Epidemiological studies on health effects of ambient fine and ultrafine particles Francesco Forastiere Department of Epidemiology, Rome E Health Authority, Rome, Italy
Outline What are (urban air) ultrafines? Ultrafines in urban air and respiratory effects Ultrafines in urban air and cardiovascular effects The Rome PM10 PNC study Do the associations with ultrafines explain the effects of PM2.5 or PM10? Are these association causal?
Science 307:1857-1861, News Focus, March 2005
Schematic diagram of a typical atmospheric aerosol particle size distribution, indicating formation pathways
mass, dm/dlogdp, µg/m3 70 60 50 40 30 20 10 Ultrafines (<0.1 µm) C SO4 NH4 NO3 C PM2.5 Al Ca Fe O Si 0 0.01 0.1 1 10 100 Local Long-distance Soil combustion transport particle aerodynamic diameter, µm
Particles Size? Or Mass? Or Number? Or What? Mass Diameter Number Surface Area (µg/m 3 ) (µ) (per ml) (µ 2 /ml) 10 2 1.2 24 10 0.5 153 120 10 0.02 2,400,000 3016 Adapted from Donaldson K et al. Occup Environ Med 2001;58:211-216
THE EFFECTS OF AIR POLLUTION ON HEALTH ARE OFTEN CONVENIENTLY CLASSIFIED: In short-term and long-term effects although there is probably a continuum of effects in the time scale, which are not yet fully understood.
Quantitative summary estimate for the percent change in all-cause all-age mortality for a 10 μg/m3 increase in PM10 from different regions of the world. Location % change (CI) Reference United States 0.27 (0.12,0.30) Dominici, 2003 Europe 0.60 (0.40,0.80) Katsouyanni, 2001 Asia 0.49 (0.23,0.76) Hei, 2004 Latin America 0.61 (0.16,1.07) PAHO, 2005 Worldwide 0.65 (0.51,0.76) Stieb, 2002
Long-term exposure and mortality POPE ET AL, JAMA 2002
Epidemiology of ultrafines and respiratory effects Several studies done in 90 s on short term effects, current focus on cardiovascular disease No studies with personal exposure conducted No studies on chronic effects conducted Several studies on closeness to traffic
Panel Studies on ultrafine particles in Finland Winter 1993/94: 39 asthmatic children in Kuopio for 2 months; Pekkanen et al., Env Res 1997 Spring 1995: 49 children with chronic respiratory symptoms in Kuopio for six weeks; Tiittanen et al., Eur Respir J 1999 Winter 96/97: 57 adult asthmatics in Helsinki for 6 months; Penttinen et al. Eur Respir J 2001
Effects of particles on PEF (Finland) Change in PEF [l/min per IQR] 2 asthmatic children 1 0-1 children with respiratory symptoms asthmatic adults -2-3 UFAC PM10 UFAC PM10 UFAC PM10
Epidemiology of ultrafines and cardiovascular effects Some recent studies, most time series or panels Plausible mechanisms No studies with personal exposure No studies on chronic effects
PM & Effects on the Circulatory System Pulmonary inflammation and/or particles absorbed into the blood may: Plasma viscosity Plasma coagulability Thrombus formation Cardiac ischemic events (First proposed by Seaton A et al. Lancet 1995; 345:176-178)
Possible biological mechanisms linking PM with cardiovascular diseases Brook et al, 2004. Air Pollution and Cardiovascular Disease American Heart Association
PM and ischemia (ST-segment at ECG) PM and cardiac symptoms The ULTRA Study
Association between PM 2.5 2 days before the clinic visit and adjusted risk of ST-segment depression >0.1 mv. The broken curves indicate 95% Cls. (Pekkanen et al. Circulation 2002;106:933-38)
ULTRA Study, winter 1998 1999. Amesterdam, Erfurt, Helsinki. Panel of elderly subjects with coronary heart disease Odds Ratios for shorteness of breath. Effects for 10 µg/m 3 in PM 2.5 and 10,000 particles/cm 3 in NC 0.01 0.1 (5-day average). (de Hartog et al, Am J Epidemiol, 2003)
