Abstract

Wildland firefighters (WLFFs) experience lung function decline due to occupational exposure to fire smoke. WLFFs typically do not wear respiratory personal protective equipment, and if they do, it is a simple bandana, which is not effective at filtering smoke. To pinpoint the biological underpinnings of abnormal respiratory function following 3–7 years of WLFF service, we exposed mice to Douglas fir smoke (DFS) over 8 weeks. Following exposure, we assessed changes in lung structure through Magnetic Resonance Imaging (MRI) and histological analysis, which was supported by immunohistochemistry staining. With MRI, we found that the signal decay time, T2*, from ultrashort echo time (UTE) images was significantly shorter in mice exposed to DFS compared to air controls. In addition, the variation in T2* was more heterogeneously distributed throughout the left lung in DFS-exposed mice, compared to air controls. As confirmed by histological analysis, shorter T2* was caused by larger parenchyma airspace sizes and not fibrotic remodeling. Destruction of the alveolar spaces was likely due to inflammation, as measured by an influx of CD68+ macrophages and destruction due to enhanced neutrophil elastase. In addition, measurements of airspace dimensions from histology were more heterogeneously distributed throughout the lung, corroborating the enhanced relative dispersion of T2*. Findings from this study suggest that the decline in lung function observed in WLFFs may be due to emphysema-like changes in the lung, which can be quantified with MRI.

References

1.
Caton
,
S. E.
,
Hakes
,
R. S. P.
,
Gorham
,
D. J.
,
Zhou
,
A.
, and
Gollner
,
M. J.
,
2016
, “
Review of Pathways for Building Fire Spread in the Wildland Urban Interface Part I: Exposure Conditions
,”
Fire Technol.
,
53
(
2
), pp.
429
473
.10.1007/s10694-016-0589-z
2.
Rice
,
M. B.
,
Henderson
,
S. B.
,
Lambert
,
A. A.
,
Cromar
,
K. R.
,
Hall
,
J. A.
,
Cascio
,
W. E.
,
Smith
,
P. G.
, et al.,
2021
, “
Respiratory Impacts of Wildland Fire Smoke: Future Challenges and Policy Opportunities. An Official American Thoracic Society Workshop Report
,”
Ann. Am. Thorac. Soc.
,
18
(
6
), pp.
921
930
.10.1513/AnnalsATS.202102-148ST
3.
Westerling
,
A. L.
,
Hidalgo
,
H. G.
,
Cayan
,
D. R.
, and
Swetnam
,
T. W.
,
2006
, “
Warming and Earlier Spring Increase Wester US Forest Wildfire Activity
,”
Science
,
313
(
5789
), pp.
940
943
.10.1126/science.1128834
4.
Doubleday
,
A.
,
Schulte
,
J.
,
Sheppard
,
L.
,
Kadlec
,
M.
,
Dhammapala
,
R.
,
Fox
,
J.
, and
Busch Isaksen
,
T.
,
2020
, “
Mortality Associated With Wildfire Smoke Exposure in Washington State, 2006-2017: A Case-Crossover Study
,”
Environ. Health
,
19
(
1
), p.
4
.10.1186/s12940-020-0559-2
5.
Faustini
,
A.
,
Alessandrini
,
E. R.
,
Pey
,
J.
,
Perez
,
N.
,
Samoli
,
E.
,
Querol
,
X.
,
Cadum
,
E.
, et al.,
2015
, “
Short-Term Effects of Particulate Matter on Mortality During Forest Fires in Southern Europe: Results of the MED-PARTICLES Project
,”
Occup. Environ. Med.
,
72
(
5
), pp.
323
329
.10.1136/oemed-2014-102459
6.
Johnston
,
F.
,
Hanigan
,
I.
,
Henderson
,
S.
,
Morgan
,
G.
, and
Bowman
,
D.
,
2011
, “
Extreme Air Pollution Events From Bushfires and Dust Storms and Their Association With Mortality in Sydney, Australia 1994–2007
,”
Environ. Res.
,
111
(
6
), pp.
811
816
.10.1016/j.envres.2011.05.007
7.
