576181
research-article2015
AORXXX10.1177/0003489415576181Annals of Otology, Rhinology & LaryngologyChung et al
Article
Altered Quality of Life and Psychological Health (SCL-90-R) in Patients With Chronic Rhinosinusitis With Nasal Polyps
Annals of Otology, Rhinology & Laryngology 2015, Vol. 124(8) 663–670 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003489415576181 aor.sagepub.com
Jae Ho Chung, MD1, Yun Jae Lee, MD1, Tae Wook Kang, MD1, Kyung Rae Kim, MD1, Dong Pyo Jang, PhD2, In Young Kim, PhD2, and Seok Hyun Cho, MD1
Abstract Objectives: To investigate the impact of olfactory dysfunction on quality of life (QOL) and psychological status in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: A retrospective observational study was conducted from January 2011 to May 2012 with 130 patients with septal deviation (SD) (n = 59) and CRSwNP (n = 71). All patients underwent computed tomography (CT), allergy tests, and sniffin’ stick olfactory test. Anosmia was defined by Threshold-Discrimination-Identification (TDI) scores less than 16. QOL and psychological symptoms were assessed with the Sinonasal Outcome Test-20 (SNOT-20) and Symptom Checklist-90-Revised (SCL-90-R). Results: Odor discrimination and identification scores were significantly lower in CRSwNP than in SD (P = .008 and P = .005, respectively). In CRSwNP, identification score decreased with higher CT score (r = –0.29, P = .014). CRSwNP with anosmia showed a decreased QOL (P = .044), and SNOT-20 negatively correlated with TDI in severe CRSwNP (CT score ≥15, r = –0.714, P = .001). Anosmia patients had higher anxiety and phobia scores of SCL-90-R in both SD and CRSwNP. However, depression score increased only in CRSwNP with anosmia (P = .025). Conclusion: Olfactory dysfunction may have significant effects on QOL and psychological health. CRSwNP with anosmia is a distinct phenotype having mixed type of olfactory loss that might have a detrimental effect on depression. Keywords nasal obstruction, nasal polyposis, olfaction, otolaryngology, rhinology, sinusitis
Introduction Olfactory dysfunction is a relatively common disorder, but it is frequently unrecognized by patients and underdiagnosed by clinicians.1 Olfaction plays an important role in daily life such as food intake, has a role for defense mechanisms to detect toxic gases or spoiled food, and influences social and sexual activities. Olfactory dysfunction may affect the emotional and memory functions, especially in many neurodegenerative diseases.2 Numerous conditions can lead to the development of olfactory dysfunction, such as upper respiratory infections, head trauma, tumors, and sinonasal diseases.3 From a pathophysiologic perspective, olfactory dysfunction can be classified into conductive and sensorineural types.4 Conductive olfactory loss is characterized by blockage of air flow, preventing odorant molecules from reaching the olfactory epithelium, and sensorineural olfactory loss is caused by direct damage to either the olfactory epithelium or central olfactory pathway.5 In common nasal diseases, septal deviation (SD) can be a cause of conductive olfactory dysfunction,
and chronic rhinosinusitis with nasal polyps (CRSwNP) can be classified as a mixed (conductive and sensorineural) olfactory dysfunction.6 It has been reported that olfactory dysfunction can affect patients’ quality of life.7 Moreover, olfactory dysfunction has been linked to depression and cognitive disorders in patients with vascular dementia, Alzheimer’s disease, and Parkinson’s disease.8,9 However, few studies have investigated the effect of olfactory dysfunction on patients’ psychological health in rhinologic diseases such as SD and CRSwNP. 1
Departments of Otolaryngology-Head and Neck Surgery, School of Medicine, Hanyang University, Seoul, Korea 2 Department of Biomedical Engineering, Hanyang University, Seoul, Korea Corresponding Authors: Seok Hyun Cho, MD, Department of Otolaryngology-Head and Neck Surgery, or In Young Kim, PhD, Department of Biomedical Engineering, School of Medicine, Hanyang University, 222-Wangshimni-ro, Seongdong-gu, Seoul 133-792, Korea. Email: [email protected] or [email protected]
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The aim of this study was to evaluate the influence of olfactory dysfunction on quality of life and psychological health in patients with SD and CRSwNP. Therefore, we sought to investigate whether mixed type of olfactory dysfunction has different mechanisms altering psychological profiles in comparison to conductive type.
Methods Patients We performed the prospective observational study with 169 consecutive patients who received nasal and/or endoscopic sinus surgery in tertiary referral center from January 2011 to May 2012. Exclusion criteria included children (n = 11), history of facial trauma or nasal surgery (n = 9), paranasal sinus tumor (n = 2), presence of systemic diseases (n = 15; hypertension, cardiac diseases, diabetes mellitus, asthma, and obstructive sleep apnea), and psychological disorders (n = 2). Finally, a total of 130 eligible subjects (97 men, 33 women) were enrolled. They were divided into 2 groups: SD (n = 59) and CRSwNP (n = 71). SD were confirmed to be free of paranasal sinus inflammation by nasal endoscopy and computed tomography (CT). Diagnosis of CRSwNP was made according to the proposed criteria,10 and the severity of sinusitis was evaluated by Lund-Mackay CT score.11 All patients underwent a skin prick test to determine sensitivity to common inhaled allergens. Written informed consent was obtained from all patients. This investigation was approved by the local ethics review board and performed in accordance with the Declaration of Helsinki and good clinical practice guidelines.
