Asthma, Breathlessness, and Obesity in School Age Children


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  • Although there is evidence to suggest sedentary lifestyle contributes to the development of asthma. Symptoms of deconditioning can be similar to those of asthma, making the distinction difficult. Diagnosis is routinely based on clinical history alone. As a result, it is imperative to distinguish obese, breathless patients with asthma from those who are simply deconditioned for the purposes of providing optimal therapeutic intervention.
  • Several studies suggest that obesity may precede asthma, and that the risk of asthma increases with increasing obesity (Camargo et al, 1999; Guerra et al, 2004). These studies suggest that sedentary lifestyle and obesity could contribute to the development or worsening of asthma, rather than asthma causing sedentary lifestyle and eventually obesity.
  • Decreased deep inspiration associated with sedentary lifestyle has been shown to increase airway hyperreactivity in non-asthmatic subjects as measured by methacholine challenge (Skloot et al, 1995). Furthermore, one single deep inspiration abolishes this hyperreactivity in non-asthmatics but not in asthmatics. It appears that deep inspiration, which is a normal part of the response to exercise has a “bronchoprotective” effect in healthy individuals but not in patients with asthma (Fredburg et al, 1999). … .Obesity leads to systemic inflammation Many have proposed that the increased amount of adipose tissues in obese subjects may induce intrinsically amplified production of inflammatory mediators and that more severe asthmatic phenotypes may result from the exaggerated production of inflammatory mediators.
  • Those with asthma will have increased TH2 cytokines, exhaled nitric oxide levels, and urinary inflammatory markers compared to those with breathlessness secondary to deconditioning.
  • The pilot study design, with regard to recruitment is displayed schematically in Figure 1. Note that within the experimental group study arm, the value 1-  denotes the false-positive error rate for physician diagnosis of asthma, which we anticipate will be approximately 0.50 within this population . The adolescents will be studied using breathlessness and physical activity questionnaires.
  • Exclusion Criteria If investigator deems subject at risk for adverse events from exercise Acute infections Uncontrolled Cardiovascular disease Inability to perform exercise testing. (ie physically unable to walk on treadmill) Oral prednisone in past 6 weeks Unable to discontinue ICS, leukotriene modifiers, LABAs 24 hours prior, or SABAs 6 hours prior to study Hgb<12 female, Hgb<13 males Pregnancy
  • To investigate whether the physician diagnosis of asthma will be confirmed or refuted based on the results of exercise challenge and pulmonary function tests and if the subject’s activity is limited by cardiopulmonary pathology or deconditioning. To compare the inflammatory mediator profiles of the breathless, obese, non-asthmatic, deconditioned subjects with those of the breathless, obese, asthmatics and healthy obese and non-obese controls.
  • The primary outcome w ill be measured by graded exercise challenges (VO2 at maximal exercise and % pulmonary reserve) and pulmonary function testing. The exercise challenge will be administered according to a GCRC Modified Bruce exercise protocol to characterize the cardiopulmonary physiology of all the participants.
  • Immunologic and inflammatory biomarker measurements: CBC with differential, exhaled nitric oxide, in vitro measurements of total IgE and specific IgE antibodies to common indoor aeroallergens, urinary cotinine (elevated in smokers), other inflammatory biomarkers Methacholine challenges will be performed to conclusively rule out presence of asthma in targeted subpopulation.
  • The internal metabolic work performed by the lung muscles is represented by a linear increase in VO2 with increasing work. VO2 max defines the upper limits of exercise capacity for a person , representing the highest burst of exertion for a short period. Predicted maximum VO2 is based on normal sedentary people, and based on ht, age, sex
  • Healthy individuals should have >30-40% pulmonary reserve at maximal exercise
  • Therefore possibly, Using exercise testing can identify subclinical lung disease in normal children. Obese children (asthma and non asthmatic) are less fit than controls. Preliminary data validates our GCRC protocol, and indicates possible presence of misdiagnosis of asthma in the outpatient clinical setting. Further data assessment is ongoing. Results from this study may help further our understanding of the relationship between obesity, asthma, and physical activity.
