Acute exposure to wood smoke from incomplete combustion--indications of cytotoxicity.
BACKGROUND
Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans.


METHODS
Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 μg/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line.


RESULTS
Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, <0.05, <0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (<0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, <0.05 and <0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, <0.05, <0.05 and <0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses.


CONCLUSIONS
Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure.


BACKGROUND
NCT01488500.
Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden.
Ala
A
Muala
Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden.
Gregory
G
Rankin
Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden.
Maria
M
Sehlstedt
Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden.
Jon
J
Unosson
Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden.
Jenny A
JA
Bosson
Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden.
Annelie
A
Behndig
Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden.
Jamshid
J
Pourazar
Department of Applied Physics and Electronics, Thermochemical Energy Conversion Laboratory, Umeå University, Umeå, Sweden.
Robin
R
Nyström
Department of Applied Physics and Electronics, Thermochemical Energy Conversion Laboratory, Umeå University, Umeå, Sweden.
Esbjörn
E
Pettersson
Department of Environmental Science and Analytical Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden.
Christoffer
C
Bergvall
Department of Environmental Science and Analytical Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden.
Roger
R
Westerholm
Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
Pasi I
PI
Jalava
Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
Mikko S
MS
Happo
Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
Oskari
O
Uski
Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
Maija-Riitta
MR
Hirvonen
Environmental Research Group, MRC-PHE Centre for Environment and Health, King's College London, London, UK.
Frank J
FJ
Kelly
Environmental Research Group, MRC-PHE Centre for Environment and Health, King's College London, London, UK.
Ian S
IS
Mudway
Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden.
Anders
A
Blomberg
Department of Applied Physics and Electronics, Thermochemical Energy Conversion Laboratory, Umeå University, Umeå, Sweden.
Christoffer
C
Boman
Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden. thomas.sandstrom@lung.umu.se.
Thomas
T
Sandström
D001992:Bronchoalveolar Lavage Fluid; D006801:Humans; D019570:Inhalation Exposure; D012129:Respiratory Function Tests; D012140:Respiratory Tract Diseases / Q000209:etiology / Q000503:physiopathology; D012906:Smoke; D014934:Wood
D012906:Smoke