DLCO Testing – Techniques for Accuracy Carl Mottram, BA RRT RPFT FAARC Director - Pulmonary...

DLCO Testing – DLCO Testing – Techniques for AccuracyTechniques for Accuracy

Carl Mottram, BA RRT RPFT FAARCCarl Mottram, BA RRT RPFT FAARCDirector - Pulmonary Function Labs & RehabilitationDirector - Pulmonary Function Labs & Rehabilitation

Associate Professor of Medicine - Mayo Clinic College of MedicineAssociate Professor of Medicine - Mayo Clinic College of Medicine

Diffusing Capacity - BackgroundDiffusing Capacity - Background

Evaluates how well oxygen Evaluates how well oxygen moves into and out of the moves into and out of the lungs lungs (alveolar capillary interface) (alveolar capillary interface)

Originally described by Krogh in Originally described by Krogh in 19151915

Product of two variables; rate of Product of two variables; rate of CO uptake and the VCO uptake and the VAA

Carbon monoxide is used as a Carbon monoxide is used as a surrogate for Osurrogate for O22 Mottram CD 10th Ed. Ruppel’s

Manual of PFT. Chap. 3

Diffusing Capacity - IndicationsDiffusing Capacity - Indications

Evaluation and f/u of parenchymal lung diseases Evaluation and f/u of parenchymal lung diseases including: idiopathic pulmonary fibrosis (IPF, UIP, including: idiopathic pulmonary fibrosis (IPF, UIP, BOOP); diseases associated with dusts such as BOOP); diseases associated with dusts such as asbestos, silicosis; other lung diseases such as asbestos, silicosis; other lung diseases such as sarcoidosissarcoidosis

Evaluation and f/u of emphysema and cystic Evaluation and f/u of emphysema and cystic fibrosis and differentiating among COPD patterns fibrosis and differentiating among COPD patterns

Evaluation of PV diseases (eg, PPH, PE, or Evaluation of PV diseases (eg, PPH, PE, or pulmonary edema)pulmonary edema)

Diffusing Capacity - IndicationsDiffusing Capacity - Indications Evaluation of pulmonary involvement in systemic Evaluation of pulmonary involvement in systemic

diseases (eg, rheumatoid arthritis, lupus, Wegener’s)diseases (eg, rheumatoid arthritis, lupus, Wegener’s) Evaluation of the effects of chemotherapy agents or Evaluation of the effects of chemotherapy agents or

other drugsother drugs Bleomycin, amiodarone, both require routine DLCO testing Bleomycin, amiodarone, both require routine DLCO testing

as a monitor)as a monitor) Evaluation of pulmonary hemorrhage Evaluation of pulmonary hemorrhage As an early indication of certain pulmonary infections As an early indication of certain pulmonary infections

(eg, pneumocystis pneumonia) (eg, pneumocystis pneumonia) Quantification of disabilityQuantification of disability

Diffusing Capacity - StandardsDiffusing Capacity - Standards

• ATS – ERS Eur Respir J 2005; 26: 720–735ATS – ERS Eur Respir J 2005; 26: 720–735

• Pulmonary Function Laboratory Management and Pulmonary Function Laboratory Management and Procedure Manual Procedure Manual

AARC CPG on Single Breath DLCOAARC CPG on Single Breath DLCO Respiratory Care (Respir Care 1999; 44 (5): 539-546Respiratory Care (Respir Care 1999; 44 (5): 539-546

Diffusing Capacity - TechniquesDiffusing Capacity - Techniques

Single breath*Single breath* Steady-stateSteady-state RebreathingRebreathing Intra-breathIntra-breath** Modified Krogh TechniqueModified Krogh Technique

Diffusing Capacity – Formula’sDiffusing Capacity – Formula’s

Diffusion ConductanceDiffusion Conductance 1/DLCO = 1/Dm + 1/1/DLCO = 1/Dm + 1/ƟVƟVcc

