1. The Global Burden of Lower Respiratory Infections Attributable to Ambient and Household Air Pollution: estimates from GBD 2017
Good afternoon.
I want to thank the organizers for inviting me to speak with you today about the global burden of disease from Lower Respiratory Infections attributable to air pollution, or LRIs.
Why LRI’s? Are these the only infectious diseases associated with air pollution?
Well, they aren’t. Household air pollution has also been associated with tuberculosis, a leading cause of global morbidity and mortality, and ambient air pollution has been associated with SARS case-fatality and from ARDS, which in some cases has an infectious etiology. High levels of windblown dust, a sequela of climate change-driven desertification, have also been linked to epidemic bacterial meningitis in the Sahel region of Africa and in the US.
But LRI is the number one global cause of infectious disease mortality, responsible for 2.6 million deaths in 2017, and air pollution is a major risk factor.
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National Academy of Sciences Workshop
Washington, DC
January 15, 2019
Aaron J Cohen
Health Effects Institute /
Institute for Health Metrics and Evaluation

2. What is the Global Burden of Disease?
The most comprehensive worldwide observational epidemiological study to date. It describes mortality and morbidity from major diseases, injuries and risk factors to health at global, national and regional levels
Disease, injury, & risk burden estimates for 1990 – 2017 using comparable methods for 195 countries and territories and sub-national analyses for selected countries
Mortality from 264 specific causes and incidence and prevalence of diseases and injuries and relevant disabling sequelae, stratified by sex and 20 age groups
Burden measured as deaths in a given year and Disability Adjusted Life Years” (DALYs) – lost years of healthy life
Burden attributable to of 84 risk factors
Global collaboration coordinated by Institute for Health Metrics and Evaluation and involves > 3,000 collaborators
GBD 2017 updates previous GBD estimates with new data, methods
Major GBD 2017 were published in The Lancet November 2018
Estimates updated annually
The estimates I just cited, and that I will discuss with you today, are the most recent estimates from GBD 2017, the most recent update of the Global Burden of Disease project, a large international collaboration of more than 3,500 scientists from over 100 countries. It is led by the Institute for Health Metrics and Evaluation at UW and funded by the Bill and Melinda Gates Foundation.
GBD 2017 quantified the magnitude of health loss, in terms of DALYs (Lost-Yr. of Healthy Life) and deaths, from over 200 disease and injuries in 195 countries around the world from 1990 to 2017 and at the subnational level for countries with populations >200 million in GBD 2017 also estimated the burden of disease attributable to 84 major health risk factors including ambient and household air pollution.
GBD 2017 updates previous GBD estimates with new data, methods and the estimates are now updated yearly. The major GBD 2017 results were published in The Lancet in November 2018.
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3. Changes in Life-Expectancy at Birth 1970-2017
But before discussing the burden of disease from LRI attributable to air pollution it is important to consider the upstream forces that underlie the current burden and changes in that burden over time.
This slide shows the changes in LE at birth from for 21 global regions with 2017 on the X axis and 1970 on the Y axis. In all regions life expectancy at birth has increased, reflecting an epidemiologic transition characterized by increasing mortality from non communicable diseases and a marked decline in mortality from communicable diseases such as LRI and in mortality from maternal and neonatal diseases.
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GBD 2017 Mortality Collaborators The Lancet 2018

4. Trends in Global LRI Mortality 1990-2017
And indeed age-standardized rates of mortality from LRI have decreased worldwide since 1990 by 46% from 66.2/100K ( ) to 35.4/100K ( ), and this decrease was driven largely by major declines in LRI mortality in children under 5 yr. where rates fell by 67% from 362.7/100K ( ) to ( ).
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These changes were driven in large part by changes in multiple risk factor exposures including increased vaccination, improved sanitation, and household air pollution. Age-standardized rates s of LRI mortality from all LRI risk factors were more than halved from 1990 to 2017 (51.7 – 22.9)
GBD 2017 Cause of Death Collaborators The Lancet 2018

