ArticlePDF Available

Abstract

Output from jet nebulisers is calibrated traditionally by weighing them before and after nebulisation, but the assumption that the weight difference is a close measure of aerosol generation could be invalidated by the concomitant process of evaporation. A method has been developed for measuring aerosol output directly by using a solute (fluoride) tracer and aerosol impaction, and this has been compared with the traditional weight loss method for two Wright, six Turbo, and four Micro-Cirrus jet nebulisers and two Microinhaler ultrasonic nebulisers. The weight loss method overestimated true aerosol output for all jet nebulisers. The mean aerosol content, expressed as a percentage of the total weight loss, varied from as little as 15% for the Wright jet nebulisers to 54% (range 45-61%) for the Turbo and Micro-Cirrus jet nebulisers under the operating conditions used. In contrast, there was no discrepancy between weight loss and aerosol output for the ultrasonic nebulisers. These findings, along with evidence of both concentrating and cooling effects from jet nebulisation, confirm that total output from jet nebulisers contains two distinct fractions, vapour and aerosol. The vapour fraction, but not the aerosol fraction, was greatly influenced by reservoir temperature within the nebuliser; so the ratio of aerosol output to total weight loss varied considerably with temperature. It is concluded that weight loss is an inappropriate method of calibrating jet nebuliser aerosol output, and that this should be measured directly.
Thorax
1990;45:728-732
Jet
and
ultrasonic
nebuliser
output:
use
of
a
new
method
for
direct
measurement
of
aerosol
output
J
H
Dennis,
S
C
Stenton,
J
R
Beach,
A
J
Avery,
E
H
Walters,
D
J
Hendrick
Chest
Unit,
Newcastle
General
Hospital,
and
Newcastle
upon
Tyne
University
Department
of
Medicine
J
H
Dennis
S
C
Stenton
J
R
Beach
A
J
Avery
E
H
Walters
D
J
Hendrick
University
Department
of
Environmental
and
Occupational
Medicine
J
H
Dennis
University
Department
of
Statistics
A
J
Avery
Newcastle
upon
Tyne
Address
for
reprint
requests:
Mr
J
H
Dennis,
Chest
Unit,
Newcastle
General
Hospital,
Newcastle
upon
Tyne
NE4
6BE.
Accepted
II
July
1990
Abstract
Output
from
jet
nebulisers
is
calibrated
traditionally
by
weighing
them
before
and
after
nebulisation,
but
the
assump-
tion
that
the
weight
difference
is
a
close
measure
of
aerosol
generation
could
be
invalidated
by
the
concomitant
process
of
evaporation.
A
method
has
been
developed
for
measuring
aerosol
output
directly
by
using
a
solute
(fluoride)
tracer
and
aerosol
impaction,
and
this
has
been
compared
with
the
traditional
weight
loss
method
for
two
Wright,
six
Turbo,
and
four
Micro-Cirrus
jet
nebu-
lisers
and
two
Microinhaler
ultrasonic
nebulisers.
The
weight
loss
method
overestimated
true
aerosol
output
for
all
jet
nebulisers.
The
mean
aerosol
content,
expressed
as
a
percentage
of
the
total
weight
loss,
varied
from
as
little
as
15%
for
the
Wright
jet
nebulisers
to
54%
(range
45-61%)
for
the
Turbo
and
Micro-Cirrus
jet
nebulisers
under
the
operating
conditions
used.
In
contrast,
there
was
no
discrepancy
between
weight
loss
and
aerosol
output
for
the
ultrasonic
nebulisers.
These
findings,
along
with
evidence
of
both
concentrating
and
cool-
ing
effects
from
jet
nebulisation,
con-
firm
that
total
output
from
jet
nebu-
lisers
contains
two
distinct
fractions;
vapour
and
aerosol.
The
vapour
fraction,
but
not
the
aerosol
fraction,
was
greatly
influenced
by
reservoir
temperature
within
the
nebuliser;
so
the
ratio
of
aerosol
output
to
total
weight
loss
varied
considerably
with
temperature.
It
is
concluded
that
weight
loss
is
an
in-
appropriate
method
of
calibrating
jet
nebuliser
aerosol
output,
and
that
this
should
be
measured
directly.
Jet
nebulisers
are
widely
used
in
respiratory
medicine
in
preference
to
ultrasonic
nebu-
lisers
because
they
are
traditional,
economical,
and
efficient
in
producing
respirable
aerosols.
They
are
used
therapeutically
to
deliver
bronchodilators,
antimicrobials,
mucolytic
drugs,
and
local
anaesthetics
to
the
airways
and
gas
exchanging
tissues.
Diagnostically,
they
are
used
in
inhalation
provocation
tests
to
deliver
drugs,
allergens,
and
industrial
chemicals-for
example,
in
the
measurement
of
non-specific
bronchial
responsiveness
and
in
the
investigation
of
occupational
or
environmental
causes
of
asthma
and
alveolitis.
For
diagnostic
purposes
precision
of
dose
delivery,
through
accurate
nebuliser
calibra-
tion,
is
critical
if
threshold
values
and
dose-
response
relationships
are
to
be
defined.
The
mechanism
of
jet
nebulisation
is
well
understood.'
Compressed
air
is
forced
through
a
narrow
orifice
within
the
nebuliser
and
negative
pressure
is
created
by
the
expan-
ding
jet,
which
draws
liquid
up
a
feeder
tube
by
the
Bernoulli
effect.
The
liquid
then
enters
the
air
stream
and
is
broken
up
by
air
turbu-
lence
within
the
jet
itself
and
by
impaction
on
interior
surfaces
within
the
nebuliser.
Baffle
structures
within
the
nebuliser
filter
all
but
a
small
proportion
of
respirable
aerosols
back
to
a
common
reservoir.
The
total
mass
of
re-
leased
aerosol
defines
the
available
dose
of
solute,
and
the
size
distribution
dictates
its
potential
deposition
in
the
respiratory
tract.23
The
present
investigation
is
primarily
con-
cerned
with
measurement
of
aerosol
mass.
Nebuliser
output
is
conveniently
calibrated
by
weighing
the
nebuliser
unit
before
and
after
activation.48
This
assumes
that
no
solvent
is
lost
during
nebulisation
by
the
con-
comitant
process
of
evaporation-an
assump-
tion
known
to
be
incorrect.""
To
investigate
the
importance
of
this
potential
limitation
to
the
weight
loss
method
of
calibration
we
have
developed
a
method
for
direct
measurement
of
aerosol
output
using
a
chemical
(fluoride)
tracer.
We
have
compared
this
with
the
traditional
method
of
calibration
by
weight
loss
in
several
types
of
jet
nebuliser
and
one
type
of
ultrasonic
nebuliser.
In
addition,
we
have
used
this
new
technique
to
investigate
the
effect
of
reservoir
temperature
and
air
flow
rate
on
jet
nebuliser
output.
Methods
NEBULISERS
Three
types
of
jet
nebuliser
were
chosen
for
study,
two
Wright
(Aerosol
Medicals
Ltd,
Colchester),
four
Micro-Cirrus
(Intersurgical,
Twickenham),
and
six
Turbo
(Medic
Aid,
Pagham)
nebulisers.
Two
Microinhaler
ultrasonic
nebulisers
(Vestric,
Runcorn)
were
also
examined.
Measurements
of
weight
loss
and
aerosol
output
were
determined
in
parallel
four
to
seven
times.
