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Environmental pollution: asthma, COPD & lung function
Professor K F Chung
NHLI, Imperial College London,
UK
ERS Live lectureMay 28th 2008
‘The real culprit for asthma and COPD exacerbations?’
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
OZONE PM10
PM2.5NO2
AcidCarbon
Gauderman et al NEJM 2004; 351: 1057
Levels of environmental pollution in 12 different areas of S California
OZONEPM10
PM2.5NO2
Acid Carbon
Gauderman et al NEJM 2004; 351: 1057
Table 4Air 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)]
PM2.5 MSP Impactor with filter 28.7 (18–51) 28.5 (17–50) 0.99
PM10 MSP Impactor with filter 43.7 (29–70) 41.1 (27–68) 0.35
Time-resolved PM Nephelometer
Peak 20 (10–40) 20 (10–40) 0.93
NO2 (ppb) Passive sampling badge 21.6 (14–34) 20.9 (14–31) 0.84
O3 (ppb) Passive sampling badge 1.4 (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
CLOSE
>1500m
Predicted lung function at age 18 as function of distance from freeway in Los Angeles
Gauderman et al Lancet 2007; 369: 571
Ultrafine particle size distribution according to distance from freeway in Los Angeles
Zhu et al Atmos Environ 2002;36: 4323
A reduction in interval exposure of 10g/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
Swiss SALPADIA study
Swiss SALPADIA study
Air pollution and asthma exacerbations
• Increased symptoms• Need for bronchodilator medication• Decreased lung function• Emergency visits for attacks
Epidemiological link:Dockery 1989 ARRD 139: 587Schwartz 1993 ARRD 147: 826Sheppard 1999 Epidemiology 10: 23Ostro 2001 Epidemiology 12: 200Lin 2002 Env Health Perspect 10: 118Gent 2003 JAMA 290: 1859Mar 2004 Inhal Tox 16: 809Barnett 2005 AJRCCM 171: 1272Etc.
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
Particles and COPD morbidity and mortality
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.
Dirty Diesel
PollutantPetrol Engine
Diesel Engine
CO ++++ +
CO2 +++ ++
Benzene +++ ++
NOx + ++
Hydrocarbons ++ +++
Aldehydes ++ +++
SO2 + ++++
PAH’s + ++++
Particulates + ++++
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)
Effect of reconstituted DEP (200 g/m3) in exposure chamber in normal subjects
Induced sputum
(Nightingale et al AJRCCM 2000; 162: 161)
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.
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
Royal Brompton HospitalAsthma Lab
A ‘real world’ study in a London street
Hyde Park‘Control’ exposure site
Oxford Street‘Active’ exposure site
Oxford St - ‘a natural diesel chamber’
OXFORD
STREET
REGENT
STREET
ORCHARD
STREET
OXFORD
STREET
REGENT
STREET
ORCHARD
STREET
• Tall buildings ‘Canyon effect’
only
• Diesel exhaust ++
Hyde Park
Kensington Palace
Round Pond
The Serpentine
The Long Water
Old Police House & Rangers Lodge
WES
T C
ARR
IAG
E
DR
IVE
SOUTH CARRIAGE DRIVE
NORTH CARRIAGE DRIVE
PA
RK
LAN
ESubjects enter here
Kensington Palace
Round Pond
The Serpentine
The Long Water
Old Police House & Rangers Lodge
WES
T C
ARR
IAG
E
DR
IVE
SOUTH CARRIAGE DRIVE
NORTH CARRIAGE DRIVE
PA
RK
LAN
ESubjects enter here
• ‘relatively’ clean air
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• FEV1 84.7% (SD 10.6)
31 mild asthmatics
• GINA 1 & 2• FEV1 93.4% (SD 6.9)
Health outcomes
Health Measurement Instrument
Lung Function Spirometry Vitalograph 2120 (portable)
Symptom Score Asthmatic symptoms Questionnaire
Exhaled Nitric Oxide Oral Aerocrine NIOX Online
Exhaled Breath CondensatepH / markers of oxidative stress
Jaeger Ecoscreen
Bronchial Reactivity PC20 Metacholine
Induced SputumCell count inflammatory mediators
De Vilbiss nebuliser
BloodMarkers of Oxidative stress
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
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 < 40 (24hr)
Carbon Monoxide (mg/m-3) 1.02 1.34 < 10.0
Elemental Carbon (µg/m-3) 1.3 7.5 1-2
Temperature (oC) 9.1 10.8 -
Relative humidity 76% 66% -
Symptom reporting Oxford St cf. Hyde Park
0.00
0.40
0.80
1.20
1.60
2.00
Immediately post exposure 5 hours post exposure
Symptom score (max 15)
Time
Oxford Street
Hyde Park
• Cough
• Sputum production
• Chest tightness
• Wheeze
• Breathlessness
P < 0.02
(N = 60)
McCreanor et al NEJM 2007; 357: 2348
McCreanor et al NEJM 2007; 357: 2348
McCreanor et al NEJM 2007; 357: 2348
Sputum IL-8
All Subjects
Screening Hyde Park Oxford St
0
150
300
450
IL-8
(Pg
/ml)
Mild Asthmatics
Screening Hyde Park Oxford St
All Subjects Mild Asthmatics Moderate Asthmatics
Screening Hyde Park Oxford St
Moderate Asthmatics
% Δ in health end-points per
incremental Δ in pollutant
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
3hr6hr
3 hr4 hr5 hr6 hr7 hr
22 hr
0 5 10-5-10
% change in outcome per 10mcg/m3
FEV1
FVC
FEF
pH
eNO
pm2.52 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
3hr6hr
3 hr4 hr5 hr6 hr7 hr
22 hr
0 0.5 1 1.5-0.5-1-1.5-2
% change in outcome per 10 mcg/m3
FEV1
FVC
FEF
pH
eNO
nitrogen dioxide
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
3hr6hr
3 hr4 hr5 hr6 hr7 hr
22 hr
0 1 2 3 4-1-2-3
% change in outcome per 1mcg/m3
FEV1
FVC
FEF
pH
eNO
elemental carbon2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
3hr6hr
3 hr4 hr5 hr6 hr7 hr
22 hr
0 2 4 6-2-4-6
% change in outcome per 10.000 particles/cm3
FEV1
FVC
FEF
pH
eNO
ultrafine particles
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
3hr6hr
3 hr4 hr5 hr6 hr7 hr
22 hr
0 5 10-5-10
% change in outcome per 10mcg/m3
FEV1
FVC
FEF
pH
eNO
pm2.52 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
3hr6hr
3 hr4 hr5 hr6 hr7 hr
22 hr
0 0.5 1 1.5-0.5-1-1.5-2
% change in outcome per 10 mcg/m3
FEV1
FVC
FEF
pH
eNO
nitrogen dioxide
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
3hr6hr
3 hr4 hr5 hr6 hr7 hr
22 hr
0 1 2 3 4-1-2-3
% change in outcome per 1mcg/m3
FEV1
FVC
FEF
pH
eNO
elemental carbon2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
2 hr3 hr5 hr7 hr
22 hr
3hr6hr
3 hr4 hr5 hr6 hr7 hr
22 hr
0 2 4 6-2-4-6
% change in outcome per 10.000 particles/cm3
FEV1
FVC
FEF
pH
eNO
ultrafine particles
(point estimates & 95% confidence intervals)
Ambient air pollution triggers wheezing symptoms in infants
Anderson et al Thorax 2008 On line
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 2005;289: L724
Diaz-Sanchez 1996 JACI; 98 114
Diesel exhaust particles and allergic response
Saxon & Diaz-Sanchez Nature Immunol 2005
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.