Garg
,
P.
,
Wang
,
S.
,
Oakes
,
J. M.
,
Bellini
,
C.
, and
Gollner
,
M. J.
,
2023
, “
The Effectiveness of Filter Material for Respiratory Protection Worn by Wildland Firefighters
,”
Fire Saf. J.
,
139
, p.
103811
.10.1016/j.firesaf.2023.103811
8.
Adetona
,
O.
,
Reinhardt
,
T. E.
,
Domitrovich
,
J.
,
Broyles
,
G.
,
Adetona
,
A. M.
,
Kleinman
,
M. T.
,
Ottmar
,
R. D.
, and
Naeher
,
L. P.
,
2016
, “
Review of the Health Effects of Wildland Fire Smoke on Wildland Firefighters and the Public
,”
Inhalation Toxicol.
,
28
(
3
), pp.
95
139
.10.3109/08958378.2016.1145771
9.
Naeher
,
L. P.
,
Brauer
,
M.
,
Lipsett
,
M.
,
Zelikoff
,
J. T.
,
Simpson
,
C. D.
,
Koenig
,
J. Q.
, and
Smith
,
K. R.
,
2007
, “
Woodsmoke Health Effects: A Review
,”
Inhalation Toxicol.
,
19
(
1
), pp.
67
106
.10.1080/08958370600985875
10.
Hargrove
,
M. M.
,
Kim
,
Y. H.
,
King
,
C.
,
Wood
,
C. E.
,
Gilmour
,
M. I.
,
Dye
,
J. A.
, and
Gavett
,
S. H.
,
2019
, “
Smoldering and Flaming Biomass Wood Smoke Inhibit Respiratory Responses in Mice
,”
Inhalation Toxicol.
,
31
(
6
), pp.
236
247
.10.1080/08958378.2019.1654046
11.
Martin
,
B. L.
,
Thompson
,
L. C.
,
Kim
,
Y. H.
,
King
,
C.
,
Snow
,
S.
,
Schladweiler
,
M.
,
Haykal-Coates
,
N.
, et al.,
2020
, “
Peat Smoke Inhalation Alters Blood Pressure, Baroreflex Sensitivity, and Cardiac Arrhythmia Risk in Rats
,”
J. Toxicol. Environ. Health A
,
83
(
23–24
), pp.
748
763
.10.1080/15287394.2020.1826375
12.
Kim
,
Y. H.
,
King
,
C.
,
Krantz
,
T.
,
Hargrove
,
M. M.
,
George
,
I. J.
,
McGee
,
J.
,
Copeland
,
L.
, et al.,
2019
, “
The Role of Fuel Type and Combustion Phase on the Toxicity of Biomass Smoke Following Inhalation Exposure in Mice
,”
Arch. Toxicol.
,
93
(
6
), pp.
1501
1513
.10.1007/s00204-019-02450-5
13.
Eden
,
M. J.
,
Matz
,
J.
,
Garg
,
P.
,
Gonzalez
,
M. P.
,
McElderry
,
K.
,
Wang
,
S.
,
Gollner
,
M. J.
,
Oakes
,
J. M.
, and
Bellini
,
C.
,
2023
, “
Prolonged Smoldering Douglas Fir Smoke Inhalation Augments Respiratory Resistances, Stiffens the Aorta, and Curbs Ejection Fraction in Hypercholesterolemic Mice
,”
Sci. Total Environ.
,
861
, p.
160609
.10.1016/j.scitotenv.2022.160609
14.
Guo
,
J.
,
Cao
,
X.
,
Cleveland
,
Z. I.
, and
Woods
,
J. C.
,
2018
, “
Murine Pulmonary Imaging at 7T: T2* and T(1) With Anisotropic UTE
,”
Magn. Reson. Med.
,
79
(
4
), pp.
2254
2264
.10.1002/mrm.26872
15.
Guo
,
J.
,
Hardie
,
W. D.
,
Cleveland
,
Z. I.
,
Davidson
,
C.
,
Xu
,
X.
