1. Environmental pollution: asthma, COPD & lung function Professor K F Chung NHLI, Imperial College London, UK ERS Live lecture May 28 th 2008 ‘The real culprit for asthma and COPD exacerbations?’

2. Environmental pollution & lungs Levels/components of environmental pollution Exposure and loss of lung function Effect on exacerbations of lung disease Effect on respiratory symptoms in asthma Particles and mechanisms

3. OZONE PM10 PM2.5 NO2 Acid Carbon Gauderman et al NEJM 2004; 351: 1057 Levels of environmental pollution in 12 different areas of S California

4. OZONE PM10 PM2.5 NO2 Acid Carbon Gauderman et al NEJM 2004; 351: 1057

5. Table 4 Air pollutant concentrations in bedroom at present in inner city (Baltimore) [median (interquartile range)]. Sampling deviceAsthmaControlp-Value Bedroom air [72-hr average (μg/m 3 )] PM 2.5 MSP Impactor with filter28.7 (18–51)28.5 (17–50)0.99 PM 10 MSP Impactor with filter43.7 (29–70)41.1 (27–68)0.35 Time-resolved PMNephelometer Peak20 (10–40) 0.93 NO 2 (ppb)Passive sampling badge21.6 (14–34)20.9 (14–31)0.84 O 3 (ppb)Passive sampling badge1.4 (0.9–3.4)1.8 (0.9–4.1)0.56 Environ Health Perspect. 2007 November; 115(11): 1665–1669. Published online 2007 July 27. doi: 10.1289/ehp.10088. Home Indoor Pollutant Exposures among Inner-City Children With and Without Asthma

7. CLOSE >1500m Predicted lung function at age 18 as function of distance from freeway in Los Angeles Gauderman et al Lancet 2007; 369: 571

8. Ultrafine particle size distribution according to distance from freeway in Los Angeles Zhu et al Atmos Environ 2002;36: 4323

9. A reduction in interval exposure of 10  g/m 3 /year of PM10 led to a reduction in 6.9 ml/year in FEV 1 decline and a 22% reduction in decline in FEF 25-75 Swiss SALPADIA study

11. Air pollution and asthma exacerbations Increased symptoms Need for bronchodilator medication Decreased lung function Emergency visits for attacks Epidemiological link: Dockery 1989 ARRD 139: 587 Schwartz 1993 ARRD 147: 826 Sheppard 1999 Epidemiology 10: 23 Ostro 2001 Epidemiology 12: 200 Lin 2002 Env Health Perspect 10: 118 Gent 2003 JAMA 290: 1859 Mar 2004 Inhal Tox 16: 809 Barnett 2005 AJRCCM 171: 1272 Etc.

12. LocationYearPMMorbidity Reference Vancouver95-99PM2.5, PM10Hospital admissions Chen et al 2004 Atlanta, US93-00PM10Emergency room visits Peel 2005 US counties92-02PM2.5Hospital admissions Dominici 2006 US cities86-99PM10Hospital admissions Medina-Ramon 2006 Barcelona90-95Total particlesMortalitySunyer 2000 Mexico City94PM10MortalityTellez-Rijio 2000 Netherlands86-94PM10 PM2.5Mortality (elderly) Fischer 2003 Shanghai01PM2.5MortalityKan & Chen 2003 Salt Lake City93PM10Lung function (  FEV 1 =-2%/  100ug/m 3 PM10) Pope & Kanner 1993 Particles and COPD morbidity and mortality

13. The Diesel Engine Rudolf Diesel Paris 1858 Engineering student - Munich Polytechnik 1892 - Spark free combustion engine (coal, peanut oil!) Diesel overboard 1913, Rudolf Diesel disappears whilst on a boat trip to England.

14. Dirty Diesel Pollutant Petrol Engine Diesel Engine CO +++++ CO 2 +++++ Benzene +++++ NOx +++ Hydrocarbons +++++ Aldehydes +++++ SO 2 +++++ PAH’s +++++ Particulates +++++

15. Particulates matter Where from? Traffic (exhaust, brake dust), factories, power plants, construction, fires and natural windblown dust What? Dust, dirt, soot, smoke and liquid droplets. How big? Coarse < 10µm = PM10 Fine < 2.5µm = PM2.5 Ultrafine < 100nm = Ultrafine Particles (UFP) 83% of urban particulates derived from traffic 87% from diesel exhaust (Airborne Particle Expert Group, 1999)

16. Effect of reconstituted DEP (200  g/m 3 ) in exposure chamber in normal subjects Induced sputum (Nightingale et al AJRCCM 2000; 162: 161)

17. Exposure to PM10 (300  g m -3 ) for 1 hr Nordenhall et al. Eur Respir J 2001; 17: 909 No change in sputum histamine, ECP, MP & IL-8, except for IL-6.