European Commission QUALITY OF LIFE AND MANAGEMENT OF LIVING RESOURCES KEY ACTION N 4: ENVIRONMENT AND HEALTH HEALTH EFFECTS OF AIR POLLUTION ON SUSCEPTIBLE SUBPOPULATIONS TRADITIONAL AIR POLLUTANTS, ULTRAFINE PARTICLES AND MYOCARDIAL INFARCTION: DATABASE AND HEALTH ASSESSMENT HEAPSS EU Contract QLK4-CT-2000-0708
Relevant questions for public health What is the role of ultrafine particles? Are there measurable effects of air pollution on the cardiovascular system? Especially on ischemic heart diseases Is there a susceptible subpopulation at high risk? HEAPSS
inquinamento atmosferico Effetti a breve termine sulla sindrome coronarica HEAPSS: Health Effects of Air Pollution on Susceptible Subpopulations (1992 2001) Le cinque città di HEAPSS Augsburg Helsinki Stoccolma Obiettivi principali: Stimare il rischio di ricovero e di morte attribuibile all inquinamento atmosferico (particelle ultrafini), in soggetti con infarto del miocardio. Barcellona Roma
Condensation Particle Counter (CPC) to monitor ultrafine particles in each city
inquinamento atmosferico Effetti a breve termine sulla sindrome coronarica: HEAPSS Associazione tra PM 10, PNC e CO (lag 0) e gli eventi coronarici fatali e non fatali, Roma 1998 2000 (incrementi percentuali calcolati per range interquartile(*) ) incremento percentuale (IC 95%) 15 10 5 0-5 Eventi fatali Eventi non fatali PM 10 PNC CO PM 10 PNC CO (*) I range interquartili sono: PM 10 (lag 0): 29.7, PNC (lag 0): 28,001, CO (lag 0): 1.2
Association between air pollutants and out-of-hospital coronary deaths: % increases of risk associated to an interquartile range variation of pollutants, lag 0 to 3, Rome 1998 2000 Forastiere et al, 2005. AJRCCM
0.4 s(co, lag 0-1) s(pm 10, lag 0-1) s(pnc, lag 0-1) 0.2 0.0-0.2-0.4 0.6 0.4 0.2 0.0-0.2-0.4 0.4 0.2 0.0 20,000 40,000 60,000 80,000 100,000 120,000 140,000 PNC (lag 0-1) particles/cm 3 20 40 60 80 100 120 140 PM 10 (lag 0-1) µg/m 3 Figure 2 - Concentration -response curves of air pollutants (PNC, PM10 and CO) and out-of-hospital coronary deaths in Rome -0.2-0.4 1 2 3 4 5 6 7 CO (lag 0-1) mg/m 3
HEAPSS: Health effects of air pollution in City Augsburg Barcelona Helsinki Rome Stockholm susceptible subpopulations Acute effects on first coronary events and recurrent events Subjects First AMI 1694 1467 5148 8799 9746 CO 0.9 0.9 0.4 2.3 0.4 Pollution levels NO 2 49.8 48.0 30.2 70.0 22.7 PNC 12.6 58.1 12.3 46.8 10.4 CO averages in mg/m 3, PNC in thousands of particles per cm 3, all others in µg/m 3 PM 10 38.3 54.6 25.2 51.0 14.6
Association between air pollutants and cardiac readmissions among post-mi patients. Five HEAPSS cities, lag 0-3. vonklot et al, 2005. Circulation
Rome PM10 PNC mortality and morbidity study AIMS To evaluate the effects of PM10 and PNC (Particles Number Concentration) on daily mortality and morbidity in Rome
Wichmann HE et al. Daily mortality and fine and ultrafine particles in Erfurt, Germany part I: role of particle number and particle mass. Res Rep Health Eff Inst. 2000 Nov;(98):5-86; Over a three-year period, the concentrations of both ultrafine (< 0.1 µm in diameter) and fine particles (0.1 2.5 µm) in the ambient air were similarly associated with mortality in a distributed lag model where the contribution of the previous 4 to 5 days was evaluated. In two-pollutant models, associations of ultrafine and fine particles were largely independent of each other.
Outcome data Mortality data : deaths of residents occurring in Rome were selected by the Regional Registry of Causes of Death and classified according the ICD-9. Hospital admission data : residents hospitalized in Rome were selected by the Regional Registry of Hospital Admissions. We selected only emergency admissions* and classified them using the principal diagnoses.
