Research

JAMA Otolaryngology–Head & Neck Surgery | Original Investigation

Association of Sinonasal Factors With Chronic Laryngitis

in Korean Adults
Kijeong Lee, MD; Cha Young Kang, MD; Hoyoung Lee, MD; In Hak Choi, MD; Sang Hag Lee, MD, PhD; Tae Hoon Kim, MD, PhD

Supplemental content
IMPORTANCE Allergic laryngitis is underdiagnosed owing to overlapping clinical
manifestations that arise from other causes of laryngitis. Sinonasal conditions associated with
chronic laryngitis, including allergic laryngitis, have not been reported using population-based
epidemiologic data.

OBJECTIVE To estimate the association of the prevalence of chronic laryngitis with various
sinonasal symptoms and endoscopic findings, and to identify which of the sinonasal factors
are particularly associated with allergic cause of chronic laryngitis.

DESIGN, SETTING, AND PARTICIPANTS This cross-sectional, population-based study of 11 283

participants 18 years and older who had undergone laryngoscopic and nasal endoscopic
examination used data from 2010 through 2012 in the fifth edition of the Korea National
Health and Nutrition Examination Survey, a nationwide survey of South Korea. Participants
were extracted by stratified, multistage, clustered sampling to comprise a nationally
representative sample. Data were analyzed in September 2017.

EXPOSURES Sociodemographic characteristics, smoking status, alcohol use, questionnaires

for voice change and sinonasal symptoms, and nasal endoscopic examinations before and
after shrinkage of the nasal mucosa.

MAIN OUTCOMES AND MEASURES Chronic laryngitis diagnosed by laryngoscopic examination,

and allergic cause of laryngitis determined by specific serum immunoglobulin E tests.

RESULTS Of the 11 283 participants included in the study, the mean (SD) age was 50.1 (16.6)
years, and 6365 (56.4%) were women. In total, 343 participants (3.0%) were diagnosed with
chronic laryngitis through results of laryngoscopic examination. Chronic laryngitis was
associated with a higher rate of rhinitis symptoms (odds ratio [OR], 1.54; 95% CI, 1.21-1.96),
anterior/posterior nasal drip (OR, 2.03; 95% CI, 1.38-2.98), nasal congestion (OR, 1.49; 95%
CI, 0.99-2.25), endoscopic findings of pale mucosa (OR, 1.74; 95% CI, 1.33-2.28), mucous or
puslike discharge (OR, 1.53; 95% CI, 1.08-2.18), and puslike discharge in the middle meatus
(OR, 1.85; 95% CI, 1.19-2.88), especially in female participants and participants older than
50 years. Subgroup analysis revealed that all participants with allergic laryngitis showed
sensitization to Dermatophagoides farinae, and the allergic laryngitis group (n = 9) had a
higher presence of rhinitis symptoms (n = 5; 56%) than did the nonallergic laryngitis group
(n = 1 of 12; 8%) among participants younger than 50 years (risk difference, 47%; 95% CI,
4%-78%).

CONCLUSIONS AND RELEVANCE The association of various sinonasal factors with chronic
laryngitis were prominent in female participants, as well as those 50 years and older.
Nevertheless, the presence of rhinitis symptoms in patients with chronic laryngitis was
associated with allergic cause of laryngitis solely in participants younger than 50 years. Author Affiliations: Department of
In young adults, presence of rhinitis symptoms might aid in considering allergic laryngitis. Otorhinolaryngology–Head & Neck
Surgery, College of Medicine, Korea
University, Seoul, Korea.
Corresponding Author: Tae Hoon
Kim, MD, PhD, Department of
Otorhinolaryngology–Head & Neck
Surgery, College of Medicine,
Korea University, 73 Inchon-ro,
JAMA Otolaryngol Head Neck Surg. 2019;145(10):919-925. doi:10.1001/jamaoto.2019.2134 Seongbuk-gu, Seoul 02841,
Published online August 15, 2019. South Korea (doctorthk@gmail.com).