MEASUREMENT
OF
TOTAL
OUTPUT
BY
GRAVIMETRIC
ANALYSIS
Before
and
after
each
activation
period,
during
which
aerosol
was
collected
as
described
below,
jet
nebulisers
(the
nebuliser
itself,
nebuliser
reservoir,
and
fitted
T
piece)
were
disconnec-
ted
and
weighed
on
a
Mettler
analytical
balance
728
group.bmj.com on January 13, 2017 - Published by http://thorax.bmj.com/Downloaded from
Jet
and
ultrasonic
nebuliser
output:
use
of
a
new
methodfor
direct
measurement
of
aerosol
output
(model
H6GD,
Gallen
Camp,
Loughborough)
to
the
nearest
0.01
mg.
For
measurement
of
weight
loss
from
the
Microinhaler
ultrasonic
nebuliser
the
reservoir
container
(a
20
ml
glass
vial)
was
removed
and
weighed
in
a
similar
way.
The
time
taken
to
weigh
an
individual
nebuliser
unit
was
about
30
seconds.
From
a
separate
study
of
repeatability
of
weighings
it
was
found
that
the
95%
confidence
interval
for
the
difference
of
a
pair
of
weighings
was
+0-89
mg.'6
MEASUREMENT
OF
AEROSOL
OUTPUT
BY
FLUORIDE
TRACER
METHOD
Aerosol
generation
and
preparation
of
solute
tracer
Fresh
solutions
of
1
-00%
w/v
sodium
fluoride
(BDH
Chemicals
Ltd,
Blyth)
were
prepared
in
distilled
water
(10-0
g/l),
and
5
ml
aliquots
were
placed
in
each
nebuliser.
Compressed
air
(British
Oxygen
Company
medical
grade)
was
driven
through
the
Turbo
and
Micro-Cirrus
nebulisers
from
a
pressure
of
20
lb/in2
(138
kPa),
which
resulted
in
a
flow
rate
of
7-5
1/min.
For
the
Wright
nebuliser
a
flow
rate
of
8-0
1/
min
was
used.
A
2-00
second
nebulisation
through
the
Micro-Cirrus
and
Turbo
nebul-
isers
was
directed
by
a
locally
designed,
microprocessor
controlled
dosimeter.'7
For
the
Wright
jet
nebulisers
we
used
three
minutes
of
continuous
nebulisation.
The
ultrasonic
nebul-
isers
were
manually
activated
in
short
bursts
of
0.5-5
0
seconds.
Collection
of
aerosol
output
During
activation
of
nebulisers
ambient
air
was
drawn
at
15
1/min
through
a
fitted
T
piece
over
the
nebulisers
by
a
modified
(reversed
flow)
MiniNeb
Compressor
(Bard Ltd,
Sunder-
land).
This
entrained
and
impacted
aerosols
on
to
a
25
mm
Whatman
glass
fibre
(GF/A)
filter
(BDH
Chemicals
Ltd)
held
within
a
metal
cassette
positioned
5
cm
from
the
nebuliser
head
(fig
1).
Aerosols
from
the
ultrasonic
nebulisers
were
similarly
impacted
on
to
37
1
tr
.to
vacuum
pump
Glass
fibre
filter
onto
which
NaF
laden
aerosols
impact
jet
nebuliser
reservoir
containing
1
%
w/v
NaF
mm
GF/A
filters,
through
which
air
was
drawn
at
25
1/min.
A
higher
flow
rate
and
larger
filter
were
used
for
the
ultrasonic
nebulisers
because
the
filter
could
not
be
positioned
as
close
to
the
source
of
nebulisation.
After
aerosol
collection
GF/A
filters
were
removed
and
stored
for
later
analysis.
For
flow
rates
of
15
1/min
and
above
and
for
aerosols
having
a
mass
median
diameter
of
0
3
gm
or
more
the
collection
efficiency
of
GF/A
filters
exceeds
99
9%.18
When
a
second
filter
was
placed
in
series
we
detected
no
aerosol
breakthrough.
Analysis
of
aerosol
output
Total
ionic
strength
adjustment
buffer
(TISAB;
BDH
Chemicals
Ltd)
was
prepared
as
a
50%
solution
in
distilled
water,
and
20
ml
were
added
to
each
Whatman
filter
within
25
ml
plastic
Universal
bottles.
The
bottles
were
then
sealed
and
fluoride
was
allowed
to
desorb
overnight.
The
recovery
of
fluoride
from
filters
was
complete
(>
98%)
and
no
fluoride
was
detected
in
unused
filters.
Fluoride
analysis
followed
well
established
protocols.'9
Fluoride
standards
were
prepared
by
microlitre
injec-
tions
of
5
0,
10-0,
and
15-0
pl
of
1
00%
sodium
fluoride
into
20
ml
aliquots
of
50%
TISAB
buffer,
resulting
in
5-95E-5M,
1
19E'M,
and
1
*78E'M
fluoride
solutions.
Both
standard
and
test
solutions
were
equilibrated
to
25°C
in
a
water
bath.
Fluoride
concentrations
within
the
buffered
solutions
were
then
measured
electro-
chemically
with
a
fluoride
specific
ion
electrode
(Corning
Ltd,
Halstead)
on
a
Corning
255
pH/
ion
meter
with
a
calomel
reference
electrode.
This
electrochemical
system
had
a
log-linear
relation
between
concentration
and
activity
(mV)
from
10-'M
to
10'M
F.
All
solutions
were
continually
agitated
during
analysis
with
an
electromagnetic
stirrer.
An
internal
two
point
calibration
was
established
with
the
5
and
15
pl
fluoride
standards
and
its
accuracy
was
checked
with
the
10
p1
standard.
The
standard
curve
was
used
to
quantify
all
test
solutions
and
reported
directly
the
microlitre
quantity
of
aerosol
fluoride
impacted
on
and
desorbed
from
the
test
filters.
The
error
of
fluoride
determination
was
within
+
2%.
Given
that
the
concentration
of
the
chemical
tracer
used
in
this
method
is
only
1%
(w/v
as
sodium
fluoride),
the
density
of
the
solution
is
virtually
unity,
allowing
direct
comparison
of
weight
loss
and
aerosol
output-that
is,
1
mg
=
1
pl.
CONCENTRATION
AND
TEMPERATURE
CHANGES
WITHIN
NEBULISER
SOLUTIONS
For
investigating
the
effect
of
jet
nebulisation
on
reservoir
concentration
and
temperature
in
a
Wright
jet
nebuliser
we
used
5
ml
of
1
-00%
sodium
fluoride
solution
and
an
air
flow
rate
of
8
0
1/min.
Temperature
was
monitored
with
a
thermocouple
0-1°C),
which
lay
in
the
reservoir
solution.
At
time
0
and
at
roughly
three
minute
intervals
the
reservoir
tem-
perature
was
recorded
and
nebulisation
was
interrupted
for
30
seconds
so
that
three
10
pl
aliquots
of
the
reservoir
solution
could
be
removed
for
fluoride
analysis.
A
similar
inves-
tigation
was
made
with
an
ultrasonic
nebuliser
except
that
reservoir
temperatures
and
concen-
'.
.
i
I;
,
...
compressed
air
Figure
1
Schematic
representation
of
method
of
aerosol
collection.
A
glassfibrefilter
is
held
in
front
of
the
nebuliser.
Fluoride
laden
aerosols
emittedfrom
the
nebuliser
during
activation
are
entrained
in
an
airstream
and
impact
on
the
filter.
