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
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
(Chest Research Foundation, 2007)
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
(Chest Research Foundation, 2007)
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
(Chest Research Foundation, B.J. Medical College)
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
(Chest Research Foundation, B.J. Medical College)
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