Measuring DLco:
What Could Possibly
Go Worng?
Brian Graham, PhD
Division of Respirology, Critical Care and Sleep Medicine
University of Saskatchewan
Saskatoon, Canada
Disclosures:
In the past 2 years, funding/support has been received from:
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AstraZeneca
Boehringer-Ingelheim
COSMED
GSK
Merck Frosst
Novartis
Nycomed
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Pfizer
Prairie Oxygen
Roche
Trudell
Vitalaire
zu.com
Objectives:
• Describe limitations and sources of error in
DLco measurements
• Describe steps to ameliorate their effects
• Describe how current technology can be better
applied to DLco measurements
Diffusing Capacity
of the lung for carbon monoxide: DLco
[single breath]
• It’s not just diffusion
• It’s not a capacity
• It’s more precisely called Transfer Factor
flow = pressure x conductance
gas
Palv
Pcap
for CO, assume Pcap = 0
DM
VA·ΔFAco/Δt = PAco · DLco
Krogh equation:
DLCO = VA·ln[FACO(t2)/FACO(t1)]
PB·(t2-t1)
only valid during breath hold
Krogh M. The diffusion of gases through the lungs of man. J Physiol (London) 1914
1. DLco varies with
blood volume
1 = 1 +
1 .
DLco DMco co·Vc
2. DLco varies with
oxygen tension
co  as PaO2 
co
Vc
Roughton & Forster, J Apple Physiol 1957
0.3%
gas
concentration
Ogilvie
breath hold time
0
alveolar
gas
sample
TLC
volume
DLCO = VA·ln[FACO/FICO ·FITr/FATr]
PB·tBH
RV
0
time
Ogilvie CM et al. J Clin Invest 1957
0.3%
gas
concentration
breath hold time
alveolar
gas
sample
(85ml)
0
TLC
DLCO = VA·ln[FACO/FICO ·FITr/FATr]
volume
PB·tBH
Jones & Meade
RV
0
time
Jones RS, Meade F. Q J Exp Physiol 1961
0.3%
gas
concentration
3 equation
0
alveolar
gas
TLC
VMAX·dFACO(t)/dt = -DLCO·PB·FACO(t)
volume
V(t)·dFACO(t)/dt = -DLCO·PB·FACO(t)
V(t)·dFACO(t)/dt = -DLCO·PB·FACO(t)+(FICO(t)-FACO(t))dV(t)/dt
RV
0
time
Graham et al, IEEE Trans Biomed Eng 1980
All methods yield similar DLco values
in young, healthy, trained subjects
3 equation
Ideal J&M
Ogilvie
ATS*
Graham et al, J Appl Physiol 1981
Effect of lower flow and shorter breath hold
150%
normalised
DLco % fast
125%
3 equation
100%
Ideal J&M
Ogilvie
0%
ATS*
fast
10s BH
slow
10s BH
slow
5s BH
Graham et al, J Appl Physiol 1981
0.3%
gas
concentration
ATS/ERS dead space washout
- 0.75 – 1 litre
- 0.5 litres if VC < 2 litres
0
TLC
1.0 litre
0.75 litre
volume
Problems with dead space washout
RV
0
time
ATS/ERS DLco Standardisation. Eur Resp J 2005
ATS/ERS dead space washout
allow 0.75 to 1 litre
1.0 litre
0.75 litre
1 litre sample
collection
Measure dead
space washout
With current
technology we can
measure the point
of dead space
washout so that
dead space gas is
not included in the
alveolar sample
TLC
Graham et al. Can Resp J 1996
Effect of delaying alveolar sample collection
○ Jones & Meade in
10 healthy subjects
x
o
x
x
x

x
x
- J&M lung model
x
x
- 3 equation method
fast manoeuvre
Graham et al, J Appl Physiol 1981
Effect of delaying alveolar sample collection
○ Jones & Meade in
10 healthy subjects

x
o
x
x
x
x
x
x
- J&M lung model
x
- 3 equation method
slow manoeuvre
Graham et al, J Appl Physiol 1981
Calculation of alveolar volume
0.3%
gas
concentration
0
VI·FITr = VA·FATr + VD·FITr
VA = (VI – VD) · (FITr/FATr)
ATS/ERS DLco Standardisation. Eur Resp J 2005
Why not use all of the available information
for a more accurate measurement of VA???
Measure all of the tracer gas that went onto the lung
and subtract all of the tracer gas that came out to get
the amount of tracer gas left in the lung at end
expiration.
Use the concentration measured at end expiration to
estimate the concentration of tracer gas in the lung:
Lung volume = amount of tracer gas - dead space
concentration of tracer gas
tf
At end exhalation: VA =
t
FTr(t)dV(t) / FTr(tf) - VD
0
Graham et al. Can Resp J 1996
0.3%
gas
concentration
CH4 concentration
at end exhalation
0
TLC
Calculate
absolute lung
volume at end
exhalation
volume
RV
0
time
Comparison of lung volume measurements
15 normal, healthy trained subjects
3-equation
ATS
TLC
litres
breath
hold time
2 sec
5 sec
10 sec
body
box
Graham et al, J Appl Physiol 1985
COPD Patient
CH4
CO
pressure
volume
flow
COPD Patient
CH4
CO
Comparison of lung volume measurements
10 COPD patients
3-equation
ATS
*
*
TLC
*
litres
breath
hold time
2 sec
5 sec
10 sec
body
box
Graham et al, J Appl Physiol 1985
Comparison of lung volume measurements
11 Asthma patients
3-equation
ATS
TLC
litres
breath
hold time
2 sec
10 sec
body
box
Graham et al, J Appl Physiol 1985
Do we really need to measure VA? YES!
