Toxicology Repo s 2 (2015) 357–364
Con en s lis s a ailable a ScienceDi ec
Toxicology Repo s
jou nal homepage: www.else ie .com/loca e/ ox ep
Sys emic inflamma o y esponses ollowing welding
inhala ion challenge es
Paula Kauppia,b,∗, Me ja Jä eläc, Timo Tuomic, Ri a Luukkonend,
Tuula Lindholme, Riina Nieminen , Ee a Moilanen , Timo Hannub,g
aUni e si y o Helsinki and Helsinki Uni e si y (Cen al) Hospi al, Respi a o y Diseases and Alle gology, Helsinki, Finland
bOccupa ional Medicine, Finnish Ins i u e o Occupa ional Heal h, Helsinki, Finland
cAe osols, Dus s and Me als, Finnish Ins i u e o Occupa ional Heal h, Helsinki, Finland
dS a is ical Se ices, Finnish Ins i u e o Occupa ional Heal h, Helsinki, Finland
ePhysical Wo k Capaci y, Finnish Ins i u e o Occupa ional Heal h, Helsinki, Finland
The Immunopha macology Resea ch G oup, Uni e si y o Tampe e School o Medicine and Tampe e Uni e si y Hospi al, Tampe e,
Finland
gThe Hjel Ins i u e, Uni e si y o Helsinki, Helsinki, Finland
a i c l e i n o
A icle his o y:
Recei ed 5 No embe 2014
Recei ed in e ised o m
18 Decembe 2014
Accep ed 23 Decembe 2014
A ailable online 2 Janua y 2015
Keywo ds:
Cy okines
Exposu e
Mild s eel
Occupa ional as hma
S ainless s eel
Welding
Chemical compounds s udied in his a icle:
Ch omium (PubMed CID: 23976)
I on (PubMed CID: 23925)
Manganese (PubMed CID: 23930)
Nickel (PubMed CID: 935)
a b s a c
Aim: The aim o his s udy was o in es iga e inflamma o y and espi a o y esponses o
welding ume exposu e in pa ien s wi h suspec ed occupa ional as hma.
Me hods: Six een pa ien s e e ed o he Finnish Ins i u e o Occupa ional Heal h unde -
wen mild s eel (MS) and s ainless s eel (SS) welding challenge es s, due o suspicion o
OA. Pla ele coun , leucocy es and hei di e en ial coun , hemoglobin, sensi i e CRP, lipids,
glucose and fib inogen we e analyzed in addi ion o in e leukin (IL)-1␤, IL-6, IL-8, TNF-␣,
endo helin-1, and E-selec in in plasma samples. Peak expi a o y flow (PEF), o ced expi a-
o y olume in 1 min (FEV1) and exhaled ni ic oxide (NO) measu emen s we e pe o med
be o e and a e he challenge es . Pe sonal pa icle exposu e was assessed using IOM and a
mini sample . Pa icle size dis ibu ion was measu ed by an Elec ic Low P essu e Impac o
(ELPI).
Resul s: The numbe o leukocy es, neu ophils, and pla ele s inc eased significan ly, and
he hemoglobin le el and numbe o e y h ocy es dec eased significan ly a e bo h he MS
and SS exposu e es s. Fi e o he pa ien s we e diagnosed wi h OA, and hei maximum all
in FEV1 alues was 0.70 l (±0.32) 4 h a e SS exposu e. MS welding gene a ed an a e age
inhalable pa icle mass concen a ion o 31.6, and SS welding o 40.2 mg/m3. The mean
pa icle concen a ion measu ed inside he welding ace shields by he mini sample was
30.2 mg/m3and 41.7 mg/m3, espec i ely.
Conclusions: Exposu e o MS and SS welding ume esul ed in a mild sys emic inflamma-
o y esponse. The pa icle concen a ion om he b ea hing zones co ela ed wi h he
measu emen s inside he welding ace shields.
© 2015 The Au ho s. Published by Else ie I eland L d. This is an open access a icle unde
he CC BY-NC-ND license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/).
∗Co esponding au ho a : Skin and Alle gy Hospi al, Helsinki Uni-
e si y Cen al Hospi al, Meilahden ie 2, PO BOX 160, FI-00029 Helsinki,
Finland. Tel.: +358 50 428 6802; ax: +358 9 471 86503.
E-mail add ess: paula.kauppi@hus.fi (P. Kauppi).
1. In oduc ion
Welding is a p ocess ha joins ma e ial, usually me als
o alloys, by using hea and/o comp ession. Welde s a e
exposed o umes con aining di e en gases and pa icles,
depending on he composi ion o he welding elec odes,
h p://dx.doi.o g/10.1016/j. ox ep.2014.12.015
2214-7500/© 2015 The Au ho s. Published by Else ie I eland L d. This is an open access a icle unde he CC BY-NC-ND license (h p://c ea i ecommons.
o g/licenses/by-nc-nd/4.0/).
358
P.
Kauppi
e
al.
/
Toxicology
Repo s
2
(2015)
357–364
welded
ma e ial,
and
he
welding
me hod
used.
Welding
pa icles
include
bo h
fine
(0.1–2.5
␮m)
and
ul afine
pa -
icles
(<
0.1
␮m)
[1].
Welding
ume
exposu e
has
been
associa ed
wi h
se e al
ad e se
heal h
ou comes
such
as
ch onic
b on-
chi is,
pneumonia,
me al
ume
e e ,
lung
unc ion
changes,
and
a
possible
ele a ed
isk
o
lung
cance
and
dea h
om
ischemic
hea
disease
[2–8].
In
addi-
ion,
popula ion-based
s udies
ha e
shown
ha
welde s
a e
a
an
almos
wo old
isk
o
de eloping
as hma
[9,10].
