Asthma, Breathlessness, Asthma, Breathlessness, and Obesityand Obesity

in School Age Children in School Age Children

Autumn Ford, MDAutumn Ford, MDAllergy FellowAllergy Fellow

Study CoordinatorStudy Coordinator

Clinical Immunology SocietyClinical Immunology Society2007 School in Hypersensitivity and Allergic Diseases2007 School in Hypersensitivity and Allergic Diseases

Estes Park, ColoradoEstes Park, ColoradoSeptember 6-10September 6-10thth

IntroductionIntroduction

We suspect that breathlessness in obese children We suspect that breathlessness in obese children is often from physical deconditioning alone and is often from physical deconditioning alone and misdiagnosed as asthma. misdiagnosed as asthma.

BackgroundBackground

The incidence of obesity and asthma has risen to The incidence of obesity and asthma has risen to epidemic proportions in children.epidemic proportions in children.

Obesity may precede asthma, and the risk of Obesity may precede asthma, and the risk of asthma increases with increasing obesity. (asthma increases with increasing obesity. (Camargo Camargo et al, 1999; Guerra et al, 2004.)et al, 1999; Guerra et al, 2004.)

Sedentary lifestyle and obesity could contribute to Sedentary lifestyle and obesity could contribute to the development or worsening of asthma, rather the development or worsening of asthma, rather than asthma causing sedentary lifestyle and than asthma causing sedentary lifestyle and eventually obesity. eventually obesity.

BackgroundBackground

In the absence of deep inspiration, the airways of In the absence of deep inspiration, the airways of nonasthmatics behave similarly to those of nonasthmatics behave similarly to those of asthmatics.asthmatics.

Deep inspiration has a “bronchoprotective” effect Deep inspiration has a “bronchoprotective” effect in healthy individuals, and this is absent in in healthy individuals, and this is absent in asthma. asthma.

Obesity may restrict deep inspiration and prevent Obesity may restrict deep inspiration and prevent the ability to stretch the airways.the ability to stretch the airways.

Furthermore…Furthermore… Obesity leads to systemic inflammation.Obesity leads to systemic inflammation.

Hypothesis Hypothesis

#1: Breathlessness in obese children with physician #1: Breathlessness in obese children with physician diagnosed asthma is often from deconditioning diagnosed asthma is often from deconditioning rather than asthma.rather than asthma.

#2: The inflammatory mediator profiles in the #2: The inflammatory mediator profiles in the children with breathlessness from children with breathlessness from deconditioning are different than those with deconditioning are different than those with breathlessness from asthma.breathlessness from asthma.

Study design Study design

case controlled cross-sectional pilot studycase controlled cross-sectional pilot study enrolling 50 adolescents (ages 12-19)enrolling 50 adolescents (ages 12-19)

• 10 normal wt controls10 normal wt controls• 10 obese nonasthmatics10 obese nonasthmatics• 30 obese asthmatics30 obese asthmatics

23 enrolled to date23 enrolled to date 18 with data analysis 18 with data analysis

Pilot Study Design

20 Non-asthmatic children

10 Obese 10 Non-obese

30 Obese/MD dxd Asthma

Children

Asthma No Asthma

30 30(1-)

No asthmaAsthma

Inclusion CriteriaInclusion Criteria

30 obese (BMI>9530 obese (BMI>95thth %tile for age) adolescents %tile for age) adolescents with MD dx asthma in past 12 monthswith MD dx asthma in past 12 months

20 nonasthmatics (10 obese, BMI>95% and 10 20 nonasthmatics (10 obese, BMI>95% and 10 non-obese, BMI<85%)non-obese, BMI<85%)

Hgb>12 femalesHgb>12 females Hgb>13 malesHgb>13 males

MethodsMethods

Breathlessness/physical activity QuestionaireBreathlessness/physical activity Questionaire Treadmill Exercise ChallengeTreadmill Exercise Challenge Spirometry and eNOSpirometry and eNO +/- Methacholine Challenge+/- Methacholine Challenge

QuestionaireQuestionaire

History of Asthma History of Asthma History of EczemaHistory of Eczema History of Allergic Rhinitis (symptom scale: # out History of Allergic Rhinitis (symptom scale: # out

of 4)of 4)• SneezingSneezing• Nasal ItchingNasal Itching• Anterior RhinorrheaAnterior Rhinorrhea• Nasal CongestionNasal Congestion

Tobacco ExposureTobacco Exposure

AGE MEAN 15 14 15

Gender M/F 4/4 2/2 4/2

Ethnicity

Caucasian 5 0 2

African American

Other

3

0

4

0

3

1

BMI mean 20 33 39

Abd circumference mean

72 105 123

FEV1% mean 98 91 83

FVC mean 102 103 97

FeV1/FVC mean 88 82 80

# w/ AR symptoms 2 2 6

# w/ H/o AD 0 1 2

# w/ H/O tob exp 4 3 1

CONTROL n=8

OBESE-NA n=4

OBESE- A n=6

AimAim

PrimaryPrimary::To determine if the subject’s breathlessness is To determine if the subject’s breathlessness is associated with cardiopulmonary abnormalities associated with cardiopulmonary abnormalities or deconditioning. or deconditioning.

