Abstract
Objectives:
In this study, we investigated the effect of functional endoscopic sinus surgery (FESS) on gustatory function in patients with chronic rhinosinusitis (CRS).
Methods:
Forty-three patients with CRS who underwent FESS were included in this study. Prior to FESS and 3 months after surgery, the severity of rhinosinusitis was assessed using the Taiwanese version of the 22-item SNOT (SNOT-22), endoscopic examination, and acoustic rhinometry. The olfactory function was evaluated using the phenylethyl alcohol odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test, and the gustatory function was evaluated using the whole mouth suprathreshold taste test (WMTT) and the taste quad test (TQT). Subgroup analyses were performed based on CRS phenotypes and endotypes.
Results:
The SNOT-22 significantly improved 3 months after FESS for all patients with CRS. The endoscopic score and olfactory function significantly improved in patients with eosinophilic CRS and in patients with nasal polyps (CRSwNP). The WMTT sweet and bitter scores were significantly lower after FESS in CRSwNP, but the TQT sweet score was significantly higher in patients without nasal polyps. In addition, patients with noneosinophilic CRS had significantly decreased WMTT and salty scores 3 months after FESS.
Conclusion:
Our results showed that the effect of FESS on gustatory function of patients with CRS was different with the different testing procedures, the association with nasal polyps, and the underlying inflammatory patterns.
Keywords
Introduction
Taste receptors on the tongue have been found to exist in the airway epithelium. 1 The bitter and sweet taste receptors are considered to regulate upper respiratory innate immunity and play an important role in killing bacteria. 2,3 When activated by bacterial products, bitter taste receptors stimulate adjacent epithelial cells to release antibacterial peptides. 4 It is postulated that the activation of sweet taste receptors inhibits the release of antibacterial peptides by bitter taste receptors, but reduction in airway mucus glucose by bacteria deactivates sweet taste receptors and removes the braking mechanism. 5
A growing body of evidence has shown that bitter and sweet taste receptors may play a role in the pathophysiology of chronic rhinosinusitis (CRS). 2,6 It is assumed that a genetic variation of the bitter taste receptor is associated with the susceptibility to gram-negative bacterial infection and the severity of CRS. 3,7,8 Insensitive bitter taste receptors and hypersensitive sweet taste receptors as indicated with a taste test were considered to be more prevalent in patients with CRS. Workman et al 4 demonstrated that the intensity rating of denatonium (bitter taste) was weaker in patients with CRS without nasal polyps (CRSsNP) than in controls, and the intensity rating of sucrose (sweet taste) in patients with CRS with nasal polyps (CRSwNP) and CRSsNP was stronger than in controls.
Recently, a systematic review and meta-analysis showed patients with CRS exhibited worse gustatory function than healthy controls. 9 The gustatory function was evaluated by taste strip tests in most studies, but the testing procedures varied. 6,10,11 The whole-mouth taste test was performed in the study by Othieno et al, but Walliczek-Dworschak et al used a regional tongue taste test to measure the gustatory function. Their results were not consistent.
Although both medical and surgical treatment of CRS have resulted in improvement in olfactory function, their effect on gustatory function remains unknown. 9 Functional endoscopic sinus surgery (FESS) has become a standard modality for treating patients with CRS whose prior medical treatment has failed, and good success rates have been reported. 12 In this study, we used solution-based whole-mouth as well as regional tongue taste tests to investigate the effect of FESS on the taste function of patients with CRS.
Materials and Methods
Participants
Patients with CRS who underwent FESS due to the failure of previous medical treatment were included in this study between August 2018 and February 2020. The diagnosis of CRS was based on the definition of the European Position Paper on Rhinosinusitis and Nasal Polyps 2012, which included a history of rhinosinusitis for more than 12 weeks, the findings of nasal endoscopy, and a radiological examination. 13 Based on the endoscopic findings, patients were divided into CRSwNP and CRSsNP. In addition, patients whose sinonasal tissues from FESS with eosinophils that outnumbered 10% of inflammatory cells were graded as eosinophilic CRS. Patients with a history of immunodeficiency or a previous sinus surgery were excluded from the study. Eligible patients were assessed for rhinosinusitis severity, olfactory function, and gustatory function before surgery and 3 months after FESS. After FESS, all patients only received nasal local treatment and nasal irrigation for postoperative management. No antihistamine or steroid was prescribed.
