Assessment of the Allergic Child

Robin J Green

PhD Dept Paediatrics, University Pretoria

The Hypersensitivity Reactions

• Type I: Immediate

• Type II: Cytotoxic

• Type III: Immune complex

• Type IV: Delayed

Gell & Coombs

Atopy

• ‘Inherited tendency to produce increased amounts of IgE in response to small quantities of allergen, and to produce a clinical syndrome (asthma, allergic rhinitis, atopic eczema)’

• = Allergy + Clinical disease entity

• Non-atopic conditions with elevated IgE: Bee venom hypersensitivity/Drug reactions

Allergy Diagnosis

• History and Examination

• Identification of the Atopic Patient

• Identification of the Causative Allergen

• Evaluation of the Patient’s Environment

• Monitoring Allergic Inflammation

Total IgE Useful for Screening:• Small children < 3 years old

• Parasite infestation not common

• Allergic Broncho-pulmonary Aspergillosis

• Non Aero-allergen Allergy – Food/Occupational

• Suspected Allergy but Negative Specific Allergy Tests

• Otherwise diagnosed allergic/atopic condition not resolving

Identification of Causative Allergen

• Skin Prick Test

• ImmunoCap – Individual / Mixed

• CAST Assay

• Other – Patch testing

• - MELISA Test

Decision on Positive RAST for Foods

• Food Decision/Cut Point (kU/l) > 2 years < 2 years

• Egg 7 2

• Milk 15 5

• Peanut 14

• Fish 20

• Soya 30

• Wheat 26

Sampson H 2003

Obstructive airway disease

All volumes reduced

FEF25-75 markedly reduced

FEV1:FVC < 80%

Measuring airway inflammationExhaled NO – screening of Inflammation with a portable device (NIOX, Aerocrine)

Alving K et al. ERS 2004. Adults

Skin and Allergy Hospital, 2005 Children

0

5

10

15

20

25

30

35

0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0

Mino (ppb)

Nio

x (p

pb

)

Asthma in Pre-School Children

12

The Various Marches That Set Up Asthma

Asthma

The Atopic March

Wheezing Often Persists After Bronchiolitis

• In a study of 83 children aged <2 years hospitalised with bronchiolitis, a large proportion had subsequent wheezing

Korppi M et al. Am J Dis Child 1993;146:628-631

Childrenwith

wheezing (%)

58%

76%

0

20

40

60

80

100

1-2(n=83)

2-3(n=76)

Age (years)

15

Wheezing Phenotypes

• Tuscon:

- Transient early wheezing

- Persistent early-onset wheezing

- Late-onset wheezing (Martinez FD, 1995)

• ERS Task-Force:

- Viral induced wheeze

- Multi-trigger wheeze (Brand PLP, 2008)

ERS Definitions used in the present report

• The majority of the Task Force agreed not to use the term asthma to describe preschool wheezing illness since there is insufficient evidence showing that the pathophysiology of preschool wheezing illness is similar to that of asthma in older children and adults.

Brand PLP, et al ERJ 2008

Outcome of wheeze in infancy

Martinez FD, et al. N Engl J Med 1995; 332: 133-138

Causes of Recurrent Wheezing in Infancy

AsthmaMultiple trigger wheeze

Episodic viral wheeze

Other causes

Viruses and Asthma

Atopy

Asthma

Rhinovirus

RSV

Genes

Influenza

Rhinovirus and asthma

Atopy

Decrease in lamda interferon

Increase in ICAM - 1

Rhinovirus

Asthma exacerbations Remodeling

Vitamin D deficiency

Rhinovirus and Airway Remodeling

Rhinovirus

Increased epithelial cell cytotoxicity

Increased VGEF expression and production

Angiogenesis

Remodeling

Papadopolous N. ERS 2007

Acute Exacerbations of Asthma

• Viral infection of LRT – Infects epithelial cells

Release of Type I interferon

Airway Dendritic cellls

Increase FcERI Binding IgE

Activation TH2 cells

Release IL-4/IL-13

Antigen binding

DIAGNOSING ASTHMA

Features Suggestive of Asthma• Wheezing more than 1x/ month (Evidence C)

• Activity-induced cough or wheeze (Evidence A)

• Cough at night (Evidence A)

• Absence of seasonal variation (Evidence B)

• Symptoms persisting after the age of 3 years (Evidence A)

• Symptoms worsening with certain exposures (Evidence B)

• Colds repeatedly going to the chest (Evidence B)

• Response to a bronchodilator (Evidence B)

• Response to a 10-day oral steroid course (Evidence B)

• Concomitant rhinitis, eczema or food allergies (Evidence B)

• Family history of allergy (Evidence B)

• Response to a bronchodilators in children under 5 (FEV>12%, PEFR> (FEV>12%, PEF>20% of pre-bronchodilators PEF) (Evidence A)

• Diurnal variation of PEF >20% with twice daily readings (Evidence A)

Asthma Prediction Index

Major Criteria Family history of asthma

Positive history of

atopic eczema

Positive SPT

Minor Criteria Eosinophilia > 4%

Positive history of

allergic rhinitis

Wheeze without viral infections

Asthma = 1 Major or 2 Minor

Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD.

