3rd GRF One Health Summit 2015
Her Royal Highness Princess CHULABHORN, Professor, Dr, President of the Chulabhorn Research Institute is the youngest daughter of Their Majesties King Bhumibol Adulyadej and Queen Sirikit of Thailand
Cardiac Output, Venous Return, and Their Regulation
Honorary Lecture: Human Health as a Key Factor for Sustainable Development, Professor Dr HRH Princess CHULABHORN
1. Human Health as a Key Factor forHuman Health as a Key Factor for
Sustainable DevelopmentSustainable Development
byby
Professor Dr. HRH Princess ChulabhornProfessor Dr. HRH Princess Chulabhorn
Chulabhorn Research Institute, Bangkok, ThailandChulabhorn Research Institute, Bangkok, Thailand
2. ““Health is a precondition for and an outcomeHealth is a precondition for and an outcome
and indicator of all three dimensions ofand indicator of all three dimensions of
sustainable development”sustainable development”
““The goals of sustainable development can onlyThe goals of sustainable development can only
be achieved in the absence of a high prevalencebe achieved in the absence of a high prevalence
of debilitating communicable and non-of debilitating communicable and non-
communicable diseases, and where populationscommunicable diseases, and where populations
can reach a state of physical, mental and socialcan reach a state of physical, mental and social
well-being”well-being”
UNCSD, 2012UNCSD, 2012
One of the main risk areas forOne of the main risk areas for
sustainable development is human health.sustainable development is human health.
3. Can development affect human health?Can development affect human health?
Public Health is seriously threatened by:-Public Health is seriously threatened by:-
• a lack of access to safe and nutritious food,a lack of access to safe and nutritious food,
clean water and sanitation.clean water and sanitation.
• poor air quality and environmentalpoor air quality and environmental
deterioration, including climate changedeterioration, including climate change
• unhealthy lifestyles.unhealthy lifestyles.
These factors contribute to anThese factors contribute to an
unprecedented burden of diseaseunprecedented burden of disease
• Chronic, non-communicable diseases (NCD)Chronic, non-communicable diseases (NCD)
4. Non-Communicable Diseases (NCD)Non-Communicable Diseases (NCD)
Chronic diseases of long duration and generallyChronic diseases of long duration and generally
slow progression.slow progression.
• The 4 main types (82% of all NCD deathsThe 4 main types (82% of all NCD deaths
worldwide):-worldwide):-
1.1. Cardiovascular diseases (include heart attacks andCardiovascular diseases (include heart attacks and
stroke)stroke)
2.2. CancerCancer
3.3. Chronic respiratory diseases (COPD and asthma)Chronic respiratory diseases (COPD and asthma)
4.4. DiabetesDiabetes
5. Total NCD mortality:Total NCD mortality:
• 38 million of the 56 million global38 million of the 56 million global
deaths in 2012.deaths in 2012.
• 28 million deaths in low and28 million deaths in low and
middle-income countries.middle-income countries.
WHO: Global Health Observatory DataWHO: Global Health Observatory Data
7. Non-Communicable Diseases (NCD)Non-Communicable Diseases (NCD)
Driving factors:-Driving factors:-
• AgeingAgeing
• Rapid unplannedRapid unplanned
urbanizationurbanization
• Globalization ofGlobalization of
unhealthy lifestyles:-unhealthy lifestyles:-
unhealthy dietsunhealthy diets
blood pressureblood pressure
blood glucoseblood glucose
blood lipidsblood lipids
obesityobesity
All of these are key metabolic and physiologicalAll of these are key metabolic and physiological
changes that increase the risk of NCDs.changes that increase the risk of NCDs.
8. Non-Communicable Diseases (NCD)Non-Communicable Diseases (NCD)
Cancer:Cancer: now the second leading cause ofnow the second leading cause of
death worldwide after cardiovascular diseases.death worldwide after cardiovascular diseases.
IARC/ WHO estimated that, globally,IARC/ WHO estimated that, globally,
• 2012:-2012:- 14.1 million new cancer cases.14.1 million new cancer cases.
-- 8.2 million cancer deaths.8.2 million cancer deaths.
• by 2025:by 2025: 19.3 million cancer-related deaths19.3 million cancer-related deaths
worldwide.worldwide.