Psychophysical Olfactory Test Using the Sniffin’ Sticks Test Odorants were presented in felt-tip pens (Korean version II of the Sniffin’ sticks test; KVSS II), which were modified and customized for the Korean population.12 KVSS II comprises 3 test batteries: olfactory threshold, odor discrimination, and odor identification tests. The tests were performed in order, with 5-minute intervals between them. Briefly, olfactory threshold (score range, 1-16) was defined as the concentration at which n-butanol (highest concentration 4%, 1:2 serial dilutions in 16 steps) was correctly identified 4 times in a row using a single-staircase, 3-alternative forced choice. In the odor discrimination test (score range, 0-16), triplets of odorants (2 identical and 1 different) were presented in a random order at intervals of 20 to 30 seconds, and subjects were asked to choose the odd odorant. Odor identification test (score range, 0-16) consisted of 16 odors familiar to Koreans. The sum of the 3 tests represented the ThresholdDiscrimination-Identification (TDI) score. Patients with a total score of 0 to 15 were diagnosed with anosmia, 16 to 29
with hyposmia, and over 30 with normosmia. The validity and reliability of KVSS II severity criteria have been checked for by comparison with a cross-cultural smell identification test (CC-SIT) and T&T olfactometry.13,14
Measurement of Sinonasal Symptoms and Quality of Life We measured sinonasal symptoms and quality of life with a modified Sinonasal Outcome Test-20 (SNOT-20), which contains the same 20 items as in the original test to assess 10 sinonasal symptoms as well as 10 social and emotional criteria that measure the influence of sinusitis on patient’s physical condition and quality of life.15 Each question was graded on a 4-point scale (0, no symptom; 1, mild symptom; 2, moderate symptom; and 3, severe symptom). A total score (range, 0-60) and scores for each of the 4 symptom domains (rhinological, ear/facial, sleep, and psychological function) were calculated.
Symptom Checklist-90-Revised Symptom Checklist-90-Revised (SCL-90-R) is a selfreported multidimensional questionnaire consisting of 90 questions concerning psychological health. Subjects were asked to rate the severity of their experience of 90 symptoms over the preceding week on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The symptoms were assigned to 9 categories (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism). Results of the questionnaire were presented as T scores with a mean of 50 and a standard deviation of 10. A score of 70, two standard deviations from the mean, is considered to be clinically abnormal in SCL-90-R.16
Statistical Analysis The collected data were exported to SPSS, version 19.0 for Windows to perform statistical analyses. Analysis of variance (ANOVA) and Tukey’s range test were used to compare the average scores of the questionnaire. Student t test and Pearson correlation test were used to evaluate the association between olfactory dysfunction and the results of the questionnaire. For each test, a P value of .05 or less was treated as statistically significant.
Results Different Types of Olfactory Dysfunction Between SD and CRSwNP One hundred thirty subjects were enrolled in this study. Table 1 shows their clinical characteristics and the results of the
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Chung et al Table 1. Demographic Data of the SD and CRSwNP.a SD (n = 59) Clinical characteristics Age (y) Sex (M:F) Lund-Mackay CT score Positive allergy test (%) KVSS II test TDI Threshold Discrimination Identification SNOT-20 Total Rhino Ear/facial Sleep Psycho Olfactory function Normosmia, n (%) Hyposmia, n (%) Anosmia, n (%)
CRSwNP (n = 71)
P Value
32.25 (17.0) 45:14 2.6 (2.7) 52.5
40.37 (16.9) 52:19 11.4 (5.6) 39.4
.008 .693 .001 .135
26.34 (6.6) 6.76 (4.2) 9.68 (3.1) 9.90 (2.9)
21.90 (7.9) 5.34 (4.3) 8.14 (3.3) 8.42 (2.9)
.001 .062 .008 .005
14.91 (7.75) 5.22 (3.49) 1.0 (1.59) 5.28 (3.59) 3.28 (2.73)
16.47 (9.84) 6.97 (4.36) 1.77 (2.17) 4.66 (3.07) 3.27 (3.12)
20 (34) 36 (61) 3 (5)
14 (20) 39 (55) 18 (25)
.462 .067 .091 .438 .991 .001
Abbreviations: CRSwNP, chronic rhinosinusitis with nasal polyp; CT, computed tomography; KVSS, Korean Version of the Sniffin’ Sticks Test; SD, septal deviation; SNOT-20, sinonasal outcome test-20; TDI, Threshold-Discrimination-Identification. a Unless otherwise noted, values are reported as mean (standard deviation).
psychophysical olfactory test and quality of life (SNOT20). The 2 groups had similar sex ratios (%) and frequencies of comorbid allergic rhinitis. The mean age of CRSwNP was older than that of SD (P = .008). CRSwNP had significantly lower TDI scores than the SD group (P = .001), especially in discrimination and identification scores (P = .008 and P = .005, respectively). Although CRSwNP had significantly higher CT scores than SD, there was no difference of quality of life (SNOT-20) between the 2 groups.
Table 2. Correlation Between Threshold-DiscriminationIdentification (TDI) Scores and Lund-Mackay Computed Tomography Scores in Chronic Rhinosinusitis With Nasal Polyp.
Severe Inflammation in CRSwNP Associated With a Mixed Type of Olfactory Loss
Decreased Quality of Life in Severe CRSwNP With Anosmia
To access effects of the olfactory dysfunction, the subjects were classified into 3 olfactory subgroups (anosmia, hyposmia, and normosmia) according to the results of the KVSS II test. Table 1 shows that the majority of patients in both groups were classified as hyposmia, but anosmia (%) was significantly higher in CRSwNP (P = .001). Although the olfactory function (TDI score) decreased with increased sinonasal inflammation (CT score) in CRSwNP (r = –0.316, P = .007) (Table 2), a negative correlation was found only in identification (r = –0.29, P = .014). Therefore, this finding indicates that CRSwNP could have a sensorineural component of olfactory loss.