Mo eo e ,
o he
epidemiological
s udies
ha e
indi-
ca ed
ha
exposu e
o
welding
umes
may
indeed
be
a
di ec
cause
o
as hma
[11,12].
Some
case
se ies
ha e
e ealed
occupa ional
as hma
(OA)
in
wo ke s
exposed
o
s ainless
s eel
welding
umes
in
pa icula
[13–15].
The
unde lying
mechanisms
esponsible
o
hese
ca -
dio espi a o y
e ec s
a e
la gely
unknown.
One
line
o
esea ch
has
in es iga ed
he
possible
associa ion
be ween
welding
ume
exposu e
and
acu e
sys emic
inflamma-
o y
esponses
[16–18].
The
hypo hesis
is
ha
sho - e m
exposu e
o
welding
umes
may
induce
a
local
as
well
as
sys emic
inflamma o y
eac ion,
which
may
be
espon-
sible
o
ch onic
lung
and
ca dio ascula
disease
i
he
exposu e
pe sis s
o
a
long
ime
[18].
In
ou
own
ecen
s udy
[19],
welding
umes,
as
well
as
dus s
and
umes
om
shee
me al
wo k,
caused
a
sligh
acu e
inflamma ion
du ing
a
wo k
shi
in
ac ual
wo kplace
con-
di ions.
The
aim
o
he
p esen
s udy
was
o
u he
in es-
iga e,
on
he
basis
o
p io
s udies,
whe he
sho
exposu e
o
high
concen a ion
o
welding
umes
is
capa-
ble
o
inducing
acu e
e ec s
on
hema ological,
sys emic
inflamma o y
and
espi a o y
pa ame e s
by
ollow-
ing
welding
challenge
es
in
pa ien s
wi h
suspec ed
OA.
2.
Subjec s
and
me hods
2.1.
S udy
subjec s
The
s udy
consis ed
ini ially
o
18
pa ien s
who
we e
e e ed
o
he
Finnish
Ins i u e
o
Occupa ional
Heal h
(FIOH)
by
pulmonologis s
o
local
cen al
hospi als
o
by
physicians
o
local
occupa ional
heal h
uni s
om
all
o e
Finland
in
2007.
Six een
o
he
pa ien s
had
been
diag-
nosed
wi h
as hma
p e iously
and
wo
pa ien s
had
as hma
like
symp oms
bu
no
specific
diagnosis
o
as hma;
all
pa ien s
we e
suspec ed
o
ha ing
OA
caused
by
welding
umes.
One
pa ien
was
excluded
om
he
s udy
because
his
exposu e
es s
we e
no
pe o med
on
consecu i e
days,
and
ano he
was
excluded
because
he
was
gi en
medica-
ion
du ing
he
s udy
which
may
ha e
a ec ed
he
blood
esul s.
The e o e,
he
final
s udy
popula ion
comp ised
16
pa icipan s.
They
we e
all
male,
and
wo ked
as
welde s
(N
=
7),
shee
me al
wo ke s
(N
=
7),
assemble s
(N
=
1)
and
me al
wo ke s
(N
=
1).
All
o
hem
we e
exposed
o
weld-
ing
umes
in
hei
wo k
ega dless
o
hei
occupa ional
i le.
As hma
medica ion
was
discon inued
be o e
es ing
a
FIOH.
2.2.
S udy
p o ocol
Welding
challenge
es s
we e
pe o med
in
a
special
welding
chambe
(6
m3).
Fi een
o
he
pa icipan s
we e
exposed
o
mild
s eel
(MS)
(con ol
es )
and
s ainless
s eel
(SS)
welding
umes
on
consecu i e
days
as
desc ibed
ea -
lie
o
suspicion
o
OA
[15].
One
subjec
was
exposed
o
MS
welding
umes
only.
The
manual
me al
a c
welding
(MMAW)
exposu e
ime
was
30
min.
Du ing
he
exposu e,
fi e
ods
we e
consumed
in
he
MS
con ol
es
(OK
48.00;
ESAB
AB,
Go henbu g,
Sweden)
and
11
ods
in
he
ST
weld-
ing
es
(OK
63.30;
ESAB
AB,
Go henbu g,
Sweden)
[14].
OA
was
diagnosed
acco ding
o
Eu opean
guidelines
[20].
S udy
pa icipan s
we e
moni o ed
o
24
h
a e
each
challenge.
Al oge he
fi e
enous
blood
samples
(one
blood
sam-
ple
be o e
each
o
he
challenge
es s
and
one
blood
sample
a e
each
o
he
challenge
es s
and
he
fi h
one
on
he
nex
day
a e
he
es s)
we e
aken
om
each
o
he
sub-
jec s
(Fig.
1).
Baseline
measu emen s
o
peak
expi a o y
flow
(PEF),
o ced
expi a o y
olume
in
1
min
(FEV1),
and
exhaled
ni ic
oxide
(NO)
we e
pe o med
be o e
MS
expo-
su e,
and
hen
app oxima ely
22
h
a e
he
MS
and
SS
exposu e.
Each
pa icipan
ga e
w i en
in o med
consen
and
filled
in
a
ques ionnai e
conce ning
wo k
and
exposu e
his o y,
smoking
habi s,
lung
and
ca dio ascula
disease
his o y,
and
medica ion.
The
s udy
p o ocol
was
app o ed
by
he
E hics
Commi ee
o
he
Hospi al
Dis ic
o
Helsinki
and
Uusimaa.
2.3.