The
quantity
of
fluoride
on
the
filter
is
subsequently
desorbed
and
measured
electrochemically.
729
group.bmj.com on January 13, 2017 - Published by http://thorax.bmj.com/Downloaded from
Dennis,
Stenton,
Beach,
Avery,
Walters,
Hendrick
trations
were
measured
before
and
after
the
period
of
nebulisation
only.
EFFECT
OF
TEMPERATURE
ON
WEIGHT
LOSS
AND
AEROSOL
OUTPUT
The
effect
of
temperature
on
jet
nebuliser
weight
loss
and
aerosol
output
was
investigated
in
a
dosimeter
driven
Turbo
nebuliser.
Separate
sodium
fluoride
solutions
(1
00%,
5ml)
were
warmed
to
400C
or
cooled
to
5°C
and
allowed
to
equilibrate
to
ambient
temperature
(21°C)
for
15
minutes.
Temperature
was
measured
continuously
with
a
thermocouple.
At
0-5-2
minute
intervals
reservoir
tem-
perature
was
recorded
and
the
nebuliser
was
activated
for
2-0
seconds
at
a
flow
rate
of
7-5
1/
min.
Output
was
determined
by
both
the
weight
loss
and
the
fluoride
tracer
methods
at
each
temperature
point.
EFFECT
OF
AIR
FLOW
RATE
ON
JET
NEBULISER
OUTPUT
A
Wright
jet
nebuliser
was
filled
with
fresh
5
ml
solutions
of
1
00%
sodium
fluoride
and
activated
for
periods
of
20
seconds
at
flow
rates
of
3,
5,
7,
9,
and
11
1/min.
Weight
loss
and
aerosol
outputs
were
determined
in
triplicate
for
each
flow
rate.
In
a
similar
but
more
prolonged
experiment
using
an
airflow
rate
of
4.5
1/min
the
nebuliser
was
activated
until
at
least
half
of
the
reservoir
solution
(10
ml
of
1
-00%
sodium
fluoride)
had
dissipated;
during
this
period
any
aerosol
emitted
was
captured
on
a
GF/A
filter.
Results
MEASUREMENT
OF
NEBULISER
OUTPUT
The
mean
weight
loss
from
the
nebulisers
under
the
operating
conditions
used
ranged
from
356
mg
with
a
Wright
nebuliser
to
9
3
mg
with
a
Micro
Cirrus
nebuliser
(table).
Weight
loss
substantially
overestimated
aerosol
output
for
all
jet
nebulisers.
Mean
aerosol
output
expressed
as
a
proportion
of
total
weight
loss
varied
from
as
little
as
15%
for
the
Wright
jet
nebuliser
to
54%
(range
45-61%)
for
Turbo
and
Micro-Cirrus
jet
nebulisers.
No
significant
difference
between
total
weight
loss
and
aerosol
output
was
noted
for
the
ultrasonic
nebulisers.
EFFECT
OF
NEBULISATION
ON
CONCENTRATION
AND
TEMPERATURE
OF
JET
NEBULISER
SOLUTIONS
Activation
of
a
Wright
nebuliser
for
35
minutes
dissipated
3-6
ml
of
the
5.0
ml
reservoir
solu-
tion.
The
concentration
of
fluoride
increased
from
1-00%
to
3-01%
and
the
reservoir
tem-
perature
fell
from
22°C
to
9°C
(fig
2).
Activa-
tion
of
the
ultrasonic
nebuliser
for
six
minutes
dissipated
4
0
ml
of
an
original
5
0
ml
solution
but
had
no
appreciable
effect
on
the
reservoir
concentration
of
fluoride
(before
1-00%,
after
1.01%)
or
temperature
(before
22°C,
after
23°C).
EFFECT
OF
RESERVOIR
TEMPERATURE
ON
JET
NEBULISER
OUTPUT
The
total
weight
loss
from
the
Turbo
jet
nebuliser
increased
substantially
with
the
tem-
perature
of
the
reservoir
solution
(fig
3),
weight
loss
approximately
tripling
over
the
tem-
perature
range
5-40TC.
Over
the
range
5-35°C
the
increase
was
approximately
linear
(inter-
cept
9
5;
slope
0-58;
Fl,24
=
188,
p
<
00001).
By
contrast,
the
change
in
aerosol
output,
though
statistically
significant
(intercept
8-8,
slope
0
083;
F,
24
=
114,
p
<
0
00
1),
was
only
13
fold
over
this
temperature
range,
and
negligible
over
the
normal
range
of
operating
temperatures
(10-25°C).
EFFECT
OF
AIR
FLOW
RATE
ON
JET
NEBULISER
OUTPUT
Mean
weight
loss
increased
approximately
lin-
early
with
airflow
rate
through
a
Wright
nebul-
iser
(fig
4).
For
aerosol
output,
however,
there
was
a
threshold
flow
rate,
near
7
1/min,
below
which
aerosol
output
was
negligible.
At
higher
Mean
composition
of
nebuliser
output
for
the
different
models
Mean
(SD)
Mean
(SD)
Mean
vapour
Mean
(SD)
No
of
aerosol
weight
loss
content
aerosolfraction
Nebulisation
deter-
output
(AO)
(WL)
(WL-AO)
(AO/WL)
time
(s)
minations
(mg)
(mg)
(mg)
(%)
JET
NEBULISERS
Wright
1
180
6
52-0(4-6)
356-0(14-2)
306-0
14-6(1-0)
Wright2
180
4
48-0(5-2)
320-0(15
9)
272-0
14
3(1-0)
Turbo
1
2-00
5
6
4(0-2)
14-2(0-6)
7-8
45-0(1-9)
Turbo
2
2
00
5
7-4
(0-1)
14-4
(1-0)
7
0
51-2
(3
9)
Turbo
3
2-00
5
10-1
(0
2)
18-7
(0
7)
8-6
54
0
(2-4)
Turbo4
200
5
11-4(0-3)
20-1
(1-2)
8-7
56-8(3-1)
Turbo
5
200
5
11-8
(0-3)
20-5(1-1)
8-7
57-7(39)
Turbo
6
2-00
5
12
0
(0
6)
21-2
(0-8)
9-2
56-4
(5
5)
Micro-Cirrus
1
2-00
4
5-1
(0
3)
9'3
(0-5)
4-2
54-2
(1-7)
Micro-Cirrus
2
200
4
56(0-1)
11-0
(0.4)
5-4
50-8
(2.2)
Micro-Cirrus
3
2
00
4
6-2
(0-2)
11-7
(0-5)
5-5
53-0
(2
6)
Micro-Cirrus
4
2
00
4
6-9
(0-2)
11-4
(0-3)
4-5
61-2
(2
9)
Nebulisation
No
of
Aerosol
Weight
Aerosolfraction
time
deter-
output
loss
(s,range)
minations
(mg,
range)
(mg,
range)
(mg,
range)
(%,
mean
(SD))
ULTRASONIC
NEBULISERS*
Microinhaler
1
0
5-5
5
8-66-123
94-115-0
849-107
97
5
(9
2)
Microinhaler
2
05-5
7
18-0
-82-2
16-5-
85-0
939-109
99-8
(5-1)
*Ultrasonic
nebulisation
time
was
controlled
by
a
manual
trigger
and
ranged
from
about
0-5
to
5
seconds.
