Evaluation of the Prevalence of and Factors Associated With Laryngeal Diseases Among the General Population

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1 The Laryngoscope VC 2015 The American Laryngological, Rhinological and Otological Society, Inc. Evaluation of the Prevalence of and Factors Associated With Laryngeal Diseases Among the General Population J. Hun Hah, MD; Songyong Sim, PhD; Soo-Youn An, MD; Myung-Whun Sung, MD; Hyo Geun Choi, MD Objectives/Hypothesis: Despite the high prevalence of voice disorders, the prevalence of laryngeal disease in the general population has not been determined using laryngoscopy. Factors considered associated with laryngeal disease have mostly been assessed using patient data or highly specific populations. We evaluated the prevalence of and associated factors with laryngeal diseases in the general Korean population. Study Design: Cross-sectional study. Methods: We analyzed data from the Korea National Health and Nutrition Examination Survey for 19,039 participants assessed between 2008 and The prevalence, subjective discomforts rates of, and odd ratios (demographics, life-style factors, and diseases factors) for laryngeal disease were analyzed using simple and multiple logistic regression analyses, taking into account the complex sampling structure of the data. Results: The top five laryngeal diseases in prevalence were laryngitis (3,513/100,000), vocal nodules (1,487/100,000), vocal polyp (404/100,000), Reinke s edema (347/100,000), and epiglottic cyst (296/100,000). Prevalence of laryngeal disease was higher in males, whereas the rate of subjective voice complaints was higher in females. In the logistic regression analysis, gender was not associated with laryngeal diseases after adjusting for other factors. We observed a positive association between low body mass index (BMI) and vocal nodules, and between high BMI and laryngitis, smoking and epiglottic cyst/ hyperkeratosis/laryngeal cancer, higher education level and vocal nodules, and allergic rhinitis and vocal nodules/laryngitis/ epiglottic cyst. Conclusions: The rate of subjective voice complaints and laryngeal disease co-occurrence was low. This study provides more reliable information of laryngeal disease because it includes participants without subjective complaints. Key Words: Voice, larynx, vocal cords, prevalence, etiology, risk factors, epidemiology, bias. Level of Evidence: 2b. Laryngoscope, 125: , 2015 INTRODUCTION Voice problems are common among the general population; with a lifetime prevalence reported at 29.9%, 6.6% to 7.6% of the population are currently experiencing voice problems. 1 3 However, the majority of previous studies concerning voice problems in the general population have involved telephone interviews or questionnaires 1,2,4 rather than laryngoscope examination. Without laryngoscopy, the causes of voice problems, that is, particular laryngeal diseases, cannot be discerned. To Additional Supporting Information may be found in the online version of this article. From the Department of Otorhinolaryngology Head & Neck Surgery and Cancer Research Institute, Seoul National University, College of Medicine (J.H.H., M-W.S.), Seoul; the Department of Statistics, Hallym University (S.S.), Chuncheon; the Department of Otorhinolaryngology Head & Neck Surgery, Thyroid/Head & Neck Cancer Center of the Dongnam Institute of Radiological & Medical Sciences (DIRAMS) (S-Y.A.), Busan; and the Department of Otorhinolaryngology Head & Neck Surgery, Hallym University Sacred Heart Hospital (H.G.C.), Anyang, Korea Editor s Note: This Manuscript was accepted for publication May 15, This work was supported by a Research Grant funded by Hallym University Sacred Heart Hospital (HURF ). The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Hyo Geun Choi, MD, Department of Otorhinolaryngology Head & Neck Surgery, Hallym University Sacred Heart Hospital, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, , Republic of Korea. pupen@naver.com DOI: /lary date, no epidemiological study has assessed laryngeal disease among the general population using laryngoscopy; the prevalence of laryngeal disease has been investigated only for treatment-seeking populations or in the context of specific occupations such as teaching and nursing. 5 8 The majority of the risk factors for laryngeal disease have been identified using patient data. 9,10 To the best of our knowledge, the present study is the largest to evaluate laryngeal disease using laryngoscopy and the first to be conducted in the general population. Using laryngoscopy, we evaluate the laryngeal disease in those who have no subjective symptom. Furthermore, this nationwide study employed precise sample design techniques and adjusted for weighted values. We aimed to determine the precise prevalence of laryngeal disease and to identify potential risk factors among the general population. We also compared the prevalence of voice complaints between males and females separately for each type of laryngeal disease. MATERIALS AND METHODS Study Population and Data Collection This study was approved by the Institutional Review Board of the Korea Centers for Disease Control and Prevention. Written informed consent was obtained from all of the participants prior to survey commencement.