The influence of impaired olfactory function on the quality of life that related to sinonasal symptoms was analyzed (Figure 1). In SD, neither the total nor any of the 4 domains of SNOT-20 differed significantly between the olfactory subgroups. However, in CRSwNP, the anosmia patients had a significantly higher score in the rhinological domain of SNOT-20 than the hyposmia or normosmia patients (P = .044). To clarify the effects of sinonasal inflammation on the relationship between olfactory loss and quality of life, the subjects with CRSwNP were categorized into 3 groups by CT score: group A (0-9), group B (10-14), and group C (≥15). As seen in Table 3, TDI scores had a significant
TDI Threshold Discrimination Identification
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Correlation Coefficient (r )
P Value
−0.316 −0.228 −0.197 −0.290
.007 .056 .099 .014
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Figure 1. Effect of olfactory loss on the quality of life (Sinonasal Outcome Test-20) in patients with (A) septal deviation and (B) chronic rhinosinusitis with nasal polyp.
Table 3. Correlation Between TDI Score and Quality of Life (SNOT-20) According to Severity of Rhinosinusitis (LundMackay CT score). SNOT-20 Lund-Mackay CT scores Group A (0-9) Group B (10-14) Group C (≥ 15) Total population
r
P Value
0.143 −0.091 −0.714 −0.278
.311 .688 .001 .007
Abbreviations: CT, computed tomography; SNOT-20, Sinonasal Outcome Test-20; TDI, Threshold-Discrimination-Identification.
negative association with SNOT-20 only in group C (r = –0.714, P = .001). Therefore, this finding suggests that olfactory dysfunction has a significant negative effect on the quality of life in CRSwNP with severe inflammation.
Higher Depression Scores in the Mixed Type of Olfactory Loss Figure 2 presents the psychological profiles (SCL-90-R questionnaire) of SD and CRSwNP groups according to the olfactory status. No patient had a pathologically high score of over 70 in any symptomatic domain of SCL-90-R that
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Figure 2. Effect of olfactory loss on the psychological profiles (SCL-90-R questionnaire) in patients with (A) septal deviation and (B) chronic rhinosinusitis with nasal polyp. ANX indicates anxiety; DEP, depression; HOS, hostility; IS, interpersonal sensitivity; O-C, obsessive-compulsive; PAR, paranoid ideation; PHOB, phobic anxiety; PSY, psychoticism; SCL-90-R, Symptom Checklist-90-Revised; SOM, somatization.
might point to a psychiatric disease. Of the 9 domains, scores for anxiety and phobia were significantly higher in anosmia than normosmia in both groups. In addition, the anosmia patients in CRSwNP had a higher depression score than the normosmia and hyposmia patients (P = .025). Therefore, these findings suggest that anxiety and phobia may be common and early psychological manifestations affected by any type of olfactory loss, but depression may be a specific psychological marker for mixed type of olfactory loss.
Discussion In the present study, we investigated the effect of olfactory deficits on the quality of life and psychological profiles in
patients with common rhinological diseases. SD can cause conductive olfactory loss, and CRSwNP is a typical cause of mixed (sensorineural and conductive) olfactory loss.17 Therefore, by comparison between the 2 groups, we addressed how the sensorineural olfactory loss evoke different mechanisms interfering with the quality of life and psychological health. Our results can be summarized as follows. First, CRSwNP was characterized by a more severe olfactory loss than SD, especially in the sensorineural component (odor discrimination and identification). Second, a high CT score appeared to be an important clinical indicator of anosmia in patients with CRSwNP. Third, CRSwNP with anosmia showed decreased quality of life (SNOT-20). Fourth,
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anxiety and phobia increased in both conductive and mixed type of anosmia. And finally, depression, which increased only in anosmia patients with CRSwNP, may be a potential psychological marker susceptible to the mixed type of olfactory loss. Upper airway infection, head trauma, allergic rhinitis, congenital anomaly, endocrine disease, and drugs are known to cause olfactory dysfunction.18 Among them, nasal obstruction and chronic rhinosinusitis are considered to be the most common causes of olfactory loss. The incidence of olfactory dysfunction in patients with chronic rhinosinusitis has been reported to vary from 14% to 19%.19-21 In the present study, 73% of patients with CRSwNP had hyposmia or anosmia, and higher rate of olfactory dysfunction might be due to the inclusion of severe cases that required surgical management of CRSwNP. Septal deviation and/or chronic rhinitis are frequently accompanied by hyposmia,22 which is consistent with our study. In addition, SD and CRSwNP may have different mechanisms of olfactory dysfunction. Nasal cavity disease, such as SD or allergic rhinitis, can alter olfactory function by the disturbance of the airflow into the olfactory fissure, which results in conductive olfactory loss.23 By contrast, in CRSwNP, olfactory dysfunction results from (1) obstruction of the olfactory fissure by mucosal lesions, (2) altered olfactory mucus (Bowman’s gland) and olfactory receptor cells, (3) squamous metaplasia, and (4) increased apoptosis of olfactory neuroepithelium.6 Therefore, CRSwNP represents mixed type olfactory loss.24 Odor threshold is a neurologically peripheral parameter, but odor discrimination and identification are more influenced by higher-order cognitive functions.25 In the present study, odor discrimination and identification scores were significantly lower in CRSwNP than SD, but odor threshold was not different between the 2 groups. Therefore, it can be assumed that cognitive indicators (discrimination and identification) are more sensitive markers for