9. A. Breast cancer B. Prostate cancer C. Colon cancer (male)
73-77 78-82 83-87 88-92 93-97 98-02
Year
30
20
10
0
73-77 78-82 83-87 88-92 93-97 98-02
Year
100
80
60
40
20
0
73-77 78-82 83-87 88-92 93-97 98-02
Year
120
100
80
60
40
20
0
Asia USA Europe
Trends of Cancer Incidence Rates inTrends of Cancer Incidence Rates in
Asia, USA and Europe.Asia, USA and Europe.
Source: Parks et. al. Asian Pacific Journal of Cancer Prevention. 2008; 9:371.Source: Parks et. al. Asian Pacific Journal of Cancer Prevention. 2008; 9:371.
10. Asia:
•Populations: ~ 4 billion (approx. 60% of the world)
•Cancer has become the leading cause of death in many
countries.
•In 2012: ~ 6.8 million new cancer cases
> 4.5 million cancer-related deaths.
10
11. Non-Communicable Diseases (NCD)Non-Communicable Diseases (NCD)
Environment:- a major determinantEnvironment:- a major determinant
of health and a major risk factorof health and a major risk factor
contributing to cancer development.contributing to cancer development.
70% - 80% of cancers are attributable70% - 80% of cancers are attributable
to environmental and lifestyle factorsto environmental and lifestyle factors
(IARC).(IARC).
12. Environmental factors contributingEnvironmental factors contributing
to cancer incidence in Asia:to cancer incidence in Asia:
outdoor air pollutionoutdoor air pollution
indoor air pollutionindoor air pollution
pesticidespesticides
food contaminants and food additivesfood contaminants and food additives
metals and metalloidsmetals and metalloids
Environmental FactorsEnvironmental Factors
13. Air pollution:- The world’s largest singleAir pollution:- The world’s largest single
environmental health risk (Global Healthenvironmental health risk (Global Health
Observatory, 2015)Observatory, 2015)
• 4.3 million deaths each year occur from4.3 million deaths each year occur from
exposure to household (indoor) air pollutionexposure to household (indoor) air pollution
• 3.7 million deaths each year – attributable to3.7 million deaths each year – attributable to
ambient air pollution.ambient air pollution.
Indoor and outdoor air pollution are both amongIndoor and outdoor air pollution are both among
the leading causes of disease and death globally.the leading causes of disease and death globally.
Air PollutionAir Pollution
14. Deaths from Urban (Ambient) Air PollutionDeaths from Urban (Ambient) Air Pollution
•In 2002:In 2002: 800,000 deaths worldwide800,000 deaths worldwide (WHO, 2005)(WHO, 2005)
•In 2004:In 2004: 1.2 million deaths worldwide1.2 million deaths worldwide (WHO, 2009)(WHO, 2009)
•In 2012:In 2012: 3.7 million deaths worldwide3.7 million deaths worldwide (WHO, 2014)(WHO, 2014)
15. Indoor Air PollutionIndoor Air Pollution
Second-hand cigaretteSecond-hand cigarette
smokesmoke
CookingCooking
Burning fuelBurning fuel
Pesticide usesPesticide uses
Building materials andBuilding materials and
furnishing (asbestos, PCBs,furnishing (asbestos, PCBs,
PVCs)PVCs)
Cleaning products, paintsCleaning products, paints
and finishesand finishes
MoldMold
Indoor vs. Outdoor Air PollutionIndoor vs. Outdoor Air Pollution
Outdoor Air PollutionOutdoor Air Pollution
a complex mix of gases anda complex mix of gases and
particulate matter (PM)particulate matter (PM)
originates fromoriginates from
incomplete combustion ofincomplete combustion of
fossil fuelfossil fuel
construction.construction.
