IMPACT OF AIR POLLUTION ON LUNG DISEASE IN THE ......NAC 600mg OD NAC 600mg BD p = 0.001 p = 0.005 p...

IMPACT OF AIR POLLUTION ON LUNG DISEASE IN THE SOUTH ASIAN SUBCONTINENTDr Sundeep Salvi MD, DNB, PhD(UK), FCCP(USA)

DirectorChest Research Foundation, Pune, INDIA

[email protected]

The Telegraph2nd Sept. 2011

FVC and FEV1 values are 30%lower than the

Europeans/North Americans

• Ethnic factors• Nutritional factors• Quality of air we breathe

(ATS Abstract, May 2011)

GLOBAL MORTALITY DUE TO CHRONIC RESPIRATORY DISEASES

Mortality due to Chronic respiratory diseases, Global Health Observatory Data Repository, World Heath Organisation (WHO), viewed 4th November, 2011

0

10000000

20000000

30000000

40000000

50000000

60000000

70000000

Cancer IHD Stroke Diabetes Chronic respiratory disease

0.6 million

25 million

1 million

28 million

65 million

ESTIMATED MORBIDITY FOR NON COMMUNICABLE DISEASES IN INDIA

(Nongkynrih B et al, JAPI 2004 Feb; 52: 118‐123

Murthy, NCMH Background Papers, GOI, 2005)

Asthma

COPD

(45 million)

(57.2 million) 2016

0

1

2

3

4

5

6

7

8

Cancer IHD Stroke DiabetesChronic Resp diseasesInjuries

2.92

1.201.02

0.21

5.77

7.49

ESTIMATED MORTALITY FOR NON COMMUNICABLE DISEASES IN INDIA

(Nongkynrih B et al, JAPI 2004 Feb; 52: 118‐123)

WHO, 2002 data

Number in lacs

LEADING CAUSES OF MORTALITY IN RURAL INDIA ‐ 1994

(Ramanakumar et al, The Internet J Epidemiol 2005: 2(2): DOI: 10.5580/3ed

0

1000

2000

3000

4000

5000

6000

COPD + Asthma

Cardiac Arrest

Stroke IHD Accidents

Premature / Low birth wt

Liver Cirrhosis

CCF DM Suicide

TOP 10 CAUSES OF DEATH IN MAHARASHTRA, INDIA

(Health Status Maharashtra 2009: State Health Systems Resource Centre; 2010, Pg 20‐21.)

(2008)

17% smokers in Maharashtra

(http://www.worldmapper.org/display_extra.php?selected=459)

GLOBAL ASTHMA MORTALITY

(http://www.worldmapper.org/display_extra.php?selected=458)

GLOBAL COPD MORTALITY

0

200000

400000

600000

800000

1000000

1200000

1400000

1600000

1800000

2000000

Tuberculosis Malaria

HIV/AIDS

COPD

2008 2015 2030

CAUSES OF DEATHS IN SOUTH‐EAST ASIAN REGION

From: The Global Burden of Disease, WHO 2008

Total deaths

Diabetes

888 cities and towns across India

13,225 doctors across India‐ General Physicians‐ General Practitioners‐ Pediatricians

1st February 2011

2,04, 912 patients

WHAT AILS INDIA?

0%

10%

20%

30%

40%

50%

60%

36%

19%

10%

3%

51%

25%

13%9%

7% 6% 6%

18%Prev

alen

ce (%

)

Prevalence of Different symptoms in Indian Population

MOST COMMON SYMPTOMS FOR WHICH A PATIENT VISITS A DOCTOR (NON-SPECIALIST) IN INDIA

(Times of India, 5th May 2009)

Pune city

2003 – 2.9%2008 – 5.4%

>20,000 children

0

2000

4000

6000

8000

10000

12000

14000

1995 2000 2005 2010 2015

Current If we follow guidelines

US $ 2.5 billion

(Murthy KJR et al, NCMH Background Papers, 2005)

ECONOMIC BURDEN OF ASTHMA AND COPD IN INDIA (Estimated figures for 2010)

05000

100001500020000250003000035000400004500050000

1996 2001 2006 2011 2016

US $ 7.5 billion

ASTHMA COPD

Remote sensing of air pollution from space

(Van Donkelaar et al. Environ Health Perspect 2010; 118(6): 847 DOI: 10.1289/ehp.0901623)

(Indian Inst. of Tropical Meterology)

(http://www.ewg.org/reports/bodyburden2/execsumm.php)

Environmental Working Group, July 2005

287 pollutants, chemicals, pesticides identified in the umbilical cord blood

10 newborn babies randomly selected by Red Cross from USA

DO POLLUTANTS INHALED BY THE MOTHER ENTER INTO THE GROWING FETUS?