We selected healthy patients, matched to CRSwNP and CRSsNP, and patients with eosinophilic CRS or noneosinophilic CRS, for age and sex from our normative dataset as controls. 14 The matching criteria were the same gender and an age difference of less than 5 years. They all received 2 types of solution-based taste tests: the whole mouth suprathreshold test (WMTT), and the taste quad test (TQT) to evaluate their gustatory function.
This study was approved by the Ethics Committee of Taichung Veterans General Hospital. Written consent was obtained from each patient. The study was carried out in compliance with the Helsinki Declaration.
Assessment of Rhinosinusitis Severity
Before and 3 months after the FESS, patients completed the Taiwanese version of the SNOT-22 questionnaire. 15 They also received endoscopic examination and acoustic rhinometry. SNOT-22 is a 22-item questionnaire that is used to assess the degree of rhinitis and rhinosinusitis. Based on the frequency and severity of symptoms, the patient scores each question from 0 to 5 (0 indicating “no problem”, and 5 indicating “problem as bad as can be”). The total score is the sum of the scores of all the items (range 0-110). The endoscopic appearances were scored on a 0- to 2-point scale according to the Lund-Kennedy endoscopic grading system. 16 Endoscopic appearances included the presence of polyps, discharge, edema, scarring, and crusting. The total score is the sum of all the scores of the bilateral endoscopic findings (range 0-20). Acoustic rhinometry was performed to measure the second minimal cross-sectional area (MCA2) of the nasal cavity. The MCA2 of the right and left nasal cavity was averaged to give a mean MCA2 (cm2).
Evaluation of Olfactory Function
The smell function was evaluated by a phenylethyl alcohol (PEA) threshold test and a traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC; Sensonics, Inc).
The PEA threshold test uses different concentrations of a rose-like odorant (PEA) to measure the odor threshold. A 2-alternative forced-choice single-staircase procedure was applied. Two sniff bottles containing PEA dissolved in mineral oil or mineral oil alone are opened and positioned under the patient’s nose in a random order. The patient indicates the bottle which is giving off a stronger odor. If a difference cannot be made, a guess is required. At the beginning of the test, correct identification of the bottle giving off the stronger odor in 5 successive trials is needed to trigger a reversal of the staircase to the next lower concentration, whereas a single incorrect identification triggers the reversal of the staircase to the next higher concentration. After that, correct identification of the bottle giving off the stronger odor in 2 successive trials triggers a reversal of the staircase to the next lower concentration. A total of 7 reversals is acquired to finish the test, and the geometric mean of the last 4 reversed concentrations is used as the PEA threshold estimate. In this study, PEA concentrations ranged from 10−1 to 10−9 log vol/vol in half-log concentration steps.
University of Pennsylvania Smell Identification Test is an odor identification test modified from the North American version of UPSIT-TC. Eight odorants have been replaced in the UPSIT-TC to take into account cultural differences. 17 The UPSIT-TC consists of 40 tests. In each test, an odorant is embedded in 10-µm to 50-µm microcapsules fixed in a proprietary binder and positioned on a strip. The patient releases each odorant by scratching the strip with a pencil tip. Then the patient sniffs the released odorant and identifies the odorant by choosing a name from a set of 4 odor descriptors. The test is scored as the number of odors identified correctly. A guess is required for each test even if no odor is perceived.
Evaluation of Gustatory Function
The gustatory function was evaluated by WMTT and TQT. The methods used at the Smell & Taste Center of the University of Pennsylvania were followed. 18 Between these 2 tests, patients were allowed a break of 10 minutes. Gustatory dysfunction (hypogeusia) was determined using our normative dataset based on a ≤10th percentile each of the 6 age- and sex-adjusted groups. 14
The whole mouth suprathreshold taste test used 5 different suprathreshold concentrations of 4 basic tastant solutions. Powders of sucrose, citric acid, sodium chloride (I Chan chemical Ltd), and caffeine (Uni-Onward Corp) were dissolved in distilled water to prepare the following tastant solutions: sweet solution (concentrations of sucrose: 0.08, 0.16, 0.32, 0.64, 1.28 mol/L), sour solution (concentrations of citric acid: 0.0026, 0.0051, 0.0102, 0.0205, 0.0410 mol/L), salty solution (concentrations of sodium chloride: 0.032, 0.064, 0.128, 0.256, 0.512 mol/L), and bitter solution (concentrations of caffeine: 0.0026, 0.0051, 0.0102, 0.0205, 0.0410 mol/L).