SecondarySecondary::To compare the inflammatory mediator profiles To compare the inflammatory mediator profiles of asthmatics and nonasthmatics.of asthmatics and nonasthmatics.

Primary OutcomePrimary Outcome

Graded exercise challenges: Graded exercise challenges:

--VO2 at maximal exercise--VO2 at maximal exercise

--% pulmonary reserve--% pulmonary reserve

Airway hyperresponsivenessAirway hyperresponsiveness

--Methacholine challenges--Methacholine challenges

Secondary OutcomeSecondary Outcome

Immunologic and inflammatory biomarker Immunologic and inflammatory biomarker measurementsmeasurements

• Total and specific IgE to common indoor/outdoor Total and specific IgE to common indoor/outdoor aeroallergensaeroallergens

• Exhaled Nitric OxideExhaled Nitric Oxide• Eosinophil countEosinophil count• Serum and urinary prostaglandins and leukotrienesSerum and urinary prostaglandins and leukotrienes• Fasting blood for lipidsFasting blood for lipids• Blood sugar and Hemoglobin A1cBlood sugar and Hemoglobin A1c

VO2 maxVO2 max

The rate of oxygen uptake or consumption at The rate of oxygen uptake or consumption at maximal exercisemaximal exercise

Addresses “Is exercise capacity normal?”Addresses “Is exercise capacity normal?”

Max VO2 is expressed per kg as ml/kg/min (Max VO2 is expressed per kg as ml/kg/min (based based on ht, age, sex, activity level, +/- wt)on ht, age, sex, activity level, +/- wt)

Lower limit= 83% of predictedLower limit= 83% of predicted

Pulmonary ReservePulmonary Reserve

PR= 1- Ve/MVVPR= 1- Ve/MVV

((nl is >38nl is >38))

Addresses “is ventilatory function normal?”Addresses “is ventilatory function normal?”

Ve-Minute Ventilation Ve-Minute Ventilation • RR x VtRR x Vt

MVV-Maximal Voluntary Ventilation (L/min)MVV-Maximal Voluntary Ventilation (L/min)• FEV1x40FEV1x40

In theory..In theory..

AsthmaAsthma• Reduced exercise capacityReduced exercise capacity, VO2 max, VO2 max• Normal Cardiovascular responsesNormal Cardiovascular responses• Ventilatory limitationVentilatory limitation, decreased pulmonary reserve, decreased pulmonary reserve

DeconditionedDeconditioned• Cardiovascular responses borderline abnormalCardiovascular responses borderline abnormal, improve , improve

w/ conditioningw/ conditioning• Decreased exercise capacity, VO2 maxDecreased exercise capacity, VO2 max• No ventilatory limitationNo ventilatory limitation

ObesityObesity• Nl cardiovascular responseNl cardiovascular response• Decreased exercise capacity VO2 max/kgDecreased exercise capacity VO2 max/kg• No ventilatory limitation, nl Pulm reserveNo ventilatory limitation, nl Pulm reserve

Results

CONTROL OBESE

NON

ASTHMA

OBESE

ASTHMA

VO2/kg mean

34 24 21

% PR

mean 52 35 39

Oxygen Consumption at Maximal ExerciseVO2 max/kg

Control Obese NA Obese A0

5

10

15

20

25

30

35

40

45

ml/

kg

/min

% Pulmonary Reserve

Control Obese NA Obese A0

10

20

30

40

50

60

701-

VE

/MV

V

ConclusionsConclusions

Our exercise testing was able to detect the Our exercise testing was able to detect the presence of pulmonary insufficiency at peak presence of pulmonary insufficiency at peak exercise in breathless obese adolescents.exercise in breathless obese adolescents.

Three out of six obese asthmatics had no Three out of six obese asthmatics had no evidence of significant pulmonary impairment at evidence of significant pulmonary impairment at peak exercise, possibly disputing prior physician peak exercise, possibly disputing prior physician diagnosis of asthma.diagnosis of asthma.

eNO

Control Obese NA Obese A0

25

50

75

pp

b

Additional Findings..Additional Findings..

Two of the 3 obese nonasthmatics, and 2 of the 3 Two of the 3 obese nonasthmatics, and 2 of the 3 obese asthmatics with low PR, had elevated obese asthmatics with low PR, had elevated eosinophilia and eNO.eosinophilia and eNO.

Inflammatory mediators could help distinguish Inflammatory mediators could help distinguish asthmatics from poorly conditioned obese teens.asthmatics from poorly conditioned obese teens.