730
group.bmj.com on January 13, 2017 - Published by http://thorax.bmj.com/Downloaded from
Jet
and
ultrasonic
nebuliser
output:
use
of
a
new
methodfor
direct
measurement
of
aerosol
output
20
10
0
cu
z
ON-
c
0
4.
CA
0
L.
0
en
(I)
0)
10
20
30
0
nebulisation
time
(min)
Figure
2
Effect
of
nebulisation
on
temperature
(°C)
and
concentration
(%NaF)
the
reservoir
solution
of
a
Wright
jet
nebuliser;
4
ml
of
an
original
5
ml
solution
wa.
nebulised
over
35
minutes
at
aflow
rate
of
8-0
I/min.
flow
rates
aerosol
output
increased
sub
tially.
With
an
air
flow
rate
of
4-5
1/min
155
utes'
activation
reduced
an
initial
10-0376
1
00%
sodium
fluoride
solution
to
4-4045
the
Wright
nebuliser.
The
reservoir
so
fluoride
concentration
increased
to
2-
implying
that
essentially
all
the
original
so
fluoride
solute
was
still
present
in
the
rese
(calculated
initial
content
=
10-0
mg/r
10
0376
ml
=
100-4
mg;
calculated
final
20
-
0
.
weight
aerosol
0
0
0
0
0
0
0
0
U
0
o
0
0
0
0
(P
8°0
.
.
m
IV=
so
.
.
20
reservoir
temperature
(C)
Figure
3
Effect
of
reservoir
temperature
(°C)
on
weight
(mg)
and
aerosol
(mg)
from
a
Turbojet
nebuliser.
Temperature
within
the
reservoir
solution
was
monitorei
with
a
thermocouple.
At
selected
intervals
the
nebuliser
was
activatedfor
2.00
secoi
and
measurements
of
weight
loss
and
aerosol
output
were
made.
of
stan-
min-
ml
of
ml
in
nebuliser
output
(mg/s)
61
4
2-
0
O
weight
loss
*
aerosol
output
0
0
0
0
0
.
.
4
8
1
2
air
flow
rate
(I/min)
Figure
4
Effect
of
airflow
rate
(I/min)
on
rate
of
weight
loss
(mg/s)
and
aerosol
output
(mg/s)
from
a
Wright
jet nebuliser.
Simultaneous
measurements
of
weight
loss
and
aerosol
output
over
20
second
activation
periods
at
flow
rates
of
3,
6,
9,
and
11
1/min
were
made
in
triplicate,from
which
mean
values
were
calculated.
tent
=
22-9
mg/ml
x
4
4045
ml
=
100
9
mg).
In
parallel,
only
0-292
mg
sodium
fluoride
was
recovered
as
aerosol
from
the
GF/A
filter,
which
corresponds
to
less
than
0
3%
of
the
available
solute.
idium
Discussion
29%,
It
is
widely
recognised
that
solutions
in
the
idium
reservoir
of
jet
nebulisers
concentrate
and
cool
~rvoir
during
use
owing
to
evaporation
of
solvent,"'5
nl
x
and
we
have
found
these
effects
in
the
reservoir
con-
solution
of
a
Wright
jet
nebuliser.
The
corollary-that
the
weight
loss
overestimates
the
amount
of
solute
nebulised-has
not
been
fully
investigated.
This
could
exert
an
impor-
tant
confounding
influence
when
jet
nebulisers
0
calibrated
by
weight
loss
are
used
to
determine
threshold
levels
and
dose-response
relation-
ships
from
inhalation
provocation
tests.
Evaporation
of
solvent
would
not
be
expec-
ted
from
ultrasonic
nebulisation
and
we
detec-
ted
neither
concentrating
nor
cooling
effects
within
ultrasonic
nebuliser
reservoirs.
Nor
did
we
find
differences
between
aerosol
output
measured
by
the
fluoride
tracer
method
and
weight
loss.
This
close
agreement
validates
the
fluoride
tracer
method
as
a
means
of
collecting
and
measuring
true
aerosol
output.
The
princi-
*
ples
of
using
chemical
tracers
and
aerosol
impaction
have
been
successfully
applied
in
similar
systems.20
21
By
contrast,
there
were
substantial
differences
between
total
weight
loss
and
aerosol
output
for
all
the
jet
nebulisers
tested,
total
weight
loss
being
as
much
as
six
times
aerosol
output
in
the
case
of
the
Wright
4
nebuliser.
40
°
These
results,
supported
by
the
findings
on
concentration
and
cooling
effects,
suggest
that
the
process
of
jet
nebulisation
releases
appreciable
amounts
of
water
vapour.
On
dUtput
entering
the
nebuliser
compressed
air
is
almost
ids
completely
dry.
Within
the
high
velocity
air
turbulence
of
the
nebuliser
jet,
air
may
be
0
C)
0
%-0.
o
c0
L.
L.
(I)
0
&n
40
-
E
0.
4.'
0
(I)
._
0
n3
0
i
I
731
group.bmj.com on January 13, 2017 - Published by http://thorax.bmj.com/Downloaded from
Dennis,
Stenton,
Beach,
Avery,
Walters,
Hendrick
expected
to
become
saturated
with
water
vapour.
This
alone
did
not
fully
account
for
all
the
differences
observed
between
total
weight
loss
and
aerosol
output.
Compressed
air
driven
through
the
Micro-Cirrus
and
Turbo
jet
nebulisers
from
our
dosimeter
per
2-0
second
nebulisation
acquired
a
mean
volume
of
250
ml
when
expanded
to
atmospheric
pressure
and
a
mean
temperature
of
16°C.
Under
these
condi-
tions
it
could
theoretically
absorb
some
48
,ul
of
water
vapour
before
saturation
occurs
(psy-
chometric
chart).
Whereas
this
agrees
closely
with
the
mean
vapour
loss
measured
from
the
Micro-Cirrus
jet
nebuliser
of
4-9
(range
4-2-
5
5)l
ul,
higher
vapour
losses
were
noted
from
the
Turbo
nebuliser
(mean
8-3,
range
7-0-9-2
pl).
These
may
be
attributed
to
the
Turbo
nebuliser
design,
which
causes
additional
los-
ses
to
ambient
air
drawn
through
the
nebuliser
during
activation.
The
temperature
of
the
reservoir
solution
strongly
influenced
the
amount
of
weight
loss
but
not
aerosol
output,
implying
that
tem-
perature
exerted
a
major
effect
on
vapour
generation.
The
weak
but
significant
effect
of
reservoir
temperature
on
aerosol
output
is
likely
to
be
due
to
temperature
dependent
changes
in
surface
tension
and
viscosity.
Because
jet
nebuliser
temperature
decreases
during
nebulisation
the
relation
between
weight
loss
and
aerosol
output
will
vary
during
use.
This
means
that
measurements
of
weight
loss
cannot
readily
be
adjusted
to
provide
an
accurate
estimate
of
aerosol
output.
Like
other
investigators
we
found
that
weight
loss
from
the
Wright
jet
nebuliser
was
directly
related
to
airflow
rate.22
23
Aerosol
output,
however,
showed
no
relation
to
air
flow
rate
until
a
threshold
flow
around
7
1/min
was
reached.
That
this
threshold
flow
rate
exists
was
confirmed
by
the
prolonged
use
of
the
Wright
nebuliser
at
a
flow
rate
of
4-5
1/mim.
From
this
we
measured
a
negligible
aerosol
output
by
the
fluoride
tracer
method,
and
recovered
essentially
all
the
original
solute
in
the
concentrated
solution
at
the
end
of
nebul-
isation.