Cord blood collected and sent for analysis for different pollutants

Residential Proximity to main roads during Pregnancy and Risk of Asthma

Japanese Birth Cohort Study, 756 pregnant mothers, Babies followed for 2 yrs after birth

<50 mts versus >200 mts

Doctor diagnosed asthma: 4.0 (1.4‐11.2)

Doctor diagnosed eczema: 2.3 (1.1‐4.6)

(Miyake Y et al, Pediatr Allergy Immunol 2010; 21: 22‐28)

Maternal exposure to vehicular pollutants during pregnancy is strongly associated

with early childhood asthma

(Brunekreef B et al, Environ Health Perspect 2009; 117: 1791‐1798)

TRUCK TRAFFIC DENSITY AND CHILDHOOD ASTHMA

Current wheeze vs Truck traffic on street of residence(n = 513,087; 98 countries, 238 centers) ISAAC III Study

*Wheeze*Rhinoconjunctivitis

*EczemaTruck traffic density

Living in homes close to busy roads (<50m) is significantly associated with increased asthma risk in children

0

5

10

15

20

25

30

35

Low traffic Heavy traffic Heavy traffic + low socioeconomic

%age

Traffic density around school and prevalence of Asthma amongst school children

11.5%

19.3%

31.1%

(Paramesh H. Indian J Paed 2002; 69(4): 309-312)

(n = 6550; Bangalore, India)

2‐fold increase in prevalence

IgE IgE

(Knox et al, Clin Exp Allergy 1997

Takenaka et al, J Allergy Clin Immunol 1995; 95: 103‐115)

Diesel exhaust particles increase allergenicity by up to 50‐fold

Pollen become more allergenic when these trees grow in an urban environment

(Bryce M et al., Int Arch Alergy Immunol 2010; 151: 45‐65)

Carbon coreAdsorbed hydrocarbonsSoluble organic fractionSulphates

Vapour phase hydrocarbons

Diesel exhaust particles

CadmiumArsenic

DNA methylation

? Increase in allergic diseases that may last for several generations

(Baccarelli A et al., Am J Respir Crit Care Med 2009; 179: 572-578)

EPIGENETICS

WHICH MODE OF TRANSPORT EXPOSES YOU TO MORE AIR POLLUTANTS?

Autorickshaw Bus Motor cycle

Station to KothrudDeccan to Hadapsar

(Chest Research Foundation, 2007)

Difference between CO levels for 3 different transportation modes from station - kothrud

0

10

20

30

40

50

60

70

1 6 11 16 21 26 31 36

Time points (in mins)

CO

(in

ppm

)

BusRickshawBike

AUC value for CO levles for 3 different transportation Mode from Pune station ‐ Kothrud

319.88

643.13 663.50

0.00

100.00

200.00

300.00

400.00

500.00

600.00

700.00

Bus Rickshaw Bike

CO levels

CARBON MONOXIDE


WHO safety limit

Mean difference in SO2 levels for 3 different transportation mode from Station - Kothrud

-0.1

0

0.1

0.2

0.3

0.4

1 6 11 16 21 26 31 36 41

SO2

leve

ls (i

n pp

m)

BusRickshawBike

0.00

1.23

1.05

0.00

0.30

0.60

0.90

1.20

1.50

AUC values

Bus Rickshaw Bike

Difference in AUC values for SO2 for 3 different transportation mode from Station ‐ Kothrud

SULPHUR DIOXIDE


WHO safety limit

MEAN CHANGES IN SO2 LEVELS (ppm)

Before Diwali

During DiwaliAfter Diwali

‐1

01

2

3

45

6

SO2 levels ( in ppm

)