damage to the olfactory epithelium in CRSwNP than peripheral indicator (odor threshold). Previous studies reported inconsistent results on the association between olfactory dysfunction and the severity of CRSwNP.19,22 However, in the present study, higher CT scores in CRSwNP significantly correlated with decreased olfactory ability, especially with identification scores, indicating sensorineural component. Therefore, we can suppose that sensorineural olfactory loss may be aggravated by the increased inflammation in patients with CRSwNP. In addition, the presence of anosmia may indicate the most severe phenotype or endotype of CRSwNP. A recent review concluded that most patients with olfactory dysfunction seemed to cope well with their disability.7 However, one-third of the patients had more severe problems and reported a significant reduction in quality of life.7 In addition, a retrospective survey revealed that patients
having persistent olfactory loss reported a higher level of disability and lower quality of life than those with improved olfactory function. These results emphasized the importance of counseling or psychological support in the treatment of olfactory dysfunction.26 In the present study, most of the SD group suffered from hyposmia, but their decreased olfactory ability did not affect their quality of life (SNOT20). However, CRSwNP with anosmia was found to suffer from decreased quality of life. These results support the hypothesis that quality of life can be decreased by severe olfactory loss (anosmia) but mechanisms of anosmia may influence on this disability. Numerous studies have been conducted to investigate the association between the olfactory dysfunction and psychological health.27,28 Moreover, olfactory loss itself affects brain function, particularly for emotion and memory through reduced sensory input from the olfactory bulb via the amygdala into the limbic system.29 Deems et al30 reported that about a quarter to one-third of patients with olfactory disorders exhibited depression. A recent study proposed the concept of anxiety state–dependent olfactory processing and neural circuitry adaptation, which supports an olfactory etiology model of emotional disorders.28 It is recommended that patients with olfactory dysfunction should be informed about coping strategies because restrictions in daily life may reduce patients’ participation in social life and make them more prone to depression.7,31 In the current study, anxiety and phobia scores increased in anosmic subjects of both CRSwNP and SD. However, depression scores increased only in anosmic CRSwNP. This might support that olfactory impairment can affect some aspects of patients’ emotion regardless of mechanisms of olfactory loss. Furthermore, increased depression in CRSwNP may suggest that olfactory impairment with sensory neural damage has more significant psychological effects. Although the presence of apparent psychological disease was not observed in the study, relatively high scores of SNOT-20 and SCL-90-R in SD and CRSwNP might disturb patients’ daily life. We acknowledge that there are weakness and limitations of the present study. The duration of olfactory loss could not be considered because most patients hardly recall the exact onset of olfactory dysfunction. In addition, other etiologies of olfactory loss, such as viral infection, head trauma, and neurodegenerative disorders, could not be included in the current study. Further study with a full spectrum of olfactory losses would help clarify the influences of olfactory loss on quality of life and psychological profile.
Conclusions Anosmia has a negative effect on the quality of life of patients with CRSwNP. In addition, anxiety and phobia can be susceptible in anosmic patients regardless of mechanisms.
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Chung et al However, depression might be associated with the mixed type of olfactory loss. In conclusion, CRSwNP with anosmia may be an important phenotype with decreased quality of life and increased psychological symptoms. Therefore, we suggest that psychological support and consideration of qualityof-life issues would be helpful when treating patients with severe olfactory dysfunction. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2013R1A1A2007651). Role of the Sponsor: Research Foundation of Korea 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
References 1. Seo HS, Jeon KJ, Hummel T, Min BC. Influences of olfactory impairment on depression, cognitive performance, and quality of life in Korean elderly. Eur Arch Otorhinolaryngol. 2009;266(11):1739-1745. 2. Rahayel S, Frasnelli J, Joubert S. The effect of Alzheimer’s disease and Parkinson’s disease on olfaction: a meta-analysis. Behav Brain Res. 2012;231(1):60-74. 3. Murphy C, Doty RL, Duncan HJ. Clinical disorders of olfaction. In: Doty RL, ed. Handbook of Olfaction and Gustation. New York: Marcel Dekker; 2003. 4. Gil-Carcedo LM, Gil-Carcedo E, Vallejo LA, Ortega P. Proposed classification scheme for quantitative olfactory function alterations. Otolaryngol Head Neck Surg. 1999;121(6):820-825. 5. Patel RM, Pinto JM. Olfaction: anatomy, physiology, and disease. Clin Anat. 2014;27(1):54-60. 6. Kern RC, Conley DB, Haines GK, III, Robinson AM. Pathology of the olfactory mucosa: implications for the treatment of olfactory dysfunction. Laryngoscope. 2004;114(2):279-285. 7. Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life—an updated review. Chem Senses. 2014;39(3):185-194. 8. Kim KI, Kim SW, Hong BK, Kang JM, Jung WC. Olfactory changes in patients of dementia. Korean Journal of Otolaryngology-Head and Neck Surgery. 1997;40(10):14191424. 9. Takeda A, Baba T, Kikuchi A, et al. Olfactory dysfunction and dementia in Parkinson’s disease. J Parkinsons Dis. 2014;4(2):181-187. 10. Fokkens WJ, Lund VJ, Mullol J, et al. European position paper on rhinosinusitis and nasal polyps 2012. Rhinol Suppl. 2012;(23):1-298.
