Divergent bitter and sweet taste perception intensity in chronic rhinosinusitis patients

Abstract

Background:

Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that one of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes one type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses.

Methods:

We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (N=426) and without (N=226) nasal polyps and controls (N=356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt.

Results:

CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (FDR<0.05) and CRS patients and controls did not differ in their ratings of salt (FDR>0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small.

Conclusion:

CRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients.

Introduction

Chronic rhinosinusitis (CRS) is a common disease with considerable social burden. It is defined as symptomatic inflammation of the sinonasal mucosa with evidence of inflammation on exam and/or imaging lasting more than 12 weeks.^1–2 Aggregated costs of rhinosinusitis are approximately $8 billion annually³, and an estimated 16% of the population in the United States is affected.⁴ Patients with CRS have significant decrements in quality of life, with patients requiring sinus surgery having worse scores for physical pain and social functioning than those suffering from chronic obstructive pulmonary disease, congestive heart failure, back pain, or angina.^5–6 Despite this socioeconomic burden and diminished quality of life, treatment for CRS continues to be a challenge. Today, rhinosinusitis accounts for one in five antibiotics prescribed to adults in the outpatient setting in the US ⁷ and an estimated 433,000 sinus surgeries per year.⁸ However, the use of antibiotics often fails to eradicate sinus infections and thus, through repetitive courses, contributes to the increase in antibiotic resistance. A subset of these patients has sub-optimal results following surgery, thought to be due to chronic biofilm formation and compensatory persistent inflammation.

CRS is categorized into two subtypes: without (sans) nasal polyps (CRSsNP) and with nasal polyps (CRSwNP).^{1, 9} CRSwNP is dominated by type 2 inflammation and is more difficult to treat, exhibiting worse outcomes and higher incidence of comorbid conditions, such as asthma and atopy.^10–11

Bitter taste receptors (T2Rs) are proteins expressed on taste cells, and their activation results in the perception of bitterness, but these receptors are also involved in CRS pathophysiology and act through at least two mechanisms and cell types. Ciliated cells express at least one bitter receptor (TAS2R38, encoded by the TAS2R38 gene) that responds to quorum-sensing molecules released by gram-negative bacteria, resulting in the release of nitric oxide (NO), which in turn increases mucociliary clearance and has bactericidal properties in the mucus.^12–13 Common polymorphisms of the TAS2R38 gene are linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria in response to quorum-sensing molecules.¹⁴

The second sinonasal cell type that expresses bitter receptors is the solitary chemosensory cell (SCC),¹⁵ and these cells modulate the epithelial innate immune system in the upper airway through both bitter and sweet taste receptors.^16–18 When stimulated through their bitter taste receptors, SCC signals elicit an intracellular Ca²⁺ response that causes immediate release of antimicrobial peptides from adjacent epithelial cells.^19–20 The sweet receptors on these cells modulate the immune defense responses by suppressing the signaling of bitter receptors when stimulated by sweet ligands.^{14, 21} This suppression is hypothesized to be lifted in the presence of bacterial pathogens due to their glucose consumption, allowing for an amplified antimicrobial response.

We hypothesized that other bitter receptors may respond to microbial signals in addition to TAS2R38 and that insensitivity of the receptors may be evaluated through taste tests of other common bitter stimuli. We speculated that individuals with insensitive bitter taste receptors (and/or hypersensitive sweet taste receptors) would be unable to respond appropriately to curb pathogenic colonization and therefore would be more predisposed to developing CRS. We used human sensory responses to sweet and bitter compounds (taste tests) ²² to indirectly measure taste receptor function, building on the results from a similar study.²³

Materials and methods

Patients.