DM = membrane conductanceDM = membrane conductance

Ɵ = reaction rate of HbƟ = reaction rate of Hb

VVcc= pulm capillary blood volume= pulm capillary blood volume

Diffusing Capacity – Formula’sDiffusing Capacity – Formula’s

T = breath-holdT = breath-hold

FFACOoACOo = fraction of CO alveolar gas at the = fraction of CO alveolar gas at the

beginning of BHbeginning of BH

FFACOtACOt = fraction of CO alveolar gas at the end of BH = fraction of CO alveolar gas at the end of BH

T

O

CO

ACO

ACO X

X B

XA L

F

FLn

(T) 47) -(P

60 V SBD

Diffusing CapacityDiffusing Capacity

Different vendors use different inert tracer Different vendors use different inert tracer gasesgases Jaeger – HeliumJaeger – Helium Sensormedics – MethaneSensormedics – Methane nSpire – MethanenSpire – Methane Medical Graphics – NeonMedical Graphics – Neon

ATS/ERS Standards ATS/ERS Standards Standardization of Diffusing CapacityStandardization of Diffusing Capacity

Patient conditions for measurement Patient conditions for measurement (pre-test (pre-test conditions)conditions)

Factors that affect pulmonary capillary blood volume (e.g. Factors that affect pulmonary capillary blood volume (e.g. exercise, body position), and hemoglobin affinity for CO exercise, body position), and hemoglobin affinity for CO (eg alveolar PO2, COHb) should be standardized.(eg alveolar PO2, COHb) should be standardized.

If clinically acceptable, the subject should not breathe If clinically acceptable, the subject should not breathe supplemental oxygen for 10 minutes prior to a standard supplemental oxygen for 10 minutes prior to a standard test.test.


Recent smokingRecent smoking Patient should not have smoked for 24 hours prior to Patient should not have smoked for 24 hours prior to

testingtesting Time of last cigarette should be recordedTime of last cigarette should be recorded Back pressure of CO in blood will cause measured Back pressure of CO in blood will cause measured

DDLCOLCO to be lower to be lower (10% COHgb = 10% reduction in (10% COHgb = 10% reduction in

DDLCOLCO))


Hemoglobin adjustmentsHemoglobin adjustments Men (expected Hb 14.6):Men (expected Hb 14.6):

Women and adolescents (expected Hb 13.4):Women and adolescents (expected Hb 13.4):

Hb) (10.22

Hb) (1.7 x )(predictedDL Hb)for (predictedDL COCO

Roughly 3.5% per gm Hb below expected

Hb) (9.38

Hb) (1.7 x )(predictedDL Hb)for (predictedDL COCO


DLCO affected by altitudeDLCO affected by altitude DLCO varies inversely with changes in alveolar DLCO varies inversely with changes in alveolar

oxygen pressure (Poxygen pressure (PAAOO22). ).

PPAAOO22 changes as a function of altitude, as well as changes as a function of altitude, as well as

with the partial pressure of oxygen in the test gas. with the partial pressure of oxygen in the test gas.

DLCO pred. for altitude = DLCO pred. / (1.0 + DLCO pred. for altitude = DLCO pred. / (1.0 + 0.0031[PIO2 - 150])0.0031[PIO2 - 150])


Inspiratory maneuverInspiratory maneuver Inspiration should be rapid (85% of VC in Inspiration should be rapid (85% of VC in < <

4.0 seconds)4.0 seconds) DLCO calculation assumes instantaneous DLCO calculation assumes instantaneous

introduction of test gas into alveolar regions.introduction of test gas into alveolar regions. Long inspirations result in lower mean lung Long inspirations result in lower mean lung

volume during the measured breath hold time volume during the measured breath hold time (lower D(lower DLCOLCO))


Inspired vital capacityInspired vital capacity IVC should be at least IVC should be at least 85%85% of patient’s of patient’s

previous best VC.previous best VC. Because it appears that VI reductions as much as Because it appears that VI reductions as much as

15% of the known VC will reduce the DLCO less 15% of the known VC will reduce the DLCO less than 5%, a VI target of 85% of the largest known than 5%, a VI target of 85% of the largest known VC seems both reasonable and attainable.VC seems both reasonable and attainable.