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 Research Original Investigation
C
hronic laryngitis is a condition of laryngeal inflamma-
tion with a lifetime incidence of up to 21%.1 The most
common presenting symptoms of chronic laryngitis in-
clude dysphonia, throat clearing, cough, sore throat, and glo-
bus sensation. Various medical conditions, including laryn-
gopharyngeal reflux (LPR), poor laryngeal hygiene, infections,
or allergen sensitization, can induce chronic inflammation of
the larynx; however, it is difficult to distinguish among the pri-
mary causes because their clinical manifestations are similar.2,3
Allergic laryngitis, an inflammatory condition of the lar-
ynx caused by sensitized allergens, was initially described in
1971, but its importance and underdiagnosis have recently been
emphasized.3-5 Randhawa and colleagues6 suggested that al-
lergic laryngitis is misdiagnosed as LPR because the number
of patients with chronic laryngitis with positive skin prick test
(SPT) was more than 3 times higher than patients with posi-
tive results based on the reflux symptom index/reflux find-
ing score. A retrospective study7 that included a medical rec-
ord review of 998 patients indicated that the laryngitis group
showed similar odds ratios (ORs) of allergen sensitization com-
pared with the rhinitis or chronic sinusitis groups, indicating
the importance of allergen sensitivity test for laryngitis. A
study 8 that included animal models of allergen-induced
chronic laryngitis indicated that the combination of iron soot
and Dermatophagoides farinae resulted in eosinophilia of the
glottis, subglottic, and tracheal epithelium.
Moreover, the association between chronic laryngitis and
sinonasal diseases has been demonstrated with the unified
airway concept.9,10 Indeed, patients with either allergic rhi-
nitis or nonallergic rhinitis had higher prevalence of dyspho-
nia and more severe laryngeal symptoms than participants
without rhinitis.11 A study12 investigating the interrater vari-
ability of assessment of laryngeal findings for reflux and al-
lergic rhinitis based on SPT indicated that the presence of thick
endolaryngeal mucous was a significant predictor of allergic
rhinitis or laryngitis. Nevertheless, none of those studies in-
vestigated the correlation between various nasal symptoms or
findings through nasal endoscopic examination and chronic
laryngitis, including allergic laryngitis diagnosed based on the
laryngoscopy findings and specific serum immunoglobulin E
(IgE) level.
The objectives of this nationwide study are to investigate
the association between the prevalence of subjective/objective
nasal manifestations and chronic laryngitis, as well as to reveal
possible sinonasal indicators for allergic cause of laryngitis.
Methods
Survey Used for Data Collection
This cross-sectional study includes data from the fifth Korea
National Health and Nutrition Examination Sur vey
(KNHANES V) from 2010 through 2012. The KNHANES is a na-
tionwide survey conducted by the Korea Centers for Disease
Control and Prevention; includes a health interview, nutri-
tional survey, and physical examination; and is representative
of the nonindustrialized South Korean population. The survey
data were extracted by stratified, multistage clustered sam-
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Association of Sinonasal Factors With Chronic Laryngitis in Korean Adults
Key Points
Question How are various sinonasal factors associated with
chronic laryngitis and allergic cause of chronic laryngitis?
Findings In this cross-sectional study of 11 283 participants, among
various sinonasal factors associated with prevalence of chronic
laryngitis, only the presence of rhinitis symptoms was associated
with allergic causes in participants younger than 50 years.
Meaning The results of this study suggest that coexistence of
rhinitis symptoms could be used as a factor for considering allergic
cause of chronic laryngitis in young adults.
pling based on national census data. The Korean Society of
Otorhinolaryngology–Head and Neck Surgery participated in
KNHANES V. Endoscopic ear, nose, and throat examination and
medical interview were conducted by 150 otorhinolaryngology
residents from 47 institutions who underwent training in a stan-
dard manner. The study was approved by the institutional re-
view board of the Korea Centers for Disease Control and Pre-
vention, and all participants provided written informed consent.
Study Population
Among the 25 534 participants, participants younger than 18
years, without nasal endoscopic or laryngoscopic examina-
tions, having a lesion suspected for cancer after endoscopic
or laryngoscopic examination, or with incomplete data were
excluded. In total, 11 283 participants were enrolled (Figure).
General Characteristics
Data regarding the participants’ age, sex, household income,
residency, education level, smoking status, and alcohol con-
sumption were collected. Household income was catego-
rized by quartile (<25%, 25%-50%, 51%-75%, >75%). Resi-
dency was classified into urban and rural areas according to
the official addresses of the participants. Education level was
classified into 4 groups (less than elementary, less than high
school, less than college, more than college). Smoking his-
tory was categorized into 2 groups: current smoker or ex-
smoker and nonsmoker. Alcohol consumption was catego-
rized into 2 groups: drinking 4 or more times a week and
drinking fewer than 4 times a week or nondrinker.
Assessment of Variables
The results of the questionnaires and physical examinations of
the participants’ nasal cavities and larynges in this study are sum-
marized in Table 1. The diagnoses of rhinitis, nasal septal devia-
tion, chronic sinusitis, and chronic laryngitis were made based
on these findings. Participants with rhinitis were defined as those
who reported to have rhinorrhea, sneezing, and itching sensa-
tion of the nose. Septal deviation was defined based on the na-
sal endoscopic findings of asymmetrical deviation of the nasal
septum after shrinkage of the nasal mucosa. The diagnosis of
chronic rhinosinusitis was based on the epidemiological section
of the European study on rhinosinusitis and nasal polyp.13 Ques-
tions related to chronic rhinosinusitis addressed the following
4 symptoms of at least 12 weeks’ duration: anterior/posterior na-
sal drip, nasal obstruction, facial pain or pressure, and olfactory
jamaotolaryngology.com
 Association of Sinonasal Factors With Chronic Laryngitis in Korean Adults Original Investigation Research

