Epidemiological Studies of Childhood Wheeze

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Epidemiological Studies of Childhood Wheeze

Risk Factors and Long-term Outcome

Emma Goksör

Department of Paediatrics

Institute of Clinical Sciences

Sahlgrenska Academy

University of Gothenburg

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Risk Factors and Long-term Outcome

Emma Goksör

Department of Paediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg

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List of abbreviations!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!"10

Introduction!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!" 11

Wheezing and asthma: definitions... 12

Wheezing phenotypes... 13

Transient and persistent wheezing... 13

Episodic viral wheeze and multiple-trigger wheeze... 14

Cohort studies exploring asthma and allergy development... 15

Birth cohorts... 15

Cross-sectional studies... 17

Prospective studies of virus-induced bronchiolitis or

obstructive bronchitis... 18

Definitions... 18

Finnish post-bronchiolitis study... 20

Finnish viral wheeze study... 21

Wheezing bronchitis follow-up... 21

Swedish post-RSV study... 22

Predicting persistent asthma... 23

Asthma Predictive Index, API... 23

Isle of Wight and PIAMA indices... 23

Hospital API for severe viral wheeze... 25

Identifying risk factors and protective factors... 25

Viral infections... 25

Heredity... 28

Other allergic manifestations... 30

Gender... 31 Obesity... 32 Smoking... 33 Antibiotics... 35 Paracetamol... 36 Fish... 37 Vitamin D... 38 Breast-feeding... 40



Methods... 45

Children of Western Sweden Study: Papers ! and !!...

45

Participants... 45

Ethical approval... 45

Procedures... 45

Response rate... 45

Questionnaire... 45

Swedish Medical Birth Register (MBR)... 47

Outcome variables... 47

Statistics – background... 48

Statistics – Papers ! and !!... 50

Wheezing bronchitis follow-up: Papers !!!, !" and "...

52

Participants... 52

Ethical approval... 52

Procedures... 52

Questionnaire... 52

Data on smoke exposure... 53

Allergy testing... 53

Airway function testing... 53

Outcome variables... 54

Statistics... 55

Results and Discussion... 57

Children of Western Sweden Study: Papers ! and !!...

57

Prevalence... 57

Heredity... 59

Other allergic manifestations... 60

Gender... 62 Smoke exposure... 63 Neonatal antibiotics... 64 Paracetamol... 66 Fish... 67 Breast-feeding... 70

Other factors of interest... 71

Phenotype differences... 73

Representativeness of the sample... 73



Asthma prevalence in adolescence... 75

Airway function in adolescence... 77

Virus or host... 79

Heredity... 80

Other allergic manifestations... 81

Gender... 83

Pre- and postnatal smoke exposure... 86

Current smoke exposure... 88

Other factors of interest... 89

Pathogenic model... 91

Strengths and weaknesses... 92

General Discussion... 95

Virus or host?... 95

Family history and development of allergic disease... 95

Gender... 95

Window of opportunity... 95

Smoking habits 1983-2003... 96

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Introduction

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Wheezing and asthma: definitions

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Transient and persistent wheezing

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Birth cohorts

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obstructive



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Special features Pneumonia group, n = 44 - - Treatment at admission: cromolyn group, budesonide group or control group

Control group 72 no atopic heredity, no wheeze < 2 y 294 Age matched at 17-20 y 93 Age and gen

-der matched, no early RSV

-Re- investigations 2-3 y, 4.4-6 y, 8-10 y, 14.9 y, 18-21 y, 27 y 3-4.5 y, 10 y, 17-20 y, 26 y (mean, ongoing) Mean 1 y, 3 y, 7.5 y, 13.4 y, 18 y 1.5 m, 4 m, 8 m, 12 m, 3 y, 6 y and 11 y after admission (me

-dian age 12.3 y at last re-invest)

Viral agents (RSV%)

All

(40%) _{All (28%) RSV only (100%)} All (31%)

First wheezing episode in

74% 56% 98% 87%

Bronchiolitis/wheezing bronchitis definition Wheezing or prolonged expiration during respira

-tory infection Wheezing, retraction, rhonchi,

tachypnea

during

respiratory infection Tachypnea, prolonged expiration, dyspnea, and wheezing during respira

-tory infection Wheezing and respiratory distress, during acute respiratory tract infection

Age at inclusion < 24 mo. (median = 10 m) < 24 mo. (median = 10 m) < 12 months (mean = 116 days) > 24 months (median = 10 m)

Male % 67% 61% 45% 72%

No. included

83 ₁₀₁ 47 ₁₀₀

Started year 1981-82 1984-85 1989-91 1992-93

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Finnish post-bronchiolitis study

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Finnish viral wheezing study

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Wheezing bronchitis follow-up

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Predicting persistent asthma