Lung volume effects - low VI • Less than maximal VILess than maximal VI

lower VC and Dm (dark)lower VC and Dm (dark)• Lobectomy/pneumonectomyLobectomy/pneumonectomy

lower Dm, VC recruitedlower Dm, VC recruited(light)(light)

• Simple Simple DDLL/Va/Va does NOT “correct” does NOT “correct”

(ie not 1:1)(ie not 1:1) Eur Respir J 2001; 17: 168–174


Breath hold timeBreath hold time 10 10 ++ 2 seconds 2 seconds Avoid valsalva (expiratory efforts against a Avoid valsalva (expiratory efforts against a

closed airway) and Mclosed airway) and Müüller maneuvers ller maneuvers (inspiratory efforts against a closed airway) (inspiratory efforts against a closed airway) during the breath-hold, by decreasing and during the breath-hold, by decreasing and increasing thoracic blood volume respectively, increasing thoracic blood volume respectively, will decrease and increase DLCO respectivelywill decrease and increase DLCO respectively

Ogilive “classic”- measures BHT at beginning inspiration to Ogilive “classic”- measures BHT at beginning inspiration to beginning of alveolar collection.beginning of alveolar collection.

Jones - Meade - 0.70 of inspiratory time and half of sample timeJones - Meade - 0.70 of inspiratory time and half of sample time.. Epidemiologic Standardization Project measures BHT the time of Epidemiologic Standardization Project measures BHT the time of

50% of VI to the beginning of alveolar sample collection.50% of VI to the beginning of alveolar sample collection.


Washout volumeWashout volume

Pre-sample washout volume should be 0.75 to Pre-sample washout volume should be 0.75 to 1.0 liter (clear deadspace)1.0 liter (clear deadspace)

0.5 liter in patients with IVC < 2.0 liter0.5 liter in patients with IVC < 2.0 liter

A gas sample taken before anatomic dead space has A gas sample taken before anatomic dead space has cleared will be contaminated by inspired gas (not pure cleared will be contaminated by inspired gas (not pure alveolar).alveolar).

In patients with maldistribution of ventilation (COPD) timing In patients with maldistribution of ventilation (COPD) timing of gas collection may be more importantof gas collection may be more important..


Sample collection volumeSample collection volume Sample volume of 0.50 to 1.00 L Sample volume of 0.50 to 1.00 L

should be collected for analysisshould be collected for analysis In patients with VC < 1 L, smaller sample In patients with VC < 1 L, smaller sample

volumes below 0.50L may be used if it volumes below 0.50L may be used if it can be assured that VD has been clearedcan be assured that VD has been cleared

Allow 4 minutes in between tests Allow 4 minutes in between tests (especially in patients with obstruction)(especially in patients with obstruction)


Continuous Gas Continuous Gas AnalyzerAnalyzer Allows for analysis of Allows for analysis of

lower VC < 1 literlower VC < 1 liter Adjust washout Adjust washout

volume once a volume once a plateau is achievedplateau is achieved

Mottram CD 10th Ed. Ruppel’s Manual of PFT. Chap. 3


Miscellaneous factorsMiscellaneous factors Diurnal variationDiurnal variation

One study showed DLCO fell 1.2-2.2% per hour One study showed DLCO fell 1.2-2.2% per hour throughout the daythroughout the day..