16. Exposure to air pollutants, including fineExposure to air pollutants, including fine
particulate matter is a leading risk factor forparticulate matter is a leading risk factor for
non-communicable diseases:-non-communicable diseases:-
• Ischemic heart diseaseIschemic heart disease
• StrokeStroke
• Chronic obstructive pulmonary diseases
• CancerCancer
• AsthmaAsthma
Indoor vs. Outdoor Air PollutionIndoor vs. Outdoor Air Pollution
17. Short-term:-Short-term:-
Acute respiratory infection, acute asthmatic attack,Acute respiratory infection, acute asthmatic attack,
cardiac arrhythmia, triggering of heart attackcardiac arrhythmia, triggering of heart attack
Long-term:-Long-term:-
At high levels – causing chronic disease:-At high levels – causing chronic disease:-
- Cardiovascular diseasesCardiovascular diseases
- Respiratory diseases, COPDRespiratory diseases, COPD
- StrokeStroke
- CancerCancer
At low levels (below WHO Air Quality GuidelinesAt low levels (below WHO Air Quality Guidelines
proposed levels) – some adverse health effects.proposed levels) – some adverse health effects.
Health Effects of Air PollutionHealth Effects of Air Pollution
18. IARC (Oct. 2013):IARC (Oct. 2013):
““Outdoor air pollution is a leadingOutdoor air pollution is a leading
environmental cause of cancer deaths.”environmental cause of cancer deaths.”
“The air we breathe has become polluted
with a mixture of cancer causing
substances. We now know that outdoor air
pollution is not only a major risk to health
in general, but also a leading environmental
cause of cancer death”
Dr. Kurt Straif,
Head of the IARC Monographs Sections
19. WHO-IARC (Oct. 2013) classified:-WHO-IARC (Oct. 2013) classified:-
Outdoor air pollution - carcinogenic to humans (Group 1).Outdoor air pollution - carcinogenic to humans (Group 1).
Particulate matter - carcinogenic to humans (Group 1).Particulate matter - carcinogenic to humans (Group 1).
20. Exposure to outdoor air pollution causesExposure to outdoor air pollution causes
lung cancer.lung cancer.
A positive association between exposure toA positive association between exposure to
air pollution and an increased risk of bladderair pollution and an increased risk of bladder
cancer.cancer.
2012:- 223,000 deaths from lung cancer2012:- 223,000 deaths from lung cancer
worldwide resulted from air pollution.worldwide resulted from air pollution.
Epidemiological studies:- People living inEpidemiological studies:- People living in
metropolitan areas have an increased risk ofmetropolitan areas have an increased risk of
lung cancer.lung cancer.
WHO-IARC (Oct. 2013): Outdoor Air PollutionWHO-IARC (Oct. 2013): Outdoor Air Pollution
21. Particulate matter (PM), a major componentParticulate matter (PM), a major component
of outdoor air pollution was evaluatedof outdoor air pollution was evaluated
separately by IARC, and was also classifiedseparately by IARC, and was also classified
as a Group 1 carcinogen.as a Group 1 carcinogen.
An increasing risk of lung cancer withAn increasing risk of lung cancer with
increasing levels of exposure to particulateincreasing levels of exposure to particulate
matter and air pollution.matter and air pollution.
WHO-IARC (Oct. 2013): Particulate MatterWHO-IARC (Oct. 2013): Particulate Matter
22. Environmental air pollution is a mixture ofEnvironmental air pollution is a mixture of
gases and particles that varies in compositiongases and particles that varies in composition
depending on the source, weather,depending on the source, weather,
topography and other variables.topography and other variables.
When different carcinogenic pollutants areWhen different carcinogenic pollutants are
combined, the health effects from exposurecombined, the health effects from exposure
may be greater than expected if the effectsmay be greater than expected if the effects
were simply additive.were simply additive.
Health Effects of Air PollutionHealth Effects of Air Pollution
23. Main source:- traffic congestion whichMain source:- traffic congestion which
releases carcinogenic compounds:-releases carcinogenic compounds:-
Polycyclic aromatic hydrocarbonsPolycyclic aromatic hydrocarbons
(PAHs)(PAHs)
BenzeneBenzene
1,3-Butadiene1,3-Butadiene
Particulate matter (PM)Particulate matter (PM)
Urban Air PollutionUrban Air Pollution
24. School ChildrenSchool Children Traffic PoliceTraffic Police
Health Effects from Exposure toHealth Effects from Exposure to
Carcinogenic Air PollutantsCarcinogenic Air Pollutants
Personal monitoringPersonal monitoring:-:-
Exposure levels of benzene, 1,3-butadiene andExposure levels of benzene, 1,3-butadiene and
PAHs and their metabolite levels.PAHs and their metabolite levels.