With institutional review board approval, we enrolled adult patients who had chronic rhinosinusitis (CRS) with endoscopic evidence of sinonasal inflammation (mucosal edema or polypoid degeneration) or overt mucopurulence. Selection for the study was limited to immune-competent patients with CRS over age 18, and exclusion criteria included patients with genetic disorders affecting mucociliary clearance, history of chemotherapy, immunodeficiencies, or rhinologic granulomatous disease. Basic demographic data were also collected from self-report and chart review, including medical history and use of nasal therapeutics. All patients were recruited from the Department of Otorhinolaryngology – Head and Neck Surgery at the University of Pennsylvania from May 10, 2010, to June 22, 2018, and the data were managed through the REDCap web application.²⁴

The control subjects were screened for chronic sinonasal disease from the same clinic site (n=49) or recruited at a community event (n=307). Each subject answered demographic questions and was asked to complete the SNOT-22 respiratory disease questionnaire, a tool used to measure quality of life scores in sinonasal disorders²⁵. Any controls with prior sinus surgery or a sinus infection treated with antibiotics or steroids in the previous six months were excluded. The results from a subset of these data have been previously published.²⁶

Comorbidities of CRS were recorded, including asthma, aspirin-exacerbated respiratory disease, allergic fungal sinusitis, allergic rhinitis, and other common comorbidities. Cell culture tests were conducted on the sputum of CRS patients for standard clinically relevant microbiota.

Taste measures.

Taste sensory ratings of five compounds [3.5e⁻¹ M sucrose; 2.5e⁻¹ M sodium chloride; 1.8e⁻⁶ M denatonium benzoate (DB); 1.8e⁻⁴ M phenylthiocarbamide (PTC); and 5.6e⁻⁵ M quinine] were collected following previously established protocols.²² Subjects rated 5 mL solutions of each compound twice (i.e., two trials) in a predetermined order. DB and quinine were chosen because they are ligands for several bitter receptors other than TAS2R38²⁷ and are used in clinical taste testing.²² PTC was chosen because it is a ligand for TAS2R38.²³ Saliva from all subjects was collected and genotyped for three variants (rs713598, rs10246939, rs1726866), as these genetic variants create taster and non-taster forms of the TAS2R38 receptor.²³ In cases where a variant could not be genotyped (3%), we imputed the missing genotype using the haplotype frequencies as a guide.²⁸

Analysis.

We grouped and compared subjects by their case-control status for demographic and clinical variables using the Fisher’s exact test for categorical variables and t-tests for continuous variables. CRS patients were also grouped by polyp status and compared with the control group. The taste intensity scores for the two trials were averaged for each taste compound for every subject. For the averaged taste intensity ratings (as well as the SNOT-22 scores), we used a linear regression model with sex, age, smoking history, asthma and the case-control status (CRS or CRS stratified by nasal polyps). We checked the relative importance of each variable in the model by calculating %R² using R package relaimpo.²⁹ To determine whether groups differed, we conducted an ANOVA with the linear regression model using type 1 sequential sum of squares and calculated the effect size (partial ɳ²).³⁰ To evaluate the case-control effect on PTC bitterness, we grouped patients by whether they had one or more “taster” alleles (PAV+) and patients with no “taster” allele (PAV-) and conducted the same analysis. (For this analysis, we dropped subjects with rare diplotypes of TAS2R38, who are grouped as ‘Other’ in Table 1). We used the false discovery rate (FDR)³¹ to correct for multiple tests (i.e., the four taste compounds; α < 0.05). The data analyses were conducted in R (version 3.5.1) and R Studio (version 1.1.456; RStudio, Inc). Graphics were plotted using ggplot2.³² The data and R scripts are available for download (https://github.com/Cailu086Lin/REDcapTasteSensitivity_Analyses).

Table 1.

Subject characteristics

Demographic	Control	CRS	P	CRSsNP	P	CRSwNP	P
Total enrollment	349	652		226		426
Female, N (%)	159 (45.6)	380 (57.8)	<0.001	112 (49.6)	0.234	160 (37.6)	<0.001
Race, N (%)			0.48		0.111		0.834
White	300 (86.5)	572 (87.9)		206 (91.2)		366 (86.1)
Non-white	49 (13.5)	80 (12.1)		20 (8.7)		60 (13.9)
Smoker, N (%)			<0.001		<0.001		<0.001
Never	281 (80.5)	367 (56.3)		117 (51.8)		250 (58.7)
Ever	68 (19.5)	285 (43.7)		109 (48.2)		176 (41.3)
Comorbidities, N (%)
Asthma	45 (14.6)	345 (52.9)	<0.001	75 (33.2)	<0.001	270 (63.4)	<0.001
Continuous variables	mean (SD)	mean (SD)		mean (SD)		mean (SD)
Age at enrollment	42 (16)	50 (15)	<0.001	50 (16)	<0.001	50 (14)	<0.001
SNOT-22	10 (12)	46 (23)	<0.001	46 (22)	<0.001	46 (23)	<0.001
TAS2R38 diplotype, N (%)			0.856		0.712		0.970
AVI/AVI	91 (26.1)	172 (26.4)		62 (27.4)		110 (25.8)
AVI/PAV	148 (42.4)	256 (40.6)		85 (37.6)		180 (42.3)
PAV/PAV	60 (17.2)	124 (19.0)		44 (19.5)		80 (18.8)
Other	50 (14.3)	91 (14.0)		35 (15.5)		56 (13.1)

