The Relation Between Obesity, Adipose Tissue Content of Fatty Acids and Systemic and Airway Inflammation
Condition: Asthma, Allergies and Obesity
MeSH terms: Obesity; Inflammation
Study type: Observational

Summary: 
      Obesity has been recognized as a risk factors for developing asthma. In a cohort of 5384
      children aged 15-17, we aim to:

        1. To investigate the association of asthma prevalence at age 15-17 with body mass index
           (BMI) at age 15-17 and BMI at age 11-12 years Part II

        2. To investigate the association of BMI in adolescence and BMI at age 11-12 years with:

             1. Prevalence of allergic sensitization

             2. Lung function

             3. Levels of airway inflammation at age 16-18 years

             4. Severity of asthma

      Secondly, to assess diet and physical activity involvement as effect modifiers in these
      possible associations.
    

Detailed description: 
      Cross-sectional studies in Northern America, Northern Europe and Asia indicate an increased
      prevalence and severity of asthma in the obese whereas longitudinal studies have indicated
      that increasing BMI is associated with increased risk of incident asthma in women. However,
      the mechanisms through which where-by obesity increases the risk for asthma remain unclear.
      There are only few studies from North America and Asia that suggested that obesity is
      associated with increased skin test reactivity and atopic diseases and many more that suggest
      obesity has no association with atopy. In adult asthmatics, it has also been shown that both
      medical and surgical weight loss is consistently associated with dramatic improvements in
      lung function, asthma symptoms, and medication usage. However, in children no study has
      elaborated on the potential benefits of reducing weight.

      Total fat intake has also been associated with the diagnosis of asthma. N-3 fatty acids have
      been noted to inversely correlate with body fat, while levels of N-6 fatty acids correlated
      positively with body fat. Increased dietary intake of N-3 fatty acid (such as
      eicosapentaenoic acid) (mainly fish oils) has been generally associated with protection from
      asthma, while intake of N-6 fatty acids (such as linoleic acid) may increase asthma risk,
      although this remains controversial. Linoleic acid may act as a precursor of arachidonic acid
      which subsequently serves as a precursor of 4-series leukotrienes that are highly active
      mediators of inflammation.

      There are only two studies that investigated the levels of exhaled nitric oxide (ENO) as
      indicator of airway inflammation in relation with obesity and asthma. One study showed
      significant increase of ENO with increasing BMI in healthy adults. However, the levels of ENO
      and exhaled leukotriene B4 were recently found to be increased in lean and obese asthmatic
      children but not related to their BMI's.

      In Southern European countries, there are no representative epidemiological data on the
      contribution of obesity to asthma burden. In this area of the world, there are also no
      studies on the effect of important lifestyle factors including diet and physical activity on
      the association of adiposity with asthma pathophysiology. In addition, no information exists
      on levels of airways inflammation both in non-asthmatics and asthmatics subjects in relation
      to body content in fat and the impact of weight reduction on airway inflammation.

      In years 2001-2003, a national health survey was conducted in Cyprus focusing on nutrition
      and physical fitness of all children aged 11-12 years (attending the 6th form of all primary
      schools). With this project we proposed to approach this group of children in years 2007-2009
      to investigate the following hypotheses:

      AIMS:

      The aims of the study are as follows:

      Part I To investigate the association of asthma prevalence at age 15-17 with body mass index
      (BMI) at age 15-17 and independently with BMI at age 11-12 years Part II

      To investigate the association of BMI at age 16-18 and independently of BMI at age 11-12
      years with:

        1. Prevalence of allergic sensitization

        2. Lung function

        3. Levels of airway inflammation at age 16-18 years

        4. Severity of asthma

      Secondly, to assess diet and physical activity involvement as effect modifiers in these
      possible associations.

      PART I METHODOLOGY:

      Study population Part I took place during the months of January 2007 to June 2007 and
      children attending the 1st (15-16 years) and 2nd (16-17 years) classes in all public and
      private Lyceia schools across the Republic of Cyprus were invited to participate. The
      targeted population were 19849 children that participated in an earlier study in years 2001-3
      and had amongst other assessments anthropometric measurements, assessment of
      cardio-respiratory fitness and serum lipids taken at that time.

      For the assessment of children's asthma status we used the Greek version of the ISAAC
      (International Study of Asthma and Allergies in Childhood) core questionnaire supplemented
      with questions relating to potential person-based risk factors such as the place of birth of
      the child, ethnic origin of the parents, birth order, parental education level, parental
      smoking, history of atopy in the immediate family (siblings and parents with a history of
      asthma, eczema and or hay fever), personal uptake of smoking, pet ownership and place of
      residence.

      All participating students had also their weight, percentage body fat and Body Mass Index
      (BMI) measured. The subjects' BMI had been classified as normal weight, overweight or obese
      according to sex and age specific cut-offs (six months intervals), suggested by the
      International Obesity Task Force (IOTF).

      Compilation of Dataset

      An effort to match subjects on the 2007 cross-sectional database with subjects on the
      2001-2002 old cross-sectional database was carried out using various matching parameters. A
      dataset of 5384 subjects was constructed with matched BMI values in 2007 (aged 15-17 years)
      and in 2001-2003 (aged 11-12 years).

      Statistical Analysis

      Using answers to the basic questions for asthma and respiratory morbidity of the ISAAC
      questionnaire the case definition was further refined to:

        1. Active asthma: positive answers to questions on ever having asthma and current wheeze
           and or night time cough unrelated to colds in the past 12 months

        2. Inactive asthma: positive answer to question on ever having asthma and negative answers
           to questions for current wheeze and night time cough unrelated to colds in the past 12
           months

        3. Respiratory symptoms without asthma: negative answer to question on ever having asthma
           and positive answer(s) to questions on current wheeze and or night time cough unrelated
           to colds in the past 12 months.

      The associations between disease outcomes and obesity predictors (BMI z-score and body fat
      %), were analyzed through univariate analysis and the odds ratio (OR) were calculated with
      95% confidence intervals (CI). In addition to the univariate analysis, multiple logistic
      regression was also performed to further investigate the associations of obesity predictors
      and disease outcomes adjusting for confounders and stratifying by significant effect
      modifiers. Statistical significance was set at P < 0.05.
    

Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Part I took place in 2007 and children 15-16 and 16-17 years across Cyprus were invited to
        participate. The targeted population were 19849 children that participated in an earlier
        study in years 2001-3 and had anthropometric measurements, assessment of cardio-respiratory
        fitness and serum lipids taken at that time. The subjects of the second part of the study
        were selected from the 5384 subjects that had participated in the first part and had
        matched data on current and past BMI. We targeted subjects for part two of the study with
        the following criteria:1. Current Wheezers: All active asthmatics across all BMI subgroups.
        Definition of Current Wheezer: Positive answer to the question in ISAAC questionnaire:
        "Have you had wheezing in the past 12 months?" 2. Never Wheezers: 700 controls selected in
        a random way across all BMI groups. Definition of Never Wheezer: Negative answers to both
        of the following two questions: "Have you ever had wheezing?" and "Have you ever had
        asthma?"
      
Keywords: asthma; allergies; obesity