Transcript Environmental pollution: asthma, COPD & lung function Professor K F Chung

ERS Live lecture
May 28th 2008
Environmental pollution: asthma,
COPD & lung function
‘The real culprit for asthma and COPD exacerbations?’
Professor K F Chung
NHLI, Imperial College London,
UK
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
Levels of environmental pollution in 12 different areas of S California
OZONE
NO2
Acid
PM10
PM2.5
Carbon
Gauderman et al NEJM 2004; 351: 1057
OZONE
NO2
Acid
PM10
PM2.5
Carbon
Gauderman et al NEJM 2004; 351: 1057
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)]
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
20 (10–40)
Peak
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.
Predicted lung function at age 18 as function of distance
from freeway in Los Angeles
>1500m
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
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
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: 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.
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
Pope & Kanner 1993
(FEV1=-2%/
100ug/m3 PM10)
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
Pollutant
Petrol
Engine
Diesel
Engine
CO
++++
+
CO2
+++
++
Benzene
+++
++
NOx
+
++
Hydrocarbons
++
+++
Aldehydes
++
+++
SO2
+
++++
PAH’s
+
++++
Particulates
+
++++
Particulates matter
• What?
Dust, dirt, soot, smoke and liquid droplets.
• How big?
Coarse < 10µm = PM10
Fine
< 2.5µm = PM2.5
Ultrafine < 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)
Effect of reconstituted DEP (200 mg/m3)
in exposure chamber in normal subjects
Induced sputum
(Nightingale et al AJRCCM 2000; 162: 161)
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
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
A ‘real world’ study in a London street
Oxford Street
‘Active’ exposure site
Hyde Park
‘Control’ exposure site
Royal Brompton Hospital
Asthma Lab
Oxford St - ‘a natural diesel chamber’
NT
REGE
HAR
ORC

EET
STR
D

RD
OXFO
T
STREE
STRE
ET
•
Diesel exhaust ++
only
• Tall buildings
‘Canyon effect’
Hyde Park
NORTH CARRIAGE DRIVE
eL
Th
ate
r
NE
K LA
Round
Pond
PAR
Old Police
House &
Rangers
Lodge
gW
on
Kensington
Palace
W
CA EST
DR RR
IV IAG
E
E
Subjects
enter here
SOUTH CA
RR
•
The
Serpentine
IAGE DR
IVE
‘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
31 mild asthmatics
• GINA 1 & 2
• FEV1 93.4% (SD 6.9)
29 moderate asthmatics
• GINA 3
• FEV1 84.7% (SD 10.6)
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 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
Exposure measurements
Pollutant
* Ultra fine Particles
(UFP)
Instrument
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)
* Temperature /
Humidity
* = Real time measurement
High Flow Personal Sample
Filter
HOBO data logger
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%
-
• Cough
Symptom reporting
• Sputum production
• Chest tightness
Oxford St cf. Hyde Park
• Wheeze
• Breathlessness
Symptom score (max 15)
2.00
P < 0.02
1.60
1.20
0.80
0.40
0.00
Immediately post exposure
5 hours post exposure
Time
Hyde Park
Oxford Street
(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
AllSubjects
Subjects
All
MildMild
Asthmatics
Asthmatics
Moderate
ModerateAsthmatics
Asthmatics
IL-8 (Pg/ml)
450
300
150
0
Screening
Hyde Park
Oxford St
Screening
Hyde Park
Oxford St
Screening
Hyde Park
Oxford St
% Δ in health end-points per
incremental Δ in pollutant
(point estimates & 95% confidence intervals)
FEV12 hr
3 hr
5 hr
7 hr
22 hr
ultrafine particles
elemental carbon
FVC
FVC 2 hr
3 hr
5 hr
7 hr
22 hr
2 hr
3 hr
5 hr
7 hr
22 hr
FEF 2 hr
3 hr
5 hr
7 hr
22 hr
hr
FEF 2
3 hr
5 hr
7 hr
22 hr
pH
FEV1
2 hr
3 hr
5 hr
7 hr
22 hr
pH
3hr
6hr
3hr
6hr
eNO 3 hr
4 hr
5 hr
6 hr
7 hr
22 hr
3 hr
eNO 4 hr
5 hr
6 hr
7 hr
22 hr
-6
-4
-2
0
2
4
-3
6
-2
-1
0
1
2
3
4
% change in outcome per 1mcg/m3
% change in outcome per 10.000 particles/cm3
FEV1
FEV123 hr
hr
2 hr
3 hr
5 hr
7 hr
22 hr
pm2.5
5 hr
7 hr
22 hr
nitrogen dioxide
FVC
2 hr
FVC23 hr
hr
3 hr
5 hr
7 hr
22 hr
5 hr
7 hr
22 hr
2 hr
5 hr
7 hr
22 hr
FEF
2 hr
pH 3hr
6hr
pH 3hr
6hr
3 hr
eNO45 hr
hr
6 hr
7 hr
22 hr
3 hr
eNO
4 hr
FEF 3 hr
3 hr
5 hr
7 hr
22 hr
5 hr
6 hr
7 hr
22 hr
-10
-5
0
5
% change in outcome per 10mcg/m3
10
-2
-1.5
-1
-0.5
0
0.5
1
% change in outcome per 10 mcg/m3
1.5
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.