CRS=Chronic rhinosinusitis; P=p-value, for each CRS group compared with control; N=number of subjects; %=percent; White = people of European ancestry by self-report, Nonwhite = otherwise; SNOT-22, Sinonasal Outcome Test, scores range from 0 to 110 with higher values indicating worse symptoms. TAS2R38 diplotype, the combination of two haplotypes of the bitter receptor, PAV is the “taster” form whereas the AVI is the “nontaster” form. Other=rare diplotypes.

Results

In total, there were 652 CRS (426 CRSwNP and 226 CRSsNP) patients and 356 controls. The CRS patients were predominantly middle-aged, of European descent, and almost half were current or previous smokers. Compared with those patients with CRS, those in the control group were similar in race (P = 0.48) but differed in other characteristics such as sex (P < 0.001), age (P < 0.001), smoking history (P < 0.001) and asthma (P < 0.001). As expected, the CRS patients had higher SNOT-22 scores (P < 0.001), indicating higher disease burden. The distribution of TAS2R38 diplotypes (AVI/AVI: 26.4%, AVP/PAV: 40.6% and PAV/PAV: 19%) in CRS patients was similar to that in the health controls (AVI/AVI: 26.1%, AVP/PAV: 42.4% and PAV/PAV: 17.2%; P = 0.86). Similar results were observed when comparing CRS subgroups with the controls (Table 1). The frequencies of TAS2R38 diplotypes were not significant deviations from the Hardy–Weinberg equilibrium either in CRS population (P = 0.27) or controls (P = 0.99). The CRS patients with other comorbidities and their microbial types in culture tests are summarized in Table 2. Of note, fewer than 7% of CRS patients were infected with Pseudomonas aeruginosa, which is relevant because these bacteria secrete chemicals that are ligands for the TAS2R38 receptor.

Table 2.

CRS patients: comorbidities and microbiota

Comorbidity	N (%)
Nasal polyps	426 (65.3)
Allergic rhinitis	168 (25.8)
Functional endoscopic sinus surgery	306 (46.9)
Aspirin-exacerbated respiratory disease	115 (17.6)
Allergic fungal sinusitis	56 (8.6)
Microbiota
Pseudomonas aeruginosa	42 (6.7)
Staphylococcus aureus	103 (15.8)
Staph. epidermidis	89 (13.7)
Haemophilus influenzae	18 (2.8)
Methicillin-resistant staphylococcus aureus	15 (2.3)
Escherichia coli	13 (2.0)
Streptococcus pneumoniae	13 (2.0)
Fungus	9 (1.4)

The main finding was that patients with CRS or CRS stratified by nasal polyps, reported DB and quinine as significantly less bitter and sucrose as significantly sweeter than did health controls (FDR < 0.05; Figure 1). There was no statistically significant case-control difference in NaCl (salty) taste intensity (FDR > 0.05). The results of the statistical tests, the relative importance of case-control and their covariates in the model, and the effect size of variables, including the covariates of age, sex, smoking history and comorbidity asthma are summarized in Table 3. Cases and controls differed in the bitterness of both denatonium benzoate and quinine but the overall effect sizes, while statistically significant, were small. Nonetheless, the relative contribution of case-control status was largest for denatonium benzoate, compared with quinine and sucrose. Age and sex also accounted for variation in these taste ratings (which differed in effect size by stimulus type) but smoking status and asthma did not.

Figure 1. Differences in the taste intensity ratings between CRS cohorts and controls.