2 Fig. 1. Study flow chart. Data from the Korean National Health and Nutrition Examination Surveys (KNHANES) covering the period and collected by the Centers for Disease Control and Prevention of Korea were analyzed. Every year, 192 districts were selected by a panel; within each district, 20 households were identified to allow for sampling reflective of the entire Korean population. The surveys evaluated data from the civilian, noninstitutionalized South Korean population using stratified, multistage clustered sampling based on national census data. Sampling was weighted by statisticians, who applied poststratification and took account of nonresponses and outliers. Of a total of 31,217 participants, young children and adolescents (< 19 years of age, n 5 7,778) were considered missing cases because they did not take part in the survey. Participants who failed or declined to undergo laryngoscopy examination (n 5 3,803), and those who did not provide data pertaining to income status, education level, alcohol consumption, smoking, pulmonary tuberculosis, asthma, and allergic rhinitis history (n 5 597) were also excluded. Therefore, 19,039 participants (8,195 males and 10,844 females) were eligible for inclusion (Fig. 1). The participants who have the missing value (n 5 4,400) were calculated as the valid missing values. Survey participants ranged in age from 19 to 97 years. After applying the weighted values recommended by KNHANES, adjusted prevalence and odds ratios (AORs) were estimated from the data, representing a total of 30,471,019 subjects (15,101,064 males, 49.6% and 15,369,955 females, 50.4%). Laryngoscopy Examination and Survey Each participant was examined by trained otorhinolaryngology residents using a 4-mm, 708-angled rigid endoscope. Laryngeal images were recorded using a charge-coupled-device camera and reviewed by otorhinolaryngology specialists. Diseases were determined by endoscopic findings and not by pathology results. The following 12 types of laryngeal disease were assessed: vocal nodules, vocal polyp, vocal cyst, laryngitis, Reinke s edema (diffuse polyposis), vocal fold palsy, sulcus vocalis, epiglottic cyst, contact granuloma, laryngeal papilloma, hyperkeratosis, and laryngeal cancer. Each participant was asked if they experienced voice discomfort. Related factors, including age; sex; body mass index (BMI) (kg/m 2 ); monthly income; educational level; alcohol consumption; smoking status; and history of pulmonary tuberculosis, asthma, and allergic rhinitis were also evaluated. Using criteria for the Asia-Pacific region, 11 three BMI groups were devised: low BMI, < 18.5; normal BMI, ; and high BMI, 25. Using the methods recommended by the Organization for Economic Cooperation and Development 12 (i.e., dividing household income by the square root of the number of household members), monthly income was divided into lowest, low-middle, upper-middle, and highest quartiles. To explore the influence of educational level, uneducated participants and those who had graduated only from elementary or middle schools were assigned to the low education group; high school and junior college graduates comprised the middle group, and graduate school and college graduates formed the high group. Alcohol consumption was divided into the following three categories: < once a month; 1 4 times a month; > twice per week. Smoking status was divided into < 5 lifetime packs (100 cigarettes) smoked, and 5 lifetime packs smoked. Possible laryngeal disease comorbidities, including pulmonary tuberculosis, asthma, and allergic rhinitis, were documented using a questionnaire and in several, participant according to diagnostic history provided by a medical doctor. Due to the limited number of laryngeal diseases and skewness in the data, BMI, education level, and pulmonary tuberculosis and asthma history were not assessed for all types of laryngeal disease. Statistical Analysis The chi-square test, with Rao-Scott correction, was used to analyze adjusted prevalence rate differences for subjective voice complaints between males and females (Table I). Multiple logistic regression analysis using data from complex sampling was employed during analysis of the association between various 2537

