POLLUTIE: wat ademen we in? Prof. Dr. W. De Backer UZA/UA

POLLUTIE: wat ademen we in? Prof. Dr. W. De Backer UZA/UA

Klinische betekenis blootstelling aan polluenten 1

Astma kinderen voor en na blootstelling polluenten Renzetti G. et al. Pediatrics 2009;123:1051-1058 2

Astma kinderen voor en na blootstelling polluenten Renzetti G. et al. Pediatrics 2009;123:1051-1058 3

Astma kinderen voor en na blootstelling polluenten Renzetti G. et al. Pediatrics 2009;123:1051-1058 4

Astma kinderen voor en na blootstelling polluenten Renzetti G. et al. Pediatrics 2009;123:1051-1058 5

Astma kinderen voor en na blootstelling polluenten Renzetti G. et al. Pediatrics 2009;123:1051-1058 6

Verband tussen polluenten en luchtweg inflammatie 7

Studies in celculturen (1) Bayram H. Et al. AJRCMB 1998;18:441-448 8

Studies in celculturen (2) Bayram H. Et al. AJRCMB 1998;18:441-44! 9

Studies in celculturen (3) Bayram H. Et al. AJRCMB 1998;18:441-44! 10

Verband verkeer en blootstelling Roselund M. et al. Thorax 2009;64:573-580 11

Verband verkeer en blootstelling (2) Roselund M. et al. Thorax 2009;64:573-580 12

Afstand tot bron (weg) Bayer-Oglesby Am J Epidemiol 2006;1190-119 13

1=0-23m 2=24-58m 3=59-117m 4=>118m-2684 Bayer-Oglesby Am J Epidemiol 2006;1190-1198 14

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Impact infrastructuur op blootstelling polluenten 16

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DISPERSIEMODELLEN 19

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Integrale benadering als oplossing 22

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Dispersie via CFD toegepast op dispersie van polluenten in steden 24

IN-PATIENT MODELING Particulate deposition in the different airway regions De Backer et al. Radiology 257 (2010) 854 862 Vinchurkar et al. Inhalation Toxicology 2011 25

Particle deposition in asthmatics 26

Case studies (1) Craeybeckxtunnel Metingen in Craeybeckxtunnel in Antwerpen van 23 Juni 2010 tot 7 Juli 2010 Consortium met VITO, Von Karmann, KUL, UA Metingen PM en UFP in aantal & samenstelling Metingen luchtstroom Metingen depositie in proefdieren (muizen) 27

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dn/dlogdp 1,60E+06 Drive through 1 (05/07/10) 1,40E+06 1,20E+06 1,00E+06 8,00E+05 6,00E+05 4,00E+05 12:49:38 12:49:48 12:49:58 12:50:08 12:50:18 12:50:28 12:50:38 12:50:48 12:50:58 12:51:08 2,00E+05 Figure 5: 6: (left)vki Size car distribution standing measured behind VITO during car; mobile (right) measurements; sonic anemometer (right) mounted size distribution VKI car measured showing increasing particle number concentration in the mode around 60 nm performed in the middle of the tunnel whereas mice were exposed at the end of the tunnel. However, UFP measurements and animal exposure were performed simultaneously. Moreover, measurements in the cage were performed during a short time (hours) using handheld CPCs (Condensation Particle Counter) measuring number concentrations in the size range 20 nm 1000 nm. The results showed no significant difference in concentrations in the cage ((129 ± 16) 10 3 cm -3 ) as compared to the tunnel 32 environment ((150 ± 25) 10 3 cm -3 ). Also in the cages with filter, similar concentrations were found 0,00E+00 1 10 Size 100 1000

through the tunnel in both directions at about 100 km/hr. The purpose was to check whether the air velocity on the middle lanes is different from the value on the emergency lane. Figure 8 shows the air velocity measured, as starting at the Carpool Kontich, then in the tunnel section from Brussels to Antwerp, turning 180 at the first traffic light and subsequently taking the tunnel section towards Brussels. The air velocity in the tunnel equals the car speed minus the measured value by the sonic anemometer on top of the moving car. The air velocity appeared to be 15-35% of the car velocity on the middle lane, thus only slightly higher than on the emergency lane, underlining the piston concept. It is interesting to note that before the tunnel section from Brussels to Antwerp, while driving closely behind trucks, the air velocity in the truck s slip stream (red curve) is similar to the air velocity in tunnel. Figure 8: Air velocity measurement on top of VKI car, driving at 100 km/hr through the Craeybeckx tunnel. 33