Before Diwali During Diwali After Diwali

Ambient SO2 levels reached values 200 times above the safety limits recommended by WHO

Symptom Pre-existing Prevalence (%)

New symptoms Prevalence (%)

Total Prevalence (%)

Cough 4.2 26.3 31.2Breathlessness 2.5 10.8 13.3Wheeze 1.8 4.3 6.1

PREVALENCE OF RESPIRATORY SYMPTOMS DURING THE DIWALI FESTIVAL

6.10%

13.30%

31.20%

45.50%

0%

10%

20%

30%

40%

50%

Wheeze Breathlessness Cough None

Percentages of complaining wheeze, breathlessness & cough during Diwali festival

n = 510

Irritation in Eyes

Runny Nose Allergic Symptoms

Itchy Skin

26.1% 9% 5.7% 4.1%

4.10% 5.70%9.00%

26.10%

51.00%

0%

10%

20%

30%

40%

50%

60%

Itching ofskin

Allergy Runny Nose Irritation ofeyes

None

(Chest Research Foundation, India, 2008)

PREVALENCE OF COPD AMONGST URBAN SLUM DWELLERS OF PUNE CITY, INDIA

Prevalence of COPD: 7.2%

56% of COPDs were never smokers

COPD inKerosene users vs LPG users

OR: 2.51 (CI; 1.1 ‐ 5.7)

(n = 12,050; Questionnaire)

(Chest Research Foundation, Pune, India, 2007)

Prevalence of COPD: 5.1%(M:6.5%, F:3.4%)

85% of COPD patients were never smokers

Risk Factors associated with COPD:• Tobacco smoking• Increasing age• Male gender• Use of biomass fuel for cooking

(22 villages; n = 3,500; Age: >25 yrs; BOLD Protocol – Questionnaire, Spirometry)

Joint Collaborative Study between Chest Research Foundation, Pune and Imperial College, London, UK

PREVALENCE OF COPD IN PUNE

(Salvi S et al, Manuscript in preparation)

‐5

0

5

10

15

20

0‐100 100‐200 200‐300 300‐400 400‐500

Prevalen

ce of C

OPD

Distance from Highway

Prevalence of COPD near Highways R2 = 0.946

p< 0.04

Proximity to highway

R2 = 0.94

Biomass fuel:OR 1.46 (1.06 – 2.0)

<500 mts

>500 mts

(Muralidharan V et al, Manuscript in preparation)

COPD RISK FACTORS

0

0.5

1

1.5

2

2.5

3

3.5

Smokers BMF‐exposed

1.1billion

3billion

Odds Ratio:Smoker developing COPD 2.5Biomass smoke exposure and COPD 2.5

Salvi SS, Barnes PJ.

Salvi SS, Barnes PJ.

Lancet 2009: 374: 733‐743

Chest 2010: 138(1): 3‐6

Collected biomass smoke particles from rural home in

India(Wood, Animal Dung)

Cyclone Particle collector

Intra-tracheal instillation in

mice(0, 20, 50, 250, 500 mcg)

(Chest Research Foundation, India andJohns Hopkins University, USA)

TOXICOLOGY OF BIOMASS SMOKE PARTICLES (Animal Exposure Studies)

PBS

Wood

Dung

Total cells

Neutrophils

Eosinophils

(Sussan T et al, Manuscript submitted, 2013)

Bronchial Hyper-responsiveness

CELLULAR AND MEDIATOR INFLAMMATORY RESPONSES(Wood Smoke versus Animal Dung Smoke)

BAL

Lung Histology

Mosquito Coil

0.3 – 0.4% Pyrethrin (insecticide)

99.6% ‐ Binders, Fillers

Burning one mosquito coil releases the same amount of PM2.5 mass as that of burning 75‐137 cigarettes.

