Effects of Tobacco Products on Live Attenuated Influenza Virus (LAIV) Infections in Human Volunteers
| Status: | Completed |
|---|---|
| Conditions: | Influenza, Smoking Cessation, Infectious Disease, Pulmonary |
| Therapuetic Areas: | Immunology / Infectious Diseases, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 45 |
| Updated: | 4/17/2018 |
| Start Date: | June 2014 |
| End Date: | June 2016 |
Chronic exposure to (cigarette smoke) CS causes biological changes, including airway
remodeling and changes in baseline gene expression profiles at the level of the epithelium.
Our own data indicate that chronic exposure to CS suppresses the ability of epithelial cells
to enhance antiviral gene expression in response to influenza infection and activate host
defense responses. While there is a large body of evidence supporting the notion that
exposure to CS causes significant changes in host defense responses, which may be linked to
permanent changes in epithelial cells at the genomic level, it is not known whether new and
emerging tobacco products have similar or distinct effects.
Using live attenuated influenza virus (LAIV) inoculation in human volunteers, this study will
compare influenza-induced responses in non-smokers (NS), cigarette smokers (CS), e-cigarette
smokers (EC), hookah smokers (HS), and Little Cigar smokers (LCS) in vivo. This will be done
by analyzing nasal viral titers, antiviral defense responses, inflammatory mediator
production, and markers of immune responses for LAIV-induced responses between the different
groups of volunteers.
remodeling and changes in baseline gene expression profiles at the level of the epithelium.
Our own data indicate that chronic exposure to CS suppresses the ability of epithelial cells
to enhance antiviral gene expression in response to influenza infection and activate host
defense responses. While there is a large body of evidence supporting the notion that
exposure to CS causes significant changes in host defense responses, which may be linked to
permanent changes in epithelial cells at the genomic level, it is not known whether new and
emerging tobacco products have similar or distinct effects.
Using live attenuated influenza virus (LAIV) inoculation in human volunteers, this study will
compare influenza-induced responses in non-smokers (NS), cigarette smokers (CS), e-cigarette
smokers (EC), hookah smokers (HS), and Little Cigar smokers (LCS) in vivo. This will be done
by analyzing nasal viral titers, antiviral defense responses, inflammatory mediator
production, and markers of immune responses for LAIV-induced responses between the different
groups of volunteers.
Cigarette smoke (CS), e-cigarette smoke (EC), hookah smoke (HS), and Little Cigar smoke
(LCS)-exposed populations will be stratified based on their responses to a smoking diary,
protocol questionnaire, as well as urine cotinine levels (which should be present in all
three groups). We are aware that many current smokers are poly-tobacco product users (i.e.
smoke cigarettes in addition to non-cigarette products), which could be confounding our
observations. This will be controlled for by having potential volunteers complete a smoking
diary and provide daily urine samples for 1 week prior to enrolling in the study. Based on
this diary, subjects will be grouped as CS (cigarettes only), EC (e-cigarette smokers and
smoking less than ½ pack of cigarettes per week), HS (hookah smokers and smoking less than ½
pack of cigarettes per week), and LCS (little cigar smokers and smoking less than ½ pack of
cigarettes per week). Individuals with mixed exposures that exceed those described above
(i.e. smoking more than ½ pack of cigarettes per week in addition to smoking hookah,
e-cigarettes, or Little Cigars) will be excluded from the studies. Potential subjects will
then complete a questionnaire regarding their smoking history, and will undergo urine
collection for measurement of cotinine for 7 consecutive days. Subjects will be assigned to
the different groups as followed: Group NS (no routine exposure to tobacco smoke, and average
log10 urine cotinine/creatinine ratio < 1.0), Group CS (active cigarette smoker and log10
urine cotinine/creatinine ratio > 4), Group EC (active e-cigarette smokers and average log10
urine cotinine/creatinine ratio 1-4), Group HS (active routine hookah smokers and average
log10 urine cotinine/creatinine ratio 1-4), or Group LCS (active routine Little Cigars smoker
and average log10 urine cotinine/creatinine ratio 1-4).
Study protocol outline:
Screening visit (2-4 weeks prior to Day 0): Obtain informed consent, history (including smoke
exposure questionnaire), physical examination, vital signs (VS), blood draw (for
anti-influenza antibody titer, HIV and T cell stimulation with flu antigen), urine (for
cotinine), nasal lavage (NL, for differential cell count, viral culture and antigen
detection, cytokine panel), nasal epithelial lining fluid (ELF, collected with filter paper
for cytokine analysis), nasal epithelial biopsy (NB) #1, pregnancy test for females of child
bearing potential. In addition, smokers will undergo spirometry.