Hema ological
and
sys emic
inflamma o y
analyses
The
concen a ions
o
in e leukin
(IL)-1␤,
IL-6,
IL-8,
umo
nec osis
ac o
alpha
(TNF-␣),
endo helin-1,
and
E-Selec in
in
he
plasma
samples
we e
de e mined
by
enzyme
immunoassay
(EIA)
using
comme cial
eagen s:
IL-1␤
(sensi i i y
0.063
pg/ml)
and
TNF-␣
(sensi i i y
0.125
pg/ml),
Quan ikine
HS
ELISA,
R&D
Sys ems
Eu ope
L d.,
Abindgon,
UK;
IL-6
(sensi i i y
0.6
pg/ml),
Peli-
Pai
ELISA,
Sanquin,
Ams e dam,
he
Ne he lands;
IL-8
(sensi i i y
1.56
pg/ml),
Op
EIA,
BD
Biosciences,
E em-
bodegem,
Belgium;
endo helin-1
(sensi i i y
0.68
pg/ml),
Quan iGlo
ELISA,
R&D
Sys ems
Eu ope
L d.,
Abindgon,
UK;
E-Selec in
(sensi i i y
20.5
pg/ml),
ELISA,
HyCul
Bio ech-
nology,
Uden,
he
Ne he lands).
Pla ele
coun ,
leucocy es
and
hei
di e en ial
coun ,
hemoglobin,
haema oc i ,
sensi i e
C- eac i e
p o ein
(CRP),
lipids,
glucose,
and
le els
o
fib inogen
we e
ana-
lyzed
using
es ablished
me hods.
All
labo a o y
analyses
we e
pe o med
blind
o
he
exposu e
s a us
o
he
s udied
pa icipan s.
2.4.
Respi a o y
measu emen s
A
po able,
pocke size
spi ome e
(One
Flow,
STI
MED-
ICAL,
Sain -Romans,
F ance)
eco ded
he
lung
unc ion
measu emen s
(PEF,
FEV1),
and
a
dec ease
o
20%
in
PEF
o
FEV1 om
he
baseline
alue
was
ega ded
as
significan
[21].
Exhaled
NO
was
measu ed
using
a
chemiluminescence
gas
analyze
(NIOX,
Ae oc ine
AB,
Solna,
Sweden),
P.
Kauppi
e
al.
/
Toxicology
Repo s
2
(2015)
357–364
359
Fig.
1.
Desc ip ion
o
s udy
p o ocol.
acco ding
o
ATS
FENO guidelines.
Values
o
>30
ppb
we e
conside ed
o
be
o e
no mal
[22].
2.5.
Exposu e
measu emen s
Pa icle
exposu e
was
assessed
by
pe sonal
sampling
om
he
b ea hing
zone
o
14
pa icipan s.
Inhalable
dus
samples
we e
collec ed
ou side
welding
ace
shields
using
an
IOM
sample
wi h
a
cellulose
ace a e
fil e
(AAWP,
diam-
e e
25
mm;
Millipo e,
Bed o d,
MA,
USA).
Sampling
ime
was
30
min
and
olume ic
flow
was
adjus ed
o
2.0
l/min.
The
samples
we e
analyzed
g a ime ically
[23].
In
addi ion,
mini
sample
measu emen s
we e
ca -
ied
ou
simul aneously
wi h
he
IOM
sampling
[24].
The
mini
samples
we e
collec ed
om
inside
he
welding
ace
shields
o
he
15
pa icipan s.
The
sampling
olume ic
flow
was
0.75
l/min
and
he
sampling
ime
30
min.
Dus
samples
we e
analyzed
g a ime ically.
Du ing
he
MS
and
SS
welding
exposu e
es s
o
h ee
pa icipan s,
pa icle
numbe
size
dis ibu ions
we e
mea-
su ed
by
an
Elec ic
Low
P essu e
Impac o
(ELPI)
(Deka i
L d.,
Finland)
in
a
size
ange
o
30
nm
o
10
␮m.
The
ELPI
measu emen
sys em
gi es
pa icula e
numbe
concen a-
ions
in
12
size
bins
co e ing
he
whole
measu emen
size
ange.
2.6.
S a is ical
analyses
Repea ed
da a
consis ed
o
he
esul s
o
inflamma o y
esponses
du ing
he
exposu e
in
he
welding
chambe .
All
esponse
a iables
we e
con inuous
and
mos ly
no mally
dis ibu ed.
The e o e,
he
pai ed
- es
was
applied
when
compa ing
he
alues
be o e
and
a e
a
challange
es .
I
he
a iable
was
non-no mally
dis ibu ed,
he
Wilcoxon
one
sample
es
was
used.
A
P- alue
o
<0.05
was
se
o
indi-
ca e
s a is ical
significance.
All
analyses
we e
pe o med
using
he
S a is ical
Analysis
Sys em,
SAS
Ve sion
9.1
(SAS
Ins i u e
Inc.,
Ca y,
NC,
USA).
3.
Resul s
3.1.
S udy
popula ion
cha ac e is ics
The
mean
age
o
he
16
s udy
pa icipan s
was
44.6
( ange
23–57
yea s),
and
hey
we e
all
men
(Table
1).
A e age
wo k
his o y
was
27.5
yea s
o
welding.
One
(6%)
was
a
cu en
smoke ,
eigh
(50%)
we e
ex-smoke s,
and
se en
(44%)
had
ne e
smoked
egula ly.
Fou een
o
he
pa ien s
had
been
diagnosed
wi h
as hma
p e i-
ously
and
wo
pa ien s
had
as hma
like
symp oms
bu
no
specific
diagnosis
o
as hma;
h ee
pa ien s
had
hype en-
sion.
The
a e age
se um
choles e ol
le el
and
plasma
as-
ing
glucose
le el
we e
high
in
he
o al
s udy
g oup.