5. Leading causes of death 2017
But LRI remains a major global cause of death.
This slide shows the leading causes of global mortality in Heart disease and stroke and COPD were the 3 leading causes but LRI was the 4th, accounting for 2.56 ( ) million deaths.
In GBD 2017 the burden of disease attributable to ambient and household PM2.5 was estimated for ischemic heart disease (IHD), stroke (ischemic and hemorrhagic), lung cancer, chronic obstructive pulmonary disease (COPD), Type 2 Diabetes Mellitus and lower respiratory infection (LRI), and the burden attributable to ozone was estimated for COPD.
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GBD 2017 Cause of Death Collaborators The Lancet 2018

6. Age-Standardized LRI Mortality 2017
Global age-standardized LRI mortality rates varied by more than 30-fold; from 4.59/100K ( ) in Austria to 159/100K ( ) in the Central African Republic.
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GBD 2017 Cause of Death Collaborators The Lancet 2018

7. So what role does air pollution play in the global burden of LRI?
Indeed LRI is a major contributor to disparities in lost years of healthy life when we classify countries according to the SDI, or Socio-demographic Index, based on income education and fertility.
So what role does air pollution play in the global burden of LRI?
Before I answer that question I want to briefly describe how we estimate the burden of disease attributable to air pollution
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GBD 2017 DALYs and HALE Collaborators The Lancet 2018

8. General approach Worldwide Health Evidence
Exposure to Ambient Air Pollution
Baseline Incidence
Country- Specific Mortality, Disease
Concentration –Response Relationships
Worldwide Health Evidence
Global Burden, DALYs, Mortality
First we estimate exposure to ambient and household air pollution on a global scale. In GBD we estimate population-weighted annual average concentrations of PM2.5 and tropospheric ozone, indicators of two relatively distinct air pollution mixtures for which there is now considerable evidence of adverse health effects.
Global annual average exposure to PM2.5 was estimated in five-year intervals from 1990 to 2017, at 0.1 x 0.1 ° (~ 11 x 11 km at the equator) resolution using estimates from satellites combined with a chemical transport model (CTM), surface measurements and geographic data
For GBD 2017 the database of ground measurements of PM2.5 included 9,945 sites in 116 countries.
Next, based on the available worldwide health evidence, we develop a mathematical relationship, or exposure-response function, that links exposure and cause-specific mortality for LRI and 5 other major causes in terms of a relative risk per unit of exposure. We use the estimated exposure and the RR to estimate the proportion of deaths in each country due to air pollution (the PAF) and multiply that proportion times cause-specific mortality rates to estimate the burden of disease attributable to air pollution for each cause and then we sum the cause-specific burdens.
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9. PM2.5 Exposure 2017
Global annual average exposure to PM2.5 was estimated in five-year intervals from 1990 to 2017, at 0.1 x 0.1 (~ 11 x 11 km at the equator) resolution using estimates from satellites combined with a chemical transport model (CTM), surface measurements and geographic data.
For GBD 2017 the database of ground measurements of PM2.5 included 9,945 sites in 116 countries.
This map shows the estimated levels of population-weighted mean PM2.5.
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For household air pollution our estimates are based on the proportion of the population in each country that uses solid fuels for cooking estimated from household survey data. We link these estimates to a global data base of household PM2.5 measurements from over 60 studies.
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Global Burden of Disease Study IHME, 2018 PRELIMINARY ESTIMATES