Subjects will return to the research lab daily the for the week prior to D0 to provide a
urine sample for cotinine. Subjects will given a daily smoking/exposure diary during this
time to continue throughout the study.
Day 0 (Monday): Obtain VS, NL, ELF, urine. Administer FluMist.
Day 1 (Tuesday): Obtain VS, NL, ELF, urine, NB #2
Day 2 (Wednesday): Obtain VS, NL, ELF, urine
Day 8 +/- 1 day (Monday-Wednesday): Obtain VS, NL, ELF, urine, NB #3
Day 21 +/- 7 days: Obtain VS, blood draw, collect completed smoking/exposure diary
(LCS)-exposed populations will be stratified based on their responses to a smoking diary,
protocol questionnaire, as well as urine cotinine levels (which should be present in all
three groups). We are aware that many current smokers are poly-tobacco product users (i.e.
smoke cigarettes in addition to non-cigarette products), which could be confounding our
observations. This will be controlled for by having potential volunteers complete a smoking
diary and provide daily urine samples for 1 week prior to enrolling in the study. Based on
this diary, subjects will be grouped as CS (cigarettes only), EC (e-cigarette smokers and
smoking less than ½ pack of cigarettes per week), HS (hookah smokers and smoking less than ½
pack of cigarettes per week), and LCS (little cigar smokers and smoking less than ½ pack of
cigarettes per week). Individuals with mixed exposures that exceed those described above
(i.e. smoking more than ½ pack of cigarettes per week in addition to smoking hookah,
e-cigarettes, or Little Cigars) will be excluded from the studies. Potential subjects will
then complete a questionnaire regarding their smoking history, and will undergo urine
collection for measurement of cotinine for 7 consecutive days. Subjects will be assigned to
the different groups as followed: Group NS (no routine exposure to tobacco smoke, and average
log10 urine cotinine/creatinine ratio < 1.0), Group CS (active cigarette smoker and log10
urine cotinine/creatinine ratio > 4), Group EC (active e-cigarette smokers and average log10
urine cotinine/creatinine ratio 1-4), Group HS (active routine hookah smokers and average
log10 urine cotinine/creatinine ratio 1-4), or Group LCS (active routine Little Cigars smoker
and average log10 urine cotinine/creatinine ratio 1-4).
Study protocol outline:
Screening visit (2-4 weeks prior to Day 0): Obtain informed consent, history (including smoke
exposure questionnaire), physical examination, vital signs (VS), blood draw (for
anti-influenza antibody titer, HIV and T cell stimulation with flu antigen), urine (for
cotinine), nasal lavage (NL, for differential cell count, viral culture and antigen
detection, cytokine panel), nasal epithelial lining fluid (ELF, collected with filter paper
for cytokine analysis), nasal epithelial biopsy (NB) #1, pregnancy test for females of child
bearing potential. In addition, smokers will undergo spirometry.
Subjects will return to the research lab daily the for the week prior to D0 to provide a
urine sample for cotinine. Subjects will given a daily smoking/exposure diary during this
time to continue throughout the study.
Day 0 (Monday): Obtain VS, NL, ELF, urine. Administer FluMist.
Day 1 (Tuesday): Obtain VS, NL, ELF, urine, NB #2
Day 2 (Wednesday): Obtain VS, NL, ELF, urine
Day 8 +/- 1 day (Monday-Wednesday): Obtain VS, NL, ELF, urine, NB #3
Day 21 +/- 7 days: Obtain VS, blood draw, collect completed smoking/exposure diary
Inclusion Criteria:
- Healthy, young nonsmoking adults age 18-45 years who are not routinely exposed to
environmental tobacco smoke
- Healthy, young adults age 18-45 years who are active regular smokers (will be
stratified based on cigarette, hookah, and Little Cigars)
Exclusion Criteria:
- Pregnancy or nursing;
- history of egg allergy;
- history of allergic rhinitis;
- aspirin therapy;
- asthma;
- immunodeficiency (HIV or other);
- on immunosuppressive drugs including corticosteroids;
- history of Guillain-Barre Syndrome;
- smokers with a forced expiratory volume in 1 second (FEV1) less than 75% predicted at
screen;
- Chronic obstructive pulmonary disorder (COPD), cardiac disease, or any chronic
cardiorespiratory condition;
- febrile and/or respiratory illness within past 3 weeks prior to entry into study
We found this trial at
1
site
Chapel Hill, North Carolina 27599
Principal Investigator: Ilona Jaspers, PhD
Click here to add this to my saved trials