  • Asthma, Breathlessness, and Obesity in School Age Children

    1. 1. Asthma, Breathlessness, and Obesity in School Age Children Autumn Ford, MD Allergy Fellow Study Coordinator Clinical Immunology Society 2007 School in Hypersensitivity and Allergic Diseases Estes Park, Colorado September 6-10 th
    2. 2. Introduction <ul><li>We suspect that breathlessness in obese children is often from physical deconditioning alone and misdiagnosed as asthma. </li></ul>
    3. 3. Background <ul><li>The incidence of obesity and asthma has risen to epidemic proportions in children. </li></ul><ul><li>Obesity may precede asthma, and the risk of asthma increases with increasing obesity. ( Camargo et al, 1999; Guerra et al, 2004.) </li></ul><ul><li>Sedentary lifestyle and obesity could contribute to the development or worsening of asthma, rather than asthma causing sedentary lifestyle and eventually obesity. </li></ul>
    4. 4. Background <ul><li>In the absence of deep inspiration, the airways of nonasthmatics behave similarly to those of asthmatics. </li></ul><ul><li>Deep inspiration has a “bronchoprotective” effect in healthy individuals, and this is absent in asthma. </li></ul><ul><li>Obesity may restrict deep inspiration and prevent the ability to stretch the airways. </li></ul><ul><li>Furthermore… </li></ul><ul><li>Obesity leads to systemic inflammation. </li></ul>
    5. 5. Hypothesis <ul><li>#1: Breathlessness in obese children with physician diagnosed asthma is often from deconditioning rather than asthma. </li></ul><ul><li>#2: The inflammatory mediator profiles in the children with breathlessness from deconditioning are different than those with breathlessness from asthma. </li></ul>
    6. 6. Study design <ul><li>case controlled cross-sectional pilot study </li></ul><ul><li>enrolling 50 adolescents (ages 12-19) </li></ul><ul><ul><li>10 normal wt controls </li></ul></ul><ul><ul><li>10 obese nonasthmatics </li></ul></ul><ul><ul><li>30 obese asthmatics </li></ul></ul><ul><li>23 enrolled to date </li></ul><ul><li>18 with data analysis </li></ul>
    7. 8. Inclusion Criteria <ul><li>30 obese (BMI>95 th %tile for age) adolescents with MD dx asthma in past 12 months </li></ul><ul><li>20 nonasthmatics (10 obese, BMI>95% and 10 non-obese, BMI<85%) </li></ul><ul><li>Hgb>12 females </li></ul><ul><li>Hgb>13 males </li></ul>
    8. 9. Methods <ul><li>Breathlessness/physical activity Questionaire </li></ul><ul><li>Treadmill Exercise Challenge </li></ul><ul><li>Spirometry and eNO </li></ul><ul><li>+/- Methacholine Challenge </li></ul>
    9. 10. Questionaire <ul><li>History of Asthma </li></ul><ul><li>History of Eczema </li></ul><ul><li>History of Allergic Rhinitis (symptom scale: # out of 4) </li></ul><ul><ul><li>Sneezing </li></ul></ul><ul><ul><li>Nasal Itching </li></ul></ul><ul><ul><li>Anterior Rhinorrhea </li></ul></ul><ul><ul><li>Nasal Congestion </li></ul></ul><ul><li>Tobacco Exposure </li></ul>
    10. 11. CONTROL n=8 OBESE-NA n=4 OBESE- A n=6 6 2 2 # w/ AR symptoms 1 3 4 # w/ H/O tob exp 2 1 0 # w/ H/o AD 80 82 88 FeV1/FVC mean 97 103 102 FVC mean 83 91 98 FEV1% mean 123 105 72 Abd circumference mean 39 33 20 BMI mean 3 1 4 0 3 0 African American Other 2 0 5 Caucasian Ethnicity 4/2 2/2 4/4 Gender M/F 15 14 15 AGE MEAN