10. GBD 2017 LRI Integrated Exposure Response Function
In order to estimate the exposure-response relationships over the entire range of exposure to ambient and household PM2.5 we use a mathematical model called the Integrated Exposure Response function, or IER. There are separate IERs for each of the six causes of death included in GBD 2017, and this is the IER for LRI with PM2.5 on the X axis and RR on the Y axis.
The IER combines estimates of the RR for ambient PM2.5 and mortality with mortality RR from other sources of PM2.5-cigarette smoking, second-hand smoke, and HAP-to estimate risk of mortality at the highest levels of ambient air pollution. This approach assumes that the risk of mortality is a function of inhaled dose of PM2.5 regardless of source.
The LRI mortality relative risks for both children and adults are estimated from this IER using 96 estimates from 36 studies of LRI incidence and mortality due to exposure to AAP (13/15), HAP (1/44), SHS (20/21) and active smoking (2/16).
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The IER was evaluated over a range of exposure from the current levels of ambient or household PM2.5
to a cleaner counterfactual level of approximately 4 µg/m3, the Theoretical Minimum Risk Exposure Level. We assigned TMREL uniform distribution bounded by the minimum and fifth percentiles of exposure distributions from ambient air pollution cohort studies ( μg/m3). The uniform distribution represents the uncertainty regarding adverse effects of low-level exposure.
We reduced the potential for double-counting of disease burden for those populations exposed to both household air pollution and ambient air pollution by differentiating exposure from these two risk factors and proportionately attributing disease burden based on the contribution of each exposure
For GBD 2017 estimates from new epidemiologic studies for ambient PM2.5, household air pollution and secondhand smoke and updated literature reviews for active smoking have been incorporated into the integrated exposure response function, including for the first time a large Chinese cohort study. The curves were fit using an iterative Bayesian approach in order to quantify the uncertainty of the estimates, which is indicated by the shaded areas and modifications to the modeling structure have stabilized the shape of the IER curves.
The overall uncertainty in the burden estimates that we calculated is a function of uncertainty in the PM2.5 estimates, the IER, the TMREL and baseline health rates.
TMREL (counterfactual) ~4 μg/m3 midpoint of a uniform distribution bounded by the minimum and fifth percentiles of exposure distributions from ambient air pollution epidemiologic studies ( μg/m3 )
GBD Risk Factor Collaborators The Lancet 2018

11. Global Mortality Risk Factor Ranking 2017
2.9 million (UI ) deaths attributable to ambient PM2.5
5.2 % of global deaths
8th ranking risk factor
432 K (UI ) LRI deaths
1.6 million (UI ) deaths attributable to Household Air Pollution
2.9% of global deaths
13th ranking risk factor
459 K (UI ) LRI deaths
Air pollution ranked among the most important global risk factors in High blood pressure, tobacco smoking and high fasting blood glucose were the top 3 global mortality risk factors. 
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Ambient PM2.5 was the 8th, contributing to 2.9 million deaths or 5.2% of global deaths, largely from heart disease and stroke.  432K attributable deaths, or 15%, were from LRI
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PM2.5 from household burning of solid fuels was the 13th leading risk factor for mortality in 2017, contributing to 1.6 million deaths or 2.9% of global mortality. 459K attributable deaths, or 29%, were from LRI   
All told, ambient and household PM2.5 contributed to an estimated 4.9 million deaths in 2017, 8.7% of all global deaths, making it the 5th leading risk factor for mortality following diet, high blood pressure and tobacco. 891K deaths, or 18 %, were from LRI
PM2.5 air pollution contributed to 4.9 million deaths in 2016 (UI )
8.7 % of global mortality
5th leading global risk factor
0.89 million (UI ) LRI deaths
GBD 2017 Risk Factor Collaborators The Lancet 2018

12. Source: J Apte U Texas Austin Personal Communication
Although it is the number of deaths due to air pollution exposure that often gets the most attention in the press, a critical, and arguably more important, question for epidemiology and public policy is whether people die earlier as a result of exposure to air pollution and what is the effect of exposure on life expectancy.
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Joshua Apte (of the University of Texas) and colleagues recently estimated the impact of exposure to ambient PM2.5 on life expectancy at birth for 185 countries using GBD cause- and age-specific mortality data. In 2016, PM2.5­ exposure reduced average global life expectancy by ~ 1 y with reductions of ~ 1.2 – 1.9 years in highly- polluted countries of Asia and Africa. In China LE at birth was reduced by an estimated 1.3 y.
In 2016 LRI was responsible for a significant share of lost life expectancy, approximately 20% on a global scale and 50-60% in Sub-Saharan Africa.
Source: J Apte U Texas Austin Personal Communication