Early biological effectsEarly biological effects
25. Ambient concentrations of benzene, 1,3-butadiene
and total PAHs at various roadsides and school areas
ParametersParameters
Urban (Bangkok)Urban (Bangkok) Rural (Chonburi)Rural (Chonburi)
Roadside School area Roadside School area
BenzeneBenzene
(μg/m(μg/m33
))
56.98 ***56.98 ***
(n=20)(n=20)
26.48 ***26.48 ***
(n=12)(n=12)
14.4114.41
(n=10)(n=10)
8.708.70
(n=9)(n=9)
1,3-Butadiene1,3-Butadiene
(μg/m(μg/m33
))
9.61 **9.61 **
(n=20)(n=20)
3.483.48
(n=27)(n=27)
0.930.93
(n=4)(n=4)
0.400.40
(n=13)(n=13)
PAHsPAHs
(ng/m(ng/m33
))
30.39 ***30.39 ***
(n=22)(n=22)
5.78 ***5.78 ***
(n=22)(n=22)
1.501.50
(n=12)(n=12)
1.121.12
(n=14)(n=14)
Values are expressed as means.
**, *** Statistically significant difference from Chonburi at p<0.01 and 0.001, respectively.
26. EExposure /xposure / Disease ParadigmDisease Paradigm
BodyBodyAmbientAmbient
EnvironmentEnvironment
INTERNALINTERNAL
DOSEDOSE
BIOLOGICALLYBIOLOGICALLY
EFFECTIVEEFFECTIVE
DOSEDOSE
EXPOSUREEXPOSURE DISEASESDISEASES
EARLYEARLY
BIOLOGICALBIOLOGICAL
EFFECTSEFFECTS
CANCERCANCERDNA Damage
• DNA Adducts
• 8-OHdG
• Strand Breaks
DNA Repair Capacity
BenzeneBenzene
Blood benzene levels,
t,t-Muconic acid,
S-PMA
1,3-Butadiene1,3-Butadiene MHBMA
Albumin Adducts
PAH-DNA Adducts
PAHsPAHs 1-OHP
26
Biomarkers of Exposure
Biomarkers of
Early Effects
27. Exposure to benzene, 1,3-butadiene and PAHs:
Biomarkers of exposure in school children
Values are expressed as means.
*,**,*** Statistically significant difference from rural children at p<0.005, 0.01 and 0.001, respectively.
Parameters City children Rural children
Benzene exposure (μg/m3
) 17.55 *** (n=43) 8.10 (n=32)
Blood benzene (ppt) 77.97 (n=40) 46.23 (n=30)
Urinary t,t-muconic acid (mg/g creatinine) 0.12 *** (n=115) 0.06 (n=63)
1,3-Butadiene exposure (μg/m3
) 2.42 ** (n=79) 0.65 (n=45)
Urinary MHBMA (mg/g creatinine)
Afternoon 0.07 * (n=48) 0.05 (n=29)
PAH exposure
Total PAHs (ng/m3
)
B(a)P equivalent (ng/m3
)
4.13 *** (n=114)
1.50 *** (n=114)
1.18 (n=68)
0.43 (n=68)
Urinary 1-HOP (μmol/molcreatinine)
Afternoon 0.22 *** (n=100) 0.12 (n=61)
28. Biomarkers of early biological effectsBiomarkers of early biological effects
associated with exposure to carcinogens:associated with exposure to carcinogens:
• DNA damage:-DNA damage:-
8-OHdG - a marker of oxidative damage8-OHdG - a marker of oxidative damage
DNA strand breaks (Comet assay)DNA strand breaks (Comet assay)
• DNA repair capacity (Cytogenetic challengeDNA repair capacity (Cytogenetic challenge
assay).assay).
29. DNA damages and DNA repair capacity in
school children
ParametersParameters City childrenCity children Rural childrenRural children
DNA DamageDNA Damage
•8-OHdG8-OHdG
- Leukocyte 8-OHdG/10- Leukocyte 8-OHdG/1055
dGdG
•DNA strand breaksDNA strand breaks
0.25*** (n = 76)0.25*** (n = 76) 0.10 (n = 37)0.10 (n = 37)
- Tail length (µm)- Tail length (µm) 1.93*** (n = 115)1.93*** (n = 115) 1.28 (n = 69)1.28 (n = 69)
- Olive tail moment (µm)- Olive tail moment (µm) 0.23*** (n = 115)0.23*** (n = 115) 0.16 (n = 69)0.16 (n = 69)
DNA repair capacityDNA repair capacity
- Dicentrics/metaphase- Dicentrics/metaphase 0.34*** (n = 91)0.34*** (n = 91) 0.21 (n = 55)0.21 (n = 55)
- Deletions/metaphase- Deletions/metaphase 0.45*** (n = 91)0.45*** (n = 91) 0.26 (n = 55)0.26 (n = 55)
Values are expressed as mean S.E.Values are expressed as mean S.E.