Prior to the beginning of the whole mouth test, each patient was instructed not to smoke or eat for at least one hour. A small cup containing 10 mL of each tastant solution was presented to the patient in a counterbalanced order. The solution in the cup was sipped, swished in the mouth for 10 seconds, and expectorated. The patient was asked to select one of the 4 tastes (sweet, sour, bitter, or salty) for each solution and to make a best guess if in doubt. One point was scored if a correct identification of the taste was made. The patient was also instructed to rate the intensity of each solution. The intensity of the solution was rated using a 9-point scale: (1) not present at all, (2) very slight, (3) slight, (4) definitely present, (5) moderate, (6) moderately strong, (7) strong, (8) very strong, and (9) extremely strong. Between successive cups, the patient was instructed to rinse his or her mouth with distilled water. Each of the 5 suprathreshold concentrations for the 4 tastant solutions was tested twice by the patient. Therefore, a total of 40 tests were performed to generate a maximum correct quality identification score of 40.
Taste quad test used a single suprathreshold concentration of solution for each of the 4 basic tastants as follows: a 0.49 mol/L sucrose solution (sweet), a 0.015 mol/L citric acid solution (sour), a 0.31 mol/L sodium chloride solution (salty), and a 0.04 mol/L caffeine solution (bitter). Prior to beginning the test, the patient was instructed to protrude his or her tongue, which was visually divided by the tester into 4 quadrants (quadrant 1: right posterior tongue, quadrant 2: right anterior tongue, quadrant 3: left anterior tongue, and quadrant 4: left posterior tongue). Then, the tester used a micropipette to apply a drop (15 μL) of the tastant solution onto 1 of the 4 quadrants. The patient indicated which taste (sweet, sour, bitter, or salty) was present and made a best guess if in doubt. The patient also rated the intensity of the solution using the same 9-point scale in the whole mouth test. On each tongue quadrant, 4 tastant solutions were tested 6 times in a counterbalanced order. One point was scored if a correct identification of the taste was made. Therefore, a total of 96 tests were performed for each subject to generate a maximum score of 96.
Statistical Analyses
Sample size was calculated by use of the power analysis program G* Power 3.1. 19 The effect size was calculated based on a previous study compared gustatory function before and after ESS in patients with CRS. 10 With an α value of .05 and a power value of 0.9, the results of calculation indicated approximately 42 patients with CRS were required for this study.
All data are presented as mean ± standard deviation. The SNOT-22 score, endoscopic score, mean MCA2, PEA threshold, and UPSIT-TC score both before and after FESS were compared by the Wilcoxon signed-rank test. The correct quality identification scores and intensity rating of WMTT and TQT were compared between patients with CRS and the controls using Mann-Whitney U test. The WMTT and TQT scores and intensity rating before and after FESS were compared by the Wilcoxon signed-rank test. The WMTT and TQT scores and intensity rating were compared between CRSwNP and CRSsNP, and between patients with and without eosinophilic CRS by the Mann-Whitney U test. All computations were performed using SPSS version 17.0 (SPSS, Inc). Two-tailed P values <.05 were considered statistically significant.
Results
Participants
Forty-three patients completed the study. Among them, 26 were male and 17 were female. Their ages ranged from 21 to 80 years old with a mean of 46.33 years. Eighteen patients were CRSwNP, and 25 were CRSsNP. According to the pathologic features, 25 of the patients had eosinophilic CRS and 18 had noneosinophilic CRS. There were 13 males and 5 females in CRSwNP, 13 males and 12 females in CRSsNP, 13 males and 12 females in patients with eosinophilic CRS, and 13 males and 5 females in patients with noneosinophilic CRS. The mean age of each group was 49.61 years (CRSwNP), 43.96 years (CRSsNP), 49.20 years (eosinophilic CRS), and 42.33 (noneosinophilic CRS). There were no significant differences in age and sex between CRSwNP and CRSsNP or between patients with eosinophilic and noneosinophilic CRS.