The taste intensity ratings (y axis) were adjusted in a linear regression model with covariates of sex, age, smoking history and comorbidity asthma. (A) All CRS cases are grouped; (B) CRS patients are stratified by polyps and CRS without (sans) nasal polyps (CRSsNP) and with nasal polyps (CRSwNP). For correcting multiple tests for taste compounds, Benjamini and Hochberg FDR was applied for the significance threshold (α < 0.05), and thus the tests for DB, quinine and sucrose reached statistical significance (adjusted P <0.0375) but not for NaCl, whether CRS patients were grouped or stratified by polyps. Horizontal black bars are medians, boxes are interquartile ranges, and vertical lines are confidence intervals. NaCl = sodium chloride.

Table 3.

Summary of statistics for taste scores by cases versus controls

Compound	term	CRS vs. Controls					CRSsNP vs. CRSwNP vs. controls
		df	%R2	F	P	partial η2	df	%R2	F	P	partial η2
PTC	CRS-Control	1, 915	0.15	3.3	0.071	0.0036	2, 914	0.165	1.8	0.163	0.0040
	Age	1, 915	0.07	0.4	0.521	0.0004	1, 914	0.070	0.4	0.517	0.0005
	Sex	1, 915	0.64	6.8	0.009	0.0073	1, 914	0.633	6.5	0.011	0.0071
	Smoker	1, 915	0.03	0.0	0.971	0.000	1, 914	0.026	0.0	0.947	0.0000
	Asthma	1, 915	0.11	0.9	0.333	0.001	1, 914	0.105	0.8	0.368	0.0009
DB	CRS-Control	1, 918	0.42	65.4	< .001	0.0665	2, 917	0.418	32.7	< .001	0.0665
	Age	1, 918	0.19	10.5	0.001	0.0113	1, 917	0.185	10.5	0.001	0.0113
	Sex	1, 918	0.26	22.8	< .001	0.0243	1, 917	0.264	22.9	< .001	0.0243
	Smoker	1, 918	0.06	1.0	0.318	0.0011	1, 917	0.062	1.0	0.327	0.0010
	Asthma	1, 918	0.07	1.9	0.167	0.0021	1, 917	0.071	2.2	0.135	0.0024
Quinine	CRS-Control	1, 908	0.17	9.2	0.002	0.0100	2, 907	0.262	6.6	0.001	0.0143
	Age	1, 908	0.14	2.6	0.106	0.0029	1, 907	0.129	2.7	0.102	0.0030
	Sex	1, 908	0.59	16.2	< .001	0.0175	1, 907	0.526	14.9	< .001	0.0161
	Smoker	1, 908	0.05	0.1	0.721	0.0001	1, 907	0.046	0.3	0.615	0.0003
	Asthma	1, 908	0.05	0.7	0.398	0.0008	1, 907	0.038	0.2	0.672	0.0002
Sucrose	CRS-Control	1, 921	0.55	6.1	0.014	0.0065	2, 920	0.610	3.8	0.023	0.0081
	Age	1, 921	0.21	3.8	0.052	0.0041	1, 920	0.198	3.7	0.053	0.0041
	Sex	1, 921	0.00	0.1	0.782	0.0001	1, 920	0.004	0.2	0.692	0.0002
	Smoker	1, 921	0.03	0.6	0.446	0.0006	1, 920	0.028	0.4	0.503	0.0005
	Asthma	1, 921	0.19	0.7	0.389	0.0008	1, 920	0.160	0.3	0.577	0.0003
NaCl	CRS-Control	1, 924	0.02	0.2	0.649	0.0002	2, 923	0.248	2.7	0.065	0.0059
	Age	1, 924	0.81	12.9	< .001	0.0137	1, 923	0.650	12.8	< .001	0.0137
	Sex	1, 924	0.03	0.2	0.624	0.0003	1, 923	0.014	0.1	0.79	0.0001
	Smoker	1, 924	0.07	0.7	0.396	0.0008	1, 923	0.048	0.5	0.496	0.0005
	Asthma	1, 924	0.08	1.2	0.272	0.0013	1, 923	0.040	0.3	0.601	0.0003
SNOT-22	CRS-Control	1, 885	0.79	662.3	< .001	0.4280	2, 884	0.785	331.0	< .001	0.4282
	Age	1, 885	0.02	7.8	0.005	0.0087	1, 884	0.018	7.7	0.006	0.0087
	Sex	1, 885	0.01	15.0	< .001	0.0166	1, 884	0.010	15.2	< .001	0.0169
	Smoker	1, 885	0.03	2.0	0.159	0.0022	1, 884	0.027	2.1	0.144	0.0024
	Asthma	1, 885	0.16	22.2	< .001	0.0244	1, 884	0.160	22.0	< .001	0.0243