The emission of formaldehyde can be as high as that released from burning 51 cigarettes

(Liu W et al, Environ Health Perspect 2003; 111: 1454-1460)

MOSQUITO COIL

Polyaromatichydrocarbons

Cigarette(x 10‐6)

Mosquito Coil(10‐6)

Benzo[a]pyrene 170 16Benzo[b]fluoranthene 2.0 1.2Benzo[k]fluoranthene 110 50Pyrene 21 60Dibenz[a,h]anthracene 3 110Chrysene 0.5 ND

PAHs inCigarettes vs Mosquito coil smoke

(Al‐Rawas et al, BMC Pulm Med 2009; 9: 23)

Aromatic woods, herbs, flowers, essential oils, perfumes

PAH, Benzene, CO, Isoprene

INCENSE BURNING AND ASTHMA

40% of asthmatic children reported worsening of

symptoms due to incense burning

Oman, Muscat2441 children 10 yrs

Taipei, Taiwan3764 children, 10 yrs

Incense burning at home was associated with a significantly increased risk of asthmaAssociation was strongest in those who had a GSTT1 null genotype

(Wang IJ et al, Eur Respir J 2011; 37(6): 1371‐1377)

SMOKE PARTICLES FROM DHOOP AGARBATTIS

50 Pujaris from 35 temples in Pune city

Spirometry:25% showed presence of Obstructive Airways Disease

OBSTRUCTIVE AIRWAYS DISEASE IN PUJARIS

GSH ‐tocopherol UA

Reactive oxygen species

Blood

Ozone, NO2, Diesel exhaust particles

ANTIOXIDANT PROPERTIES OF THEEPITHELIAL LINNG FLUID

Vit C

Alveolar macrophages

CODEFENSE LINE

DOES N‐ACETYL CYSTEINE AS AN ANTIOXIDANT REDUCE LUNG OXIDATIVE STRESS AND IMPROVE

LUNG FUNCTION IN PMT BUS DRIVERS?

PMT Bus Drivers

(n = 72)

Placebo

NAC 600mg/day

NAC 1200mg/day

X 4 weeks

(Chest Research Foundation, B.J. Medical College)

Mean eCO change at different time pointsfrom baseline

1

1.5

2

2.5

3

3.5

4

Baseline 15 days 30 days 45 days 60 days

Mean

eCO levels

( ppm

)

Placebo

NAC 600mg OD

NAC 600mg BD

p = 0.001p = 0.005

p = 0.00 p = 0.00

p = 0.00 p = 0.00 p = 0.00

4 week treatment of NAC/Placebo on lung oxidative stress in PMT bus drivers


020406080

100120140

Placebo NAC 600mg NAC 1200mg

FEV1

FVC

20 10 10 80 90 130

*

*

mL change

4 week treatment of NAC/Placebo on lung function changes in PMT bus drivers


THE NEED

RESPIRATORY REVOLUTION• Improve Quality of Research in Respiratory

Medicine

• Improve Quality of Care to patients with Respiratory Diseases

• Improve Quality of Undergraduate and Postgraduate Medical Education in Respiratory Medicine

Good quality doctors Good quality researchers Good quality educators

SPIROMETRY SIMPLIFIEDWeb-based E-learning module

3 hoursComplete training module

http://www.crflearning.org

PURVIEWPractical Updates for Respiratory PGs via the Web

1. Basics of Lung Physiology and How to Select a Dissertation Topic

2. COPD – I3. Tuberculosis Update 20124. COPD – II5. Radiology in Chest Medicine6. Asthma – Beyond Prescription7. Understanding Spirometry8. Diffuse Parenchymal Lung

Disease9. ILD in Systemic Vasculitis and

Autoimmune Vasculitis10.Hospital Acquired Pneumonias

11. Pleural DiseasesJune 2013 (http://www.crfindia.com)

(Salvi S, Agrawal A, JAPI 2012 Feb; 60: 5‐7)

1st COPD CONFERENCE OF INDIAJanuary 2014, Pune, India

Develop ideas that will guide future research and funding support in the area of interventional and preventive strategies for COPD

Bring together clinicians, researchers and stakeholders from all parts of the world at a common platform in India

Giving an identity to COPD in India Phenotyping and management of COPD Translation of basic research to develop novel

therapies

2-day Conference

10-12 overseas speakers10-12 Indian speakers

Nationwide competition to give an Indian identity to COPD – PG students

THANK YOU

[email protected]

IMPACT OF AIR POLLUTION ON LUNG DISEASE IN THE ......NAC 600mg OD NAC 600mg BD p = 0.001 p = 0.005 p...

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