The case–control normal group, matched to CRSwNP included 36 healthy patients, and matched to CRSsNP included 50 healthy patients. Similarly, 50 healthy patients were matched to patients with eosinophilic CRS, and 36 healthy patients were matched to patients with noneosinophilic CRS to compare their gustatory function.
Comparison of Rhinosinusitis Severity and Olfactory Function Before and 3 Months After FESS
The results of rhinosinusitis severity and olfactory function are shown in Table 1. The SNOT-22 score and endoscopic score were significantly improved in CRSwNP (P < .0001 and .005, respectively), and SNOT-22 score and MCA2 were significantly improved in CRSsNP (P < .0001 and =.011, respectively). The PEA threshold decreased, and UPSIT-TC score increased in CRSwNP and CRSsNP although only UPSIT-TC score increased significantly in CRSsNP (P = .019).
Comparison of Rhinosinusitis Severity and Olfactory Function Before and 3 Months After FESS.
Abbreviations: CRS, chronic rhinosinusitis; CRSsNP, chronic rhinosinusitis without nasal polyps; CRSwNP, chronic rhinosinusitis with nasal polyps; FESS, functional endoscopic sinus surgery; MCA2, second minimal cross-sectional area of the nasal cavity; PEA, phenylethyl alcohol; SD, standard deviation; UPSIT-TC, traditional Chinese version of the University of Pennsylvania Smell Identification Test.
a Wilcoxon signed-rank test
b P < .05.
In terms of underlying inflammatory patterns, the SNOT-22 significantly improved 3 months after surgery in both patients with eosinophilic and noneosinophilic CRS (P < .0001 and =.001, respectively). Of note, the endoscopic score, PEA threshold, and UPSIT score all significantly improved in patients with eosinophilic CRS 3 months after FESS (P = .004, .015, and <.0001, respectively).
Gustatory Function Before FESS
Using previously published age- and sex-adjusted cutoffs for WMTT and TQT, 14 none of CRSwNP but 2 CRSsNP were hypogeusic on the total WMTT correct quality identification score. Two CRSwNPs and 6 CRSsNPs were hypogeusic on the total TQT correct quality identification score. In terms of inflammatory patterns, one patient with eosinophilic CRS and one patient with noneosinophilic CRS were hypogeusic on the total WMTT correct quality identification score. Two patients with eosinophilic CRS and 6 patients with noneosinophilic CRS were hypogeusic on the total TQT correct quality identification score.
Comparisons of WMTT and TQT scores and intensity rating between CRSwNP and healthy patients, and between CRSsNP and healthy patients are shown in Table 2. There were no significant differences in total WMTT and TQT scores, and individual score, as well as intensity rating of each taste between CRSwNP and healthy patients. There were no significant differences in gustatory function between CRSsNP and healthy patients as well, except for the score of TQT sweet taste.
Comparison of WMTT and TQT Scores and Intensity Rating Between CRSwNP or CRSsNP and Matched Healthy Patients.
Abbreviations: CRS, chronic rhinosinusitis; CRSsNP, chronic rhinosinusitis without nasal polyps; CRSwNP, chronic rhinosinusitis with nasal polyps; SD, standard deviation; TQT, taste quad test; WMTT, whole mouth suprathreshold test.
a Mann-Whitney U test; P < .05.
b P < .05.
Comparisons of WMTT and TQT scores and intensity rating between patients with eosinophilic subtypes and matched healthy patients are shown in Table 3. There were no significant differences in gustatory function between patients with eosinophilic CRS or noneosinophilic CRS and their matched healthy patients, except for the score of TQT salty taste in those with noneosinophilic CRS.
Comparison of WMTT and TQT Scores and Intensity Rating Between Patients With Eosinophilic CRS or Noneosinophilic Patients and Matched Healthy Patients.
Abbreviations: CRS, chronic rhinosinusitis; SD, standard deviation; TQT, taste quad test; WMTT, whole mouth suprathreshold test.
a Mann-Whitney U test; P < .05.
b P < .05.