11. Lund VJ, Mackay IS. Staging in rhinosinusitus. Rhinology. 1993;31(4):183-184. 12. Kobal G, Hummel T, Sekinger B, Barz S, Roscher S, Wolf S. “Sniffin’ sticks”: screening of olfactory performance. Rhinology. 1996;34(4):222-226. 13. Cho JH, Jeong YS, Lee YJ, Hong SC, Yoon JH, Kim JK. The Korean version of the Sniffin’ stick (KVSS) test and its validity in comparison with the cross-cultural smell identification test (CC-SIT). Auris Nasus Larynx. 2009;36(3): 280-286. 14. Hong SM, Park IH, Kim KM, Shin JM, Lee HM. Relationship between the Korean Version of the Sniffin’ Stick Test and the T&T Olfactometer in the Korean Population. Clin Exp Otorhinolaryngol. 2011;4(4):184-187. 15. 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(5): 736-741. 16. Derogatis L. SCL-90-R: Administration, Scoring, and Procedures Manual. Minneapolis: National Computer system, Inc; 1994. 17. Feldman JI, Wright HN, Leopold DA. The initial evaluation of dysosmia. Am J Otolaryngol. 1986;7(6):431-444. 18. Shin KS, Cho SH, Ahn TH, et al. Sinonasal and psychological symptoms in rhinologic patients (SNOT-20 & SCL-90-R). Korean Journal of Otolaryngology-Head and Neck Surgery. 2009;52:816-821. 19. Umeda R, Furukawa M. Clinical measurement of smell in rhinosinusitis including Electro-Olfactogram (EOG). ORL Tokyo Suppl. 1988;7:770-773. 20. Kim SW, Nam IC, Kim BG, et al. The evaluation of olfactory function in patients with septal and turbinate surgery. Korean Journal of Otolaryngology-Head and Neck Surgery. 2004;47:1107-1111. 21. Friedrich JP. The treatment of nasoethmoid polyposis using endoscopic surgery. Ther Umsch. 1987;44(2):86-92. 22. Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol. 2008;122(suppl 2):S1-S84. 23. Damm M, Eckel HE, Jungehulsing M, Hummel T. Olfactory changes at threshold and suprathreshold levels following septoplasty with partial inferior turbinectomy. Ann Otol Rhinol Laryngol. 2003;112(1):91-97. 24. Shin SH, Park JY, Sohn JH. Clinical value of olfactory function tests after endoscopic sinus surgery: a short-term result. Am J Rhinol. 1999;13(1):63-66. 25. Hedner M, Larsson M, Arnold N, Zucco GM, Hummel T. Cognitive factors in odor detection, odor discrimination, and odor identification tasks. J Clin Exp Neuropsychol. 2010;32(10):1062-1067. 26. Miwa T, Furukawa M, Tsukatani T, Costanzo RM, DiNardo LJ, Reiter ER. Impact of olfactory impairment on quality of life and disability. Arch Otolaryngol Head Neck Surg. 2001;127:497-503. 27. Wasan A, Fernandez E, Jamison RN, Bhattacharyya N. Association of anxiety and depression with reported disease severity in patients undergoing evaluation for chronic rhinosinusitis. Ann Otol Rhinol Laryngol. 2007;116(7): 491-497.
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28. Krusemark EA, Novak LR, Gitelman DR, Li W. When the sense of smell meets emotion: anxiety-state-dependent olfactory processing and neural circuitry adaptation. J Neurosci. 2013;33(39):15324-15332. 29. Morales-Medina JC, Juarez I, Venancio-Garcia E, et al. Impaired structural hippocampal plasticity is associated with emotional and memory deficits in the olfactory bulbectomized rat. Neuroscience. 2013;236:233-243.
30. Deems DA, Doty RL, Settle RG, et al. Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center. Arch Otolaryngol Head Neck Surg. 1991;117(5):519-528. 31. Nordin S, Blomqvist EH, Olsson P, Stjarne P, Ehnhage A. Effects of smell loss on daily life and adopted coping strategies in patients with nasal polyposis with asthma. Acta Otolaryngol. 2011;131(8):826-832.
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research-article2015
AORXXX10.1177/0003489415576181Annals of Otology, Rhinology & LaryngologyChung et al
Article
Altered Quality of Life and Psychological Health (SCL-90-R) in Patients With Chronic Rhinosinusitis With Nasal Polyps
Annals of Otology, Rhinology & Laryngology 2015, Vol. 124(8) 663–670 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003489415576181 aor.sagepub.com
Jae Ho Chung, MD1, Yun Jae Lee, MD1, Tae Wook Kang, MD1, Kyung Rae Kim, MD1, Dong Pyo Jang, PhD2, In Young Kim, PhD2, and Seok Hyun Cho, MD1
Abstract Objectives: To investigate the impact of olfactory dysfunction on quality of life (QOL) and psychological status in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: A retrospective observational study was conducted from January 2011 to May 2012 with 130 patients with septal deviation (SD) (n = 59) and CRSwNP (n = 71). All patients underwent computed tomography (CT), allergy tests, and sniffin’ stick olfactory test. Anosmia was defined by Threshold-Discrimination-Identification (TDI) scores less than 16. QOL and psychological symptoms were assessed with the Sinonasal Outcome Test-20 (SNOT-20) and Symptom Checklist-90-Revised (SCL-90-R). Results: Odor discrimination and identification scores were significantly lower in CRSwNP than in SD (P = .008 and P = .005, respectively). In CRSwNP, identification score decreased with higher CT score (r = –0.29, P = .014). CRSwNP with anosmia showed a decreased QOL (P = .044), and SNOT-20 negatively correlated with TDI in severe CRSwNP (CT score ≥15, r = –0.714, P = .001). Anosmia patients had higher anxiety and phobia scores of SCL-90-R in both SD and CRSwNP. However, depression score increased only in CRSwNP with anosmia (P = .025). Conclusion: Olfactory dysfunction may have significant effects on QOL and psychological health. CRSwNP with anosmia is a distinct phenotype having mixed type of olfactory loss that might have a detrimental effect on depression. Keywords nasal obstruction, nasal polyposis, olfaction, otolaryngology, rhinology, sinusitis
Introduction Olfactory dysfunction is a relatively common disorder, but it is frequently unrecognized by patients and underdiagnosed by clinicians.1 Olfaction plays an important role in daily life such as food intake, has a role for defense mechanisms to detect toxic gases or spoiled food, and influences social and sexual activities. Olfactory dysfunction may affect the emotional and memory functions, especially in many neurodegenerative diseases.2 Numerous conditions can lead to the development of olfactory dysfunction, such as upper respiratory infections, head trauma, tumors, and sinonasal diseases.3 From a pathophysiologic perspective, olfactory dysfunction can be classified into conductive and sensorineural types.4 Conductive olfactory loss is characterized by blockage of air flow, preventing odorant molecules from reaching the olfactory epithelium, and sensorineural olfactory loss is caused by direct damage to either the olfactory epithelium or central olfactory pathway.5 In common nasal diseases, septal deviation (SD) can be a cause of conductive olfactory dysfunction,
and chronic rhinosinusitis with nasal polyps (CRSwNP) can be classified as a mixed (conductive and sensorineural) olfactory dysfunction.6 It has been reported that olfactory dysfunction can affect patients’ quality of life.7 Moreover, olfactory dysfunction has been linked to depression and cognitive disorders in patients with vascular dementia, Alzheimer’s disease, and Parkinson’s disease.8,9 However, few studies have investigated the effect of olfactory dysfunction on patients’ psychological health in rhinologic diseases such as SD and CRSwNP. 1
Departments of Otolaryngology-Head and Neck Surgery, School of Medicine, Hanyang University, Seoul, Korea 2 Department of Biomedical Engineering, Hanyang University, Seoul, Korea Corresponding Authors: Seok Hyun Cho, MD, Department of Otolaryngology-Head and Neck Surgery, or In Young Kim, PhD, Department of Biomedical Engineering, School of Medicine, Hanyang University, 222-Wangshimni-ro, Seongdong-gu, Seoul 133-792, Korea. Email: [email protected] or [email protected]
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The aim of this study was to evaluate the influence of olfactory dysfunction on quality of life and psychological health in patients with SD and CRSwNP. Therefore, we sought to investigate whether mixed type of olfactory dysfunction has different mechanisms altering psychological profiles in comparison to conductive type.
