Findings of the WHO REVIHAAP Study:Areas of Consensus and Contention

Dr Ian MudwayIan.mudway@kcl.ac.uk

R: Review of EVI: EVIdence onH: HealthA: Aspects ofA: AirP: Pollution

It all begins with a book.....

WHO project jointly financed by WHO and EC

Evidence review in response to 24 key policy

questions from the EC

Particulate matter PM2.5 and PM10 (7 questions)

Ground-level ozone (4 questions)

Other air pollutants (NO2, SO2, metals, PAHs) and

their mixtures (10 questions)

General questions

New evidence on health effects post 2005

Concentration response functions & thresholds

Policy implications

Critical data gaps

This can’t be summarised in 20 minutes

Scientific Advisory Committee H. Ross Anderson, United Kingdom

Bert Brunekreef, The Netherlands

Aaron Cohen, United States

Klea Katsouyanni, Greece

Daniel Krewski, Canada

Wolfgang G. Kreyling, Germany

Nino Künzli, Switzerland

Xavier Querol, Spain

AuthorsRichard Atkinson, United Kingdom

Lars Barregård, Sweden

Tom Bellander, Sweden

Rick Burnett, Canada

Flemming Cassee, The Netherlands

E. de Oliveira Fernandes, Portugal

Francesco Forastiere, Italy

Bertil Forsberg, Sweden

Susann Henschel, Ireland

Gerard Hoek, The Netherlands

Stephen T Holgate, United Kingdom

Nicole Janssen, The Netherlands

Matti Jantunen, Finland

Frank Kelly, United Kingdom

Nino Kunzli, Switzerland

Timo Lanki, Finland

Inga Mills, United Kingdom

Ian Mudway, United Kingdom

Mark Nieuwenhuijsen, Spain

Bart Ostro, United States

Annette Peters, Germany

David Phillips, United Kingdom

C. Arden Pope III, United States

Regula Rapp, Switzerland

Gerd Sällsten, Sweden

Evi Samoli, Greece

Peter Straehl, Switzerland

Annemoon van Erp, United States

Heather Walton, United Kingdom

Martin Williams, United Kingdom

External reviewers Joseph Antó, Spain

Alena Bartonova, Norway

Vanessa Beaulac, Canada

Michael Brauer, Canada

Hyunok Choi, United States

Bruce Fowler, United States

Sandro Fuzzi, Italy

Krystal Godri, Canada

Patrick Goodman, Ireland

Dan Greenbaum, United States

Jonathan Grigg, United Kingdom

Otto Hänninen, Finland

Roy Harrison, United Kingdom

Peter Hoet, Belgium

Barbara Hoffmann, Germany

Phil Hopke, United States

Fintan Hurley, United Kingdom

Barry Jessiman, Canada

Haidong Kan, China

Thomas Kuhlbusch, Germany

Morton Lippmann, United States

Robert Maynard, United Kingdom

Sylvia Medina, France

Lidia Morawska, Australia

Antonio Mutti, Italy

Tim Nawrot, Belgium

Juha Pekkanen, Finland

Mary Ross, United States

Jürgen Schneider, Austria

Joel Schwartz, United States

Frances Silverman, Canada

Jordi Sunyer, Spain

Observers Markus Amann, IIASA

Arlean Rhode, CONCAWE

Wolfgang Schoepp, IIASA

André Zuber, European Commission

WHO Secretariat (ECEH Bonn)

Marie-Eve Héroux

Michal Krzyzanowski

Svetlana Cincurak

Kelvin Fong

Elizabet Paunovic

Helena Shkarubo

The Team

“Toxicology & clinical studies areIrrelevant to the setting of population based AQGs”

“How many more epidemiological studies do we

need to perform?”

Association Features

Strength of Association

Specificity of Association

Consistency of Association

Other Evidence

Coherence of Theory

Biological Plausibility

Analogy

Exposure / Outcome

Temporal Sequence

Dose Response

Reversibility(Experiment)

Bradford Hill’s Criteria for Inferring Causality

Why both these positions are wrong

Epi.

Epi.

Epi. Epi.

Epi.

Tox.

Tox.

Tox.

Tox.

Tox.

Tox.

Benefits of improved air quality

Increased volume of evidence Broader range of evidence

Role of fractions / components / sources

Recent developments in the evidence of the health effects of traffic pollutants – PM2.5

We have a much better understandingof the magnitude of the problem

Lim et al. LANCET (2012)

Ambient air pollution (PM2.5):

Globally:

- 3.1 million deaths

- ~ 3.0% of all DALYs

In Western, Central and Eastern Europe:

- 430,000 premature deaths;

- over 7 million years of healthy life lost Lim et al. LANCET (2012)

Meta-analysis of the association between long-term exposure to PM2.5 and all-cause mortality

Hoek et al, EnvHealth 2013

These are all, by and large, associations derived from old cohorts exposed to

historic levels of air pollution.

What do they tell us about contemporary exposures?