Asthma Predictive Index, API

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Isle of Wight and PIAMA indices

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Asthma Predictive Index (API) from the Tucson Study

Major criteria

Doctor-diagnosed parental asthma Doctor-diagnosed eczema in child

Minor criteria

Doctor-diagnosed allergic rhinitis in child Wheezing in between colds

Eosinophilia

*One major or two minor criteria required for positive index

Modified Asthma Predictive Index (API)

Major criteria

Doctor-diagnosed parental asthma Doctor-diagnosed eczema in child Sensitisation to aeroallergens

Minor criteria

Allergic sensitisation to milk, eggs or peanuts Wheezing in between colds

Eosinophilia

Hospital Asthma Predictive Index from the Korppi group

Major criteria

Doctor-diagnosed parental asthma

Doctor-diagnosed eczema and/or food allergy in child Parental (especially maternal) smoking

Minor criteria

Sensitisation to aeroallergens Wheezing due to non-RSV infection

Eosinophilia or lack of eosinophilic response during viral infection

Predictive Index from the Isle of Wight Study

Family history of asthma

Recurrent chest infections in second year of life Atopic sensitisation at age 4 years

Absence of recurrent nasal symptoms first year

Predictive Index from the PIAMA Study

Male gender Post-term delivery Parental education Inhaled medication Wheezing frequency

Wheezing or dyspnea apart from colds Respiratory tract infections

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Hospital API for severe viral wheeze

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Identifying risk factors and protective factors

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425/617-46336.7-:(36.=-Viral infections

Triggers of wheeze

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Increased risk of asthma

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Age at infection and viral load

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Allergy and viral infection



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Gender and genes



Other allergic manifestations

Allergic march

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Impact on persistence of viral wheeze

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Gender

Course of wheezing in boys and girls

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Smoking

Impact of exposure to tobacco smoke

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Allergy and smoking

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Antibiotics

Impact on wheeze and asthma

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Marker of asthma?

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Paracetamol

Increased risk of asthma

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Effect on asthma and allergy

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Vitamin D

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Effect on immune system



Breast-feeding

Effect on immune system?

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Eczema and breast-feeding

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Data on smoke exposure

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Allergy testing

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Airway function testing

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Airway function measurements

FEV₁ Forced expiratory volume in 1 second FVC₁ Forced vital capacity

FEV₁/FVC Ratio of forced expiratory volume in 1 second over forced vital capacity MEF₅₀ Maximum expiratory flow at 50% of the FVC

MEF₂₅ Maximum expiratory flow at 25% of the FVC R_5Hz Airway resistance measurements at 5Hz

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Outcome variables

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Statistics

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Multivariate



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Multivariate models for asthma

Current factors Allergy

BHR Active smoking Gender

All factors Allergy

BHR Active smoking Gender

Family history of atopy Early passive smoking

Infantile factors Gender

Family history of atopy Early passive smoking

Y)A*&#ZA

Multivariate model for abnormal airway function

Cohort

Infantile factors GenderPrenatal smoking Intense disease in early life

Cohort

All factors GenderPrenatal smoking Intense disease in early life Current asthma

Current allergic sensitisation Current BHR

Current active smoking

Study group

Infantile factors GenderSevere wheezing in early life (belonging to the cohort)

Study group

All factors GenderSevere wheezing in early life (belonging to the cohort) Current asthma

Current allergic sensitisation Current BHR

Current active smoking

Y)A*&#Z3

Multivariate models for pre- and postnatal smoke exposure

Outcomes Asthma

BHR

Allergic sensitisation Active smoking

Adjustments Family history of atopy

Gender



Results and Discussion

Children of Western Sweden Study, Papers ! and !!

Prevalence – Papers !#and !!

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Proxy for asthma

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Corresponding prevalence

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Heredity – Paper !

Increased risk of wheeze

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Parental asthma, eczema and rhinoconjunctivitis

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Other allergic manifestations – Paper !

Allergic manifestations in infancy



Allergic manifestations at preschool age

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allergy# Allergy test positive

Peanut

allergy# Eczema# Eczema treated ##

Eczema

ever Symp-toms of allergic rhinitis Allergic rhinitis# No re-current wheeze 4.0% 7.6% 0.7% 8.3% 14.6% 30.0% 4.4% 1.4% Re- current wheeze 13.0%*** 27.0%*** 2.5%*** 14.0%** 24.0%*** 51.0%*** 25.0%*** 7.0%*** MTW 23.0%*** 43.0%*** 5.0%*** 19.4%*** 28.0%*** 57.0%*** 47.0%*** 14.6%*** EVW 5.1% 13.2%* 0.7% 9.5% 20.4% 44.5%** 8.8%* 1.5%

Gender – Paper !

Increased risk of wheeze

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Smoke exposure – Paper#!

Prevalence

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No significant effect on preschool wheeze