CRS, chronic rhinosinusitis; PTC, phenylthiocarbamide; DB, denatonium benzoate; SNOT-22, Sinonasal Outcome Test. %R², the relative proportion of variance explained by a variable, which averaged the sequential R² across orderings; partial ɳ²: effect size; a variable with a relatively large portion of R² consistently has a relatively large effect size (partial ɳ²) in the model.

The CRS patients with sensitive TAS2R38 alleles reported PTC as significantly less bitter than did controls with the same genotype (P < 0.01; Figure 2). Table 4 provides the results of the statistical tests for ratings of PTC intensity when subjects were grouped by genotype and case-control status. The case-control effect size for people with the ‘taster’ allele while statistically significant was also small. Women reported PTC as more intense than did men but there was no effect for smoking or age. For cases or controls with the insensitive ‘non-taster’ allele, there were no differences in the bitterness ratings of PTC, which were uniformly low (P > 0.05).

Figure 2. CRS patients with one or more taster alleles of the bitter receptor gene TAS2R38 rated PTC as less intense than did controls of the same genotype (PAV+), but there were no differences between patients and controls who lacked the taster allele (PAV-).

For other details see Figure 1.

Table 4.

Summary of statistics for PTC taste scores by cases versus controls and TAS2R38 diplotype

Haplotype	term	CRS vs. Controls					CRSsNP vs. CRSwNP vs. Controls
		df	%R2	F	P	partial η2	df	%R2	F	P	partial η2
PAV−	CRS-Control	1, 240	0.07	0.1	0.787	0.0003	2, 239	0.48	1.5	0.231	0.0122
	Age	1, 240	0.10	0.4	0.534	0.0016	1, 239	0.06	0.3	0.559	0.0014
	Sex	1, 240	0.24	0.8	0.380	0.0032	1, 239	0.14	0.5	0.472	0.0022
	Smoker	1, 240	0.07	0.4	0.529	0.0017	1, 239	0.05	0.4	0.530	0.0017
	Asthma	1, 240	0.52	1.9	0.169	0.0079	1, 239	0.26	1.0	0.325	0.0041
PAV+	CRS-Control	1, 576	0.26	11.1	0.001	0.0189	2, 575	0.26	5.7	0.003	0.0195
	Age	1, 576	0.07	0.8	0.382	0.0013	1, 575	0.07	0.8	0.380	0.0013
	Sex	1, 576	0.61	15.7	0.000	0.0265	1, 575	0.60	15.4	0.000	0.0260
	Smoker	1, 576	0.04	0.2	0.630	0.0004	1, 575	0.04	0.3	0.612	0.0004
	Asthma	1, 576	0.02	0.1	0.715	0.0002	1, 575	0.02	0.1	0.767	0.0002

PAV−, no taster allele; PAV+, one or more taster alleles. For other details see Table 3.

Discussion

In this study, we demonstrated that patients with CRS differ from controls in several ways. They rate bitter compounds as less intense and sucrose as more intense, which aligns with the roles of bitter T2R and sweet (T1R2/3) receptors in sinonasal innate immune defenses. We have previously reported a smaller subset of our data demonstrating similar findings.²⁶ Previous studies demonstrated that the TAS2R38 genotype was associated with CRS through the discovery that quorum-sensing Pseudomonas secretes ligands that bind the bitter receptor TAS2R38 on ciliated cells. This results in the release of NO and increased ciliary beat frequency, both of which contribute to innate immunity.¹⁴ From a clinical standpoint, persons with functional TAS2R38 alleles also have a reduced risk of developing CRS that requires surgical intervention,^12–13 and they have improved surgical outcomes compared to individuals with the nonfunctional form.¹² These observations have now been confirmed in an independent sample of US residents,³³ as well as Canadian,³⁴ Polish,³⁵ Australian,³⁶ and Italian³⁷ cohorts of CRS patients, but with an exception in another Italian population³⁸ with different clinical characteristics. However, broadening the scope of T2Rs and their role in CRS is warranted because CRS is a heterogeneous disorder and only a small fraction of patients tested here were infected with Pseudomonas aeruginosa. Our hypothesis is that these other bitter receptors may respond to products produced by other pathogens. While taste testing is only a proxy measure of taste receptor function, these results indicate that further study of receptors as agents in sinonasal infections is warranted.