,
Madala
,
S. K.
, and
Woods
,
J. C.
,
2019
, “
Longitudinal Free Breathing MRI Measurement of Murine Lung Physioloigy in a Progressive Model of Lung Fibrosis
,”
J. Appl. Physiol.
,
126
, pp.
1149
1149
.10.1152/japplphysiol.00993.2018
16.
Stecker
,
I. R.
,
Freeman
,
M. S.
,
Sitaraman
,
S.
,
Hall
,
C. S.
,
Niedbalski
,
P. J.
,
Hendricks
,
A. J.
,
Martin
,
E. P.
,
Weaver
,
T. E.
, and
Cleveland
,
Z. I.
,
2021
, “
Preclinical MRI to Quantify Pulmonary Disease Severity and Trajectories in Poorly Characterized Mouse Models: A Pedagogical Example Using Data From Novel Transgenic Models of Lung Fibrosis
,”
J. Magn. Reson. Open
,
6–7
, p.
100013
.10.1016/j.jmro.2021.100013
17.
Jacob
,
R. E.
,
Amidan
,
B. G.
,
Soelberg
,
J.
, and
Minard
,
K. R.
,
2010
, “
In Vivo MRI of Altered Proton Signal Intensity and T2 Relaxation in a Bleomycin Model of Pulmonary Inflammation and Fibrosis
,”
J. Magn. Reson. Imaging
,
31
(
5
), pp.
1091
1099
.10.1002/jmri.22166
18.
Takahashi
,
M.
,
Togao
,
O.
,
Obara
,
M.
,
van Cauteren
,
M.
,
Ohno
,
Y.
,
Doi
,
S.
,
Kuro-O
,
M.
,
Malloy
,
C.
,
Hsia
,
C. C.
, and
Dimitrov
,
I.
,
2010
, “
Ultra-Short Echo Time (UTE) MR Imaging of the Lung: Comparison Between Normal and Emphysematous Lungs in Mutant Mice
,”
J. Magn. Reson. Imaging
,
32
(
2
), pp.
326
333
.10.1002/jmri.22267
19.
Garg
,
P.
,
Roche
,
T.
,
Eden
,
M.
,
Matz
,
J.
,
Oakes
,
J. M.
,
Bellini
,
C.
, and
Gollner
,
M. J.
,
2021
, “
Effect of Moisture Content and Fuel Type on Emissions From Vegetation Using a Steady State Combustion Apparatus
,”
Int. J. Wildland Fire
,
31
(
1
), pp.
14
23
.10.1071/WF20118
20.
Reed
,
G. F.
,
Lynn
,
F.
, and
Bd
,
M.
,
2002
, “
The Use of Coefficient of Variation in Assessing Variability of Quantitative Assays
,”
Clin. Vaccine Immunol.
,
9
(
6
), pp.
1235
1239
.10.1128/CDLI.9.6.1235-1239.2002
21.
Matz
,
J.
,
Farra
,
Y. M.
,
Cotto
,
H. M.
,
Bellini
,
C.
, and
Oakes
,
J. M.
,
2023
, “
Respiratory Mechanics Following Chronic Cigarette Smoke Exposure in the Apoe -/- Mouse Model
,”
Biomech. Model Mechanobiol.
,
22
(
1
), pp.
233
252
.10.1007/s10237-022-01644-8
22.
Ferruzzi
,
J.
,
Bersi
,
M. R.
,
Uman
,
S.
,
Yanagisawa
,
H.
, and
Humphrey
,
J. D.
,
2015
, “
Decreased Elastic Energy Storage, Not Increased Material Stiffness, Characterizes Central Artery Dysfunction in Fibulin-5 Deficiency Independent of Sex
,”
ASME J. Biomech. Eng.
,
137
(
3
), p.
031007
.10.1115/1.4029431
23.
Landini
,
G.
,
Martinelli
,
G.
, and
Piccinini
,
F.
,
2021
, “
Colour Deconvolution: Stain Unmixing in Histological Imaging
,”
Bioinformatics
,
37
(
10
), pp.
1485
1487
.10.1093/bioinformatics/btaa847
24.
Oakes
,
J. M.
,
Marsden
,
A. L.
,
Grandmont
,
C.
