Non-allergic asthma Neil Pearce

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1 Non-allergic asthma. Neil Pearce Centre for Public Health Research Massey University Wellington Campus Wellington, New Zealand Faculty of Epidemiology and Population Health London School of Hygiene and Tropical Medicine London, United Kingdom

2 Established asthma risk factors House dust mite allergen Other indoor allergens Colds Parental smoking Diet Air pollution Stress Occupational exposures Genetic factors

3 Asthma Is an Allergic Disease Allergen exposure, particularly in infancy produces atopic sensitization Continued exposure results in asthma through the development of bronchial hyperresponsiveness, airway inflammation and reversible airways obstruction

4 Models of asthma causation Allergen exposure Atopy Asthma Rhinitis Eczema

5 ISAA C Phase One Wheeze in last 12 mths y r age grp 20% 10 to <20% 5 to <10% <5% 1998

6 Asthma Is an Allergic Disease 1. Is BHR a valid measure of asthma prevalence? 2. How much asthma is really attributable to atopy? 3. Is allergen exposure a primary cause of asthma?

7 How Much Asthma Is Really Attributable to Atopy? Neil Pearce, Juha Pekkanen, Richard Beasley Thorax 1999

8 Population Attributable Risk Suppose an exposure doubles the risk of developing asthma For every two cases that occur in exposed people, one would have occurred anyway, and one is an extra cases caused by exposure Suppose that 40% of cases are exposed Then 20% of all cases are caused by the exposure

9 Example: Sears et al (1989) Age = 13 Asthmatics: N = 315, % atopic = 57% Non-cases: N = 399, % atopic = 35% Odds ratio = 2.5 Proportion of atopic cases due to atopy = 1.5/2.5 = 0.6 PAR = 57 * 0.6 = 34%

10 How much asthma is attributable to atopy in children of the general population? (Pearce et al., Thorax 1999) PAR Gergen et al Burrows et al Sears et al Norrman et al Von Mutius et al Von Mutius et al Martinez et al Brooke et al Sporik et al Remes et al Weighted mean PAR due to atopy PAR due to non-atopic mechanism

11 How much asthma is attributable to atopy in adults of the general population? (Pearce et al., Thorax 1999) PAR Burrows et al Burrows et al Mensinga et al Sparrow et al Wuhtrich et al Settipane et al Bodner et al Siracusa et al Weigted mean PAR due to atopy PAR due to non-atopic mechanism

12 Current wheeze v skin prick test for atopy Estonia, Tallinn Germany, Dresden Munich Greece, Athens Thessaloniki* Italy, Rome Netherlands, Utrecht New Zealand, Hawkes Bay Norway, Tromso Spain, Almeria Cartagena Madrid Valencia Sweden, Linkoeping Oestersund UK, West Sussex Combined Western Albania, Tirana Georgia, Tbilisi Ghana, Kintampo India, Bombay Palestine, Ramallah Turkey, Ankara Combined Non-Western Western Non-Western * not considered in combine estimate due to heterogenity Odds ratio with 95% confidence interval

13 Non-eosinophilic asthma: importance and possible mechanisms. Douwes J, Gibson P, Pekkanen J, Pearce N. Thorax 2002; 57:

14 How much asthma is attributable to eosinophilia in adults of the 100 general population (Douwes et al., Thorax 2002) % Turner et al Fahy et al pizzichini et al Gibson et al wenzel et al Berlyne et al Pavord et al Jatakonen Lemiere wark et al Tarado de la Fuente et al Ordonez et al Giannini et al Ottanelli et al fahy et al Weigted mean % non-eosinophilia % eosinophilia

15 Non-eosinophilic asthma At most 50% of asthma cases are attributable to eosinophilic airway inflammation The remainder may be due to neutrophilic airway inflammation triggered by environmental exposure to bacterial endotoxin, air pollution, ozone, viral infections, etc

16 Acquired and innate immune pathways leading to asthma (Douwes et al., Thorax 2002) Paucigranulocyti c???

17 Is Allergen Exposure a Major Primary Risk Factor for Asthma? Neil Pearce, Jeroen Douwes, Richard Beasley Thorax 2000

18 Is Allergen Exposure a Major Primary Risk Factor for Asthma? Only five cohort studies have been conducted (all in selected populations) of allergen exposure in infancy and asthma risk after age six years One study (Sporik et al) was positive, but not statistically significantly; the others found no association between allergen exposure and subsequent asthma risk

19 Mean Der P 1 Levels, and Prevalence of HDM Atopy and Total Atopy in Six Australian Centres

20 Models of asthma causation Allergen exposure Atopy Asthma Rhinitis Eczema

21 Models of asthma causation Allergen exposure Other exposures Atopy Asthma Rhinitis Eczema

22 Models of asthma causation Atopy Allergen exposure Other exposures Asthma Rhinitis Eczema

23 Models of asthma causation Exposure A Exposure B Susceptibility Atopy Exposure C Exposure D Susceptibility Asthma

24 Is asthma a collection of different diseases? It depends on your definition Allergic inflammation of the airways Variable airways obstruction (bronchospasm) Is there evidence of different phenotypes? Unclear currently Is atopy a risk factor for asthma? If it is, it accounts for less than half of all cases It may simply be associated with asthma (like rhinitis is) rather than a causal factor

25 Why is it important to differentiate between asthma phenotypes? Treatment Corticosteroids Disease progress Fixed airflow obstruction Aetiology Hygiene hypothesis only applies to atopic asthma Causes Causal exposures

26 Non-allergic asthma. Neil Pearce Centre for Public Health Research Massey University Wellington Campus Wellington, New Zealand Faculty of Epidemiology and Population Health London School of Hygiene and Tropical Medicine London, United Kingdom