Figure. Flowchart of Participant Selection

25 534 KNHANES V participants

(2010-2012)

14 251 Excluded
6683 No endoscopic examination
5703 Younger than 18 y
1763 Incomplete data
82 Lesion suspected of cancer
after nasal endoscopic examination
20 Lesion suspected of cancer after
laryngoscopic examination

11 283 Total study participants

345 With chronic laryngitis 10 938 Without chronic laryngitis

298 Excluded (without serum-

specific IgE test)

47 Subgroup analysis participants

IgE indicates immunoglobulin E;

KNHANES V, Korea National Health
17 With allergic laryngitis 30 With nonallergic laryngitis
and Nutrition Examination Survey,
fifth edition.

dysfunction. Chronic rhinosinusitis was diagnosed when more
than 2 of these symptoms with at least 1 of either anterior/
posterior nasal drip or nasal obstruction being present, or if the
nasal polyp was identified by endoscopic findings.
Laryngoscopic examination using a 4-mm, 70-degree–
angled rigid endoscope by trained otorhinolaryngology
residents was performed, and recorded images using a charge-
coupled device camera were further reviewed by otorhinolar-
yngology specialists. Chronic laryngitis was defined as a posi-
tive finding for chronic laryngeal inflammation with erythema,
edema, pseudosulcus, Reinke edema, or thick endolaryngeal
mucous under laryngoscopic examination, as described
previously.14,15 Each participant was asked if they experienced
voice problems, and those who provided affirmative re-
sponses were asked if the duration of voice change was fewer
than 3 weeks or 3 weeks or more.
In 2010, 10% of total participants underwent Immuno-
CAP 100 (Thermo Scientific; Uppsala, Sweden) testing in which
the levels of specific IgEs for 3 common indoor allergens
(D farinae, cockroaches, and dogs) were measured with a cut-
off value of 0.35 kU/L. Among participants with laryngo-
scopic findings of chronic inflammation indicating chronic
laryngitis, participants who were positive for at least 1 of the
3 specific IgEs were defined to have allergic laryngitis, while
the others were defined to have nonallergic laryngitis. Al-
though only a small subpopulation met the inclusion criteria,
the data were used for further evaluation of the association
between nasal findings and allergic laryngitis.
Statistical Analysis
Statistical analyses were performed using Statistical Package
for the Social Sciences, version 20 (IBM). Participants’ char-
acteristics were described using the mean and standard de-
viation for continuous variables, and number and percentage
for categorical variables. For the differences of general char-
acteristics between participants with chronic laryngitis and
control participants, continuous variables were analyzed by
t test, and categorical variables were analyzed by χ2 test. To
calculate the effect size, we used Cohen d for t test and
Cramer V statistic for χ2 test with bootstrap CIs using the R soft-
ware, version 3.5.1 (R Foundation for Statistical Computing).
Univariable and multivariable logistic regression analyses were
used to evaluate the associations between chronic laryngitis
and sinonasal factors. Odds ratios with 95% CIs for each sino-
nasal factor were calculated. According to the adjusted con-
founding factors, 3 models were established: univariable analy-
sis was conducted in model 1, adjustment for variables with
age and sex was completed in model 2, and final adjustment
for variables with sex, age, residency, household income, edu-
cational level, smoking status, and alcohol consumption was
performed in model 3. Subsequently, the interaction of the par-
ticipants’ sex and age to the association between chronic lar-
yngitis and sinonasal factors was evaluated. The χ2 test and
Fisher exact test were used to compare the presence of sino-
nasal factors between the allergic laryngitis and nonallergic lar-
yngitis groups, and risk difference with 95% CIs were calcu-
lated using SAS software, version 9.4 (SAS Institute Inc).
Results
Baseline Characteristics
Among the 11 283 participants analyzed in this study, 345 par-
ticipants were diagnosed with chronic laryngitis. Participants

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 Research Original Investigation Association of Sinonasal Factors With Chronic Laryngitis in Korean Adults