3 TABLE I. Prevalence and Subjective Voice Complaints of Laryngeal Diseases. Disease Prevalence (per 100,000) Subjective Voice Complaints (%) M F Total* P Value M F Total P Value Laryngitis 4,424 2,618 3,513 < < Vocal nodules 1,406 1,567 1, Vocal polyp Reinke s edema Epiglottic cyst < Vocal fold palsy Sulcus vocalis Laryngeal papilloma Hyperkeratosis < Vocal cyst < Contact granuloma Laryngeal cancer *Laryngeal diseases are listed in order of adjusted total prevalence (high to low). Chi-square test with Rao-Scott correction to assess differences in the adjusted prevalence of subjective voice complaints rates between males and females. A value of P < 0.05 was taken to indicate significance. factors and each type of laryngeal disease. Independent variables were selected using backward elimination within multiple logistic regression analyses employing complex sampling; initial and final models are described in Supporting Tables SI-A, SI-B, and Table II-. Two-tailed analyses were conducted; a value of P < 0.05 was taken to indicate statistical significance. Adjusted prevalence and odds ratios with 95% confidence intervals (CIs) for each laryngeal disease were calculated. Independent variables were selected using backward elimination within multiple logistic regression analyses employing complex sampling; initial and final models are described in Supporting Tables SI-A and SI-B. All results are presented as weighted values, and all analyses were conducted using the SPSS for Windows software 21 package (IBM Corp., Armonk, NY). RESULTS Prevalence of Laryngeal Diseases and Subjective Voice Complaints Laryngitis represented the most common laryngeal disease (3,513/100,000), followed by vocal nodules (1,487/ 100,000), vocal polyp (404/100,000), and Reinke s edema (347/100,000). Prevalence of laryngeal disease was significantly higher in males versus females for several diseases (laryngitis, vocal polyp, Reinke s edema, epiglottic cyst, sulcus vocalis, hyperkeratosis, and laryngeal cancer). All remaining laryngeal diseases, aside from vocal nodules, were more prevalent in males, but not significantly (Table I). Less than 35% of participants complained of subjective voice discomfort for every type of laryngeal disease. Participants with Reinke s edema complained of voice discomfort most frequently (33.2%), whereas no participant with laryngeal papilloma complained of subjective symptoms. The subjective voice complaint rate was significantly higher in females than males in the context of laryngitis, vocal nodules, Reinke s edema, hyperkeratosis, and vocal cyst; the rate was higher in males only in the context of laryngeal cancer (Table I). Analysis of Related Factors In the final multiple logistic regression model, aging (110 y) was positively associated with vocal cyst (AOR, 1.25; 95% CI, ), laryngitis (AOR, 1.26; 95% CI, ), Reinke s edema (AOR, 1.29; 95% CI, ), vocal fold palsy (AOR, 1.53; 95% CI, ), sulcus vocalis (AOR 1.56; 95% CI, ), and laryngeal cancer (AOR, 1.57; 95% CI, ). Female gender was negatively associated with laryngitis (AOR, 0.56; 95% CI ), but AORs for sex did not achieve statistical significance for any other laryngeal disease. Compared to normal BMI subjects, the low BMI group was characterized by an inverse association with vocal nodules (AOR, 0.43; 95% CI, ), whereas the high BMI group exhibited a positive association with laryngitis (AOR, 1.35; 95% CI, ). Compared to the lowest educational level group, the AOR of the middle and highest education groups were 2.49-fold (95% CI, ) and 3.24-fold (95% CI, ) higher, respectively, for vocal nodules. Smoking was positively associated with vocal polyp (AOR, 2.09; 95% CI, ), Reinke s edema (AOR, 2.72; 95% CI, ), epiglottic cyst (AOR, 3.79; 95% CI, ), hyperkeratosis (AOR, 14.37; 95% CI, ), and laryngeal cancer (AOR, 9.62; 95% CI ). A history of pulmonary tuberculosis was adversely associated with Reinke s edema (AOR, 0.17; 95% CI, ); a history of allergic rhinitis was positively associated with vocal nodules (AOR, 1.47; 95 CI, ), laryngitis (AOR, 1.41; 95 CI, ) and epiglottic cyst (AOR, 2.14; 95 CI, ), and was negatively associated with vocal polyp (AOR, 0.17; 95 CI, ) (Table II-). 2538

4 TABLE II-A. Multiple Logistic Regression Analysis of Related Factors for Laryngeal Diseases (Final Model). Vocal Nodules Vocal Polyp Vocal Cyst Laryngitis Reinke s Edema Vocal Fold Palsy AOR (95% CI) P Value AOR (95% CI) P Value AOR (95% CI) P Value AOR (95% CI) P Value AOR (95% CI) P Value AOR (95% CI) P Value Age (10 years) 1.25( ) 0.036* 1.26( ) < 0.001* 1.29( ) 0.001* 1.53( ) < 0.001* Sex < 0.001* Male 1 Female 0.56( ) BMI(kg/m 2 ) 0.032* 0.013* < ( ) 0.94( ) 18.5, < ( ) 1.35( ) Income Lowest Low-middle Upper-middle Highest Education < 0.001* Low 1 Middle 2.49( ) High 3.24( ) Alcohol consumption < 1 times a month 1 4 times a month 2 times a week Smoking 0.005* < 0.001* < 5 Pack Pack 2.09( ) 2.72( ) Pulmonary tuberculosis 0.17( ) 0.017* Asthma 2.93( ) 0.038* Allergic Rhinitis 1.47( ) 0.043* 0.25( ) 0.002* 1.41( ) 0.038* *Significance at P < AOR 5 adjusted prevalence and odds ratios; BMI 5 body mass index; CI 5 confidence interval. 2539

