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.