Bitter taste compounds and specific taste effects.

Overall, people with CRS rated the bitter compounds as less intensely bitter than did control subjects. One of the bitter compounds we tested was DB, a commonly used bitter compound in human taste tests because it is nontoxic and is intensely bitter at low concentrations.³⁹ Moreover, DB is known to stimulate SCCs,⁴⁰ eliciting an immune response.^{18, 41} Quinine is also a commonly used bitter compound in taste testing, and both DB and quinine are broad bitter agonists, each activating multiple receptors.^{27, 42}

The results of this study show that, overall, the CRS patients demonstrate decreased sensitivity to DB and quinine, as well as increased sensitivity to sucrose. When stratified by polyp status, the DB results were replicated in both CRSsNP and CRSwNP. However, decreased sensitivity to quinine and increased sensitivity to sucrose were significant only in the CRSwNP subgroup. This result indicates that the differences between patient and control groups in quinine responsive taste receptor function is most marked in people who also have polyps, and we speculate that this pathway may be part of the polypoid disease etiology.

With regard to PTC, people with the nontaster form of TAS2R38 cannot taste low concentrations of PTC.²³ As we would expect, we did not see differences between cases and controls among people with the nontaster genotype. However, in people with one or more taster alleles, CRS patients rated PTC as less intense than did controls. We believe these effects are not due to a nonspecific taste loss because CRS patients rated sucrose as more intense than did controls and did not differ in their perception of salt. These observations likely rule out the idea that CRS patients are generally less able to taste stimuli as well as controls.

Taste test applications and limitations.

It has been hypothesized that taste testing is a proxy measure of medicine potency^{22, 43} and that sensory responses mirror receptor function in other parts of the body. Here we suggest that taste sensitivity to bitter and sweet compounds may be a proxy for taste receptor function in other tissues, including tissues in the upper airway. However, the use of taste tests has several limitations. First, the sweet taste proxy measure may not be a surrogate for T1R function because there may a second pathway, a T1R-independent mechanism⁴⁴, that aids in the detection or perceived intensity of sucrose. A second limitation is the difference in the concentration of bitter and sweet molecules sensed by sinonasal receptors, which are presumably lower than the much higher concentrations used in the taste tests. In other words, the concentrations of these compounds are higher than the physiologic concentrations that receptors in the upper airway would be exposed to and stimulated by. Thus, it is possible that assessing the lowest concentration at which a person can detect a particular compound might be a better proxy measure (i.e., threshold vs suprathreshold perception) or at least add complementary information. A third limitation is that the overall effect sizes were small which may be due to the different receptor affinities for bitter and sweet ligands evinced between taste receptors in the tongue and those expressed in upper respiratory epithelium.¹⁹ However, future studies that test a full spectrum of concentrations may prove to be useful in identifying more accurate and relevant concentrations of compounds to use.

Conclusion

The ability to assess airway taste receptor variation with a taste test is possible, as differences in airway taste receptor function may reflect impaired innate immunity and predisposition to certain respiratory infectious/inflammatory disorders. In this study, we have found a variety of bitter compounds that are rated less intensely and a sweet compound that is rated more intensely by CRS patients compared to controls. These bitter compounds target different bitter receptors found on cells in the upper airway, with PTC targeting only one receptor and DB and quinine each targeting multiple different ones. Thus, a taste test with the appropriate parameters may provide information on underlying disease pathogenesis, with potential utility in the diagnosis of CRS and treatment decisions. The potential of a taste test has implications for health care expenditures, antibiotic stewardship, and patient quality of life.