5 TABLE II-B. Multiple Logistic Regression Analysis of Related Factors for Laryngeal Diseases (Final Model). Sulcus Vocalis Epiglottic Cyst Contact Granuloma Laryngeal Papilloma Hyperkeratosis Laryngeal Cancer AOR (95% CI) P Value AOR (95% CI) P Value AOR (95% CI) P Value AOR (95% CI) P Value AOR (95% CI) P Value AOR (95% CI) P Value Age (10 years) 1.56( ) < 0.001* 1.25( ) 0.017* 1.57( ) < 0.001* Sex Male 1 Female 0.36( ) BMI(kg/m 2 ) < , < Income Lowest Low-middle Upper-middle Highest Education Low Middle High Alcohol consumption < 1 times a month 1 4 times a month 2 times a week Smoking < 0.001* < 0.001* 0.003* < 5 Pack Pack 3.79( ) 14.37( ) 9.62( ) Pulmonary tuberculosis Asthma Allergic rhinitis 2.14( ) 0.037* *Significance at P < AOR 5 adjusted prevalence and odds ratios; BMI 5 body mass index; CI 5 confidence interval. 2540

6 DISCUSSION We assessed the prevalence of various laryngeal diseases in the general population, which had not been specifically evaluated previously. Approximately one-third of our laryngeal disease patients complained of voice problems. Prevalence of laryngeal diseases was higher in males, whereas subjective voice complaining rates were higher in females. In logistic regression analysis, gender was not associated with laryngeal diseases. Laryngitis represented the most frequent laryngeal disease and the most common diagnosis among our treatment-seeking population. 6 In previous reports, the prevalence of vocal nodules was 2.29% to 16.9% in teachers and 4.34% in normal controls; that of vocal polyp was 2.4% in teachers. 7,8,13 Because previous studies were conducted using specific, susceptible populations, the reported rates were much higher compared to the present study with respect to vocal nodules (1.5%) and vocal polyp (0.4%). In our study, < 35% of laryngeal disease patients complained of voice problems for all types of laryngeal disease (Table I). Therefore, > 65% of patients without subjective voice discomfort may have been missed in other studies using treatment-seeking populations. Moreover, a relative minority of patients (5% 22.1%) with voice problems seek health care and treatment. 2,3 The capture of such patients in our study may render the rates of laryngeal disease that we observed more reliable as compared to previous reports. None of our laryngeal papilloma patients reported voice problems, which in contrast represented the most common symptom of laryngeal papilloma 14 such that our laryngeal papilloma prevalence rate (126 per 100,000 population) was markedly higher compared to a previous report (3.9 per 100,000 population). 15 Epiglottic cyst are generally asymptomatic and tend to be discovered incidentally. 16 In accordance with a previous report, 17 few of our epiglottic cyst (7.7%) patients complained of voice problems; to the best of our knowledge, no previous study has evaluated the prevalence of this laryngeal disease. According to previous data, females are more likely to suffer from voice problems 1,2,6,18 due to a shorter vocal fold that produces a higher fundamental frequency and due to a reduced amount of vocal fold hyaluronic acid that is essential for wound repair. 19,20 Vocal nodules also occur more frequently in females, 5,21 and Reinke s edema tends to affect females in their 50s. 10,20 However, in our study vocal nodules prevalence did not differ according to sex, and Reinke s edema was significantly more frequent in males. We think these differences are caused by the higher rate of subjective voice complaints in females versus males. Among vocal nodules patients, only 15.1% of males complained of voice problems compared to 39.6% of females. Among Reinke s edema patients, 22.5% of males complained of voice problems compared to 53.1% of females. Similar results were observed for the other types of laryngeal disease. Because females might experience greater voice discomfort than males, we suggest that they also visit hospitals more often such that selection bias may have affected the results of previous, hospital-based studies. Similarly, females may have reported more voice problems in telephone or questionnaire surveys, resulting in detection bias. We suspect that male patients may frequently not experience subjective voice discomfort during laryngeal disease and thus not visit a hospital, distorting previous studies results. In our multiple logistic regression analysis, female gender was associated only with laryngitis; moreover, the association was negative. Males typically have louder voices than females, 22 which could produce a heavier vocal load, thereby countervailing their anatomical advantages. Our male participants were also more likely to smoke than were females. We suggest that the relatively higher prevalence of Reinke s edema among our male versus females subjects is more reliable compared to previous, contrary result 20 ; males are typically more likely to smoke than females, 23 and smoking is a well-known risk factor for Reinke s edema. 