Our
findings
reinforce
recent
observations
of
other
investigators.
O'Callagan
et
al
collected
the
output
of
nebulised
sodium
cromoglycate
from
three
brands
of
jet
nebuliser
in
a
multi-
stage
liquid
impinger
and
compared
the
aerosol
content
as
assayed
by
spectrophotometric
means
with
the
observed
weight
loss.
"
They
concluded
that
drug
output
calculated
from
weight
loss
may
result
in
overestimation
of
the
true
drug
output
by
as
much
as
50%.
Cockcroft
et
al
measured
sodium
concentration
changes
in
saline
solutions
of
Wright
jet
nebuliser
reservoirs
before
and
after
nebulisation,
and
calculated
that
aerosol
output
was
about
a
quarter
of
that
predicted
by
weight
loss.'5
We
conclude
that
use
of
the
gravimetric
method
to
determine
aerosol
output
from
jet
(but
not
ultrasonic)
nebulisers
is
inappropriate,
and
that
direct
measurement
(by
the
fluoride
tracer
method,
for
example)
should
be
used.
JHD
was
supported
in
part
by
the
Asthma
Research
Council
and
JRB
by
the
Newcastle
Health
Authority
Research
Committee.
1
Mercer
TT.
Production
and
characterisation
of
aerosols.
Arch
Intern
Med
1973;131:39-50.
2
Tillery
MI,
Wood
GO,
Ettinger
HJ.
Generation
and
characterisation
of
aerosols
and
vapours
for
inhalation
experiments.
Environ
Health
Perspec
1976;16:25-40.
3
Clay
MM,
Pavia
D,
Newman
SP,
Clarke
SW.
Factors
influencing
the
size
distribution
of
aerosols
from
jet
nebulisers.
Thorax
1983;38:755-9.
4
Cockroft
DW,
Killian
DN,
Mellon
JJA,
Hargreave
FE.
Bronchial
reactivity
to
inhaled
histamine:
a
method
and
clinical
survey.
Clin
Allergy
1977;7:235-43.
5
Nieminen
MM,
Holli
H,
Lahdensuo
A,
Muittari
A,
Karvonen
J.
Aerosol
deposition
in
automatic
dosimeter
nebulization.
Eur
J
Respir
Dis
1987;71:145-52.
6
Newman
SP,
Pellow
PGD,
Clarke
SW.
In
vitro
comparison
of
DeVilbiss
jet
and
ultrasonic
nebulizers.
Chest
1987;
92:991-4.
7
Tsanakas
JN,
Wilson
AJ,
Boon
AW.
Evaluation
of
nebulisers
for
bronchial
challenge
tests.
Arch
Dis
Child
1987;62:506-8.
8
Kongerud
J,
Soyseth
V,
Johansen
B.
Room
temperature
influences
output
from
the
Wright
jet
nebulizer.
Eur
Respir
J
1989;2:681-4.
9
Wright
BM.
A
new
nebuliser.
Lancet
1958;ii:24-5.
10
Clay
MM,
Pavia
D,
Newman
SP,
Lennard-Jones
T,
Clarke
SW.
Assessment
of
jet
nebulisers
for
lung
aerosol
therapy.
Lancet
1983;ii:592-4.
11
Wood
JA,
Wilson
RSE,
Bray
C.
Changes
in
salbutamol
concentration
in
the
reservoir
solution
of
a
jet
nebulizer.
Br
J
Dis
Chest
1986;80:
164-9.
12
Clay
MM,
Clarke
SW.
Wastage
of
drug
from
nebulisers:
a
review.
J
R
Soc
Med
1987;80:38-9.
13
Schoni
MH,
Kraemer
R.
Osmolality
changes
in
nebulizer
solutions.
Eur
Respir
J
1989;2:887-92.
14
O'Callaghan
C,
Clarke
AR,
Milner
AD.
Inaccurate
calcu-
lation
of
drug
output
from
nebulisers.
Eur
J
Pediatr
1989;
148:473-4.
15
Cockroft
DW,
Hurst
TS,
Gore
BP.
Importance
of
evaporative
water
losses
during
standardized
nebulized
inhalation
provocation
tests.
Chest
1989;96:505-8.
16
Bland
MS,
Altman
DG.
Statistical
methods
for
assessing
agreement
between
two
methods
of
clinical
measurement.
Lancet
1986;i:307-10.
17
Connolly
MJ,
Avery
AJ,
Walters
EH,
Hendrick
DJ.
The
relationship
between
bronchial
responsiveness
to
metha-
choline
and
bronchial
responsiveness
to
histamine
in
asthmatic
subjects.
Pulmon
Pharm
1988;1:53-8.
18
Cotes
JC,
Steel
J.
Environmental
monitoring.
Work-related
lung
disorders.
Oxford:
Blackwell,
1987:23-48.
19
Crosby
NT,
Dennis
ALM,
Stevens
JG.
An
evaluation
of
some
methods
for
the
determination
of
fluoride
in
potable
waters
and
other
aqueous
solutions.
Analyst
1968;93:
643-52.
20
Donna
E,
Danta
I,
Kim
CS,
Waner
A.
Relationship
between
deposition
of
and
responsiveness
to
inhaled
methacholine
in
normal
and
asymptomatic
subjects.
J
Allergy
Clin
Immunol
1989;83:456-61.
21
Kim
CS,
Lewars
GG,
Eldridge
MA,
Sackner
MA.
Deposi-
tion
of
aerosol
particles
in
a
straight
tube
with
an
abrupt
obstruction.
J
Aerosol
Sci
1984;15:167-76.
22
Ryan
G,
Dolovich
MB,
Obminski
G,
et
al.
Standardization
of
inhalation
provocation
tests:
influence
of
nebulizer
output,
particle
size,
and
method
of
inhalation.
J
Allergy
Clin
Immunol
1981;67:156-61.
23
Hickey
AJ,
Byron
PR.
Effect
of
solution
flow
rate
on
the
output
of
two
modified
commercially
available
jet
nebulizers.
J
Pharm
Sci
1987;76:338-40.
732
group.bmj.com on January 13, 2017 - Published by http://thorax.bmj.com/Downloaded from
aerosol output.
new method for direct measurement of
Jet and ultrasonic nebuliser output: use of a
Hendrick
J H Dennis, S C Stenton, J R Beach, A J Avery, E H Walters and D J
doi: 10.1136/thx.45.10.728
1990 45: 728-732 Thorax
http://thorax.bmj.com/content/45/10/728
Updated information and services can be found at:
These include:
service
Email alerting box at the top right corner of the online article.
Receive free email alerts when new articles cite this article. Sign up in the
Notes
http://group.bmj.com/group/rights-licensing/permissions
To request permissions go to:
http://journals.bmj.com/cgi/reprintform
To order reprints go to:
http://group.bmj.com/subscribe/
To subscribe to BMJ go to:
group.bmj.com on January 13, 2017 - Published by http://thorax.bmj.com/Downloaded from
... Regarding the temperature changes in compressor nebulizers, Dennis and colleagues found that the solution temperature started decreasing as soon as nebulization began [38]. Conversely, ultrasonic and mesh nebulizers increase the sample temperatures [32], and we attributed the temperature changes as one of the contributing factors for explaining the best conservation of the analyzed subsets after the compressor nebulization. ...
