Transcript Karen Ahijevych, PhD, RN, FAAN

Bitter Taste Phenotype
& Oral NRT Adherence
Karen Ahijevych, PhD, RN, FAAN
Professor and Associate Dean for Academic Affairs
Research Team
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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.
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)
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)
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)
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)
Study Design
Baseline
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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 years
 Cigarette smoker > 1 year, at least 10
cigarettes/day
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Willing to quit smoking for 2 weeks
Not pregnant or lactating
No prescription meds altering taste
No 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)
Female
Education ≤ 12th grade
Single marital status
Race – White
Race – African American
Cigarettes/day
Baseline cotinine (ng/ml)
Menthol cigarettes
Non-tasters of bitter
32.1 ± 10.3
47.5%
36.7%
58%
65.8%
27.5%
15.4 ±5.7
329 ±180
40.3%
48.3%
Results – NRT use
Lozenges per Inhaler Cartridges
Day
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)
Summary
Implications
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.
Comments and Questions …