• DLco = VA · Kco
• The Krogh coefficient: Kco = ln(Δ[CO])/Δt/PB
• Kco units are min-1 · mmHg-1
• Using ml · min-1 · mmHg-1 · litre is misleading
• Kco should never be labelled DLco/VA
• The relationship between DLco and lung volume is
not linear, so DLco/VA and DLco/TLC do NOT
provide an appropriate way to normalise DLco for
lung volume
ATS/ERS DLco Standardisation. Eur Resp J 2005
Calculation of VA: dead space
ATS/ERS 2005 Guidelines state:
VD can be estimated from various formulae or
simply use 150 ml as a fixed value
Effect of VD error on DLco depends on VA, ranging
from 1% to 3%
BUT equipment dead space (including filter – up to
350 ml) must also be subtracted or the error can
be up to 10%
ATS/ERS DLco Standardisation. Eur Resp J 2005
Why not measure VD???
TLC
Graham et al. Can Resp J 1996
DLco predicted adjustment for Hb
DLco adjustment: 1.7·Hb /(102.2+Hb) for males
DLco adjustment: 1.7·Hb /(93.8+Hb) for females
& children< 15 yrs
Hb
20% high
10% high
standard
10% low
20% low
males
175.2
160.6
146
131.4
116.8
adjustment
females
160.8
147.4
134
120.6
107.2
7.37%
3.89%
0.00%
-4.38%
-9.33%
ATS/ERS DLco Standardisation. Eur Resp J 2005
DLco predicted adjustment for COHb and
CO back pressure
• CO in the lung prior to the DLco test has both an
“anemia effect” and a CO back pressure effect
• Predicted DLco is reduced 1% for every 2%
increase in COHb for COHb levels > 2%
• Baseline COHb in smokers can be as high as 15%
• COHb rises with each DLco manoeuvre (almost
1% per manoeuvre in normal healthy subjects)
ATS/ERS DLco Standardisation. Eur Resp J 2005
DLco predicted adjustment for COHb and
CO back pressure
COHb
(%)
fractional concentration of alveolar CO (ppm)
Graham et al. Am J Resp Crit Care Med 2002
DLco predicted adjustment for COHb and
CO back pressure
 CO
COHb = 11.2%
control
COHb = 1.2%
**
**
DLco
ml/min/mmHg
no
correction
FAco
correction
both
corrections
Graham et al. Am J Resp Crit Care Med 2002
Effect of alveolar oxygen on DLco
• DLco increases ~ 0.35% for each 1 mmHg
decrease in PAO2
• The alveolar oxygen tension can be calculated
from the simplified alveolar gas equation:
PAO2 = FIO2(PB-47) - PaCO2 (FIO2 + [1- FIO2] / R)
• As PB decreases or PaCO2 increases,
PAO2 decreases and DLco increases
• Correction for PIO2 = 1/(1+0.0031(PIO2 -150))
where PIO2 = FIO2(PB-47)
ATS/ERS DLco Standardisation. Eur Resp J 2005
Increase in DLCO due to
decreasing PIO2 with altitude
8%
Calgary
6%
Edmonton
Saskatoon
4%
2%
0%
-2%
Vancouver
Montreal
Halifax
Winnipeg
Toronto
Pay attention to the O2 in test gas
• Typically test gas has 21% O2 in North America
• In Europe, many test gas was often 17 - 20%
• Crapo’s DLco reference values were measured
with a test gas concentration of 25% to correct
for altitude.
• A single breath of test gas at a different O2
might mix sufficiently well in normals but
probably not in lung disease patients.
Kendrick Thorax 1993; Crapo Am Rev Resp Dis 1981
Other factors affecting DLco
• Pressure during breath hold: Valsalva Muller
• Volume history – previous deep breath DLco
• Menstrual cycle variations (independent of Hb)
ATS/ERS DLco Standardisation. Eur Resp J 2005
Calibration
• Daily - volume - 3 litre syringe
• Weekly – leak check
– use 3 litre syringe as test subject
– “biologic control”
• Quarterly – gas analyser linearity check
ATS/ERS DLco Standardisation. Eur Resp J 2005
Summary
• The standardised DLco test was not designed to
measure gas exchange in patients with airflow
obstruction
• The standardised DLco test remains constrained
by limitations to the original instrumentation and
manual computation
• Using existing equipment, more accurate and
precise DLco measurements can be made from a
patient-friendly, more physiologic manoeuvre
Summary
• In spite of the many limitations of the
standardised test, DLco is a valuable measure
of pulmonary function, but it has the potential
to be a much more useful test
If the application of
technology to
communication had
proceeded in the same
manner as the
application of
technology to diffusing
capacity, this is what a
smart phone would
like today
Thanks to the Saskatchewan DLco Team
Joseph T Mink
David J Cotton