,
Darquenne
,
C.
, and
Vignon-Clementel
,
I. E.
,
2015
, “
Distribution of Aerosolized Particles in Healthy and Emphysematous Rat Lungs: Comparison Between Experimental and Numerical Studies
,”
J. Biomech.
,
48
(
6
), pp.
1147
1157
.10.1016/j.jbiomech.2015.01.004
25.
Olsson
,
L. E.
, and
Hockings
,
P. D.
,
2016
, “
In Vivo Measurements of T2 Relaxation Time of Mouse Lungs During Inspiration and Expiration
,”
PLoS One
,
11
(
12
), p.
e0166879
.10.1371/journal.pone.0166879
26.
Olsson
,
L. E.
,
Lindahl
,
M.
,
Onnervik
,
P. O.
,
Johansson
,
L. B.
,
Palmer
,
M.
,
Reimer
,
M. K.
,
Hultin
,
L.
, and
Hockings
,
P. D.
,
2007
, “
Measurement of MR Signal and T2* in Lung to Characterize a Tight Skin Mouse Model of Emphysema Using Single-Point Imaging
,”
J. Magn. Reson. Imaging
,
25
(
3
), pp.
488
494
.10.1002/jmri.20840
27.
Chua
,
F.
, and
Laurent
,
G. J.
,
2006
, “
Neutrophil Elastase: Mediator of Extracellular Matrix Destruction and Accumulation
,”
Proc. Am. Thorac. Soc.
,
3
(
5
), pp.
424
427
.10.1513/pats.200603-078AW
28.
Hamakawa
,
H.
,
Bartolak-Suki
,
E.
,
Parameswaran
,
H.
,
Majumdar
,
A.
,
Lutchen
,
K. R.
, and
Suki
,
B.
,
2011
, “
Structure-Function Relations in an Elastase-Induced Mouse Model of Emphysema
,”
Am. J. Respir. Cell Mol. Biol.
,
45
(
3
), pp.
517
524
.10.1165/rcmb.2010-0473OC
29.
Nelson
,
T. M.
,
Quiros
,
K. A. M.
,
Dominguez
,
E. C.
,
Ulu
,
A.
,
Nordgren
,
T. M.
, and
Eskandari
,
M.
,
2023
, “
Diseased and Healthy Murine Local Lung Strains Evaluated Using Digital Image Correlation
,”
Sci. Rep.
,
13
(
1
), p.
4564
.10.1038/s41598-023-31345-w
30.
Hurtado
,
D. E.
,
Erranz
,
B.
,
Lillo
,
F.
,
Sarabia-Vallejos
,
M.
,
Iturrieta
,
P.
,
Morales
,
F.
,
Blaha
,
K.
,
Medina
,
T.
,
Diaz
,
F.
, and
Cruces
,
P.
,
2020
, “
Progression of Regional Lung Strain and Heterogeneity in Lung Injury: Assessing the Evolution Under Spontaneous Breathing and Mechanical Ventilation
,”
Ann. Intensive Care
,
10
(
1
), p.
107
.10.1186/s13613-020-00725-0
31.
Zurek
,
M.
,
Boyer
,
L.
,
Caramelle
,
P.
,
Boczkowski
,
J.
, and
Cremillieux
,
Y.
,
2012
, “
Longitudinal and Noninvasive Assessment of Emphysema Evolution in a Murine Model Using Proton MRI
,”
Magn. Reson. Med.
,
68
(
3
), pp.
898
904
.10.1002/mrm.23281
32.
Sato
,
A.
,
Hirai
,
T.
,
Imura
,
A.
,
Kita
,
N.
,
Iwano
,
A.
,
Muro
,
S.
,
Nabeshima
,
Y.
,
Suki
,
B.
, and
Mishima
,
M.
,
2007
, “
Morphological Mechanism of the Development of Pulmonary Emphysema in Klotho Mice
,”
Proc. Natl. Acad. Sci. U. S. A
,
104
(
7
), pp.
2361
2365
.10.1073/pnas.0607882104
You do not currently have access to this content.