As
much
as
75%
(N
=
12)
had
an
ele a ed
le el
o
o al
se um
choles e ol,
31%
(N
=
5)
o
iglyce ides
and
19%
(N
=
3)
o
abno mal
plasma
as ing
glucose
le el.
In
addi ion,
mean
BMI
(body
mass
index)
was
27.5,
showing
mild
o e -
weigh .
Table
1
Cha ac e is ics
o
pa icipan s
(N
=
16).
Values
o
age,
BMI,
measu ed
lab-
o a o y
es
esul s,
welding
yea s,
and
exposu e
gi en
in
means
wi h
s anda d
de ia ion.
Age,
yea s
44.6
(10.7)
BMI
27.5
(4.2)
Baseline
FEV1,
l
3.7
(0.47)
Baseline
PEF,
l/min
552
(92)
Choles e ol,
mmol/l
5.5
(1.0)
HDL,
mmol/l
1.3
(0.38)
T iglyce ides,
mg/l 1.6
(0.68)
Glucose,
mmol/l
5.7
(0.49)
Diagnosed
as hma
14/16
Welding,
yea s
23.8
(13.0)
Smoking
habi s
Cu en
smoke s,
N
1/16
Ex-smoke s,
N
8/16
Non-smoke s,
N
7/16
BMI:
body
mass
index;
FEV1:
o ced
expi a o y
olume
in
1
min;
PEF:
peak
expi a o y
flow;
HDL:
high
densi y
lipop o ein
360
P.
Kauppi
e
al.
/
Toxicology
Repo s
2
(2015)
357–364
3.2.
Hema ological
and
sys emic
inflamma o y
ma ke s
A e
he
MS
exposu e
es ,
hemoglobin
le el
dec eased
significan ly
om
157
g/l
o
154
g/l
and
he
numbe
o
e y h ocy es
om
5.0
o
4.9
(1012 cells
L−1),
whe eas
he
numbe
o
leukocy es
inc eased
significan ly
om
6.5
o
7.4
(109cells
L−1),
neu ophils
om
3.7
o
4.4
(109cells
L−1),
and
pla ele s
om
273
o
291
(109cells
L−1)
(Table
2).
Sim-
ila
s a is ically
significan
changes
we e
ound
ollowing
he
SS
exposu e
es .
O
he
sys emic
immune
pa ame e s,
he
concen a ion
o
E-selec in
dec eased
significan ly,
bu
only
in
he
MS
exposu e
es
( om
48.7
o
46.2
ng/ml)
(Table
2).
3.3.
Respi a o y
unc ion
The
base
le el
o
exhaled
ni ic
oxide
was
ele a ed
(>30
ppb)
in
fi e
pa icipan s
(31%).
The e
we e
no
s a is i-
cally
significan
changes
22
h
a e
he
welding
exposu e
es s
(Table
3).
Howe e ,
exhaled
NO
concen a ion
inc eased
by
o e
30%
in
fi e
s udy
pa icipan s
a e
he
MS
exposu e
es ,
and
in
wo
pa icipan s
a e
he
SS
exposu e
es
compa ed
o
he
base
le el
measu ed
be o e
he
fi s
exposu e
es .
The e
we e
sligh
and
s a is ically
significan
educ ions
in
he
FEV1(mean
FEV13.74
l
in
he
baseline
and
3.65
l
a e
MS
(P
0.032)
and
3.59
l
(P
0.26)
a e
SS
weld-
ing)
and
PEF
alues.
Respec i ely,
he
mean
PEF
alue
was
566
l/min
a
he
baseline,
543
l/min
a e
MS
(P
0.017)
and
529
l/min
(P
0.022)
22
h
a e
SS
welding
es s.
Fi e
pa icipan s
had
a
posi i e
eac ion
(a
dec ease
o
20%
o
PEF
o
FEV1 om
baseline
alue)
in
he
SS
chal-
lenge
es
and
we e
he e o e
diagnosed
wi h
OA.
In
he
es
o
he
pa ien s
(N
=
11),
he
final
diagnoses
a e
he
examina ions
a
he
FIOH
we e
as hma
(N
=
9),
as hma
like
symp oms
(N
=
1)
and
ch onic
obs uc i e
pulmona y
dis-
ease
(N
=
1).
In
he
pa ien s
wi h
OA
(N
=
5),
he
a e age
FEV1 alue
was
4.0
l
(±0.38)
and
he
PEF
alue
617
l/min
(±100)
be o e
he
welding
challenge
es s.
The
maximum
all
in
he
FEV1and
PEF
alues
was
0.70
l
(±0.32)
and
140
l/min
(±62),
espec i ely,
4
h
a e
SS
exposu e.
In
pa -
icipan s
wi h
no
confi med
OA
(N
=
11),
leucocy es
and
neu ophils
inc eased
significan ly,
whe eas
e y h ocy es
dec eased
significan ly
ollowing
bo h
he
welding
chal-
lenge
es s
(Table
4).
In
pa icipan s
wi h
confi med
OA,
only
pla ele
coun
inc eased
significan ly,
om
273
±
76.5
o
288
±
83.0
a e
he
MS
exposu e
es
(P
0.014),
and
om
290
±
81.9
o
304
±
77.3
a e
he
SS
exposu e
es
(P
0.014).
3.4.
Pa icle
exposu e
Pa icle
concen a ion
measu ed
in
he
b ea hing
zone
o
14
pa icipan s
by
he
IOM
sample
a ied
om
12.7
o
79.4
mg/m3in
he
MS
and
om
15.9
o
100
mg/m3in
he
SS
exposu e
es s.