Table 1. Questionnaires and Endoscopic Evaluations Performed
in KNHANES V
Questionnaires and Endoscopic
Evaluations (n = 11 283)
Laryngoscopic Findings
Chronic laryngitis: laryngeal
inflammation with erythema, edema,
pseudosulcus, Reinke edema, thick
endolaryngeal mucous
Questionnaire regarding laryngeal
diseases: voice problem, wk
<3
≥3
Questionnaire Regarding Rhinitis Symptoms
Have you ever experienced rhinitis
symptoms such as sneezing, runny nose,
blockage of the nose, and itchy nose in
the past year or less, regardless of cold
(fever, throat pain)?
Questionnaires Regarding Chronic Sinusitis Symptoms
Have you experienced anterior/posterior
nasal drip for at least the past 3 mo?
Have you experienced nasal congestion
for at least the past 3 mo?
Have you experienced facial
pain/pressure for at least the past 3 mo?
Have you experienced anosmia/hyposmia
for at least the past 3 mo?
Nasal Endoscopic Findings
Before shrinkage
Pale mucosa
Watery discharge
Mucous or puslike discharge
After shrinkage
Nasal septal deviation
Nasal polyp
Middle meatus puslike discharge
Abbreviations: KNHANES V, the fifth edition of the Korea National Health and
Nutrition Examination Survey (2010-2012); NA, not applicable.
with chronic laryngitis (mean [SD] age, 53.9 [14.4] years) were
4 years older than the controls (mean [SD] age, 49.9 [16.6] years)
with strong association (Cramer V, 0.23; 95% CI, 0.13-0.34). With
Unweighted No. (Weighted %)
regard to sinonasal disease, the chronic laryngitis group had 7.6%
Yes No
(95% CI, 3.1%-13.9%) greater prevalence of chronic rhinitis
(n = 111; 32.2%) (Cramer V, 0.02; 95% CI, 0.01-0.05) and 8.5%
345 (3.1) 10 938 (96.9) (95% CI, 3.2%-13.9%) higher prevalence of nasal septal devia-
tion (n = 197;57.1%) (Cramer V, 0.03; 95% CI, 0.01-0.05) com-
pared with the control group. Chronic rhinosinusitis had simi-
793 (6.3) 10 489 (93.7)
lar prevalence between the 2 groups. Participants with chronic
332 (2.7) NA laryngitis had higher prevalence of voice change for either fewer
459 (3.6) NA
than 3 weeks (9.0%) or 3 weeks or more (2.8%) than the con-
trols (eTable 1 in the Supplement).
2801 (24.8) 78 482 (75.2)
Association Between Chronic Laryngitis
and Nasal Symptoms/Findings
Association of symptoms positive for rhinitis or chronic sinus-
itis with chronic laryngitis was analyzed (Table 2). Univari-
569 (5.0) 10 714 (94.9) able analysis revealed that symptoms of rhinitis (OR, 1.44; 95%
CI, 1.16-1.83), anterior/posterior nasal drip over 3 months (OR,
633 (5.6) 10 650 (94.4) 2.13; 95% CI, 1.48-3.06), and nasal congestion (OR, 1.51; 95%
CI, 1.02-2.24) showed positive association with chronic laryn-
66 (0.6) 11 217 (99.4)
gitis. After adjusting for confounding factors (in models 2 and
609 (5.4) 10 674 (94.6) 3), symptoms of rhinitis, anterior/posterior nasal drip, and na-
sal congestion showed association with chronic laryngitis. For
nasal endoscopic findings, pale mucosa (OR, 1.68; 95% CI, 1.30-
2.18), mucous or puslike discharge (OR, 1.72; 95% CI, 1.23-
1651 (14.6) 9632 (85.4) 2.40), nasal septal deviation (OR, 2.07, 95% CI, 1.35-3.17), and
1570 (13.9) 9713 (86.1) puslike discharge in the middle meatus (OR, 1.41; 95% CI, 1.14-
835 (7.4) 10 448 (92.6) 1.75) were shown to have association with chronic laryngitis
in model 1. After adjustment for confounding factors, includ-
5511 (48.8) 5772 (51.2) ing the baseline characteristics (in models 2 and 3), endo-
300 (2.7) 10 983 (97.3) scopic findings of pale mucosa, watery discharge, and mu-
406 (3.6) 10 877 (96.4) cous or puslike discharge before shrinkage, as well as nasal
septal deviation and puslike discharge in the middle meatus
after shrinkage, showed association with higher prevalence of
chronic laryngitis.