Methods Patients We performed the prospective observational study with 169 consecutive patients who received nasal and/or endoscopic sinus surgery in tertiary referral center from January 2011 to May 2012. Exclusion criteria included children (n = 11), history of facial trauma or nasal surgery (n = 9), paranasal sinus tumor (n = 2), presence of systemic diseases (n = 15; hypertension, cardiac diseases, diabetes mellitus, asthma, and obstructive sleep apnea), and psychological disorders (n = 2). Finally, a total of 130 eligible subjects (97 men, 33 women) were enrolled. They were divided into 2 groups: SD (n = 59) and CRSwNP (n = 71). SD were confirmed to be free of paranasal sinus inflammation by nasal endoscopy and computed tomography (CT). Diagnosis of CRSwNP was made according to the proposed criteria,10 and the severity of sinusitis was evaluated by Lund-Mackay CT score.11 All patients underwent a skin prick test to determine sensitivity to common inhaled allergens. Written informed consent was obtained from all patients. This investigation was approved by the local ethics review board and performed in accordance with the Declaration of Helsinki and good clinical practice guidelines.
Psychophysical Olfactory Test Using the Sniffin’ Sticks Test Odorants were presented in felt-tip pens (Korean version II of the Sniffin’ sticks test; KVSS II), which were modified and customized for the Korean population.12 KVSS II comprises 3 test batteries: olfactory threshold, odor discrimination, and odor identification tests. The tests were performed in order, with 5-minute intervals between them. Briefly, olfactory threshold (score range, 1-16) was defined as the concentration at which n-butanol (highest concentration 4%, 1:2 serial dilutions in 16 steps) was correctly identified 4 times in a row using a single-staircase, 3-alternative forced choice. In the odor discrimination test (score range, 0-16), triplets of odorants (2 identical and 1 different) were presented in a random order at intervals of 20 to 30 seconds, and subjects were asked to choose the odd odorant. Odor identification test (score range, 0-16) consisted of 16 odors familiar to Koreans. The sum of the 3 tests represented the ThresholdDiscrimination-Identification (TDI) score. Patients with a total score of 0 to 15 were diagnosed with anosmia, 16 to 29
with hyposmia, and over 30 with normosmia. The validity and reliability of KVSS II severity criteria have been checked for by comparison with a cross-cultural smell identification test (CC-SIT) and T&T olfactometry.13,14
Measurement of Sinonasal Symptoms and Quality of Life We measured sinonasal symptoms and quality of life with a modified Sinonasal Outcome Test-20 (SNOT-20), which contains the same 20 items as in the original test to assess 10 sinonasal symptoms as well as 10 social and emotional criteria that measure the influence of sinusitis on patient’s physical condition and quality of life.15 Each question was graded on a 4-point scale (0, no symptom; 1, mild symptom; 2, moderate symptom; and 3, severe symptom). A total score (range, 0-60) and scores for each of the 4 symptom domains (rhinological, ear/facial, sleep, and psychological function) were calculated.
Symptom Checklist-90-Revised Symptom Checklist-90-Revised (SCL-90-R) is a selfreported multidimensional questionnaire consisting of 90 questions concerning psychological health. Subjects were asked to rate the severity of their experience of 90 symptoms over the preceding week on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The symptoms were assigned to 9 categories (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism). Results of the questionnaire were presented as T scores with a mean of 50 and a standard deviation of 10. A score of 70, two standard deviations from the mean, is considered to be clinically abnormal in SCL-90-R.16
Statistical Analysis The collected data were exported to SPSS, version 19.0 for Windows to perform statistical analyses. Analysis of variance (ANOVA) and Tukey’s range test were used to compare the average scores of the questionnaire. Student t test and Pearson correlation test were used to evaluate the association between olfactory dysfunction and the results of the questionnaire. For each test, a P value of .05 or less was treated as statistically significant.