The
a e age
pa icle
concen a ions
we e
31.6
and
40.2
mg/m3,
espec i ely.
The
mean
pa icle
con-
cen a ion
measu ed
inside
he
welding
ace
shields
by
he
mini
sample
was
30.2
mg/m3in
he
MS
exposu e
es s,
and
41.7
mg/m3in
he
SS
exposu e
es s.
Compa ed
o
he
IOM
esul s,
he
pa icle
concen a ion
measu ed
by
he
mini
sample
was
4.4%
lowe
in
he
MS
and
3.7%
highe
in
SS
exposu e
es s.
Fig.
2
p esen s
he
pa icle
numbe
size
dis ibu ions
in
he
MS
and
SS
exposu es
o
one
pa icipan .
Pa icle
size
Table
2
Inflamma o y
and
hema ological
pa ame e s
be o e
and
a e
welding
exposu e
es s.
Blood
pa ame e s
Day
1,
mild
s eel
exposu e
MS
(N
=
16)
Day
2,
s ainless
s eel
exposu e
SS
(N
=
15)
Blood
sample
5
Compa ison
5–1
Be o e
A e
P
Be o e
A e
P
Mean
(±SD)
P
Hemoglobin,
g/l
157
±
12.8
154
±
11.7
0.016
158
±
12.0
155
±
12.3
0.019
157
±
11.3
n.s
Leukocy es,
109cells
L−1
6.5
±
1.2
7.4
±
1.5
0.009
6.7
±
0.99
7.8
±
1.6
0.004
6.7
±
0.9
n.s.
Neu ophils,
109cells
L−1
3.7
±
1.2
4.4
±
1.3
0.002
3.8
±
0.94
4.8
±
1.4
0.004
3.9
±
1.0
n.s.
Lymphocy es,
109cells
L−1
2.2
±
0.66
2.2
±
0.45
ns
2.3
±
0.56
2.3
±
0.46
ns
2.1
±
0.64
n.s.
Eosinophils,
109cells
L−1
0.20
±
0.09
0.16
±
0.09
0.012
0.25
±
0.09
0.20
±
0.09
0.022
0.23
±
0.11
0.025
E y ocy es,
1012 cells
L−1
5.0
±
0.38
4.9
±
0.34
0.013
5.0
±
0.34
4.9
±
0.31
0.008
4.9
±
0.32
n.s.
Monocy es,
109cells
L−1
0.40
±
0.11
0.51
±
0.15
0.012
0.38
±
0.08
0.56
±
0.20
<0.001
0.37
±
0.13
n.s.
Basophils,
109cells
L−1
0.03
±
0.05
0.06
±
0.05
ns
0.04
±
0.05
0.06
±
0.05
ns
0.04
±
0.05
n.s.
Pla ele
coun ,
109cells
L−1
273
±
62.5
291
±
61.3
<0.001
282
±
57.3
293
±
59.9
0.008
278
±
52.4
n.s.
Sensi i e
CRP,
mg/ml
1.46
+
2.24
1.51
+
2.25
ns
1.58
+
2.21
1.60
+
2.14
ns
1.46
±
2.24
n.s.
P-fib inogen,
g/l
3.4
±
0.98
3.1
±
0.93
ns
3.4
±
0.91
3.5
±
1.1
ns
3.6
±
1.01
n.s.
IL-1␤,
pg/ml
0.57
±
0.43
0.45
±
0.30
ns
0.65
±
0.86
0.65
±
0.76
ns
0.46
±
0.30
n.s.
IL-6,
pg/ml 2.7
±
1.6 2.5
±
1.6
ns
2.5
±
1.4
2.4
±
1.1
ns
2.6
±
1.4
n.s.
IL-8,
pg/ml
7.7
±
2.8
7.2
±
3.6
ns
8.3
±
4.8
7.4
±
2.7
ns
7.4
±
3.3
n.s.
TNF-␣,
pg/ml
2.0
±
0.68
2.0
±
0.83
ns
2.1
±
1.1
1.8
±
0.53
ns
1.8
±
0.6
n.s.
Endo elin
1,
pg/ml
0.92
±
0.23
0.86
±
0.22
ns
0.87
±
0.21
0.88
±
0.35
ns
0.90
±
0.26
n.s.
E-selec in,
ng/ml
48.7
±
20.9
46.2
±
19.1
0.04
47.2
±
19.2
47.3
±
20.2
ns
45.9
±
19.8
n.s.
Compa ison
5–1:
compa ison
o
Blood
es
5
on
Day
3,
and
o
Blood
es
1
on
Day
1.
P.
Kauppi
e
al.
/
Toxicology
Repo s
2
(2015)
357–364
361
Table
3
A e age
exhaled
ni ic
oxide
(NO),
FEV1and
PEF
alues
wi h
s anda d
de ia ion
(SD)
be o e
and
a e
exposu e
es s.
Be o e
exposu e
es s
(N
=
16)
A e
mild
s eel
exposu e
(N
=
16)
A e
s ainless
s eel
exposu e
(N
=
15)
Mean
(SD)
Range
Mean
(SD)
Range
Mean
(SD)
Range
Exhaled
NO,
ppb
25
(22)
4.9–74
25
(24)
4.5–79
28
(27)
6.2–86
FEV1,
l
3.74
(0.47)
3.65
(0.46)
3.59
(0.48)
PEF,
l/min
566
(92)
543
(79)
529
(87)
FEV1:
o ced
expi a o y
olume
in
1
min;
PEF:
peak
expi a o y
flow.
Table
4
Inflamma o y
blood
pa ame e s
be o e
and
a e
welding
exposu e
es s
on
pa icipan s
wi h
no
confi med
occupa ional
as hma.