Article
Full-text available
Background and objectives: Drug delivery by nebulization has become a crucial strategy for treating different respiratory and lung diseases. Emerging evidence implicates stem cell therapy as a promising tool in treating such conditions, not only by alleviating the related symptoms but by improving the prognosis. However, delivery of human peripheral blood-derived stem cells (hPBSCs) to the respiratory airways remains an innovative approach yet to be realized. This study is an analytic, translational, and in vitro research to assess the viability and morphological changes of identified cell populations in hPBSCs cocktail derived from COVID-19 patients. Methods and results: Peripheral blood (PB) samples were obtained from patients enrolled in the SENTAD-COVID Study (ClinicalTrials.gov Reference: NCT04473170). hPBSCs cocktails (n=15) were provided by the Cells Processing Laboratory of Abu Dhabi Stem Cells Center, and were nebulized by three different methods of nebulization: compressor (jet), ultrasonic, and mesh. Our results reported that nucleated CD45dim cell count was significantly lower after the three nebulization methods, but nucleated CD45- cells show a significant decrease only after mesh nebulization. Mesh-nebulized samples had a significant reduction in viability of both CD45dim and CD45- cells. Conclusions: This study provides evidence that stem cells derived from PB of COVID-19 patients can be nebulized without substantial loss of cell viability, cell count, and morphological changes using the compressor nebulization. Therefore, we recommend compressor nebulizers as the preferable procedure for hPBSCs delivery to the respiratory airways in further clinical settings.
... 24 Modern nebulizers, especially those with high-efficiency (breathactuated or breath-enhanced), have been shown to increase the inhaled mass of medication and reduce ambient drug loss. 21,25,26 These delivery methods may offer multiple safety advantages to pulmonary function laboratory personnel by reducing both exposure to nebulized methacholine and potentially infectious aerosolized particles. ...
Article
Background: Methacholine bronchoprovocation or challenge testing (MCT) is commonly performed to assess airway hyper-responsiveness in the setting of suspected asthma. Nebulization is an aerosol-generating procedure, but little is known about the risks of MCT in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. We aimed to quantify and characterize aerosol generation during MCT by using different delivery methods and to assess the impact of adding a viral filter. Methods: Seven healthy subjects performed simulated MCT in a near particle-free laboratory space with 4 different nebulizers and with a dosimeter. Two devices continuously sampled the ambient air during the procedure, which detected ultrafine particles, from 0.02-1 μm, and particles of sizes 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm, respectively. Particle generation was compared among all the devices, with and without viral filter placement. Results: Ultrafine-particle generation during simulated MCT was significant across all the devices. Ultrafine-particle (0.02-1 μm) concentrations decreased 77%-91% with the addition of a viral filter and varied significantly between unfiltered (P < .001) and filtered devices (P < .001). Ultrafine-particle generation was lowest when using the dosimeter with filtered Hudson nebulizer (1,258 ± 1,644 particle/mL). Ultrafine-particle concentrations with the filtered nebulizer devices using a compressor were higher than particle concentrations detected when using the dosimeter: Monaghan (3,472 ± 1,794 particles/mL), PARI (4,403 ± 2,948), Hudson (6,320 ± 1,787) and AirLife (9,523 ± 5,098). Conclusions: The high particle concentrations generated during MCT pose significant infection control concerns during the COVID-19 pandemic. Particle generation during MCT was significantly reduced by using breath-actuated delivery and a viral filter, which offers an effective mitigation strategy.
... During jet nebulisation the temperature may fall by 10®C or more. This will increase the viscosity of the solution and nebuliser output will be reduced (Dennis et al, 1990). In contrast during ultrasonic nebulisation the temperature increases. ...
Thesis
This thesis focuses on the potential use of nebulisation to deliver therapeutic proteins. Liposomes were investigated as a means to protect unstable proteins against degradation during nebulisation. Lactate dehydrogenase (LDH) and mushroom tyrosinase (TYR) were chosen as model proteins and the effects of jet and ultrasonic nebulisation on protein solutions and liposomal protein formulations were examined. The effects of nebulisation on protein activity and concentration, size distribution of the aerosols and temperature of nebuliser fluid were investigated. The duration of nebulisation time and the mass output of the nebulisers were measured and compared for all nebulisers and protein formulations. A twin impinger was utilised to determine the delivery of total and active protein. Inter and intra-nebuliser variability was also investigated. LDH was found to be more sensitive to degradation during nebulisation than TYR. The Omron U1 ultrasonic nebuliser was found to be the nebuliser of choice because TYR was not degraded and LDH showed less degradation using this nebuliser than the others. Liposomal entrapment protected against protein degradation during nebulisation. High sensitivity differential scanning calorimetry (HSDSC) and a Langmuir trough were used to establish how the proteins interacted with the liposomes and to explore why this protection occurred. The interaction between proteins and liposomes was electrostatic and no evidence of penetration of the proteins into the bilayer was observed. This interaction was believed to stabilise the protein by protecting against shear forces which occurred during nebulisation. Also by encapsulation of protein within liposomes, unfolding of protein structure and consequent denaturation of protein at air/water interfaces of aerosolised droplets was hindered. This work has demonstrated the ability of liposomes to protect proteins during nebulisation. The considerable differences in the characteristics of aerosols produced by different nebulisers highlight that manufacturers should specify the appropriate nebuliser to be used with a particular protein formulation.
... A small proportion of the generated aerosol, the "secondary aerosol", is released for inhalation whilst the largest proportion, the "primary aerosol", is too large (15-500 fxm) and hence is deflected by the baffles (Fig. 1.4) and walls of the nebuliser and recycled within the nebuliser reservoir to be atomised into smaller droplets suitable for inhalation (McCallion et al., 1996a;O'Callaghan and Barry, 1997). The aerosol output comprises aerosolised droplets and solvent vapour which saturates the outgoing air (Mercer et al., 1968;Dennis et al., 1990). This induces a decrease in fluid temperature and an increase in solute concentration within the nebuliser (Cockcroft et al., 1989;McCallion et al., 1996a). ...
Thesis
This study aims to investigate the ability of proliposomes to generate liposomes for delivery using air-jet, ultrasonic and vibrating-mesh nebulisers. Particulate-based proliposomes successfully generated liposomes under static conditions. Manually dispersed proliposomes generated multilamellar vesicles, with formulation having a small effect on the liposome size. Using sucrose as a carrier, liposomes were generated or dispersed in situ from proliposomes within the medical nebulisers investigated. The Pari (air-jet) and the Omron (vibrating-mesh) nebulisers produced large mass and lipid outputs with a large lipid fraction deposited in the lower stage of a two stage impinger. The Liberty (Ultrasonic) nebuliser failed to deliver more than 6% of the lipid employed. Multilamellar liposomes were generated from ethanol-based proliposomes. The resultant vesicles entrapped 62% of the available salbutamol sulphate compared to only 1.23% entrapped by liposomes made by the thin film method. Aeroneb Pro or Aeroneb Go vibrating-mesh nebulisers generated aerosol droplets of larger volume median diameter and narrower size distribution than the Pari (air-jet) nebuliser. Unlike the vibrating-mesh nebulisers, the performance of the jet nebuliser was largely independent of formulation. A nebuliser-dependent significant loss of the originally entrapped drug was demonstrated. A customised large mesh Aeroneb Pro reduced the drug losses during nebulisation. High sensitivity differential scanning calorimetry showed that the phospholipid phase transitions and liposomal bilayer interaction with beclometasone dipropionate were dependent on the method of liposome manufacture. Ethanol-based proliposomes produced liposomes having no pretransition, with a very low incorporation of the steroid (max. 1 mole%). This was attributed to an alcohol-induced interdigitation of the bilayers. 1 to 2.5 mole% steroid seemed to be optimal for incorporation in liposomes manufactured by the thin film or particulate-based proliposome method. Jet-nebulisation of particulate-based proliposomes delivered vesicles with enhanced steroid incorporation compared to liposomes generated by manual dispersion of these proliposomes.