Comparisons of WMTT and TQT scores and intensity rating between CRSwNP and CRSsNP, and between patients with eosinophilic and noneosinophilic CRS. The results are shown in Table 4. There were no significant differences in total WMTT and TQT scores, and individual score, as well as intensity rating of each taste between between CRSwNP and CRSsNP. Similarly, there were no significant differences in the gustatory function between patients with eosinophilic and noneosinophilic CRS. However, the score of TQT salty taste was significantly lower in patients with noneosinophilic CRS than that of patients with eosinophilic CRS.
Comparison of WMTT and TQT Scores and Intensity Rating Between CRSwNP and CRSsNP, and Between Patients With Eosinophilic and Noneosinophilic CRS Before Surgery.
Abbreviations: CRS, chronic rhinosinusitis; CRSwNP, chronic rhinosinusitis with nasal polyps; CRSsNP, chronic rhinosinusitis without nasal polyps; SD, standard deviation; TQT, taste quad test; WMTT, whole mouth suprathreshold test.
a Mann-Whitney U test.
b P < .05.
Comparison of Gustatory Function Before and 3 Months After FESS
Using previously published age- and sex-adjusted cutoffs for WMTT and TQT, 14 1 CRSwNP and 5 CRSsNP was hypogeusic on the total WMTT correct quality identification score, and 5 CRSwNP and 6 CRSsNP were hypogeusic on the total TQT correct quality identification score after FESS. In terms of inflammatory patterns, 1 patient with eosinophilic CRS and 5 patients with noneosinophilic CRS were hypogeusic on the total WMTT quality identification score, and 7 patients with eosinophilic CRS and 4 patients with noneosinophilic CRS were hypogeusic on the total TQT correct quality identification score after FESS.
Table 5 shows comparisons of WMTT and TQT scores and intensity rating before and 3 months after FESS in CRSwNP and CRSsNP. There was no significant difference in total WMTT score, but the WMTT sweet and bitter scores significantly decreased after FESS in CRSwNP. The total TQT score and the individual score did not significantly change after FESS. There was no significant difference in intensity rating of each taste before and after FESS. For CRSsNP, there was no significant difference in total WMTT score, but the WMTT salty score was significantly lower after FESS. The total TQT score did not significantly change after FESS, but TQT sweet score was significantly higher. There was no significant difference in intensity rating of each taste before and after FESS.
Comparison of WMTT and TQT Scores and Intensity Rating Before and 3 Months After FESS in CRSwNP and CRSsNP.
Abbreviations: CRSwNP, chronic rhinosinusitis with nasal polyps; CRSsNP, chronic rhinosinusitis without nasal polyps; FESS, functional endoscopic sinus surgery; SD, standard deviation; TQT, taste quad test; WMTT, whole mouth suprathreshold test.
a Wilcoxon signed ranks test.
b P < .05.
Table 6 showed comparisons of WMTT and TQT scores and intensity rating before and 3 months after FESS in patients with eosinophilic and noneosinophilic CRS. The total WMTT score and salty taste intensity rating significantly decreased 3 months after FESS in patients with noneosinophilic CRS (P = .031 and = .035, respectively).
Comparison of WMTT and TQT Scores and Intensity Rating Before and 3 Months After FESS in Patients With Eosinophilic and Noneosinophilic CRS.
Abbreviations: CRS, chronic rhinosinusitis; FESS, functional endoscopic sinus surgery; SD, standard deviation; TQT, taste quad test; WMTT, whole mouth suprathreshold test.
a Wilcoxon signed-ranks test.
b P < .05.
Discussion
This study showed that there were no significant differences in total WMTT and TQT scores, and individual score, as well as intensity rating of each taste between CRSwNPs and CRSsNPs. If we divided patients with their inflammatory endotype, we found that there were no significant differences in gustatory function in patients with eosinophilic or noneosinophilic CRS either. This is the first study to compare the gustatory function between CRS phenotypes and endotypes. However, the number of patients was small in our study. Further studies are needed to verify our results.