*,**,*** Statistically significant different from rural children as p<0.005,0.01 and 0.001, respectively.*,**,*** Statistically significant different from rural children as p<0.005,0.01 and 0.001, respectively.
30. Risks associated with exposures in school childrenRisks associated with exposures in school children
a. Aa. Additional casedditional casess perper 100,000100,000 population,population, according to WHO Air Quality Guidelines for Europeaccording to WHO Air Quality Guidelines for Europe
(10(10 additional cancer case peradditional cancer case per 100,000100,000 exposed individuals atexposed individuals at 11 ng/mng/m33
BaPBaP))
bb,, AAccording to National Industrial Chemical Notification and Assessment Scheme, Australiaccording to National Industrial Chemical Notification and Assessment Scheme, Australia
(2(2 additional deaths peradditional deaths per 100,000100,000 populations atpopulations at 11 ppbppb))
c. According to US EPA, 2009.c. According to US EPA, 2009. (Probability of a person developing cancer calculated based on(Probability of a person developing cancer calculated based on
inhalation unit risk estimate of 3x10inhalation unit risk estimate of 3x10-5-5
per mg/mper mg/m33
))
ParametersParameters Bangkok childrenBangkok children Rural childrenRural children
Individual exposure
BaP equivalent (ng/m3
) 1.50 0.43
Estimated cancer risk a
(additional cases/100,000) 15 4
Individual exposure
Benzene (ppb) 5.50 2.54
Estimated leukemia risk b
(additional deaths/100,000) 11 5
Individual exposure
1,3-Butadiene (µg/m3
) 2.42 0.65
Estimated cancer risk c
(additional cases/100,000) 6 1.8
33. ConclusionConclusion
Daily human activityDaily human activity
Levels of emissions of many toxicLevels of emissions of many toxic
chemical pollutants in a measurable waychemical pollutants in a measurable way
Exposures in many groups of theExposures in many groups of the
populationpopulation
34. ConclusionConclusion
Human body has the ability to resist diseaseHuman body has the ability to resist disease
development from chemical insult through variousdevelopment from chemical insult through various
biological mechanisms.biological mechanisms.
Cancer takes a significant time to develop, and isCancer takes a significant time to develop, and is
therefore relatively more difficult to assess throughtherefore relatively more difficult to assess through
traditional epidemiological studies.traditional epidemiological studies.
Measurements of biomarkers of exposure andMeasurements of biomarkers of exposure and
early biological effects demonstrate that there isearly biological effects demonstrate that there is
an association between elevated ambient levels ofan association between elevated ambient levels of
air pollutants and elevated internal body burdens.air pollutants and elevated internal body burdens.
DNA damage and DNA repair are examples ofDNA damage and DNA repair are examples of
these indicators of increased risk.these indicators of increased risk.
35. ConclusionConclusion
Development is a goal shared by all nationsDevelopment is a goal shared by all nations
and all cultures.and all cultures.
Human health is an integral part ofHuman health is an integral part of
everyone’s standard of living.everyone’s standard of living.
Affecting human health affects the presentAffecting human health affects the present
and future workforce, which would in turnand future workforce, which would in turn
affect development that depends on thataffect development that depends on that
workforce, thereby making the developmentworkforce, thereby making the development
non-sustainable.non-sustainable.
36. ConclusionConclusion
Awareness of the types of effects on healthAwareness of the types of effects on health
that are occurring through our dailythat are occurring through our daily
activities improve our standard of life.activities improve our standard of life.
With this information, we can thenWith this information, we can then
implement corrective and preventive actionsimplement corrective and preventive actions
to address this significant concern, and toto address this significant concern, and to
reduce the risks associated with thesereduce the risks associated with these
activities.activities.