20 Although sex was not associated with Reinke s edema, smoking was associated with the disease in multiple logistic regression analyses. Voice disorders are more common among the elderly 6,24 due to vocal muscle atrophy, thinning of the elastic fiber of vocal ligaments, and mucous gland degeneration that occurs during normal aging. 25,26 Furthermore, the prevalence of cancer increases with age and can cause vocal cord palsy. In accordance with previous studies, 2,27 age was positively associated with vocal cyst, laryngitis, Reinke s edema, vocal fold palsy, sulcus vocalis, epiglottic cyst, and laryngeal cancer. Obesity may also affect voice quality and function; underweight and obese individuals exhibit different aerodynamic voice characteristics. 28 In our study, low BMI decreased the AOR for vocal nodules, and high BMI increased the AOR for laryngitis possibly because the reduced laryngeal airway tissue volume of the low BMI group decreased airway resistance, 29 and by extension, vocal load. Obesity increases laryngopharyngeal reflux risk and may cause laryngeal inflammation, 30 thus increasing laryngitis risk. A higher education level was positively associated with vocal nodules. Voice overuse is the most wellestablished cause of vocal nodules, which are particularly frequent in the teaching profession 13 ; we suggest that vocations associated with a higher education level may frequently necessitate increased use of the voice. In accordance with previous studies, smoking was associated with vocal polyp, Reinke s edema, hyperkeratosis, laryngeal cancer, and epiglottic cyst. Because the majority of epiglottic cyst are discovered incidentally, 16 their associated risk factors have never been reported. Smoking influences larynx inflammation 35 and approximately 75% of epiglottic cyst are caused by collective glandular duct obstruction. 36 Chronic inflammation precipitated by smoking might affect cyst formation in the epiglottis. Alcohol consumption, a risk factor for dysplasia and squamous cell carcinoma of the larynx, 37,38 was not associated with any type of laryngeal disease in the present study. 2541

7 Respiratory condition is also associated with voice disorder risk. 39 Asthma patients experience voice disorders more frequently than healthy subjects, 18,39 possibly due to vocal cord trauma caused by chronic coughing, which can result in laryngeal disease. 39 However, we observed no association between asthma and laryngeal disease. A history of pulmonary tuberculosis was associated with Reinke s edema, but the reasons for this association remain unclear. Allergic rhinitis can induce throat-clearing and chronic upper airway irrigation, thus increasing laryngitis risk. 40 We suggest it could also affect vocal nodules and epiglottic cyst formation. However, the reason underlying the negative association that we observed between allergic rhinitis and vocal polyp remains unclear. Despite its numerous advantages, this study was also characterized by several limitations. First, we did not use a stroboscope, and we analyzed only organic voice diseases (characterized by structural or neurological abnormalities) and thus could not evaluate functional voice disorders. Second, we did not perform objective voice analysis (e.g., using aerodynamic methods, acoustic analysis, or spectrography), and laryngeal diseases such as papilloma and laryngeal cancer were not confirmed by pathology. Third, no medication histories, including for aspirin and warfarin, were obtained. Fourth, this study included only Korean populations. Finally, although we analyzed many factors, the study was subject to the same limitations that affect all cross-sectional studies, including possible reverse causality; therefore, our calculated ORs should be interpreted with caution. CONCLUSION Only about one-third of our laryngeal disease patients complained of voice problems. 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