A clinical index to define risk of asthma in young children with recurrent wheezing.Am J Respir Crit Care Med. 2000;162(4 Pt 1):1403-6.

56% Asthmatic Children in Pretoria Atopic

Figure 1. Inhalant Allergens. % of positive tests (Only 28 of 50 patients positive)

27%

21%9%2%5%

12%

19%5% Bermuda grass

Grass mix

Tree mix

Cat epithelium

Dog dander

HDM

Cockroach

Horse

Diagnosing Asthma in Young children

• Modified Bronchodilator Response Test : Administer a bronchodilator to the child (via spacer or nebuliser) and assess the clinical response at 10 – 15 minutes

• Bronchodilator and diary card over 2 weeks

• Trial of oral corticosteroids for 7 – 14 days

SACAWG 2009

• ‘However, the overwhelming message that should be conveyed is that there is significant difficulty diagnosing asthma in pre-school children and whatever label is given this should be continually revised and all therapies continually evaluated for efficacy.’

Motala C, et al SAMJ 2009 Motala C, et al SAMJ 2009

Differential Diagnosis of Asthma in Children < 5 Years Old• Infections:

- Recurrent respiratory tract infections

- Chronic rhino-sinusitis

- Tuberculosis

- HIV disease

• Congenital problems:

- Tracheomalacia

- Cystic fibrosis

- Bronchopulmonary dysplasia

- Congenital malformation causing narrowing of the intrathoracic airways

- Primary ciliary dyskinesia syndrome

- Immune deficiency

- Congenital heart disease

• Mechanical problems:

- Foreign body aspiration

- Gastroesophageal reflux

Other causes

• HIV-related infections

• Tuberculosis

• Foreign body

• Cardiac failure

• Cystic fibrosis

• Bronchiectasis

• ILD

• Gastro-oesophageal reflux

Small Airway Disease/Bronchiolitis

Acute

Viral

BronchiolitisAsthma

Acute exacerbation of chronic process

Chronic

Persistent

Viral induced wheeze

Multi-trigger Wheeze/Asthma

Eosinophilic Bronchiolitis

Auto-immune/CT Disease

Chronic Infection

Panbronchiolitis

Necrotising Bronchiolitis

Cystic Fibrosis

Viral-induced Wheeze

Cardiac Causes

Recurrent

Congenital/ BPD Follicular

BronchiolitisGastro-oesophageal Reflux INTERSTITIAL

LUNG DISEASE

Preschool Wheeze – Finding a Cause

Recurrent wheeze in a preschool child

Anthropometry

Thriving Not thriving

Very early age of onset

Yes No

Episodic – viral induced

Yes No

Viral-induced wheeze

Asthma

Atopic

Yes No

Other triggers (exercise, emotion, smoke)

Yes No

CXRConsider: Sweat test

TB workup

HIV workup

Induced sputum

Bronchoscopy

Immune testing

TREATING ASTHMA

T re a tm e nt O p tio n s P re -sch oo l W he e ze

M o n te lu ka s t 7 - 1 4 d a ys

E p isod ic w h e e ze

IC S orL T R A

M u ltip le trigg e r w h e e zeM ild

IC S + L A B A

P e rsis te n t a sth m aM o de ra te /S eve re

W h ee ze

If not responding – Stop Treatment and Review diagnosis

Clinical Control of Asthma

No (or minimal)* daytime symptoms

No limitations of activity

No nocturnal symptoms

No (or minimal) need for rescue medication

Normal lung function

No exacerbations* Minimal = twice or less per week

Scope of the Problem

Administration

• Inhaled therapies can be difficult to administer

Routine asthma follow-up questions

1. How often have you had asthma symptoms in the last week?

2. How often have you been woken at night because of asthma symptoms in the last week?

3. How often have asthma symptoms limited your ability to be active in the last week?

4. How many puffs of reliever medicine have you used in the last week?

5. Have you missed any days of school/work because of asthma in the last month?

Conclusion

• Asthma is difficult to diagnose in pre-school children

• Asthma is difficult to treat in pre-school children

• The most important step is trial on and off treatment

• If treatment doesn’t work – stop - think again

Acknowledgement

• Prof Refiloe Masekela

• Dr Teshni Moodley

• Dr Omolemo Kitchin

• Dr Sam Risenga

• Dr Debbie White

• Dr Carla Els

• Dr Marian Kwofie-Mensah

• Prof Max Klein

NAEP CONTACTS

• Web www.asthma.co.za

• E-mail naepr@active.co.za

asthma@oz.co.za

• Tel 0861-ASTHMA(278462)

• Fax 088 011 678 3069

• P.O Box 72128,Parkview, 2122