Environmental pollution: asthma, COPD

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Environmental pollution asthma, COPD lung
function
ERS Live lecture May 28th 2008
The real culprit for asthma and COPD
exacerbations?

• Professor K F Chung
• NHLI, Imperial College London,
• UK

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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

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Levels of environmental pollution in 12 different
areas of S California
PM10
OZONE
PM2.5
NO2
Carbon
Acid
Gauderman et al NEJM 2004 351 1057
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PM10
OZONE
PM2.5
NO2
Carbon
Acid
Gauderman et al NEJM 2004 351 1057
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Home Indoor Pollutant Exposures among Inner-City
Children With and Without Asthma
Table 4 Air pollutant concentrations in bedroom
at present in inner city (Baltimore) median
(interquartile range).
Sampling device Asthma Control p-Value
Bedroom air 72-hr average (µg/m3) Bedroom air 72-hr average (µg/m3) Bedroom air 72-hr average (µg/m3) Bedroom air 72-hr average (µg/m3) Bedroom air 72-hr average (µg/m3)
 PM2.5 MSP Impactor with filter 28.7 (1851) 28.5 (1750) 0.99
 PM10 MSP Impactor with filter 43.7 (2970) 41.1 (2768) 0.35
 Time-resolved PM Nephelometer
   Peak 20 (1040) 20 (1040) 0.93
NO2 (ppb) Passive sampling badge 21.6 (1434) 20.9 (1431) 0.84
O3 (ppb) Passive sampling badge 1.4 (0.93.4) 1.8 (0.94.1) 0.56
Environ Health Perspect. 2007 November 115(11)
16651669. Published online 2007 July 27. doi
10.1289/ehp.10088.
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(No Transcript)
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Predicted lung function at age 18 as function of
distance from freeway in Los Angeles
CLOSE
gt1500m
Gauderman et al Lancet 2007 369 571
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Ultrafine particle size distribution according to
distance from freeway in Los Angeles
Zhu et al Atmos Environ 200236 4323
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Swiss SALPADIA study
A reduction in interval exposure of 10mg/m3/year
of PM10 led to a reduction in 6.9 ml/year in
FEV1 decline and a 22 reduction in decline in
FEF25-75
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Swiss SALPADIA study
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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.

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Particles and COPD morbidity and mortality
Location Year PM Morbidity Reference
Vancouver 95-99 PM2.5, PM10 Hospital admissions Chen et al 2004
Atlanta, US 93-00 PM10 Emergency room visits Peel 2005
US counties 92-02 PM2.5 Hospital admissions Dominici 2006
US cities 86-99 PM10 Hospital admissions Medina-Ramon 2006
Barcelona 90-95 Total particles Mortality Sunyer 2000
Mexico City 94 PM10 Mortality Tellez-Rijio 2000
Netherlands 86-94 PM10 PM2.5 Mortality (elderly) Fischer 2003
Shanghai 01 PM2.5 Mortality Kan Chen 2003
Salt Lake City 93 PM10 Lung function (?FEV1-2/ ?100ug/m3 PM10) Pope Kanner 1993
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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.

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Dirty Diesel
Pollutant Petrol Engine Diesel Engine
CO
CO2
Benzene
NOx
Hydrocarbons
Aldehydes
SO2
PAHs
Particulates
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Particulates matter

• What?
• Dust, dirt, soot, smoke and liquid droplets.

• How big?
• Coarse lt 10µm PM10
• Fine lt 2.5µm PM2.5
• Ultrafine lt 100nm Ultrafine Particles (UFP)

• Where from?
• Traffic (exhaust, brake dust), factories,
  power plants,
• construction, fires and natural windblown
  dust

• 83 of urban particulates derived from traffic
• 87 from diesel exhaust
• (Airborne Particle Expert Group, 1999)

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Effect of reconstituted DEP (200 mg/m3) in
exposure chamber in normal subjects
Induced sputum
(Nightingale et al AJRCCM 2000 162 161)
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Exposure to PM10 (300 mg m-3) for 1 hr
No change in sputum histamine, ECP, MP IL-8,
except for IL-6.
Nordenhall et al. Eur Respir J 2001 17 909
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Respiratory Effects of Exposure to Diesel Traffic
in Persons with AsthmaJames 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
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A real world study in a London street
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Oxford St - a natural diesel chamber
?
?

• 
  Diesel exhaust

only

• Tall buildings
  Canyon effect

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Hyde Park

• relatively clean
  air

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Study population

• 60 Asthmatics
• Age range 18 55yr (median 31)
• 31 ?, 29 ?
• Pc 20 lt 8.0 (metacholine)
• Non-smokers
• Live / work away from Oxford St

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Health outcomes
Health Measurement Health Measurement Instrument
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
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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
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Air quality data
Pollutant Hyde Park Oxford St UK Urban
PM10 (µg/m-3 ) 72 125 40-50
PM 2.5 (µg/m-3 ) 11.9 28.3 20 - 25
Ultra fine Particles (µg/m-3 ) 18.3 63.7 15-20
Nitrogen Dioxide (µg/m-3) 20.9 142 lt 40 (24hr)
Carbon Monoxide (mg/m-3) 1.02 1.34 lt 10.0
Elemental Carbon (µg/m-3) 1.3 7.5 1-2
Temperature (oC) 9.1 10.8 -
Relative humidity 76 66 -
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Symptom reporting Oxford St cf. Hyde Park

• Cough
• Sputum production
• Chest tightness
• Wheeze
• Breathlessness

Symptom score (max 15)
P lt 0.02
Time
(N 60)
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McCreanor et al NEJM 2007 357 2348
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McCreanor et al NEJM 2007 357 2348
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McCreanor et al NEJM 2007 357 2348
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Sputum IL-8
All Subjects
Mild Asthmatics
Moderate Asthmatics
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McCreanor et al NEJM 2007 357 2348
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? in health end-points per incremental ? in
pollutant
(point estimates 95 confidence intervals)
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Ambient air pollution triggers wheezing symptoms
in infants
Anderson et al Thorax 2008 On line
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Exposure to diesel exhaust activates p-p38 MAPK,
p-JNK NFkB in epithelium
(PM10, 300 ug/m3 1 hr)
Pourazor et al Am J Physiol Lung Cell 2005289
L724
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Diaz-Sanchez 1996 JACI 98 114
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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

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