Othieno et al applied taste strips using the whole mouth method to measure correct quality identification scores in patients with CRS and found that the score of sour taste was significantly lower than those of the sweet, salty, and bitter tastes. 11 Wolf et al also applied taste strips using the whole mouth method to measure correct quality identification scores in patients with CRS and found that male patients with CRS had lower total and bitter scores than the healthy controls, but the total scores of CRSwNP were not different from those of healthy controls. 6 Walliczek-Dworschak et al applied taste strips using the regional tongue method to measure the correct quality identification scores in CRSwNP and found that the total scores and individual scores for the 4 tastes were significantly lower in CRSwNP than normative values. 10
None of these studies simultaneously used the whole mouth and regional tongue methods to measure the correct quality identification score and intensity rating of tastants in patients with CRS. They did not conduct a comparison of the taste function neither between CRSwNP and CRSsNP nor different endotypes.
We found that the total WMTT and TQT scores, and individual score, as well as intensity rating of each taste in CRSwNP or CRSsNP were not significantly different from those of healthy patients, except for the score of TQT sweet taste in CRSsNP, which was significantly lower than that of healthy patients. These findings were compatible with the finding reported by Wolf et al but were different from results obtained by Walliczek-Dworschak et al. 6,10
Workman et al 4 demonstrated that the intensity rating of bitter taste was weaker in CRSsNP than the controls, and the intensity rating of sweet taste in CRSwNP and CRSsNP was stronger than that of the controls. Our results did not show that the intensity rating of bitter taste was weaker or the intensity rating of sweet taste was stronger in CRSwNP and CRSsNP than the healthy patients.
As the results of the WMTT and the regional tongue taste test (TQT) were compared, both tests did not demonstrate significant differences in the scores and intensity rating between patients with CRS and healthy patients, except for the score of TQT sweet taste in CRSsNP, which was significantly lower than that of healthy patients. It indicated that the results of the whole mouth taste test and the regional tongue taste test were similar in evaluating the gustatory function of patients with CRS.
Walliczek-Dworschak et al reported that the total scores and individual scores for the 4 tastes of the “taste strips” test did not significantly change after FESS in CRSwNP. 10 Our results showed that the WMTT sweet and bitter scores were significantly lower after FESS in CRSwNP, but the TQT sweet score was significantly higher in CRSsNP. When the patients were divided according to their inflammatory patterns, the total WMTT score and salty taste intensity rating significantly decreased 3 months after FESS in patients with noneosinophilic CRS. Our results showed gustatory function of patients with CRS changed after FESS, but the effect of FESS on gustatory function of patients with CRS was different with the different testing procedures, the association with nasal polyps, and the underlying inflammation endotypes. Moreover, the effect of FESS on gustatory function of patients with CRS might also be affected by the timing of the gustatory test. Walliczek-Dworschak et al’s study, the gustatory function was tested on average 190 days after FESS (range, 58-310 days), 10 but in our study, the gustatory function was tested on 3 months after FESS.
There were several limitations in this study. First, the number of patients was low, and therefore, some differences might not have been statistically significant. Second, our patients were not genotyped for taste receptors, and the polymorphisms in taste receptor genes were not evaluated in our patients. Possible differences in polymorphisms of taste receptor genes between Asian patients and Western patients might have resulted in differences in taste function between our patients and those reported in previous studies.
Conclusion
Our results showed that the gustatory function of patients with CRS was not different from the gustatory function of matched healthy patients, and the gustatory function was not different between CRSwNP and CRSsNP, and between patients with and without e eosinophilic CRS. Three months after FESS, the severity of rhinosinusitis and olfactory function of patients with CRS improved. The WMTT sweet and bitter scores were significantly lower after FESS in CRSwNP, but the TQT sweet score was significantly higher in CRSsNP. In addition, the WMTT and salty taste scores significantly decreased in patients with noneosinophilic CRS 3 months after FESS. The effect of FESS on gustatory function of patients with CRS was different with the different testing procedures, the association with nasal polyps, and the inflammatory endotypes.
Footnotes
Acknowledgments
The authors are grateful to the Biostatistics Task Force, Taichung Veterans General Hospital, Taichung, Taiwan, for assistance with the statistical analysis.
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 a grant (MOST 107-2314-B-075A-005) from the Ministry of Science and Technology, Taiwan, ROC. This study was approved by the Ethics Committee of Taichung Veterans General Hospital.