    11. 12. Aim <ul><li>Primary : </li></ul><ul><li>To determine if the subject’s breathlessness is associated with cardiopulmonary abnormalities or deconditioning. </li></ul><ul><li>Secondary : </li></ul><ul><li>To compare the inflammatory mediator profiles of asthmatics and nonasthmatics. </li></ul>
    12. 13. Primary Outcome <ul><li>Graded exercise challenges: </li></ul><ul><li>--VO2 at maximal exercise </li></ul><ul><li>--% pulmonary reserve </li></ul><ul><li>Airway hyperresponsiveness </li></ul><ul><li>--Methacholine challenges </li></ul>
    13. 14. Secondary Outcome <ul><li>Immunologic and inflammatory biomarker measurements </li></ul><ul><ul><li>Total and specific IgE to common indoor/outdoor aeroallergens </li></ul></ul><ul><ul><li>Exhaled Nitric Oxide </li></ul></ul><ul><ul><li>Eosinophil count </li></ul></ul><ul><ul><li>Serum and urinary prostaglandins and leukotrienes </li></ul></ul><ul><ul><li>Fasting blood for lipids </li></ul></ul><ul><ul><li>Blood sugar and Hemoglobin A1c </li></ul></ul>
    14. 15. VO2 max <ul><li>The rate of oxygen uptake or consumption at maximal exercise </li></ul><ul><li>Addresses “Is exercise capacity normal?” </li></ul><ul><li>Max VO2 is expressed per kg as ml/kg/min ( based on ht, age, sex, activity level, +/- wt) </li></ul><ul><li>Lower limit= 83% of predicted </li></ul>
    15. 16. Pulmonary Reserve <ul><li>PR= 1- Ve/MVV </li></ul><ul><li>( nl is >38 ) </li></ul><ul><li>Addresses “is ventilatory function normal?” </li></ul><ul><ul><ul><li>Ve-Minute Ventilation </li></ul></ul></ul><ul><ul><ul><ul><li>RR x Vt </li></ul></ul></ul></ul><ul><ul><ul><li>MVV-Maximal Voluntary Ventilation (L/min) </li></ul></ul></ul><ul><ul><ul><ul><li>FEV1x40 </li></ul></ul></ul></ul>
    16. 17. In theory.. <ul><li>Asthma </li></ul><ul><ul><li>Reduced exercise capacity , VO2 max </li></ul></ul><ul><ul><li>Normal Cardiovascular responses </li></ul></ul><ul><ul><li>Ventilatory limitation , decreased pulmonary reserve </li></ul></ul><ul><li>Deconditioned </li></ul><ul><ul><li>Cardiovascular responses borderline abnormal , improve w/ conditioning </li></ul></ul><ul><ul><li>Decreased exercise capacity, VO2 max </li></ul></ul><ul><ul><li>No ventilatory limitation </li></ul></ul><ul><li>Obesity </li></ul><ul><ul><li>Nl cardiovascular response </li></ul></ul><ul><ul><li>Decreased exercise capacity VO2 max/kg </li></ul></ul><ul><ul><li>No ventilatory limitation, nl Pulm reserve </li></ul></ul>
    17. 18. Results 39 35 52 % PR mean 21 24 34 VO2/kg mean OBESE ASTHMA OBESE NON ASTHMA CONTROL
    18. 21. Conclusions <ul><li>Our exercise testing was able to detect the presence of pulmonary insufficiency at peak exercise in breathless obese adolescents. </li></ul><ul><li>Three out of six obese asthmatics had no evidence of significant pulmonary impairment at peak exercise, possibly disputing prior physician diagnosis of asthma. </li></ul>
    19. 23. Additional Findings.. <ul><li>Two of the 3 obese nonasthmatics, and 2 of the 3 obese asthmatics with low PR, had elevated eosinophilia and eNO. </li></ul><ul><li>Inflammatory mediators could help distinguish asthmatics from poorly conditioned obese teens. </li></ul>