Dispersion Models 34

Ultra Fine Particles 35

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Figure 10: Alveolar macrophages obtained by bronchoalveolar lavage from mice that remained for 5 days in the tunnel in a cage without filter cap (LEFT panels, test group) or with reinforced (2x3 layers) filter cap (RIGHT panels, control group). The macrophages from the test group contain abundant black PM, that is not seen in the macrophages from the control group However, no adverse effects could be detected in the most exposed group: body weights increased in a similar way in all groups and there were no signs of pulmonary inflammation in the group exposed to tunnel air compared to the control groups (Figure 11). Surprisingly, the group that stayed in the tunnel in a cage with reinforced filter exhibited fewer leukocytes (mainly lymphocytes) in blood than all the other groups. The reasons for this finding remain to be clarified. CONTROL GROUP TEST GROUP empty cage empty cage Figure 11: (left) Comparison of the body weight before and after the exposure time in different experimental groups; (right) the view of the experimental design in the tunnel with the zoom on the animal test cages This pilot study has demonstrated that it is feasible to expose mice to a tunnel environment for several days and that these animals clearly get exposed to PM. However, this pilot experiment also indicates that the duration of exposure needs probably to be longer before significant adverse effects (pulmonary inflammation) manifest themselves. We propose to establish dose-response relationships by appropriate combinations of duration and intensity of exposure. This should allow us to determine threshold doses of PM ( points of departure ) at which inflammatory changes become detectable in experimental animals. The further histological evaluation of the lungs tissues was performed without knowledge of the group from which the tissues were sampled. General appearance of the lung tissue was evaluated. In addition, the lung tissues were checked for infiltration by alveolar macrophages and other inflammatory cells (e.g. neutrophils) and for signs of edema (i.e. increase of interstitial tissue). The 37

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Figure 10: Alveolar macrophages obtained by bronchoalveolar lavage from mice that remained for 5 days in the tunnel in a cage without filter cap (LEFT panels, test group) or with reinforced (2x3 layers) filter cap (RIGHT panels, control group). The macrophages from the test group contain abundant black PM, that is not seen in the macrophages from the control group However, no adverse effects could be detected in the most exposed group: body weights increased in a similar way in all groups and there were no signs of pulmonary inflammation in the group exposed to tunnel air compared to the control groups (Figure 11). Surprisingly, the group that stayed in the tunnel in a cage with reinforced filter exhibited fewer leukocytes (mainly lymphocytes) in blood than all the other groups. The reasons for this finding remain to be clarified. 39

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Figure 13: (A) - Section through a capillary and type 2 alveolar cell; (B) - Detail of the multilamellar body from the type II cell depicted in A. This structure contains several particles; (C) - STEM-EDX spectrum of the region shown in B; (D) - Capillary with red blood cells and a leukocyte. 41

Toegenomen gen expressie voor inflammatoire mediatoren in de hippocampus 42

Case studie (2) Stedelijke lokatie met intens verkeer versus lokatie met weinig verkeer 43

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AIR QUALITY SURVEY Quantitative analysis of PM mass and composition Qualitative analysis of individual particle composition Collection on filter: PM1, PM2.5 Collection in six size fractions Chemical characterization Chemical characterization Gravimetry XRF Aethalometry IC SEM-EDX µ-raman Mass Elements BC Salts Elemental composition Molecular structure 46

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y are not issions on les were total size icle group bonaceous icrometer deposition r than the fed these all airway g segment (Table 1). ticles was (Pearson 2 and SO 2 p < 0.05). thwesterly the quick with low particulate definitely affect its deposition efficiency in human airways. Simulated median particle deposition rates in the lung segment of CRP are shown in Table 2, asif they were breathing Table 2. Particle Deposition Rates in the Lungs of Chronic Respiratory Patients by Date median (range), μg h 1 particle type a date heavy traffic moderate traffic p b all 15/ 7 9.5 (3.1 13) 9.0 (3.1 13) 0.753 25/ 7 5.8 (2.0 8.4) 5.0 (1.8 7.5) 0.917 toxic 15/ 7 5.5 (1.8 8.0) 5.8 (2.2 9.1) 0.753 25/ 7 4.0 (1.4 5.9) 3.5 (1.4 5.9) 0.917 anthropogenic 15/ 7 2.6 (0.88 3.8) 1.5 (0.51 2.2) 0.028 25/ 7 0.79 (0.26 1.1) 0.30 (0.09 0.42) 0.028 a All: Carbonaceous, iron-rich, minerals, ammonium salts and seasalts; Toxic: Carbonaceous, iron-rich and minerals; Anthropogenic: Carbonaceous and iron-rich (refer to text). b Significance (bold: p < 0.05) of a Wilcoxon signed rank test; H 0 : no median difference (n = 6). the air at the heavy and moderate traffic sites during two daysof the air quality survey. Differences in the particle doses received at the moderate and heavy traffic site did not manifest through 50

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Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Severe asthma Asthma child Mild asthma Asthma child Severe COPD COPD Lung deposition (µg/h) 15th July 2011 Regat ta City 25th July 2011 Regat ta Wilrij k 7.54 7.11 4.61 4.01 9.94 9.57 6.12 5.42 13.03 12.95 8.16 7.38 9.00 8.44 5.50 4.68 3.13 3.15 1.98 1.78 13.24 13.37 8.42 7.49 52

Besluit Invloed polluenten op volksgezondheid bewezen (vb astma) Polluenten zijn vaak afkomstig van verkeersemissies Metingen van de polluenten in de omgeving volstaat niet om impact op de luchtwegen te kennen Hiervoor is een integrale benadering nodig Cases die deze integrale benadering gebruiken tonen verrassend veel blootstelling in bepaalde omstandigheden 53