Day
1,
mild
s eel
exposu e
(N
=
11)
Day
2,
s ainless
s eel
exposu e
(N
=
10)
Be o e
A e
P
Be o e
A e
P
Hemoglobin,
g/l
159
±
13.3
156
±
11.6
0.031
159
±
12.8
156
±
13.8
ns
Leukocy es,
109cells
L−16.6
±
1.4
7.5
±
1.5
0.030
6.7
±
0.81
8.2
±
1.7
0.001
Neu ophils,
109cells
L−13.4
±
1.4
4.5
±
1.4
0.003
3.7
±
1.02
5.0
±
1.7
0.002
Lymphocy es,
109cells
L−12.4
±
0.68
2.3
±
0.37
ns
2.4
±
0.48
2.4
±
0.39
ns
Eosinophils
109cells
L−10.21
±
0.09
0.17
±
0.10
0.017
0.27
±
0.10
0.23
±
0.08
ns
E y ocy es,
1012 cells
L−15.1
±
0.36
5.0
±
0.31
0.013
5.1
±
0.36
5.0
±
0.33
0.024
Monocy es,
109cells
L−10.41
±
0.13
0.48
±
0.13
0.030
0.37
±
0.09
0.54
±
0.19
0.010
Basophils,
109cells
L−10.05
±
0.05
0.06
±
0.05
ns
0.05
±
0.05
0.08
±
0.04
ns
Pla ele
coun ,
109cells
L−1274
±
59.4
292
±
53.6
0.008
278
±
46.8
288
±
53.1
ns
dis ibu ion
was
e y
simila
in
bo h
exposu es.
To al
pa i-
cle
numbe
concen a ion
in
SS
welding
was
3.2
×
106cm−3
and
in
MS
welding
1.7
×
106cm−3.
SS
welding
gene a ed
a
highe
pa icle
numbe
concen a ion,
p esumably
due
o
he
highe
od
numbe
consump ion
han
in
MS
weld-
ing.
In
bo h
exposu e
es s,
mos
o
he
welding
ume
pa icles
we e
smalle
han
1
␮m.
The
middle
poin
o
he
mode
was
a ound
430
nm
in
bo h
welding
challenge
es s.
4.
Discussion
Sys emic
inflamma o y,
hema ological
and
espi a o y
esponses
we e
s udied
in
16
middle-aged
male
wo ke s
exposed
o
welding
umes
and
o
whom
14
had
as hma,
one
ch onic
obs uc i e
pulmona y
disease
and
one
had
as hma
like
symp oms.
P e ious
s udies
on
his
subjec
ha e
been
epidemiological
[11,12,25,26],
ca ied
ou
on
heal hy
ol-
un ee s
[16–18]
o
in
wo kplace
se ings
[19,27].
This
is
Fig.
2.
Pa icle
numbe
size
dis ibu ion
in
one
pa icipan ’s
mild
s eel
(MS)
and
s ainless
s eel
(SS)
exposu e
es s.

362
P.
Kauppi
e
al.
/
Toxicology
Repo s
2
(2015)
357–364
he
fi s
s udy
o
epo
he
sys emic
inflamma o y
and
hema ological
esponses
in
pa ien s
wi h
as hma.
Blood
leukocy es
and
neu ophils
inc eased
signifi-
can ly
ollowing
bo h
he
MS
and
he
SS
welding
exposu e
es s.
This
is
consis en
wi h
o he
s udies
dealing
wi h
he
acu e
e ec s
o
welding
exposu e
[17–19].
Pe iphe al
blood
neu ophilia
has
also
been
ound
ollowing
sho - e m
inhala ion
exposu e
o
o he
subs ances,
such
as
ozone
[28]
and
compos
dus
[29].
Blood
pla ele s
inc eased
significan ly
a e
bo h
he
MS
and
SS
welding
challenges.
This
finding
con adic s
hose
o
Ha mann
e
al.
[18]
and
hose
we
ou sel es
ha e
p e iously
epo ed
[19].
The
ac
ha
hese
p esen
obse a ions
could
be
seen
as
being
a
odds
wi h
hese
p io
findings
migh
also
be
due
o
di e ences
in
expo-
su e
cha ac e is ics.
In
he
o me
s udy,
he
pa icipan s
we e
exposed
o
umes
o
me al-ine -gas
(MIG)
weld-
ing
o
aluminum
and
MIG
solde ing
o
zinc-coa ed
s eel
and,
in
he
la e
s udy,
o
MS
welding
umes
and
o
dus s
and
umes
gene a ed
om
g inding
MS
pla es
o
pieces.
In
addi ion,
he e
was
a
en old
di e ence
be ween
he
a e age
pa icle
concen a ions
in
he
ea -
lie
s udies
and
hose
in
he
p esen
s udy.
Inc eased
pla ele
coun
in
pe iphe al
blood
has
p e iously
been
epo ed
as
also
occu ing
a e
inhala ion
o
diesel
exhaus
[30].
Ano he
eason
could
be
eac i e
h ombocy osis
due
o
inc eased
inflamma ion
o
bone
ma ow
s imula-
ion.
Hemoglobin
and
e y h ocy e
le els
dec eased
signifi-
can ly
ollowing
bo h
he
MS
and
SS
welding
exposu e
es s,
which
is
consis en
wi h
ou
ea lie
findings
[19].
Al hough
his
finding
has
no
been
obse ed
in
o he
s udies
dealing
wi h
he
acu e
e ec s
o
welding
umes
[17,18],
a
significan
associa ion
be ween
he
concen a-
ion
o
pa icula e
ma e
(PM10)
and
blood
hemoglobin
le els
has
been
epo ed
by
Sea on
e
al.
