryngolOtol 2008;122:1180-4.
47. Drake-Lee AB, Lowe D, Swanston A, Grace A. Clinical profile and recurrence of nasal polyps. J LaryngolOtol 1984;98:783-93.
48. Tan BK, Chandra RK, Pollak J, Kato A, Conley DB, Peters AT, et al. Incidence and associated premorbid diagnoses of patients with chronic rhinosinusitis. J Allergy Clin Immunol 2013;131:1350-60.
49. Chung SD, Hung SH, Lin HC, Lin CC. Health care service utilization among patients with chronic rhinosinusitis: a population-based study. Laryngoscope 2014;124:1285-9.
50. Min YG, Jung HW, Kim HS, Park SK, Yoo KY. Prevalence and risk factors of chronic sinusitis in Korea: results of a nationwide survey. Eur Arch Otorhinolaryngol 1996;253:435-9.