Results Different Types of Olfactory Dysfunction Between SD and CRSwNP One hundred thirty subjects were enrolled in this study. Table 1 shows their clinical characteristics and the results of the
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Chung et al Table 1. Demographic Data of the SD and CRSwNP.a SD (n = 59) Clinical characteristics Age (y) Sex (M:F) Lund-Mackay CT score Positive allergy test (%) KVSS II test TDI Threshold Discrimination Identification SNOT-20 Total Rhino Ear/facial Sleep Psycho Olfactory function Normosmia, n (%) Hyposmia, n (%) Anosmia, n (%)
CRSwNP (n = 71)
P Value
32.25 (17.0) 45:14 2.6 (2.7) 52.5
40.37 (16.9) 52:19 11.4 (5.6) 39.4
.008 .693 .001 .135
26.34 (6.6) 6.76 (4.2) 9.68 (3.1) 9.90 (2.9)
21.90 (7.9) 5.34 (4.3) 8.14 (3.3) 8.42 (2.9)
.001 .062 .008 .005
14.91 (7.75) 5.22 (3.49) 1.0 (1.59) 5.28 (3.59) 3.28 (2.73)
16.47 (9.84) 6.97 (4.36) 1.77 (2.17) 4.66 (3.07) 3.27 (3.12)
20 (34) 36 (61) 3 (5)
14 (20) 39 (55) 18 (25)
.462 .067 .091 .438 .991 .001
Abbreviations: CRSwNP, chronic rhinosinusitis with nasal polyp; CT, computed tomography; KVSS, Korean Version of the Sniffin’ Sticks Test; SD, septal deviation; SNOT-20, sinonasal outcome test-20; TDI, Threshold-Discrimination-Identification. a Unless otherwise noted, values are reported as mean (standard deviation).
psychophysical olfactory test and quality of life (SNOT20). The 2 groups had similar sex ratios (%) and frequencies of comorbid allergic rhinitis. The mean age of CRSwNP was older than that of SD (P = .008). CRSwNP had significantly lower TDI scores than the SD group (P = .001), especially in discrimination and identification scores (P = .008 and P = .005, respectively). Although CRSwNP had significantly higher CT scores than SD, there was no difference of quality of life (SNOT-20) between the 2 groups.
Table 2. Correlation Between Threshold-DiscriminationIdentification (TDI) Scores and Lund-Mackay Computed Tomography Scores in Chronic Rhinosinusitis With Nasal Polyp.
Severe Inflammation in CRSwNP Associated With a Mixed Type of Olfactory Loss
Decreased Quality of Life in Severe CRSwNP With Anosmia
To access effects of the olfactory dysfunction, the subjects were classified into 3 olfactory subgroups (anosmia, hyposmia, and normosmia) according to the results of the KVSS II test. Table 1 shows that the majority of patients in both groups were classified as hyposmia, but anosmia (%) was significantly higher in CRSwNP (P = .001). Although the olfactory function (TDI score) decreased with increased sinonasal inflammation (CT score) in CRSwNP (r = –0.316, P = .007) (Table 2), a negative correlation was found only in identification (r = –0.29, P = .014). Therefore, this finding indicates that CRSwNP could have a sensorineural component of olfactory loss.
The influence of impaired olfactory function on the quality of life that related to sinonasal symptoms was analyzed (Figure 1). In SD, neither the total nor any of the 4 domains of SNOT-20 differed significantly between the olfactory subgroups. However, in CRSwNP, the anosmia patients had a significantly higher score in the rhinological domain of SNOT-20 than the hyposmia or normosmia patients (P = .044). To clarify the effects of sinonasal inflammation on the relationship between olfactory loss and quality of life, the subjects with CRSwNP were categorized into 3 groups by CT score: group A (0-9), group B (10-14), and group C (≥15). As seen in Table 3, TDI scores had a significant
TDI Threshold Discrimination Identification
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Correlation Coefficient (r )
P Value
−0.316 −0.228 −0.197 −0.290
.007 .056 .099 .014
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Figure 1. Effect of olfactory loss on the quality of life (Sinonasal Outcome Test-20) in patients with (A) septal deviation and (B) chronic rhinosinusitis with nasal polyp.
Table 3. Correlation Between TDI Score and Quality of Life (SNOT-20) According to Severity of Rhinosinusitis (LundMackay CT score). SNOT-20 Lund-Mackay CT scores Group A (0-9) Group B (10-14) Group C (≥ 15) Total population
r
P Value
0.143 −0.091 −0.714 −0.278
.311 .688 .001 .007
Abbreviations: CT, computed tomography; SNOT-20, Sinonasal Outcome Test-20; TDI, Threshold-Discrimination-Identification.
negative association with SNOT-20 only in group C (r = –0.714, P = .001). Therefore, this finding suggests that olfactory dysfunction has a significant negative effect on the quality of life in CRSwNP with severe inflammation.
Higher Depression Scores in the Mixed Type of Olfactory Loss Figure 2 presents the psychological profiles (SCL-90-R questionnaire) of SD and CRSwNP groups according to the olfactory status. No patient had a pathologically high score of over 70 in any symptomatic domain of SCL-90-R that
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Figure 2. Effect of olfactory loss on the psychological profiles (SCL-90-R questionnaire) in patients with (A) septal deviation and (B) chronic rhinosinusitis with nasal polyp. ANX indicates anxiety; DEP, depression; HOS, hostility; IS, interpersonal sensitivity; O-C, obsessive-compulsive; PAR, paranoid ideation; PHOB, phobic anxiety; PSY, psychoticism; SCL-90-R, Symptom Checklist-90-Revised; SOM, somatization.
might point to a psychiatric disease. Of the 9 domains, scores for anxiety and phobia were significantly higher in anosmia than normosmia in both groups. In addition, the anosmia patients in CRSwNP had a higher depression score than the normosmia and hyposmia patients (P = .025). Therefore, these findings suggest that anxiety and phobia may be common and early psychological manifestations affected by any type of olfactory loss, but depression may be a specific psychological marker for mixed type of olfactory loss.