Description of health events by diagnostic group, Rome 1998-2004 Mortality Hospitalization N daily mean N daily mean Total (non-injury) (0-799) 147,982 57.9 2,235,767 874.4 Cardiovascular diseases (390-459) 61,750 24.1 391,456 153.1 Cardiac diseases (393-429) 45,013 17.6 240,175 93.9 Ischemic heart disease (410-414) 23,208 9.1 90,710 35.5 Heart rhythm disturbances (426-427) 2,102 0.8 51,809 20.3 Heart failure (428) 2,493 1.0 37,656 14.7 Cerebrovascular diseases (430-438) 13,552 5.3 72,329 28.3 Ischemic stroke (433-434;436-438) 10,166 4.0 53,566 20.9 Respiratory diseases (460-519) 8,411 3.3 173,251 67.8 Pneumonia (480-486) 1,102 0.4 30,145 11.8 COPD (490-492) 5,098 2.0 27,557 10.8 Asthma (493) 227 0.1 7,996 3.1 Diabetes mellitus (250) 5,724 2.2 20,170 7.9
Environmental variables Air pollution data : Data on PM 10 were available from the Regional Agency for Environmental Protection. Four monitors. Data on PNC has been collected in Rome since April 2001 using optical particle counters. The data were estimated retrospectively for the period 1998 April 2001. One monitor Meteorological data : daily average values of temperature, dew point and barometric pressure at sea level were calculated from values recorded from the airport meteorological station. Apparent temperature= -2.653+0.994 temperature +0.0153 (dew point) 2
Environmental variables measured in Rome, during 1998-2004 Environmental variables N % day missing Mean Stand. error Percentiles 25 50 75 Barometric pressure (hpa) 2,546 0.4 1,015.4 6.6 1,011.4 1,015.3 1,019.2 Apparent temperature ( C) 2,546 0.4 15.7 8.6 8.4 15.4 22.8 PM 10 (µg/m 3 ) 2,549 0.3 47.3 19.9 33.4 44 57.1 PNC (particles/cm 3 ) 2,385 6.7 45,474 23,388 28,710 40,871 57,455 IQR PM10 = 29.3 µg/m 3 IQR PNC =19496 particles/cm 3 29.3 : 10 = 19496 : x x=6600 particles/cm 3
Time-series of PM 10 in Rome, 1998-2004. 180 Daily mean of PM 10 160 140 120 100 80 60 40 20 1998 1999 2000 2001 2002 2003 2004
Time-series of PNC in Rome, 1998-2004. 140000 Daily mean of PNC 120000 100000 80000 60000 40000 20000 1998 1999 2000 2001 2002 2003 2004
1.60E+05 1.40E+05 1.20E+05 1.00E+05 16/02/02 24/02/02 05/03/02 13/03/02 21/03/02 29/03/02 09/04/02 17/04/02 25/04/02 05/05/02 13/05/02 21/05/02 11/06/02 19/06/02 27/06/02 05/07/02 13/07/02 19/01/03 27/01/03 05/02/03 13/02/03 21/02/03 8.00E+04 6.00E+04 4.00E+04 2.00E+04 0.00E+00 R-squared=0.712 Particles number concentrations (cm-3) orto Particles number concentrations (cm-3) iss Particles number concnetrations (cm -3 )
Case-crossover Data Analysis We used a time-stratified approach for the case crossover : the study period was divided into monthly strata, and the control days for each case were selected as the same days of the week in the stratum.
