1. Bitter Taste Phenotype & Oral NRT Adherence Karen Ahijevych, PhD, RN, FAAN Professor and Associate Dean for Academic Affairs

2. Research Team  Margaret Graham, PhD, RN, FNP  Christopher Holloman, PhD  Beverly Tepper, PhD, Rutgers University  Gail Croskey, Research Nurse  William Matcham, MS, Doctoral Candidate  Dana Longo, Graduate Research Associate  NIDA R21 Funding 2009-2012  UL1RR025755 from the National Center for Research Resources.

3. Context  Cigarette 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)

4. Oral Nicotine Replacement Therapy (NRT)  Nicotine has a bitter taste  Bitter taste phenotype (BTP) 70% of population tastes bitter 50% of smokers taste bitter (Enoch et al, 2001)

5. Problem: NRT Adherence  Differential 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)

6. Study Aims  To 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)

7. Study Design BaselineWeek 1Week 2 InhalerLozengen=55 LozengeInhalern=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

8. Inclusion Criteria  18-55 years  Cigarette smoker > 1 year, at least 10 cigarettes/day  Willing to quit smoking for 2 weeks  Not pregnant or lactating  No prescription meds altering taste  No significant acute or chronic physical/mental illness

9. 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)

10. 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)

11. 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)

12. Sample characteristics (N=120) Variable Age (yrs)32.1 ± 10.3 Female47.5% Education ≤ 12th grade36.7% Single marital status58% Race – White65.8% Race – African American27.5% Cigarettes/day15.4 ±5.7 Baseline cotinine (ng/ml)329 ±180 Menthol cigarettes40.3% Non-tasters of bitter48.3%

13. Results – NRT use Lozenges per Day Inhaler Cartridges per day Average/day4.7 ± 2.4 Median4.64 Range0 to 9 NRT provided/ week 6054

14. 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.

15. 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).

16. 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).

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

18. Heat Map of TAS2R38 genotype/phenotype data in sample Kendall tau correlation of BTP and TAS2R38 genotype classification = 0.591 (p=.0001)

19. Summary Implications

20. Proportion of Nonsmokers by NRT Type % Among Relapsers – cigarettes per day decreased from 15/day to 4 cigarettes/week (median). Harm reduction concept

21.  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.

22. Comments and Questions …