Bitter Taste Phenotype & Oral NRT AdherenceKaren Ahijevych, PhD, RN, FAANProfessor and Associate Dean for Academic Affairs

Research TeamMargaret Graham, PhD, RN, FNPChristopher Holloman, PhDBeverly Tepper, PhD, Rutgers UniversityGail Croskey, Research NurseWilliam Matcham, MS, Doctoral CandidateDana Longo, Graduate Research Associate

NIDA R21 Funding 2009-2012UL1RR025755 from the National Center for Research Resources.

ContextCigarette smoking is among the most important modifiable risk factors.

69% of smokers report wanting to quit (MMWR,

2011)

Pharmacotherapy significantly increases quitting success (2-3 times). (Guidelines, 2008)

Oral Nicotine Replacement Therapy

(NRT)

Nicotine has a bitter tasteBitter taste phenotype (BTP)

• 70% of population tastes bitter• 50% of smokers taste bitter (Enoch et

al, 2001)

Problem: NRT AdherenceDifferential adherence to various NRT products

Trial and error use of NRT’s can be discouraging and lead to rejection of potentially viable treatment options

Goal: Match bitter taste phenotype with NRT type (oral or transdermal) or other pharmacotherapy options (bupropion, varenicline)

Study AimsTo examine effect of BTP on individual’s use of oral NRT in cigarette smokers during smoking abstinence.

To characterize effect of BTP on sensory experiences of oral NRT products (inhaler and lozenge)

To investigate differences in use of the two NRT products comparing continuous (lozenge) and intermittent (inhaler) exposure by taste phenotype

Secondarily, describe relationship of bitter taste phenotype and taste receptor genotype (TAS2R38)

Study DesignBaseline Week 1 Week 2

Inhaler Lozenge n=55

Lozenge Inhaler n=65

NRT for 2 weeks Randomized order of treatment Protocol conducted CCTS Clinical Research

Center Retention - $100 at end of week 1& 2 ; Parking Blood and saliva collected at baseline BTP assessed at baseline and week 2

Inclusion Criteria

18-55 yearsCigarette smoker > 1 year, at least 10 cigarettes/dayWilling to quit smoking for 2 weeksNot pregnant or lactatingNo prescription meds altering tasteNo significant acute or chronic physical/mental illness

Measures

Bitter taste phenotype. Taster or non-taster at baseline and end of week 2. (Zhao et al, 2001)

NRT adherence: # of lozenges or inhaler cartridges per day. Record daily on Teleform® log.

NRT sensory response: 7 point scale on liking, satisfaction and strength in 5 areas (mouth, nose, throat, chest, windpipe). Record daily on Teleform® log. (Westman et al, 1995)

Measures continued

Salivary cotinine (ng/ml) baseline and end of week 1 and 2.

Carbon monoxide in exhaled air (ppm) baseline and end of week 1 and 2. 90% sensitivity and 89% specificity. (Jarvis et al, 1987)

3 single nucleotide polymorphisms (SNPs) in the TAS2R38 gene located on chromosome 7 account for approximately 85% of variability in bitter perception.

• SNPs confer super taster, intermediate taster, and non-taster phenotype. (Mangold et al, 2008)

Statistical Model Mixed effects linear model. Fixed effects were phenotype, NRT product type, addiction level, week, ratio of cotinine at end of week to baseline, and subject relapse.

Subject was a random effect to account for repeated measures.

Response variables were: NRT usage number (Aim 1), Sensory perceptions (Aim 2)

Sample characteristics (N=120)Variable Age (yrs) 32.1 ± 10.3Female 47.5%Education ≤ 12th grade 36.7%Single marital status 58%Race – White 65.8%Race – African American 27.5%Cigarettes/day 15.4 ±5.7Baseline cotinine (ng/ml) 329 ±180Menthol cigarettes 40.3%Non-tasters of bitter 48.3%

Results – NRT use

Lozenges per Day

Inhaler Cartridges per day

Average/day 4.7 ± 2.4 4.7 ± 2.4

Median 4.6 4

Range 0 to 9 0 to 9

NRT provided/ week 60 54

Results – Aim 1: Average number of NRT used per day

After adjusting for other factors BTP & addiction did not impact NRT usage.

NRT usage was significantly related to: product type (lozenge > inhaler), week (wk 1 > wk 2), and log cotinine ratios (positive relationship).

Relapse status marginally significant in relation to NRT usage.

Results - Aim 2: Sensory response Lower liking score with lozenge vs inhaler.

Positive relationship between addiction level and NRT satisfaction.

Males average sensory score was 1.2 points higher for lozenge than inhaler.

Menthol cigarette smokers had higher sensory scores than non-menthol smokers. (2.47 higher on 1-7 response scale).

Results – Aim 3

Interaction between bitter taste phenotype and NRT product:Did not impact average NRT usage

Custom hypothesis test for product effect when an individual is a non-taster. Among non-tasters of bitter, average number of lozenges/day was 0.654 higher than cartridges used, adjusting for other factors (p=.04).

Aim 4: Relationship of taste receptor phenotype (TAS2R38) and BTP

Heat Map of TAS2R38 genotype/phenotype data in sample

Kendall tau correlation of BTP and TAS2R38 genotype classification = 0.591 (p=.0001)

SummaryImplications

Proportion of Nonsmokers by NRT Type

%

Among Relapsers – cigarettes per day decreased from 15/day to 4 cigarettes/week (median). Harm reduction concept

Strong correlation of 3 polymorphisms of the TAS2R38 gene and bitter taste phenotype.

Limitation: Under-dosing of NRT limited variance.

Higher sensory responses among menthol cigarette smokers may suggest treatment implications.

Men had higher sensory scores with lozenges – continuous exposure.

Individualizing tobacco dependence treatment continues as a priority.

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