Discussion In the present study, we investigated the effect of olfactory deficits on the quality of life and psychological profiles in
patients with common rhinological diseases. SD can cause conductive olfactory loss, and CRSwNP is a typical cause of mixed (sensorineural and conductive) olfactory loss.17 Therefore, by comparison between the 2 groups, we addressed how the sensorineural olfactory loss evoke different mechanisms interfering with the quality of life and psychological health. Our results can be summarized as follows. First, CRSwNP was characterized by a more severe olfactory loss than SD, especially in the sensorineural component (odor discrimination and identification). Second, a high CT score appeared to be an important clinical indicator of anosmia in patients with CRSwNP. Third, CRSwNP with anosmia showed decreased quality of life (SNOT-20). Fourth,
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anxiety and phobia increased in both conductive and mixed type of anosmia. And finally, depression, which increased only in anosmia patients with CRSwNP, may be a potential psychological marker susceptible to the mixed type of olfactory loss. Upper airway infection, head trauma, allergic rhinitis, congenital anomaly, endocrine disease, and drugs are known to cause olfactory dysfunction.18 Among them, nasal obstruction and chronic rhinosinusitis are considered to be the most common causes of olfactory loss. The incidence of olfactory dysfunction in patients with chronic rhinosinusitis has been reported to vary from 14% to 19%.19-21 In the present study, 73% of patients with CRSwNP had hyposmia or anosmia, and higher rate of olfactory dysfunction might be due to the inclusion of severe cases that required surgical management of CRSwNP. Septal deviation and/or chronic rhinitis are frequently accompanied by hyposmia,22 which is consistent with our study. In addition, SD and CRSwNP may have different mechanisms of olfactory dysfunction. Nasal cavity disease, such as SD or allergic rhinitis, can alter olfactory function by the disturbance of the airflow into the olfactory fissure, which results in conductive olfactory loss.23 By contrast, in CRSwNP, olfactory dysfunction results from (1) obstruction of the olfactory fissure by mucosal lesions, (2) altered olfactory mucus (Bowman’s gland) and olfactory receptor cells, (3) squamous metaplasia, and (4) increased apoptosis of olfactory neuroepithelium.6 Therefore, CRSwNP represents mixed type olfactory loss.24 Odor threshold is a neurologically peripheral parameter, but odor discrimination and identification are more influenced by higher-order cognitive functions.25 In the present study, odor discrimination and identification scores were significantly lower in CRSwNP than SD, but odor threshold was not different between the 2 groups. Therefore, it can be assumed that cognitive indicators (discrimination and identification) are more sensitive markers for damage to the olfactory epithelium in CRSwNP than peripheral indicator (odor threshold). Previous studies reported inconsistent results on the association between olfactory dysfunction and the severity of CRSwNP.19,22 However, in the present study, higher CT scores in CRSwNP significantly correlated with decreased olfactory ability, especially with identification scores, indicating sensorineural component. Therefore, we can suppose that sensorineural olfactory loss may be aggravated by the increased inflammation in patients with CRSwNP. In addition, the presence of anosmia may indicate the most severe phenotype or endotype of CRSwNP. A recent review concluded that most patients with olfactory dysfunction seemed to cope well with their disability.7 However, one-third of the patients had more severe problems and reported a significant reduction in quality of life.7 In addition, a retrospective survey revealed that patients
having persistent olfactory loss reported a higher level of disability and lower quality of life than those with improved olfactory function. These results emphasized the importance of counseling or psychological support in the treatment of olfactory dysfunction.26 In the present study, most of the SD group suffered from hyposmia, but their decreased olfactory ability did not affect their quality of life (SNOT20). However, CRSwNP with anosmia was found to suffer from decreased quality of life. These results support the hypothesis that quality of life can be decreased by severe olfactory loss (anosmia) but mechanisms of anosmia may influence on this disability. Numerous studies have been conducted to investigate the association between the olfactory dysfunction and psychological health.27,28 Moreover, olfactory loss itself affects brain function, particularly for emotion and memory through reduced sensory input from the olfactory bulb via the amygdala into the limbic system.29 Deems et al30 reported that about a quarter to one-third of patients with olfactory disorders exhibited depression. A recent study proposed the concept of anxiety state–dependent olfactory processing and neural circuitry adaptation, which supports an olfactory etiology model of emotional disorders.28 It is recommended that patients with olfactory dysfunction should be informed about coping strategies because restrictions in daily life may reduce patients’ participation in social life and make them more prone to depression.7,31 In the current study, anxiety and phobia scores increased in anosmic subjects of both CRSwNP and SD. However, depression scores increased only in anosmic CRSwNP. This might support that olfactory impairment can affect some aspects of patients’ emotion regardless of mechanisms of olfactory loss. Furthermore, increased depression in CRSwNP may suggest that olfactory impairment with sensory neural damage has more significant psychological effects. Although the presence of apparent psychological disease was not observed in the study, relatively high scores of SNOT-20 and SCL-90-R in SD and CRSwNP might disturb patients’ daily life. We acknowledge that there are weakness and limitations of the present study. The duration of olfactory loss could not be considered because most patients hardly recall the exact onset of olfactory dysfunction. In addition, other etiologies of olfactory loss, such as viral infection, head trauma, and neurodegenerative disorders, could not be included in the current study. Further study with a full spectrum of olfactory losses would help clarify the influences of olfactory loss on quality of life and psychological profile.
Conclusions Anosmia has a negative effect on the quality of life of patients with CRSwNP. In addition, anxiety and phobia can be susceptible in anosmic patients regardless of mechanisms.
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Chung et al However, depression might be associated with the mixed type of olfactory loss. In conclusion, CRSwNP with anosmia may be an important phenotype with decreased quality of life and increased psychological symptoms. Therefore, we suggest that psychological support and consideration of qualityof-life issues would be helpful when treating patients with severe olfactory dysfunction. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2013R1A1A2007651). Role of the Sponsor: Research Foundation of Korea 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
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