Confounding factors considered to study the effects of PM 10 and PNC on mortality and hospitalization Influenza epidemics Population reductions in summer months Holidays ENVIRONMENTAL FACTORS Barometric pressure Apparent temperature The factors time trend and day of the week are controlled by design
Effects of PM 10 on mortality for single lag (0, 1, 2 day) and distributed lag (0-1, 0-2), by cause of death. % Change in Mortality Rate per 10 µg/m 3 increase in PM 10 (95% CI) 3 2 1 0-1 -2 Lag 0 1 2 0-1 0-2 0 1 2 0-1 0-2 0 1 2 0-1 0-2 0 1 2 0-1 0-2 Total (non injury) Cardiovascular diseases Respiratory diseases Diabetes mellitus a Percent change of risk (%) is calculated from Odds Ratio (OR) as: % = (OR-1)*100
Effects of PNC on mortality for single lag (0, 1, 2 day) and distributed lag (0-1, 0-2), by cause of death. % Change in Mortality Rate per 6600 particles/cm 3 increase in PNC (95% CI) 3 2 1 0-1 -2 Lag 0 1 2 0-1 0-2 0 1 2 0-1 0-2 0 1 2 0-1 0-2 0 1 2 0-1 0-2 Total (non injury) Cardiovascular diseases Respiratory diseases Diabetes mellitus a Percent change of risk (%) is calculated from Odds Ratio (OR) as: % = (OR-1)*100
Effects of PM 10 on hospitalization for single lag (0, 1, 2 day) and distributed lag (0-1, 0-2), by cause of admission. % Change in Hospital Admissions per 10 µg/m 3 increase in PM 10 (95%CI) 3 2 1 0-1 -2 Lag 0 1 2 0-1 0-2 0 1 2 0-1 0-2 0 1 2 0-1 0-2 Cardiovascular diseases Respiratory diseases Diabetes mellitus a Percent change of risk (%) is calculated from Odds Ratio (OR) as: % = (OR-1)*100
Effects of PNC on hospitalization for single lag (0, 1, 2 day) and distributed lag (0-1, 0-2), by cause of admission. % Change in Hospital admissions per 6600 particles/cm 3 increase in PNC (95% IC) 3 2 1 0-1 -2 Lag 0 1 2 0-1 0-2 0 1 2 0-1 0-2 0 1 2 0-1 0-2 Cardiovascular diseases Respiratory diseases Diabetes mellitus a Percent change of risk (%) is calculated from Odds Ratio (OR) as: % = (OR-1)*100
To analyze the effects of the two pollutants and compare them we considered unipollutant models and multipollutant models: the Pearson correlation coefficient between PM 10 and PNC was 0.46
EFFECTS of PM 10 and PNC (lag 0-1) 0 on MORTALITY UNIPOLLUTANT MODELS MULTIPOLLUTANT MODEL Total (non-injury) Cardiovascular diseases Cardiac diseases Ischemic heart disease Heart rhythm disturbances Heart failure Cerebrovascular diseases Ischemic stroke Respiratory diseases Pneumonia COPD Asthma Diabetes mellitus PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC
EFFECTS of PM 10 and PNC (lag 0-1) 0 on HOSPITALIZATION UNIPOLLUTANT MODELS MULTIPOLLUTANT MODEL Cardiovascular diseases Cardiac diseases Ischemic heart disease Heart rhythm disturbances Heart failure Cerebrovascular diseases Ischemic stroke Respiratory diseases Pneumonia COPD Asthma Diabetes mellitus PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC PM 10 PNC
Conclusions on the Rome study Consistent effect of PM10 on daily mortality (natural, CVD, resp, diabetes) Smaller effects of PNC on mortality CVD and Resp hospitalizations associated with both PM10 and PNC at short lag. PNC effect on ischemic heart diseases stronger than that of PM10. Measurement error should be considered
UF and Health effects: conclusions Several associations Mostly weaker than PM2.5/PM10
Do ultrafines in urban air explain the associations between PM2.5 and health? Ultrafines are not the main explanation for the acute effects of PM2.5 (time series studies) Ultrafines are unlikely to explain the PM2.5 effect in U.S. cohort studies, but main explain (part of) effect of traffic in European cohort studies
Ultrafines and health: causality?
Outdoor air vs. dose Central site Other outdoors Indoors Personal exposure Deposited dose Transport, transform I/O ratio Time activity Breathing
Individual correlations of central site and indoor concentrations RUPIOH study Helsinki Athens Amsterdaham Birming- Ultrafine 0.18 0.45 0.42 0.17 PM 2.5 0.70 0.40 0.80 0.55 Hoek et al. (manuscript)
Conclusions Several associations, but mostly weaker than PM2.5 Ultrafines are not the main explanation for the acute effects of PM2.5 Poor exposure assessment in time series => Ultrafines markers of air pollution mixture
EU, CAFE program, 2005
Mice on normal diet Mice on high-fat diet Filtered air PM2.5 Filtered air PM2.5 Long-term Air Pollution Exposure and Acceleration of Atherosclerosis Sun et al. JAMA.2005; 294: 3003-3010.
WHO Air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide Global update 2005 Summary of risk assessment http://www.who.int
Guidelines PM2.5: 10 µg/m3 annual mean 25 µg/m3 24-hour mean PM10: 20 µg/m3 annual mean 50 µg/m3 24-hour mean