1. Assessment of the Allergic Child Robin J Green PhD Dept Paediatrics, University Pretoria

2. The Hypersensitivity Reactions Type I: Immediate Type II: Cytotoxic Type III: Immune complex Type IV: Delayed Gell & Coombs

3. 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

4. Allergy Diagnosis History and Examination Identification of the Atopic Patient Identification of the Causative Allergen Evaluation of the Patient ’ s Environment Monitoring Allergic Inflammation

6. 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

7. Identification of Causative Allergen Skin Prick Test ImmunoCap – Individual / Mixed CAST Assay Other – Patch testing - MELISA Test

8. Decision on Positive RAST for Foods FoodDecision/Cut Point (kU/l) > 2 years < 2 years Egg7 2 Milk15 5 Peanut14 Fish20 Soya30 Wheat26 Sampson H 2003

10. Obstructive airway disease All volumes reduced FEF 25-75 markedly reduced FEV 1 :FVC < 80%

11. Measuring airway inflammation Exhaled NO – screening of Inflammation with a portable device (NIOX, Aerocrine) Alving K et al. ERS 2004. Adults Skin and Allergy Hospital, 2005 Children

12. Asthma in Pre-School Children 12

13. The Various Marches That Set Up Asthma Asthma

14. The Atopic March

15. 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 Children with wheezing (%) 58% 76% 0 20 40 60 80 100 1-2 (n=83) 2-3 (n=76) Age (years) 15

16. 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)

17. 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

18. Outcome of wheeze in infancy Martinez FD, et al. N Engl J Med 1995; 332: 133-138

19. Causes of Recurrent Wheezing in Infancy Asthma Multiple trigger wheeze Episodic viral wheeze Other causes

20. Viruses and Asthma Atopy Asthma Rhinovirus RSV Genes Influenza

21. Rhinovirus and asthma Atopy Decrease in lamda interferon Increase in ICAM - 1 Rhinovirus Asthma exacerbations Remodeling Vitamin D deficiency

22. Rhinovirus and Airway Remodeling Rhinovirus Increased epithelial cell cytotoxicity Increased VGEF expression and production Angiogenesis Remodeling Papadopolous N. ERS 2007

23. 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

25. DIAGNOSING ASTHMA

26. 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)

27. 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.

28. 56% Asthmatic Children in Pretoria Atopic

29. 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

30. 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

31. 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

32. Other causes HIV-related infections Tuberculosis Foreign body Cardiac failure Cystic fibrosis Bronchiectasis ILD Gastro-oesophageal reflux

33. Small Airway Disease/Bronchiolitis Acute Viral Bronchiolitis Asthma 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 Bronchiolitis Gastro- oesophageal Reflux INTERSTITIAL LUNG DISEASE

34. Preschool Wheeze – Finding a Cause Recurrent wheeze in a preschool child Anthropometry ThrivingNot 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 CXR Consider: Sweat test TB workup HIV workup Induced sputum Bronchoscopy Immune testing

35. TREATING ASTHMA

36. If not responding – Stop Treatment and Review diagnosis

37. 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

38. Scope of the Problem Administration Inhaled therapies can be difficult to administer

39. 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?

40. 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

41. 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

42. NAEP CONTACTS Web www.asthma.co.za E-mailnaepr@active.co.za asthma@oz.co.za Tel 0861-ASTHMA(278462) Fax 088 011 678 3069 P.O Box 72128,Parkview, 2122