13. LRI Mortality Risk Factors 2017
This slide ranks the ten major LRI risk factors in terms of their contribution to age-std. LRI mortality in PM2.5 from ambient and household exposure was the leading global LRI risk factor, and the leading risk factor in high-, middle-, and low-income countries. Global age-std. rates were deaths/100K, but there was considerable variation of age-standardized LRI death rates across the globe related to level of economic development: deaths/100K in the US vs in Sub-Saharan Africa, and among middle-income countries as well with 6-fold higher rates in India (24.13) than in China 4.57).
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GBD 2017 Risk Factor Collaborators The Lancet 2018

14. PM2.5-attributable LRI death rates 1990-2017
Age-standardized PM-attributable LRI global death rates and numbers of deaths have declined since 1990 for both ambient and household exposure. The age-standardized rate declined by 56.7% (28.7 – 12.4).
But trends differ between young children and the elderly and by source of exposure.
Decline in LRI mortality rates in children under 5 yr. drive this trend with 70 % declines (69.6) , and this decline was greatest for household exposure, which rates declined by 75% (74.9). But nonetheless, even these lower rates translated into a huge loss of heathy life: 32 million (26-38) DALYs in 2017
Among adults > 70 yr. rates declined by 31.2 %, due entirely to a 51.3% drop in mortality from household exposure.
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But rates from ambient exposure actually increased in the elderly by 14.5% and numbers of deaths by 143%, from 75K (58-95) in 1990 to 183 K ( ) in 2017
GBD 2017 Risk Factor Collaborators The Lancet 2018

15. Looking ahead
GBD MAPS Working Group Burden of Disease Attributable to Major Air Pollution Sources in India. Special Report 21. Boston, MA: Health Effects Institute.
Recent mortality projections from the GBD project estimate that LRI will remain an important cause of premature mortality for the next few decades.
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But a recent study by the Health Effects Institute estimated the burden of disease in India from major sources of ambient PM2.5 in 2015
and under a range of future scenarios of emission reductions from major sources of ambient PM2.5 out to With increasingly aggressive reductions, rates of lost-years of-healthy-life declined in both urban and rural areas for cardiovascular and respiratory diseases, including LRI shown in blue, where the LRI mortality rate was nearly halved in a scenario that included the elimination of household burning of solid fuels.
Foreman KJ et al. The Lancet 2018

16. Summary and Future Research Questions
Mortality from LRI has declined since 1990, especially in children under 5 yr. but remained the 4th leading global cause of death in 2017 and the 2nd leading cause in children under 5 yr.
PM2.5 air pollution is the leading global risk factor for LRI mortality, largely due to high rates of PM-attributable mortality in both children under 5 yr. and adults > 70 yr. with the highest rates in low- and middle-income countries in Asia and Sub-Saharan Africa.
LRI mortality from ambient and household exposure to PM2.5 has declined but a considerable burden of disease remains. LRI will remain a leading cause of death in the future, especially due to ambient exposure in older adults.
Reductions in burden will require concerted policy action to reduce exposure to PM2.5 air pollution from major sources and to other LRI risk factors
Research questions:
Is the LRI exposure-response relationship the same for children and adults? Can we develop separate risk functions?
Does exposure to PM2.5 cause increased TB mortality ? If so, what is the attributable burden?
Are the effects of exposure to PM2.5 and other major LRI risk factors additive, or are there joint, interactive effects?
Which sources of PM2.5 are most responsible for the LRI PM-attributable burden?

17. Thank You! acohen@healtheffects.org
For more information on the GBD Collaboration
For all data and estimates