Table 2. Association Between Each Sinonasal Factor and Prevalence of Chronic Laryngitis in KNHANES V

Odds Ratio (95% CI)

Variables Model 1a Model 2b Model 3c
Rhinitis symptoms 1.45 (1.16-1.83) 1.57 (1.25-1.99) 1.54 (1.21-1.96)
CRS symptom, >3 mo
Anterior/posterior nasal drip 2.13 (1.48-3.06) 2.13 (1.48-3.07) 2.03 (1.38-2.98)
Nasal congestion 1.51 (1.02-2.24) 1.55 (1.04-2.23) 1.49 (0.99-2.25)
Facial pain or pressure 2.06 (0.74-5.69) 2.15 (0.78-5.97) 1.69 (0.52-5.46)
Anosmia/hyposmia 1.14 (0.73-1.79) 1.01 (0.64-1.59) 0.90 (0.56-1.47)
Nasal endoscopic findings before shrinkage Abbreviations: CRS, chronic
rhinosinusitis; KNHANES V, the fifth
Pale mucosa 1.68 (1.30-2.18) 1.77 (1.37-2.30) 1.74 (1.33-2.28) edition of the Korea National Health
Watery discharge 1.31 (0.99-1.75) 1.41 (1.06-1.88) 1.43 (1.07 -1.92) and Nutrition Examination Survey
(2010-2012).
Mucous or puslike discharge 1.72 (1.24-2.41) 1.61 (1.15-2.25) 1.53 (1.08-2.18)
a
Model 1, unadjusted.
Nasal endoscopic findings after shrinkage b
Model 2, adjusted for age and sex.
Nasal septal deviation 2.07 (1.35-3.17) 1.33 (1.06-1.65) 1.25 (1.00-1.57) c
Model 3, adjusted for age, sex,
Nasal polyp 1.33 (0.74-2.40) 1.15 (0.64-2.07) 1.11 (0.60-2.05) residency, household income,
education, alcohol consumption,
Middle meatus puslike discharge 1.41 (1.14-1.75) 1.84 (1.19-2.82) 1.85 (1.19-2.88)
and smoking status.

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 Association of Sinonasal Factors With Chronic Laryngitis in Korean Adults Original Investigation Research

Table 3. Association Between Sinonasal Factors and Chronic Laryngitis by Subgroup in KNHANES V

Subgroup, Adjusted Odds Ratio (95% CI)a

Age
Variables Men Women <50 y ≥50 y
Questionnaires
Rhinitis symptoms 1.46 (1.05-2.02) 1.65 (1.16-2.35) 1.03 (0.70-1.52) 2.00 (1.48-2.70)
Anterior/posterior nasal drip 2.00 (0.50-1.98) 3.41 (2.13-5.46) 1.35 (0.65-2.80) 2.42 (1.54-3.82)
Nasal congestion 0.88 (0.46-1.69) 2.56 (1.50-4.37) 1.15 (0.58-2.30) 1.81 (1.08-3.04)
Abbreviation: KNHANES V, the fifth
Nasal endoscopic findings edition of the Korea National Health
Pale mucosa 1.48 (1.00-2.20) 2.04 (1.40-2.96) 1.34 (0.89-2.17) 2.00 (1.42-2.82) and Nutrition Examination Survey
Watery discharge 1.42 (0.96-2.11) 1.45 (0.93-2.25) 1.43 (0.93-2.18) 1.40 (0.93-2.11) (2010-2012).
a
Mucous or puslike discharge 1.40 (0.89-2.20) 1.75 (1.00-3.07) 0.66 (0.29-1.52) 2.05 (1.37-3.06) Adjusted for age, sex, residency,
Nasal septal deviation 1.34 (0.98-1.84) 1.17 (0.84-1.62) 1.25 (0.86-1.81) 1.23 (0.93-1.64) household income, education,
alcohol consumption, and smoking
Middle meatus puslike discharge 1.49 (0.81-2.73) 2.46 (1.30-4.66) 1.61 (0.64-4.03) 1.93 (1.17-3.20)
status.

Table 4. Association Between Each Sinonasal Factor and Allergic Cause of Laryngitis in KNHANES V

Positive Finding by Subgroup, No. (%)

