Interpretation Strategies diffusing capacity DLco

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Measuring DLco What Could Possibly Go
Worng? Brian Graham, PhD Division of
Respirology, Critical Care and Sleep
MedicineUniversity of Saskatchewan Saskatoon,
Canada
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DisclosuresIn the past 2 years,
funding/support has been received from

• AstraZeneca
• Boehringer-Ingelheim
• COSMED
• GSK
• Merck Frosst
• Novartis
• Nycomed

• Pfizer
• Prairie Oxygen
• Roche
• Trudell
• Vitalaire
• zu.com

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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

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Diffusing Capacity of the lung for carbon
monoxide DLcosingle breath

• Its not just diffusion
• Its not a capacity
• Its more precisely called Transfer Factor

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flow pressure x conductance for CO,
assume Pcap 0
gas
Palv
VA?FAco/?t PAco DLco
DM
Pcap
Krogh equation DLCO VAlnFACO(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
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1. DLco varies with blood volume
2. DLco varies with oxygen tension
?co
Vc
Roughton Forster, J Apple Physiol 1957
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0.3
gasconcen-tration
Ogilvie
0
DLCO VAlnFACO/FICO FITr/FATr
PBtBH
Ogilvie CM et al. J Clin Invest 1957
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0.3
gasconcen-tration
0
DLCO VAlnFACO/FICO FITr/FATr
PBtBH
Jones Meade
Jones RS, Meade F. Q J Exp Physiol 1961
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0.3
gasconcen-tration
3 equation
0
Graham et al, IEEE Trans Biomed Eng 1980
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All methods yield similar DLco values in young,
healthy, trained subjects
3 equation
Ideal JM
Ogilvie
ATS
Graham et al, J Appl Physiol 1981
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Effect of lower flow and shorter breath hold
Graham et al, J Appl Physiol 1981
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0.3
gasconcen-tration
ATS/ERS dead space washout - 0.75 1 litre
- 0.5 litres if VC lt 2 litres
0
0.75 litre
1.0 litre
Problems with dead space washout
ATS/ERS DLco Standardisation. Eur Resp J 2005
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0.3
ATS/ERS dead space washout allow 0.75 to 1
litre
0
TLC
0.75 litre
volume
RV
0
time
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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
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Effect of delaying alveolar sample collection
? Jones Meade in 10 healthy subjects
? - JM lung model
x
x
x
x
x
x
x
o
x - 3 equation method
fast manoeuvre
Graham et al, J Appl Physiol 1981
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Effect of delaying alveolar sample collection
? Jones Meade in 10 healthy subjects
? - JM lung model
x
x
x
x
x
x
x
o
x - 3 equation method
slow manoeuvre
Graham et al, J Appl Physiol 1981
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Calculation of alveolar volume
VIFITr VAFATr VDFITr VA (VI VD)
(FITr/FATr)
ATS/ERS DLco Standardisation. Eur Resp J 2005
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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
Graham et al. Can Resp J 1996
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0.3
0
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Comparison of lung volume measurements
15 normal, healthy trained subjects
TLClitres
Graham et al, J Appl Physiol 1985
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COPD Patient
CH4
CO
pressure
volume
flow
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COPD Patient
CH4
CO
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Comparison of lung volume measurements
10 COPD patients



TLClitres
Graham et al, J Appl Physiol 1985
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Comparison of lung volume measurements
11 Asthma patients
TLClitres
2 sec
10 sec
breathhold time
bodybox
Graham et al, J Appl Physiol 1985
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Do we really need to measure VA?
YES!

• DLco VA Kco
• The Krogh coefficient Kco ln(?CO)/?t/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
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Calculation of VA dead space
ATS/ERS 2005 Guidelines stateVD 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 3BUT
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
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Why not measure VD???
TLC
Graham et al. Can Resp J 1996
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DLco predicted adjustment for Hb
DLco adjustment 1.7Hb /(102.2Hb) for
males DLco adjustment 1.7Hb /(93.8Hb) for
females childrenlt 15 yrs
Hb Hb adjustment
males females
20 high 175.2 160.8 7.37
10 high 160.6 147.4 3.89
standard 146 134 0.00
10 low 131.4 120.6 -4.38
20 low 116.8 107.2 -9.33
ATS/ERS DLco Standardisation. Eur Resp J 2005
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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 gt 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
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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
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DLco predicted adjustment for COHb and CO back
pressure


DLcoml/min/mmHg
bothcorrections
nocorrection
FAcocorrection
Graham et al. Am J Resp Crit Care Med 2002
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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 equationPAO2
  FIO2(PB-47) - PaCO2 (FIO2 1- FIO2 / R)
• As PB decreases or PaCO2 increases,PAO2
  decreases and DLco increases
• Correction for PIO2 1/(10.0031(PIO2
  -150))where PIO2 FIO2(PB-47)

ATS/ERS DLco Standardisation. Eur Resp J 2005
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Increase in DLCO due to decreasing PIO2 with
altitude
8
Calgary
6
Edmonton
Saskatoon
4
Winnipeg
Toronto
VancouverHalifax
2
Montreal
0
-2
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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
• Crapos 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
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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
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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
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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

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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

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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
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Thanks to the Saskatchewan DLco Team
Joseph T Mink
David J Cotton