[31].
I
is
unclea
how
fine
pa icula e
ma e
exposu e
leads
o
changes
in
hemoglobin
o
e y h ocy e
le els,
bu
i
has
been
specu-
la ed
ha
his
could
be
due
o
a
combina ion
o
mechanisms
such
as
olume
s a us
o
s ess,
which
could
a ec
blood
iscosi y
[30].
As
a
possible
mechanism,
Sea on
e
al.
sug-
ges ed
ha
he
inhala ion
o
some
componen
o
PM10
may
cause
he
seques a ion
o
ed
cells
in
ci cula ion
[31].
In
ou
p io
s udy,
he
dec ease
in
hemoglobin
le -
els
may
ha e
been
caused
by
di e ences
in
me abolic
in ensi y
and
fluid
shi s
du ing
mode a e-
o
low-le el
physical
wo k
[19].
Ou
p esen
esul s
could
also
be
influ-
enced
by
hese
ac o s,
al hough
he
welding
was
no
as
physically
demanding
as
welding
in
ac ual
wo kplace
con-
di ions.
Taken
oge he ,
ou
pe iphe al
blood
findings
( he
inc eased
le el
o
blood
leukocy es,
neu ophils,
and
pla ele s,
and
he
dec eased
le el
o
hemoglobin
and
e y h-
ocy es)
a e
in
line
wi h
he
sugges ion
ha
a
mild
sys emic
inflamma o y
esponse
akes
place
du ing
welding
expo-
su e
[16,17,19].
This
esponse
was
a
ime-limi ed
p ocess,
because
22
h
a e
he
las
exposu e
es ,
he
esponse
was
a enua ed.
The
p esen
s udy
obse ed
no
s a is ical
di e ences
in
CRP
le els,
which
is
in
acco dance
wi h
ou
ea lie
esul s
[19].
In
gene al,
he
a ailable
da a
on
his
subjec
is
mixed,
since
some
o
he
s udies
suppo
significan
CRP
changes
ela ed
o
welding
ume
exposu e
[17,29]
while
o he s
do
no
[16,19].
This
inconclusi e
si ua ion
demands
u he
in es iga ion.
No
s a is ical
di e ences
in
he
concen a-
ions
o
acu e-phase
media o s
such
as
TNF-␣,
IL-6
and
IL-8
ha e
been
epo ed
in
humans
ollowing
welding
exposu e
[16,19].
We
also
ound
no
s a is ical
di e ences
in
he
le -
els
o
hese
cy okines,
and
he e o e,
ou
cu en
findings
confi m
p e ious
obse a ions.
The
le els
o
IL-1␤,
which
is
a
p oinflamma o y
cy okine,
in
ela ion
o
welding
ha e
hus
a
only
been
s udied
once
[19].
The
s udy
ound
ha
IL-1␤
le els
dec eased
significan ly,
which
was
unexpec ed.
In
he
p esen
s udy,
no
significan
changes
we e
obse ed
in
IL-
1␤
le els.
E-selec in
le els
in
ela ion
o
welding
ha e
also
only
been
s udied
once
o
da e
[18].
In
ou
p e ious
s udy,
he
E-selec in
le el
dec eased
significan ly,
which
was
also
obse ed
in
he
p esen
s udy,
bu
only
ollowing
expo-
su e
o
he
MS
welding
umes.
We
also
s udied
he
le els
o
endo helin-1,
which
is
a
asocons ic o
pep ide,
and
fib inogen,
which
is
a
soluble
plasmap o ein,
bu
ound
no
significan
changes
in
ei he ,
which
is
in
acco dance
wi h
p e ious
epo s
[16,18,19].
Exposu e
o
welding
umes
has
been
associa ed
wi h
educed
pulmona y
unc ion
[25–27]
and
as hma
[9,10,11].
I
has
been
sugges ed
ha
changes
in
welde s’
lung
unc-
ions
a e
ansien ,
occu ing
a
he
ime
o
exposu e
a
he
wo kplace
and
e u ning
o
no mal
du ing
non-exposed
pe iods.
Welding
umes
o
s ainless
s eel
can
cause
OA
[13,15].
In
his
s udy
we
ound
fi e
cases
o
OA,
and
hese
indi iduals
showed
ma ked
la e
phase
changes
in
pulmona y
unc ion
(FEV1,
PEF)
in
esponse
o
he
SS
welding
challenge
es .
In e es ingly,
significan
changes
in
hema ological
pa ame e s
we e
ound
in
non-occupa ional
as hma
pa ien s
bu
no
in
pa ien s
wi h
confi med
OA.
Behndig
e
al.
epo ed
pa allel
findings
in
hei
s udy,
in
which
bo h
as hma
pa ien s
and
heal hy
indi iduals
we e
exposed
o
diesel
exhaus
pa icles
o
fil e ed
ai .
They
obse ed
a
significan
inc ease
o
submucosal
neu-
ophils
and
o
neu ophil
numbe s
in
he
b onchial
wash
o
he
heal hy
pa icipan s
bu
no
among
he
as hma ics
[32].
SS
welding
gene a ed
a
highe
pa icle
mass
and
num-
be
concen a ion,
p esumably
due
o
he
highe
od
numbe
consump ion
han
ha
in
MS
welding.
In
bo h
exposu e
es s,
mos
o
he
welding
ume
pa icles
we e
smalle
han
1
␮m,
and
he
pa icle
size
dis ibu ion
was
simila
in
bo h
exposu es.
The
a e age
welding
ume
exposu e
in
challenge
es s
was
high,
bu
simila
high
momen a y
exposu es
can
also
occu
in
wo kplace
condi-
ions.