Age
Entire population Men Women
(n = 47) (n = 26) (n = 21) <50 y (n = 21) ≥50 y (n = 26)
Allergy Nonallergy Allergy Nonallergy Allergy Nonallergy Allergy Nonallergy Allergy Nonallergy
Variables (n = 17) (n = 30) (n = 9) (n = 17) (n = 8) (n = 13) (n = 9) (n = 12) (n = 8) (n = 18)
Questionnaires
Rhinitis symptoms 7 (41.2) 9 (30.0) 4 (44.5) 4 (23.5) 3 (37.5) 5 (38.5) 5 (55.6) 1 (8.3) 2 (25.0) 8 (44.4)
Anterior/posterior 1 (5.9) 3 (10.0) 0 (0.0) 1 (5.9) 1 (12.5) 2 (15.4) 1 (11.1) 1 (8.3) 0 (0.0) 2 (11.1)
nasal drip
Nasal congestion 2 (11.8) 2 (6.7) 1 (11.1) 1 (5.9) 1 (12.5) 1 (7.7) 2 (22.2) 0 0 2 (11.1)
Nasal Endoscopic Findings
Pale mucosa 3 (17.6) 5 (16.7) 1 (11.1) 2 (11.8) 2 (25.0) 3 (23.1) 2 (22.2) 1 (8.3) 1 (12.5) 4 (22.2)
Watery discharge 3 (17.6) 2 (6.7) 2 (22.2) 1 (5.9) 1 (12.5) 1 (7.7) 3 (33.3) 1 (8.3) 0 1 (5.6)
Mucous or puslike 2 (11.8) 3 (10.0) 2 (22.2) 3 (17.7) 0 0 1 (11.1) 1 (8.3) 1 (12.5) 2 (11.1)
discharge
Nasal septal deviation 11 (64.7) 20 (64.5) 7 (77.8) 11 (61.1) 4 (50.0) 9 (69.2) 5 (55.6) 8 (66.7) 6 (75.0) 12 (66.7)
Middle meatus puslike 0 1 (3.3) 0 1 (5.9) 0 0 0 0 0 1 (5.6)
discharge

Abbreviation: KNHANES V, the fifth edition of the Korea National Health and Nutrition Examination Survey (2010-2012).

Association Between Chronic Laryngitis
and Nasal Symptoms/Findings by Sex and Age
Among the nasal symptoms and findings, the 8 clinically mean-
ingful factors identified through multivariable analysis (model
3) shown in Table 2 were analyzed for their effect on chronic
laryngitis according to the participants’ sex and age (Table 3).
After the adjustment for confounding factors, the following fac-
tors showed association with higher prevalence of chronic lar-
yngitis in female participants and participants 50 years and
older: subjective symptoms of rhinitis (female participants: OR,
1.65 [95% CI, 1.16-2.35]; participants ≥50 years old: OR, 2.00
[95% CI, 1.48-2.70]), anterior/posterior nasal drip (female par-
ticipants: OR, 3.41 [95% CI, 2.13-5.46]; participants ≥50 years
old: OR, 2.42 [95% CI, 1.54-3.82]), and nasal congestion (fe-
male participants: OR, 2.56 [95% CI, 1.50-4.37]; participants
≥50 years old: OR, 1.81 [95% CI, 1.08-3.04]), as well as endo-
scopic findings of pale mucosa (female participants: OR, 2.04
[95% CI, 1.40-2.96]; participants ≥50 years old: OR, 2.00 [95%
CI, 1.42-2.82]), mucous or puslike discharge (female partici-
pants: OR, 1.75 [95% CI, 1.00-3.07]; participants ≥50 years old:
OR, 2.05 [95% CI, 1.37-3.06]), and puslike discharge in the
middle meatus (female participants: OR, 2.46 [95% CI, 1.30-
4.66]; participants ≥50 years old: OR, 1.93 [95% CI, 1.17-
3.20]). In male participants, only rhinitis symptom (OR, 1.46;
95% CI, 1.05-2.02) was associated with higher prevalence of
chronic laryngitis, and none of 8 sinonasal factors had clini-
cally meaningful association with chronic laryngitis in par-
ticipants younger than 50 years.
Association Between Allergic Laryngitis
and Nasal Symptoms/Findings
Further analysis of the ImmunoCAP data of 2010 was com-
pleted to evaluate the utility of the coexistence of nasal symp-
toms or findings in patients with chronic laryngitis as an in-
dicator for allergic cause of laryngitis. Among 1415 participants
who underwent ImmunoCAP in 2010, 47 participants were di-
agnosed with chronic laryngitis. In the laryngitis group, 17
were classified as having allergic laryngitis, and all partici-
pants with allergic laryngitis had positive results for IgE against
D farinae. The presence of rhinitis symptoms, anterior/
posterior nasal drip, and endoscopic findings of pale mucosa
showed no clinically meaningful differences between the al-
lergic laryngitis and nonallergic laryngitis subgroups when all
participants’ data were analyzed (Table 4).
Further subgroup analysis according to the participants’
sex and age revealed that only participants younger than 50