... Therefore, one could refill the residual cup with NaCl 0.9% when the volume of the solution reaches half of the initial fill within the residual cup, but this methodology can be applied only once [58]. On the other hand, the factors affecting the ultrasonic nebulizers are different as the equipment works on different principles: the temperature of the piezoelectric crystal, the time of nebulization, the addition of buffer, pH and the drug principles [57][58][59][60][61][62]. Dry powder cisplatin has been created and it could be possibly administered as local therapy [63][64][65]. ...
Article
Full-text available
Lung cancer is still diagnosed at a late stage due to a lack of symptoms. Although there are novel therapies, many patients are still treated with chemotherapy. In an effort to reduce adverse effects associated with chemotherapy, inhaled administration of platinum analogs has been investigated. Inhaled administration is used as a local route in order to reduce the systemic adverse effects; however, this treatment modality has its own adverse effects. In this mini review, we present drugs that were administered as nebulized droplets or dry powder aerosols for non-small-cell lung cancer. We present the adverse effects and methods to overcome them.
... Therefore, one could refill the residual cup when the volume of the solution reaches half of the initial fill; however, this method can only be applied once [46]. The factors affecting the ultrasound nebulizers are (a) the addition of buffer, (b) the time of nebulization, (c) the temperature of the piezoelectric crystal, and (d) the drug (the salts and viscosity) [47] [45,46,[48][49][50]. The inlet of the aerosol production systems has also influenced droplet size production [51]. ...
Article
Full-text available
Although we have new diagnostic tools for non-small cell lung cancer, diagnosis is still made in advanced stages of the disease. However, novel treatments are being introduced in the market and new ones are being developed. Targeted therapies and immunotherapy have brought about a bloom in the treatment of non-small cell lung cancer. Still we have to find ways to administer drugs in a more efficient and safe method. In the current review, we will focus on the administration of inhaled cisplatin based on published data.
... Raman spectrum of(6,5) CNTs and statistical evaluation of the G + /2D-ratio versus sonication time.Another important factor is the composition of the aerosol for reproducible output results over extended periods. The first hint is the concentration of nanotubes of the ink remaining in the vial.While literature often reports an increase in the concentration of solid components in the remaining liquid, the opposite trend was observed for aerosol-jet printing of carbon nanotubes.The increasing concentration reported in literature is mostly attributed to the evaporation of solvent.[388][389][390] However, these studies on aerosol processes focused on medical applications where different aerosolizers were used and to the best of my knowledge, there has been no study on aerosol-jet printing processes dealing with the ink composition over time. ...
Thesis
Thanks to their extremely high mobilities, semiconducting carbon nanotubes (CNTs) are a promising material for high speed electronics. Beyond that, CNT networks are inherently flexible and stretchable and can be processed from dispersions resulting in devices with still remarkable electronic properties. They can fulfill many of the various requirements for novel applications including fast switching speeds and high currents at low drive voltages. Depending on the intended use, one or another device property might be more important. CNT networks, processes, and architectures can be tailored to yield devices that can serve the respective purpose. Highly purified semiconducting CNTs are, however, still rather expensive and direct-write techniques are thus preferred to enable variable designs and reduce manufacturing costs. In this work, aerosol-jet printing is investigated as a deposition technique for CNTs that works with small ink volumes but can also be upscaled by parallelization and integrated into high-throughput roll-to-roll printing processes. After the development of printable inks, it is shown that the printing process itself has no influence on the quality of the CNTs although sonication is used to transfer the ink into an aerosol. The electronic properties of CNT networks incorporated in an established transistor structure exhibit reproducibility comparable to other deposition techniques. Moreover, additive manufacturing enables the deposition of several layers on top of each other to increase the overall film thickness up to optically dense films visible to the naked eye. Field-effect mobilities and on-conductances increase and the hysteresis decreases for thicker films compared to dense but thin networks. Based on these findings, CNT films are printed with a thickness of 50–600 nm and vertical charge transport is demonstrated. These films are subsequently sandwiched between electrodes and electrolyte-gating results in doping of CNT films throughout electrode overlap areas of several hundred µm2. The vertical device architecture decouples the printing accuracy from the critical device dimensions while supporting high currents for a small footprint. A comparison of different printed electrode materials reveals the superior properties of printed metals over mixed (metallic and semiconducting) CNTs. Electrodes based on inkjet-printed gold nanoparticles are additionally used on flexible substrates and stable device performance even after several hundred bending cycles is demonstrated for vertical and lateral CNT network transistors. These all-printed devices are promising for further development of electronic circuits that do not require high operating frequencies but rather flexibility, high-currents, and small footprints.
Article
Full-text available
Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for this purpose, and the widening scope of this therapy, even beyond the lungs; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection and other adverse outcomes. Thus, it is imperative to have a national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in nebulization practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997, and have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in acute, in-patient, out-patient and domiciliary settings in India, to address many other related issues, and to standardize nebulization practices, National College of Chest Physicians (India), constituted a National task force consisting of eminent experts in the field of Pulmonary Medicine, from different backgrounds and different parts of the country, to review the available evidence from medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines for it. This guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies/position papers/consensus reports/recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts (advisors, chairpersons, convenor and members), and as such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions based on the existing knowledge, followed by point-wise evidence statements and recommendations have been provided.
Article
Paradoxical effects (bronchoconstriction instead of bronchodilatation) have been reported after inhalation of beta2-mimetics in asthmatic children, and it has been suggested that this was due to osmolality and pH changes of the nebulizer solution. We tested commercially available nebulizer solutions and found osmolality changes after 5, 10 and 15 min of nebulization. Osmolality was measured in the nebulizer chamber and the airsteam of two types of jet nebulizers. When normal saline was nebulized chamber, from 282 +/- 7 mmol.kg-1 to 432 +/- 18 mmol.kg-1 resulted. Salbutamol ready made solution, and terbutaline respules were isotonic, whereas fenoterol, disodium cromogylcate (DSCG), beclomethasone dipropionate (BDP) and salbutamol (respirator solution 0.5%) were hypotonic (60-100 mmol.kg-1). When a mixture of sodium chloride (NaCl) and the drug solution (salbutamol, terbutaline, fenoterol) was nebulized for 10-15 min, the osmolality in the nebulizer cup increased to 420-500 mmol.kg-1. However, mixtures of the same beta 2-agonists with DSCG or with BDP remained hypo-osmolar. The same osmolality changes were present in the airstream. This study shows that after 10-15 min of nebulization osmotic changes occur in the nebulizer cup and airstream and that these changes differ according to the drug mixtures and the amount of the solution in the nebulizer chamber.
