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Measuring D L co : What Could Possibly Go Worng ? Brian Graham, PhD

Measuring D L co : 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:. AstraZeneca

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Measuring D L co : What Could Possibly Go Worng ? Brian Graham, PhD

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  1. Measuring DLco: What Could Possibly Go Worng? Brian Graham, PhD Division of Respirology, Critical Care and Sleep MedicineUniversity of Saskatchewan Saskatoon, Canada

  2. Disclosures:In 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

  3. 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

  4. 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

  5. flow = pressure x conductance for CO, assume Pcap = 0 gas Palv VA·ΔFAco/Δt = PAco · DLco DM Pcap 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

  6. 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 Physiol1957

  7. 0.3% gasconcen-tration Ogilvie breath hold time 0 alveolargas sample TLC volume DLCO = VA·ln[FACO/FICO ·FITr/FATr] PB·tBH RV 0 time Ogilvie CM et al. J Clin Invest 1957

  8. 0.3% gasconcen-tration breath hold time alveolargas sample(85ml) 0 TLC DLCO = VA·ln[FACO/FICO ·FITr/FATr] PB·tBH volume Jones & Meade RV 0 time Jones RS, Meade F. Q J ExpPhysiol1961

  9. 0.3% gasconcen-tration 3 equation 0 alveolargas 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 Eng1980

  10. All methods yield similar DLco values in young, healthy, trained subjects 3 equation Ideal J&M Ogilvie ATS* Graham et al, J Appl Physiol1981

  11. Effect of lower flow and shorter breath hold 150% normalisedDLco % fast 125% 3 equation Ideal J&M 100% Ogilvie ATS* 0% slow 5s BH slow 10s BH fast 10s BH Graham et al, J Appl Physiol1981

  12. 0.3% gasconcen-tration ATS/ERS dead space washout - 0.75 – 1 litre - 0.5 litres if VC < 2 litres 0 TLC 0.75 litre 1.0 litre volume Problems with dead space washout RV 0 time ATS/ERS DLco Standardisation. EurResp J 2005

  13. 0.3% ATS/ERS dead space washout allow 0.75 to 1 litre 1 litre samplecollection 0 TLC 0.75 litre 1.0 litre volume RV 0 time

  14. 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

  15. Effect of delaying alveolar sample collection ○ Jones & Meade in 10 healthy subjects - J&M lung model x x x x x x o x x- 3 equation method fast manoeuvre Graham et al, J Appl Physiol1981

  16. Effect of delaying alveolar sample collection ○ Jones & Meade in 10 healthy subjects - J&M lung model x x x x x x o x x- 3 equation method slow manoeuvre Graham et al, J Appl Physiol1981

  17. 0.3% Calculation of alveolar volume gasconcen-tration 0 VI·FITr = VA·FATr + VD·FITr VA = (VI – VD) · (FITr/FATr) ATS/ERS DLco Standardisation. EurResp J 2005

  18. 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  VA = FTr(t)dV(t) / FTr(tf) - VD t0 At end exhalation: Graham et al. Can Resp J 1996

  19. 0.3% gasconcen-tration CH4 concentration at end exhalation 0 TLC Calculate absolute lung volume at end exhalation volume RV 0 time

  20. Comparison of lung volume measurements 15 normal, healthy trained subjects ATS 3-equation TLClitres 5 sec 10 sec bodybox breathhold time 2 sec Graham et al, J Appl Physiol1985

  21. COPD Patient CH4 CO pressure volume flow

  22. COPD Patient CH4 CO

  23. Comparison of lung volume measurements 10 COPD patients ATS 3-equation * * * TLClitres 5 sec 10 sec bodybox breathhold time 2 sec Graham et al, J Appl Physiol1985

  24. Comparison of lung volume measurements 11 Asthma patients ATS 3-equation TLClitres breathhold time 2 sec 10 sec bodybox Graham et al, J Appl Physiol1985

  25. 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. EurResp J 2005

  26. 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. EurResp J 2005

  27. Why not measure VD??? TLC Graham et al. Can Resp J 1996

  28. 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 ATS/ERS DLco Standardisation. EurResp J 2005

  29. 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. EurResp J 2005

  30. DLco predicted adjustment for COHb and CO back pressure COHb(%) fractional concentration of alveolar CO (ppm) Graham et al. Am J RespCrit Care Med 2002

  31. DLco predicted adjustment for COHb and CO back pressure controlCOHb = 1.2%  COCOHb = 11.2% ** ** DLcoml/min/mmHg bothcorrections nocorrection FAcocorrection Graham et al. Am J RespCrit Care Med 2002

  32. 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. EurResp J 2005

  33. Increase in DLCO due to decreasing PIO2 with altitude 8% Calgary 6% Edmonton Saskatoon 4% Winnipeg Toronto VancouverHalifax 2% Montreal 0% -2%

  34. 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 Thorax1993; Crapo Am Rev Resp Dis 1981

  35. 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. EurResp J 2005

  36. 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. EurResp J 2005

  37. 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

  38. 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

  39. 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

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

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