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 Research Original Investigation
years showed positive association between the presence of
rhinitis symptoms and allergic laryngitis (risk difference, 47.20;
95% CI, 3.50-79.37) (Table 4; eTable 2 in the Supplement).
Discussion
The main finding of this study was that the presence of rhini-
tis symptoms showed positive association with allergic cause
of laryngitis in participants younger than 50 years, despite
stronger association of chronic laryngitis with various sino-
nasal factors from questionnaires and endoscopic findings in
female participants and participants 50 years and older (eFig-
ure in the Supplement). To our knowledge, this is the first study
to investigate the association between the subjective/
objective factors of sinonasal disease and chronic laryngitis and
to determine the utility of sinonasal finding of patients with
chronic laryngitis as a factor for considering allergic cause of
chronic laryngitis.
In this study, the prevalence of chronic laryngitis was 3.1%
for the overall population, and more than a third of the patients
with laryngitis (1.2%) had a positive result on the serum specific
IgE test, which suggests the importance of distinguishing the al-
lergic cause among patients with chronic laryngitis. It has been
reported that 67% of patients with primary voice disorder dem-
onstrated allergy, while only 20% of patients had reflux, which
emphasizes the possibility of overtreatment with proton pump
inhibitors (PPIs) in cases of laryngitis.6 Stein and colleagues1 con-
ducted a population-based study and reported that among a total
of 40 317 patients, 79% with a voice problem received PPIs at
their first visit to the clinic. A prospective, double-blind, placebo-
controlled study16 for laryngeal inhalant allergen challenge re-
vealed that greater phonatory threshold pressure was required
after allergen challenge, indicating a primary association be-
tween allergen exposure and vocal function impairment. Al-
though these studies emphasized the probable misdiagnosis or
mismanagement of allergic laryngitis, it is generally accepted
that the differential diagnosis between allergic laryngitis and LPR
is difficult owing to similar clinical manifestations.4,17 Therefore,
we evaluated the differences in the coexistence of various sino-
nasal factors according to allergic condition in participants with
chronic laryngitis in order to reveal possible indicators for aller-
gic laryngitis.
This study indicated that the subjects of the chronic laryn-
gitis group had higher prevalence of chronic rhinitis and nasal
septal deviation, while prevalence of CRS showed no meaning-
ful difference. The multivariable logistic analysis revealed that
among various sinonasal symptoms, presence of rhinitis symp-
toms, anterior/posterior nasal drip, and nasal congestion were
associated with chronic laryngitis. In the case of nasal endoscopic
examination, findings of pale mucosa, watery rhinorrhea, nasal
septal deviation, and mucous or puslike discharge either in front
of the nasal cavity or the middle meatus showed association with
chronic laryngitis. Subgroup analysis revealed that the associa-
tion between nasal findings and prevalence of chronic laryngi-
tis was prominent in female participants and participants 50 years
and older; however, the coexistence of nasal findings in the par-
ticipants with chronic laryngitis was not related to the allergic
924 JAMA Otolaryngology–Head & Neck Surgery October 2019 Volume 145, Number 10 (Reprinted)
© 2019 American Medical Association. All rights reserved.
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Association of Sinonasal Factors With Chronic Laryngitis in Korean Adults
cause of chronic laryngitis. Age-related changes in the upper air-
ways might affect the comorbidity of rhinitis and laryngitis; sev-
eral structural changes that occur with the normal aging process,
including decreased mucosal blood flow, viscoelastic change of
mucus, and increased cholinergic activity, could influence the
increased prevalence of chronic laryngitis associated with
rhinitis.10,18 In female individuals, estrogen may play a role in the
coexistence of rhinitis and laryngitis. Elevation in the estrogen
level aggravated the conditions of rhinitis, including nasal con-
ditions or impaired mucociliary clearance, as well as gastric acid
secretion, which could influence chronic laryngitis.19,20 In ad-
dition, the hypersecretion of airway mucous was increased by
administration of estradiol through the estrogen receptor beta,
supporting the effect of estrogen on posterior nasal drip, which
showed a dominant relationship with chronic laryngitis in the
female participants in this study.21
In contrast, patients with chronic laryngitis with rhinitis
symptoms in the group of participants younger than 50
years showed an association of these symptoms with allergic
cause. The presence of rhinitis symptoms alone had high-
risk difference with clinical importance, while endoscopic
findings of rhinitis, including pale mucosa and watery rhi-
norrhea, showed a wide range of 95% CIs despite high-risk
difference, which could be because of the much lower pro-
portion of participants with those findings in the chronic lar-
yngitis group compared with that in the participants with
rhinitis symptoms. Findings of the laryngoscopic examina-
tion suggesting allergic laryngitis could not be investigated
because we could not assess from the data collected which
specific findings among various factors indicating chronic
laryngitis were presented under laryngoscopic examination
in each individual. In addition to the previous literature
reporting thick endolaryngeal mucous as an indicator of
allergic laryngitis, the results of the present study indicate
that in patients younger than 50 years with chronic laryngi-
tis consideration for the possibility of allergic laryngitis
based on the presence of rhinitis symptoms could prevent
the overprescription of PPIs.12
In this study, all patients with allergic laryngitis had a posi-
tive result in the D farinae sensitization test. Several previous
studies have investigated the association between chronic lar-
yngitis and sensitization to specific allergens. Notably, sub-
jects with dust-mite allergen sensitization on SPT showed a
higher voice handicap index score than did nonallergic sub-
jects despite the absence of differences in acoustic data or stro-
boscopic parameters.5 Brook and collagues7 analyzed the OR for
the association between positive results on various specific
allergen tests and presenting symptoms, including rhinitis, lar-
yngitis, otitis, and sinusitis; 51.9% of participants in their study
with primary laryngeal symptoms showed a positive result for
allergen sensitivity test, and dust mite was the most common
allergen. The findings from the present study were consistent
with those from the above studies indicating that dust mite is
the major allergen; however, the proportion of allergic partici-
pants among the chronic laryngitis group was lower than that
reported by Brook and colleagues, which could be explained by
the fact that KNHANES V focused on the inclusion of data re-
garding sensitization to only indoor allergens.
jamaotolaryngology.com
 Association of Sinonasal Factors With Chronic Laryngitis in Korean Adults Original Investigation Research

