Effects of Tobacco Smoke Exposure on Epigenetic Signatures and Immunotoxicological Reactions
Condition: The Study Focused on Reducing Tobacco Smoke Exposure for Child.
Study type: Interventional

Summary: 
      Researchers have noted that active smoke exposure was possibly related to epigenetic
      mechanism,and may further influence reactive immunotoxicological reaction on human beings.
      Some studies have been reported that smoking reduction would decrease the prevalence of
      respiratory symptoms and urinary cotinine level, but the underlying epigenetic mechanism and
      the functional changes of immunotoxicological system were still unclear. We plan to examine
      the causal relationship between smoking reduction and alterations in epigenetic
      signatures/immunotoxicological reactions. Teenager Smoking Reduction Trial (TSRT) will be
      population-based trial among teenagers. Eligible teenagers will be recruited in Taipei City
      and urinary cotinine level will be used to monitor the exposure status of active smoking at
      baseline, 1-month and 3-month of the intervention process. We will assess the potential
      change in immunotoxicological markers, including Th1/Th2 cytokines and clinical immunological
      measurements, before and after the intervention program. Furthermore, whole-genome
      methylation and miRNA expression microarrays will be used to search candidate genes for
      teenager smoking exposure. We plan to develop a prediction model for immunotoxicological
      reaction by utilizing epigenetic signature data from microRNA expression and DNA methylation
      profiles based on machine learning methodologies. We will also establish a personalized
      epigenetic prediction model for allergy development and build the risk assessment platform
      for immunotoxicological reaction under tobacco smoke exposure. Finally, we will examine the
      causal relationship between epigenetic signatures and immunotoxicological reactions under an
      independent children's cohort.
    

Detailed description: 
      Teenager Smoking Reduction Trial (TSRT)

        1. Study subjects

           TSRT is a solution-oriented trial aiming to evaluate the effectiveness of tobacco smoke
           reduction among teenagers. Eligible teenagers will fit the following criteria: (a) age
           between 12 and 16 years old; (b) have active smoke habits in past 6 months; (c) amount
           of smoke exceed 10 cigarettes per week. The subjects will be recruited from our previous
           database for schoolchildren. Telephone interview will be used to screen the eligibility
           for the teenagers. Recruitment will occur over 3-month period from 2011 April to June.
           The procedure for TSRT is showed in figure 2. In this plan, we will recruit at least 31
           asthmatic children and 31 non-asthmatic children who have active smoke habits.

        2. Data collection

      A baseline data and at the 1-month and 2-month follow-up visits, the primary caregiver
      provided data by personal interview on parents reports. The demographic information in
      questionnaires included age, gender, level of education.

      Teenagers will report the frequency of cigarette smoking by using a structured questionnaire.
      The definition of tobacco smoke exposure including: (a) ''Do you currently smoke?''-yes/no;
      (b) ''When did you begin to smoke regularly?''; (c) Smokers were also asked for the number of
      cigarettes they smoked on an average day. Nicotine dependence will be examined by using
      structure questionnaires from Fagerstrom model.

      We will contact eligible teenagers individually to get informed consent before data
      collection. The effects of our teenager smoking reduction intervention program will be
      assessed by primary outcomes such as cotinine/creatinine ratio (CCR) and the status of
      tobacco smoke exposure from questionnaire. No matter which group the participant belongs to,
      intervention and usual control group, the secondary outcomes in all participants will be
      tested as follows:

        1. Cytokines. We will test levels of interleukin 4, 5, 13 (IL-4, 5, 13), tumor necrosis
           factor-α (TNF-α), interferon-gamma (INF-γ) and toll-like receptors 2, 4, 9 (TLR-2, 4,
           9).

        2. Immunotoxicological reaction. We will determine levels of exhaled nitric oxide (eNO),
           serum eosinophil cationic protein (ECP) and absolute eosinophil count (AEC).

        3. Oxidative stress markers. Levels of the markers 8-hydroxy-2-deoxyguanosine (8-OHdG),
           malondialdehyde (MDA) and F2-isoprostane (Iso-P) will be examined.

      After first session is applied, all participants will be tested for primary outcomes and
      secondary outcomes at baseline, month 1 and month 3 of the intervention process. We can then
      compare the biomarkers before and after the intervention program.
    

Intervention name(s): Tobacco smoke reduction trial intervention program
Intervention type(s): Behavioral
Intervention description(s): Both the parents and children will receive 8 times intervention program weekly in first session. The telephone counseling will reduce the child's tobacco smoke exposure every weekly in second session. The interventionist and child jointly select behavioral goals for reducing tobacco smoke exposure for the child to work toward. The goals will be formalized as a written smoke exposure reduction plan for any of four specific behaviors, as relevant to that family: (a) smoking cessation for the child, (b) making the child's primary home smoke-free, (c) making non-home locations smoke-free.
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: tobacco smoke, intervention program