The
measu ed
pa icle
mass
ange
was
qui e
wide,
depending
mos ly
on
he
pa icipan ’s
wo king
me hod.
Some
pa icipan s
we e
ben
e y
close
o
he
objec
being
welded,
he e o e
hei
b ea hing
zone
pa icle
concen-
a ions
we e
highe
han
hose
o
he
pa icipan s
who
we e
a
a
longe
wo king
dis ance
om
he
objec
being
welded.
The
umes
gene a ed
du ing
mild
s eel
weld-
ing
con ain
mainly
i on
(80–95%)
and
also
manganese
(1–15%),
whe eas
s ainless
s eel
welding
p oduces
smalle
amoun s
o
hese
bu
high
amoun s
o
ch omium
(15–30%)
and
nickel
(5–10%)
[4].
We
did
no
de e mine
he
me al
P.
Kauppi
e
al.
/
Toxicology
Repo s
2
(2015)
357–364
363
composi ion
o
he
umes
gene a ed
in
he
challenge
es s
in
he
p esen
se ies,
bu
we
ha e
done
his
p e iously
[33].
These
published
esul s
a e
in
line
wi h
hose
published
in
he
li e a u e.
The
s eng h
o
ou
s udy
was
he
possibili y
o
objec i ely
moni o
bo h
he
welding
exposu e
and
he
inflamma o y,
hema ological
and
espi a o y
esponses
a
he
indi idual
le el.
The
limi a ions
o
he
s udy
we e
he
lack
o
an
unexposed
con ol
g oup
and
he
ela i ely
small
numbe
o
pa icipan s.
Since
he
welding
challenge
es s
in
he
labo a o y
en i onmen
we e
he
only
p ocedu es
wi h
he
s udy
indi iduals
du ing
he
days,
he e
is
no
o he
explana ion
o
he
sligh
inflamma o y
esponse
e en
in
he
lack
o
unexposed
con ol
g oup.
The
s udy
pa icipan s
s ayed
a
he
FIOH
du ing
he
es
days
and
hus
wo k,
exe cise,
o
o he
en i onmen al
ac o s
can-
no
be
used
as
an
explana ion.
Also,
he
esul s
a e
in
line
wi h
ou
p e ious
s udy
on
welding
in
an
occupa-
ional/wo kplace
se ing
[19].
Fu he mo e,
a
la ge
s udy
g oup
would
p obably
ha e
gi en
mo e
significan
esul s,
a he
han
diminish
he
findings.
The
p esence
o
C
and
Ni
in
he
umes
may
cause
lung
inju y
and
inflamma ion,
lung
umo
o ma ion,
immune
dys unc ion,
and
sys emic
oxici y
[34].
Howe e ,
welding
p ocesses
p oduce
umes
consis ing
o
gaseous
and
ae osol
by-p oduc s
composed
o
me als,
me al
oxides
and
ola ilized
chemical
species
om
he
base
me als,
welding
elec ode,
o
flux
ma e ial
[1].
In
he
p esen
s udy,
we
could
no
elucida e
which
compo-
nen
o
he
welding
umes
was
esponsible
o
he
obse ed
findings.
We
canno
exclude
ha
pe o ming
he
exposu e
es s
on
consecu i e
days
could
ha e
a ec ed
he
esul s.
Un o -
una ely,
he e
is
no
wo ldwide
consensus
how
welding
exposu e
es s
should
be
pe o med.
Howe e ,
he
si u-
a ion
could
be
be e
in
he
u u e,
because
sugges ions
ha e
been
published
how
expe imen al
welding
ume
exposu e
s udies
unde
con olled
and
s anda dized
con-
di ions
should
be
ca ied
ou
([35]).
The
used
welding
challenge
es s
in
ou
se ies
ha e
been
s anda dized
[15].
The
challenge
es s
a e
he
“golden
s anda d”
o
diag-
nosing
OA.
The
p ocedu e
includes
fi s
he
placebo
es
and
he
ac i e
es
second.
I
is
impo an
ha
he
ime
be ween
he
wo
es s
should
be
minimized
since
he
pa ien s
cease
hei
as hma
medica ion,
and
he
longe
he
pe iod
be ween
he
wo
es s
is
he
less
compa able
he
es
esul s
a e.
Fu he mo e,
keeping
an
as hma
pa ien
wi hou
egula
as hma
medica ion
o
se e al
days
would
p o oke
unspecific
as hma
symp oms
and
alse
posi i e
es
esul s.
4.1.
Conclusions
In
conclusion,
we
obse ed
a
mild
sys emic
inflamma-
o y
esponse
ollowing
welding
ume
challenge
es s.
An
inc ease
was
obse ed
in
pe iphe al
blood
leukocy es,
neu-
ophils,
and
pla ele s,
and
a
dec ease
in
hemoglobin
le el
and
in
e y h ocy e
coun .
The
pa icle
size
dis ibu ion
o
welding
umes
was
simila
ega dless
o
he
exposu e;
mos
o
he
welding
ume
pa icles
we e
smalle
han
1
␮m,
and
he
IOM
measu emen s
co ela ed
well
wi h
he
mini
sample
measu emen s.
Conflic
o
in e es
D .
Hannu
and
Kauppi
epo
g an s
om
The
Finnish
Wo k
En i onmen
Fund,
du ing
he
conduc
o
he
s udy.
The
o he
au ho s
ha e
no hing
o
disclose.
T anspa ency
documen
The
T anspa ency
documen
associa ed
wi h
his
a icle
can
be
ound
in
he
online
e sion.
Acknowledgemen
The
s udy
was
suppo ed
by
he
Finnish
Wo k
En i on-
men
Fund.
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