Limitations study to evaluate the association between sinonasal factors and

This study has several limitations. Owing to the cross-sectional
study design, a causal relationship could not be defined. In ad-
dition, KNHANES V provided data of only 3 specific IgEs for com-
mon indoor allergens, and hence, we were unable to assess the
association between allergic airway conditions and seasonal al-
lergens. Finally, because questionnaires or examinations related
with acid reflux were not included in these nationwide data, the
clinical features of allergic laryngitis isolated from the effects of
LPR could not be analyzed. However, even in practice, exami-
nations for objective acid reflux verification, such as 24-hour pH
monitoring, cannot be performed in all suspected patients, and
the majority of LPR cases are diagnosed through reactivity to PPIs.
From the present study, various sinonasal factors were associ-
ated with chronic laryngitis, especially in female participants and
participants 50 years and older, and the possibility of allergic
cause could be verified if rhinitis symptoms were present in pa-
tients younger than 50 years with chronic laryngitis. This result
could be useful for suspecting other causes of chronic laryngi-
tis before testing on reflux or prescribing PPIs. The present study
has strength in that, to our knowledge, this is the first nationwide
chronic laryngitis, including allergic laryngitis, in participants who
represent the entire South Korean population. In addition, the
reliability of this study is supported by the fact that the laryngo-
scopic and nasal endoscopic examinations were conducted in a
large population by trained otolaryngologists using a standard-
ized protocol.
Conclusions
The current study included nationwide data and showed that
the association of sinonasal factors, including rhinitis symp-
toms, anterior/posterior nasal drip, endoscopic findings of pale
mucosa, and mucous or puslike discharge, with chronic laryn-
gitis was dominant in female individuals and older adults. Nev-
ertheless, the presence of rhinitis symptoms in patients with
chronic laryngitis was associated with the allergic cause of lar-
yngitis only in participants younger than 50 years. The identi-
fication of this association may enable distinguishing allergic
laryngitis from other causes of chronic laryngitis in young adults.

ARTICLE INFORMATION
Accepted for Publication: June 11, 2019.
Published Online: August 15, 2019.
doi:10.1001/jamaoto.2019.2134
Author Contributions: Drs Kim and K. Lee had full
access to all of the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis. Drs K. Lee and Young
Kang contributed equally to this work.
Study concept and design: K. Lee, S. Lee, Kim.
Acquisition, analysis, or interpretation of data:
K. Lee, Young Kang, H. Lee, Choi.
Drafting of the manuscript: K. Lee, Young Kang,
H. Lee, Choi.
Critical revision of the manuscript for important
intellectual content: S. Lee, Kim.
Statistical analysis: K. Lee, Young Kang, Choi.
Obtained funding: Kim.
Administrative, technical, or material support: K. Lee.
Study supervision: S. Lee, Kim.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by
the Korea Health Industry Development Institute
through the Ministry of Health & Welfare
(HI17C0387).
Role of the Funder/Sponsor: The sponsor had
no role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Additional Contributions: We thank the 150
residents of the otorhinolaryngology departments
of 47 training hospitals in South Korea and
members of the Division of Chronic Disease
Surveillance in Korea Centers for Disease Control &
Prevention for participating in this survey and for
their dedicated work. They were not compensated
for their contributions beyond their regular salaries.
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