Mortality and long-term PM2.5 exposure Results of a Canadian cohort study (2.1 million adults, 1991-2001)

Non accidental

Cardiovascular

Ischemic heart disease

Cerebrovascular

Crouse et al, EHP 2012

AQG

Mortality and long-term exposure to PM2.5

Results of a cohort study in Rome (1.3 million adults followed from 2001 to 2010)

EULV

AQG

4% per 10 mg/m3 6% per 10 mg/m3 10% per 10 mg/m3

Cesaroni et al, EHP 2013

Improvements in PM10 (& PM2.5) reduces respiratory symptoms

SAPALDIA Study, Schindler et al, 2009

New Cough Persistent Cough

New Wheeze Persistent Wheeze

7,019 subjects with detailed baseline examinations in 1991 and a follow-up interview in 2002

PM2.5 air pollution & life expectancy in the US

Pope et al, N Engl J Med, 2009

Reduction in PM2.5, 1980-2000 (μg/m3)

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Assessed associations between life expectancy and fine-particulate air pollution in 51 U.S. metropolitan areas, comparing data for the period from the late 1970s to the early 1980s with matched data for the period from the late 1990s to the early 2000s

Toxic Components of PM – a multitude of views (HARPIE)

UFP: 14.2%

Black Carbon – a better health indictor? Toxic component or source indicator?

Janssen et al, Environ Health Perspect, 2011

Estimated county- and season-specific relative risks (RR) of cardiovascular and respiratory hospitalization associated with PM2.5 components in 106 U.S. counties for the years 1999 through 2005

Systematic review and meta-analysis of health effects of BC compared with PM mass based on data from time-series studies and cohort studies that measured both exposures

We already know quite a lot about traffic & traffic-derived pollutants

Mortality

Asthma and Respiratory - Children

Asthma and Respiratory - Adults

All-cause and Cardiovascular mortality

Asthma onset and prevalenceAsthma is more common in children living in the street buffers with the highest concentrations of traffic-related pollution

Exacerbation of asthma symptomsChildren living in hot spots of traffic-related pollution experience more symptoms and exacerbations

Adult-onset of asthma (one study)

Exacerbation of asthma symptoms (few studies)

Hospitalisation rates

Association with Traffic Air Pollution Exposure

Sufficient

Sufficient

Sufficient

InsufficientSuggestive but not sufficient

Insufficient

Health Outcome

Respiratory Symptoms

Living in proximity to high concentration of traffic air pollution may be associated with reduced lung function

Suggestive but not sufficient

Association Features

Strength of Association

Specificity of Association

Consistency of Association

Other Evidence

Coherence of Theory

Biological Plausibility

Analogy

Exposure / Outcome

Temporal Sequence

Dose Response

Reversibility(Experiment)

Inferring Causality for PM2.5

As concluded by REVIHAPP – PM2.5

• Additional support for the effects of short- and long-term exposure to PM2.5 on both mortality and morbidity.

• Long term exposure to PM2.5 is a cause of both cardiovascular mortality and morbidity.

• More insight has been gained into physiological effects and plausible biological mechanisms of the detrimental effects of PM2.5.

• Additional studies linking long-term exposure to PM2.5 to several new health outcomes including atherosclerosis, adverse birth outcomes and childhood respiratory disease

• Possible links between long-term PM2.5 exposure and neurodevelopment and cognitive function as well as other chronic disease conditions such as diabetes.

• Black carbon, secondary organic aerosols, and secondary inorganic aerosols may provide valuable metrics for the effects of mixtures of pollutants from a variety of sources.

• Short-term exposures to coarse (including crustal material) and ultrafine particlesare associated with adverse respiratory and cardiovascular health effects, including premature mortality.

What about the thorny issue of NO2?

Forest plot for cardiac hospital admissions studies NO2 with and without adjusting for PM10

NO2 SINGLE ESTIMATES

Wong et al 2002 [London]

Wong et al 2002 [Hong Kong]

Moolgavkar 2000 [Cook County, USA]

NO2 CONTROLLING FOR PM10

Wong et al 2002 [London]

Wong et al 2002 [Hong Kong]

Moolgavkar 2000 [Cook County, USA]

0.0 0.5 1.0 1.5 2.0 2.5 3.0

Percentage change for a 10 unit change

Long-term exposure – mortality in multi-pollutant models

• Jerrett, 2009: Toronto Effects of NO2 not PM2.5, NO2

effect remained after adjustment for traffic proximity

• Hart, 2011: Truck drivers NO2 and SO2 rather than PM10

and PM2.5 (smoking adjustment only in a subset)

• Cesaroni, 2013: Rome effect independent of PM2.5 and traffic density (indirect control for smoking)

Association Features

Strength of Association

Specificity of Association

Consistency of Association

Other Evidence

Coherence of Theory

Biological Plausibility

Analogy

Exposure / Outcome

Temporal Sequence

Dose Response

Reversibility(Experiment)

Inferring Causality for NO2

As concluded by REVIHAPP – NO2

• Many new studies document associations between day-to-day variations in NO2 concentration and variations in mortality, hospital admissions, and respiratory symptoms.

• Studies have now been published, showing associations between long-term exposure to NO2 and mortality and morbidity.

• Both short- and long-term studies have found these associations with adverse effects at concentrations at or below the current EU limit values.

• The results of these new studies provide support for updating the 2005 global update of the WHO air quality guidelines which could result in lower guideline values.

• Toxicology remains non-coherent.

Areas for future work (knowledge gaps)

The results of the WHO – EC project “Review of evidence on health aspects of air

pollution - REVIHAAP”

http://www.euro.who.int/__data/assets/pdf_file/0004/193108/REVIHAAP-Final-

technical-report-final-version.pdf

• 1000’s new health studies, reviews (2006-2014)

• NPACT study (2013); ESCAPE (2013)

• REVIHAAP (July 2013); HRAPIE (Dec 2013)

• HEI Ultrafines report (2013)• WHO Black Carbon report

(2012)• IARC Diesel exhaust report

(2013)• WHO Burden of disease

report (March 2014)