Effects of Tobacco Products on Live Attenuated Influenza Virus (LAIV) Infections in Human Volunteers
Condition: Influenza, Human; Smoking; Respiratory Tract Infections; Habits
MeSH terms: Infections; Communicable Diseases; Influenza, Human; Respiratory Tract Infections
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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
    

Intervention name(s): LAIV
Intervention type(s): Biological
Intervention description(s): Standard dose of LAIV administered by a licensed health care providers.
Other intervention name(s): FluMist
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        1. Nonsmokers

          2. Cigarette smokers

          3. Primarily e-cigarette smokers

          4. Primarily hookah smokers

          5. Primarily Little Cigar smokers
      
Biospecimen description: 
      Whole blood, urine, nasal lavage fluid, nasal epithelial cells
    
Keywords: Live attenuated influenza virus (LAIV); Flu vaccine; FluMist; Smokers; New and emerging tobacco products