18. Respiratory Effects of Exposure to Diesel Traffic in Persons with Asthma James McCreanor, M.R.C.P., Paul Cullinan, M.D., Mark J. Nieuwenhuijsen, Ph.D., James Stewart-Evans, M.Sc., Eleni Malliarou, M.Sc., Lars Jarup, Ph.D., Robert Harrington, M.S., Magnus Svartengren, M.D., In-Kyu Han, M.P.H., Pamela Ohman-Strickland, Ph.D., Kian Fan Chung, M.D., and Junfeng Zhang, Ph.D. New Engl J Med 2007; 357: 2348-58

19. Royal Brompton Hospital Asthma Lab A ‘real world’ study in a London street Hyde Park ‘Control’ exposure site Oxford Street ‘ Active ’ exposure site

20. Oxford St - ‘a natural diesel chamber’ Tall buildings ‘Canyon effect’ only Diesel exhaust ++  

21. Hyde Park ‘relatively’ clean air

22. Study population 60 Asthmatics Age range 18 – 55yr (median 31) 31 ♀, 29 ♂ Pc 20 < 8.0 (metacholine) Non-smokers Live / work away from Oxford St 29 moderate asthmatics GINA 3 FEV 1 84.7% (SD 10.6) 31 mild asthmatics GINA 1 & 2 FEV 1 93.4% (SD 6.9)

23. Health outcomes Health MeasurementInstrument Lung Function Spirometry Vitalograph 2120 (portable) Symptom Score Asthmatic symptoms Questionnaire Exhaled Nitric Oxide Oral Aerocrine NIOX Online Exhaled Breath Condensate pH / markers of oxidative stress Jaeger Ecoscreen Bronchial Reactivity PC20 Metacholine Induced Sputum Cell count inflammatory mediators De Vilbiss nebuliser Blood Markers of Oxidative stress

24. Exposure measurements Pollutant Instrument * Ultra fine Particles (UFP) Condensation Particle Counter * PM 2.5 Dust-trak aerosol monitor * Nitrogen Dioxide (NO2) Draeger Pac III monitor * Carbon Monoxide (CO) Langan CO monitor Elemental Carbon (EC) High Flow Personal Sample Filter * Temperature / Humidity HOBO data logger * = Real time measurement

25. Air quality data Pollutant Hyde ParkOxford St UK Urban PM10 (µg/m -3 )7212540-50 PM 2.5 (µg/m -3 ) 11.928.320 - 25 Ultra fine Particles (µg/m -3 ) 18.363.715-20 Nitrogen Dioxide (µg/m -3 ) 20.9142< 40 (24hr) Carbon Monoxide (mg/m -3 ) 1.021.34< 10.0 Elemental Carbon (µg/m -3 ) 1.37.51-2 Temperature ( o C)9.110.8- Relative humidity76%66%-

26. Symptom reporting Oxford St cf. Hyde Park Symptom score (max 15) Time Oxford Street Hyde Park Cough Sputum production Chest tightness Wheeze Breathlessness P < 0.02 (N = 60)

27. McCreanor et al NEJM 2007; 357: 2348

30. Sputum IL-8 All SubjectsMild Asthmatics Moderate Asthmatics

31. McCreanor et al NEJM 2007; 357: 2348

32. % Δ in health end-points per incremental Δ in pollutant (point estimates & 95% confidence intervals)

33. Ambient air pollution triggers wheezing symptoms in infants Anderson et al Thorax 2008 On line

34. Exposure to diesel exhaust activates p-p38 MAPK, p-JNK & NFkB in epithelium (PM10, 300 ug/m 3; 1 hr) Pourazor et al Am J Physiol Lung Cell 2005;289: L724

35. Diaz-Sanchez 1996 JACI; 98 114

36. Diesel exhaust particles (DEP) & allergens IgE isotype switch in respiratory tissues Induces Th2 cytokine profile Adsorbs antigens, carrier for allergens Enhances antigenicity of allergen Methylation of CpG sites on promoters of Th1/Th2 cytokines Oxidant effect on dendritic cells

37. Diesel exhaust particles and allergic response Saxon & Diaz-Sanchez Nature Immunol 2005

38. Conclusions Environmental pollution is associated with loss of lung function Environmental pollution worsens asthma and induces lung inflammation, related to PM and UFs. Environmental pollution is a likely factor contributing to symptoms and exacerbations.