Human studies of exposure to wood smoke (exposure- effects studies) Jakob Bønløkke Institute of Public Health, Aarhus University, Denmark

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1 Human studies of exposure to wood smoke (exposure- effects studies) Jakob Bønløkke Institute of Public Health, Aarhus University, Denmark 1

2 Gothenburg Aarhus Umeå Lund Chapel Hill, NC 2013 Google - Kortdata 2013 Google, GeoBasis-DE/BKG ( 2009) - 2

3 Biomass smoke affects 3 billion people daily: mortality, penumonia, COPD 3

4 So why do expensive short- term human experimental studies? Understand mechanisms Complex measurements Precise characterisation of subjects and exposures Include non-exposed, i.e. wash-out periods 4

5 Exposure Facilities Aarhus University 5

6 Design Double blind Cross-over Randomized exposures o Wood-smoke high o Wood-smoke low o Filtered clean air 2 weeks apart 6

7 Methods Dress Exhaled Breath Condensate Nose volume Spirometry Nasal lavage Blood flow Symptoms feno 7

8 SPIRO FeNO EBC NAL Acoustic RH. Measurements PULSE BLOOD ENDOPAT SYMPTOMS POT URIN Hours ACCLIM EXPOSURE 8

9 5 experimental studies in humans Sällsten G, et al. (2006). Experimental wood smoke exposure in humans. Inhalation Toxicology, Barregard L, et al. (2006) "Experimental exposure to wood-smoke particles in healthy humans: effects on markers of inflammation, coagulation, and lipid peroxidation", Inhalation toxicology. Barregard L, et al. (2008) "Experimental exposure to wood smoke: effects on airway inflammation and oxidative stress", Occupational and environmental medicine. (Göteborg) Sehlstedt M, et al. (2010) "Antioxidant airway responses following experimental exposure to wood smoke in man", Particle and Fibre Toxicology. (Göteborg) Riddervold IS, et al. (2011). Wood smoke in a controlled exposure experiment with human volunteers. Inhalation Toxicology. (Århus) Ghio AJ, et al. (2012) Exposure to wood smoke particles produces inflammation in healthy volunteers. Occupational and Environmental Medicine. (NC, USA) Forchhammer L, et al. (2012). Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function. Particle and Fibre Toxicology. Riddervold IS, et al. (2012). Effects of wood smoke particles from wood-burning stoves on the respiratory health of atopic humans. Particle and Fibre Toxicology. Unosson J, et al. (2013) Exposure to wood smoke increases arterial stiffness and decreases heart rate variability in humans. Particle and Fibre Toxicology. (Umeå) Bønløkke JH, et al. (2013) Systemic effects of wood smoke in a short-term experimental Workshop Wood exposure Burning, Ghent, study of atopic volunteers. Journal of Occupational and 9 Environmental Dec Bønløkke, Medicine. AU, DK

10 Göteborg 1 Göteborg 2 Århus N Age range Characteristics Healthy, non- smokers, normal lungs Healthy, non- smokers, non- allergic Healthy, non- smokers, with atopy Duratio n 4h Exercise light 50 min 3h light 1.5h NC, USA Healthy, non- smokers 2h light/moderate 1h Umeå Healthy, non- smokers 3h light 1.5h 3h no 10

11 Göteborg 1 Sällsten/ Barregaar d Göteborg 2 Sehlstedt Århus Riddervol d NC, USA Ghio Umeå Unosson Exposures (PM 2.5 ) Filtered air Wood smoke 1 WS 2 Wood Conditions Not stated 260 µμg/m 3 birch/spruce good Not stated 224 µμg/m 3 pellet/ sawdust fuel mixture from pine and spruce Moist, air- starved 14 µμg/m µμg/m µμg/m 3 beech good Not stated 485 µμg/m 3 red oak Electric heating of wood Not stated 314 µμg/m 3 (PM 1 ) birch air- starved 11

12 Health outcomes - overview Symptoms Airways function Indices of coagulation, oxidative stress, carcinogenicity, and inflammation in the airways and systemically (blood, urine) Heart rate 12

13 Health outcomes studied Symptoms: 30+ Airways function: Nasal patency & forced vital capacity, forced expiratory volume in 1 s, peak flow, diffusing capacity Bronchial lavage: cell count, cytokines, antitrypsin, myeloperoxidase, matrixmetalloproteinase 9, ascorbate, urate, glutathione and more In blood: CC16, CRP, fibrinogen, amyloid A, cell count, IL-1b, IL-6, IL-8 and TNF-a, factor VII & VIIIc, vwf, D-dimers, 8-iso- PGF2α, COHb, LDH, DNA damage, mrna of 10 regulatory proteins In urine: CC16, 8-iso-PGF2α In exhaled air: NO, o In breath condensate: MDA, conductivity, ph, 8-isoprostane Electrocardiography: SDNN, pnn50, RMSSD, QTc, P wave Workshop complexity, Wood Burning, T Ghent, wave complexity, QRS complexity, QTc Dec dynamics Bønløkke, AU, DK 13

14 Symptoms Mild irritation after WS (Barregaard) Mild irritation in nose and throat after into the exposure (Sehlstedt) Mild irritation in indices: environmental perception, irritative body perception, psychological/neurological effects, weak inflammatory responses (Riddervold) 14

15 Nasal and lung function No changes observed 15

16 Bronchial lavage Neutrophilic cells (Ghio) i.e. inflammation Glutathione (GSH without GSSG, i.e. not oxidative stress?) (Sehlstedt) 16

17 Blood CC16, SAA, factor VIIIc 20 h post (Barregaard), i.e. increased permeability in lungs, cardiovascular risk factor, disturbed balance in coagulation IL-1β 0 h post (Ghio) i.e. pro-inflammation LDH 20 h post (Ghio) i.e. cell damage? IL-6 relative decrease and tendency for IL-1β (Bønløkke) i.e. opposite directions of inflammation 17

18 Urine No changes 18

19 Exhaled NO FeNO 270 increased 3h after WS (Barregaard), i.e. inflammation 19

20 Breath condensate MDA 3 & 20h post (Barregaard), i.e. lipid peroxidation Conductivity and ph (Riddervold) i.e.? 20

21 Heart Decrement in maximal heart rate at 0 h (Ghio) Increase in heart rate at 0-1 h (Unosson) Augmentation index, augmentation pressure and pulse wave velocity were all higher at 0 h (Unosson) i.e. arterial stiffness Heart rate variability decrease 0-1 h (Unosson) 21

22 Löndahl- Deposition of biomass combustion aerosol particles in the human respiratory 22 tra Inhal Toxicol

23 No inflammatory or lung effects observed after 5 days in a wood-fired house 23

24 Implications Short term exposures with concentrations up to 500 µg/m 3 only appears to induce In o Symptoms o Mild early inflammatory reactions in lungs o Maybe cardiovascular effects & maybe through oxidative mechanisms o Healthy young people Remember : o Children o Old people o Asthmatics o COPD patients 50 % 24

25 Implications Human experiments so far suggest that WS may be less toxic than diesel exhaust experiments However: they give no information about long-term effects Remember: No single effect has been observed in all studies, not even symptoms. 25

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27 Acknowledgements Andreas Massling Rossana Bossi Bjarne Jensen Lykke Forchhammer Steffen Loft Lars Barregaard Gerd Sällsten Lena Samuelson Anna Carin Olin Ingunn S Riddervold Torben Sigsgaard Vivi Schlünssen Søren Kjærgaard Lars Mølhave Tine Bank Vibeke Gutzke Kirsten Østergaard Frank Bødtger Preben Langballe Therese Grønborg 27