Article
Deposition of aerosol particles in a straight tube with an abrupt local obstruction was determined experimentally in model tubes with tube Re ranged between 140 and 2800. Various types of obstruction whose hydraulic throat diameters ranged between 0.22 and 0.25 cm were created locally in the middle of smooth 0.5 cm i.d. glass tubes. Aerosol deposition occurred mostly behind the obstruction within a distance equalling 10 tube diameters. The deposition in this segment was increased rapidly with increasing flow rate and reached up to more than 100 times greater for particles of 3.1 γm diameter than in the unobstructed tube. The deposition increased with increasing particle size and was well correlated with pressure drop across the obstruction regardless of the types of obstruction. Stokes number (Stk) represented the deposition only for a specific type of obstruction. Despite the difference in flow structure, the deposition behind the obstruction was well correlated with deposition parameters used for fully developed turbulent pipe flow, dimensionless deposition velocity and relaxation time and agreed closely with turbulent deposition in a rough pipe.
Article
In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old. Such investigations are often analysed inappropriately, notably by using correlation coefficients. The use of correlation is misleading. An alternative approach, based on graphical techniques and simple calculations, is described, together with the relation between this analysis and the assessment of repeatability.
Article
Control of aerosol and vapor characteristics that affect the toxicity of inhaled contaminants often determines the methods of generating exposure atmospheres. Generation methods for aerosols and vapors are presented. The characteristics of the resulting exposure atmosphere and the limitations of the various generation methods are discussed. Methods and instruments for measuring the airborne contaminant with respect to various charcteristics are also described.
Article
An easy and safe dose-response histamine-inhalation test is described, to measure the level of non-specific bronchial reactivity. The test was performed in 307 subjects. Non-specific bronchial reactivity was increased in 3% of presumed normal subjects, in 100% of active asthmatics and in 69% of asymptomatic asthmatics with previous symptoms only at times of exposure to clinically relevant allergens. It was also increased in 47% of patients with cough and no other chest symptoms, in 40% of patients with rhinitis and vague chest symptoms not by themselves diagnostic of asthma, and in 22% of patients with rhinitis and no chest symptoms. The patients with asthma were studied when their asthma was well controlled and when their minimum drug requirements had been established. The mean level of bronchial reactivity increased with increasing minimum drug requirements. The level of bronchial reactivity also showed a strong negative correlation with the forced expiratory volume in 1 sec (FEV1). Atopic subjects, with or without asthma, showed a significant positive correlation between the level of bronchial reactivity and atopic status as indicated by the number of positive allergy skin tests.
Article
Evaporative water losses from jet nebulizers produce temperature drop, reduction in total nebulizer output with increased nebulization time, and increasing concentration of solute remaining in the nebulizer. These were documented and quantitated for the Wright nebulizer which is used for one histamine/methacholine inhalation test method. Indirect determination of nebulizer aerosol output, made by estimation of total sodium lost from the nebulizer, was about 25 percent of total output as determined by weight change. A similar tendency was seen for a De Vilbiss 40 nebulizer for both reduction in total nebulizer output with increasing duration of nebulization, and increased solute concentration remaining in the nebulizer. These data must be taken into account when standardizing inhalation provocation tests. Nebulizers should be calibrated under the same conditions that they are used during the test. Histamine and methacholine solutions should be discarded after a single use in the 2-min tidal breathing Wright nebulizer method.
Article
A multistage liquid impinger was used to collect the nebulised cloud from three separate nebulisers. The output of sodium cromoglycate collected was determined by a spectrophotometric assay. Estimating drug output purely from weight loss during nebulisation resulted in a considerable overestimate compared with direct assay of the drug output from the nebulised cloud. During nebulisation, weight loss from the nebuliser occurs in the form of particle formation and also by evaporation. By only weighing the nebuliser chamber before and after nebulisation, weight loss due to evaporation is not taken into account and this is the cause of the overestimation of drug output by this method.
Article
Paradoxical effects (bronchoconstriction instead of bronchodilatation) have been reported after inhalation of beta2-mimetics in asthmatic children, and it has been suggested that this was due to osmolality and pH changes of the nebulizer solution. We tested commercially available nebulizer solutions and found osmolality changes after 5, 10 and 15 min of nebulization. Osmolality was measured in the nebulizer chamber and the airsteam of two types of jet nebulizers. When normal saline was nebulized chamber, from 282 +/- 7 mmol.kg-1 to 432 +/- 18 mmol.kg-1 resulted. Salbutamol ready made solution, and terbutaline respules were isotonic, whereas fenoterol, disodium cromogylcate (DSCG), beclomethasone dipropionate (BDP) and salbutamol (respirator solution 0.5%) were hypotonic (60-100 mmol.kg-1). When a mixture of sodium chloride (NaCl) and the drug solution (salbutamol, terbutaline, fenoterol) was nebulized for 10-15 min, the osmolality in the nebulizer cup increased to 420-500 mmol.kg-1. However, mixtures of the same beta 2-agonists with DSCG or with BDP remained hypo-osmolar. The same osmolality changes were present in the airstream. This study shows that after 10-15 min of nebulization osmotic changes occur in the nebulizer cup and airstream and that these changes differ according to the drug mixtures and the amount of the solution in the nebulizer chamber.
Article
The purpose of this study was to determine if the intersubject variability in airway responsiveness to methacholine is a function of the methacholine mass deposited in the airways and if methacholine hyperresponsiveness in asymptomatic subjects with asthma is related to increased methacholine deposition. Ten normal and 10 age-matched asymptomatic subjects with asthma inhaled, with a standardized single breath maneuver, a dry aerosol (mass median aerodynamic diameter, 1.5 micron; geometric SD, 2.1) generated from solutions of methacholine at concentrations ranging from 0.078 mg/ml to 80 mg/ml in buffered saline, mixed with a fixed concentration of the fluorescent tracer quinine. The mass of methacholine deposited was calculated from the fluorescence of the inspired and expired aerosol trapped on an absolute filter before inspiration and during expiration. Specific airway conductance (SGaw) was measured before and after the inhalation of increasing concentration of methacholine, and the provocative deposited mass corresponding to a 35% decrease in SGaw was calculated. Baseline aerosol deposition (quinine-labeled buffered saline) ranged from 63% to 94% and was similar in normal subjects (mean 85%) and asymptomatic subjects with asthma (mean 84%). There was a correlation between the decrease in SGaw and methacholine mass deposited at first dose in the normal subjects (p less than 0.001) but not in asymptomatic subjects with asthma. Mean provocative methacholine mass corresponding to a 35% decrease in SGaw was 86 micrograms (range 2 to 157 micrograms) in asymptomatic subjects with asthma and 1361 micrograms (range 157 to 3434 micrograms) in normal subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Standardization of the solute output from the Wright nebulizer is necessary in nonspecific bronchial challenge to obtain reproducible results. Airflow and driving pressure are known determinants of the output. In an epidemiological study, in which day-to-day variations in room temperature occurred, we found the reproducibility of the output from a Wright nebulizer to be outside the range of acceptance. We have, therefore, examined to what extent ambient temperature and humidity might influence the output from three Wright nebulizers. The solute output was linearly correlated not only to flow (r = 0.98) and driving pressure (r = 0.90) but also to room temperature (r = 0.96). The mean output increased approximately 23% when room temperature was increased from 19 to 24 degrees C. This is equivalent to an increase in airflow of more than one litre. Ambient humidity did not influence the nebulizer output. When temperature was included in the calibration procedure, the coefficient of variation of the output decreased from 5 to 2%. This emphasizes the need for calibration of the Wright nebulizer with regard to ambient temperature as well as to airflow and pressure, especially in epidemiological field studies in which large variations of temperature are likely to occur.