Menstrual cycleMenstrual cycle 13% fall during cycle13% fall during cycle

Alcohol useAlcohol use Bronchodilators (effect on VA)Bronchodilators (effect on VA)

Peavy, et al Chest 77 (4) Peavy, et al Chest 77 (4) 19801980

Simeone et al Simeone et al Chest 2005;128;3875-3880

Alcohol EffectAlcohol Effect

DLCO – Testing techniqueDLCO – Testing technique

Quiet breathingQuiet breathing Exhale to RVExhale to RV Inhale test gas rapidlyInhale test gas rapidly

0.3% CO, 10% He, 21% O0.3% CO, 10% He, 21% O22, Bal N, Bal N22

Breath-hold (10 sec) Breath-hold (10 sec) with no leaks with no leaks (good seal on (good seal on

mouthpiece)mouthpiece) Exhale (relatively fast)Exhale (relatively fast)

Acceptability and RepeatabilityAcceptability and Repeatability

Two acceptable maneuvers Two acceptable maneuvers Repeatability requirement Repeatability requirement

of either being within 3 mL of either being within 3 mL CO (STPD) of each other or CO (STPD) of each other or within 10% of the highest within 10% of the highest value.value.

Report meanReport mean

ExampleExample 24.524.5 26.826.8

Report 25.6Report 25.6

Diffusing CapacityDiffusing Capacity

Data is reported in STPDData is reported in STPD Units: ml/min/mmHgUnits: ml/min/mmHg

Quality ControlQuality Control


Quality Control

Diffusing Capacity – Quality Diffusing Capacity – Quality AssuranceAssurance

Daily volume accuracyDaily volume accuracy Syringe DLCOSyringe DLCO DLCO Simulator or BioQCDLCO Simulator or BioQC

Diffusing Capacity – Quality AssuranceDiffusing Capacity – Quality Assurance

Biological ModelBiological Model Normal laboratory subjectsNormal laboratory subjects Two individuals (13)Two individuals (13) Establish mean and SD Establish mean and SD

(minimum 20 samples)(minimum 20 samples)

2005 ATS/ERS Standards 2005 ATS/ERS Standards General LaboratoryGeneral Laboratory

Diffusing Capacity - QADiffusing Capacity - QA

At least weeklyAt least weekly OrOr whenever errors are suspect whenever errors are suspect OrOr whenever a calibration tank is replaced whenever a calibration tank is replaced

DLCO and VA from Diffusing Capacity BioQC Technologist #3

0

5

10

15

20

25

1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89 93 97 101 105 109 113 117

Measurement Number

DL

CO

Un

its/

Lit

ers

DLCO

VA

““Old” Evidence of Quality DLCO Old” Evidence of Quality DLCO TestingTesting

Wanger J, Irvin C Wanger J, Irvin C Resp Care 36 (12): 1991Resp Care 36 (12): 1991

13 hospitals, 7 13 hospitals, 7 different systems, 5 different systems, 5 Bio-QC Bio-QC (3 men, 2 women)(3 men, 2 women)

DLCO CV 11.5 - 18.6 DLCO CV 11.5 - 18.6 largest diff. 24 unitslargest diff. 24 units

““New” Evidence of Quality DLCO TestingNew” Evidence of Quality DLCO Testing

Certification of DLCO Measurements for Clinical TrialsCertification of DLCO Measurements for Clinical Trials Results of the initial DLco simulation tests from 125 Results of the initial DLco simulation tests from 125

pulmonary laboratoriespulmonary laboratories 94 (75.2%) Passed with coaching; no hardware 94 (75.2%) Passed with coaching; no hardware 24 (19.2%) Failed24 (19.2%) Failed. Passed after servicing. Passed after servicing 6 (4.8%) Failed. Passed with new equipment 6 (4.8%) Failed. Passed with new equipment 1 (0.8%) Site dropped 11 (0.8%) Site dropped 1

R.L. Jensen, PhD., R.O. Crapo, M.D., P.Y. Berclaz, M.D., Ph, C. Zimmer, B.S., D.M. ATS abstract 2007

18 DLCO instruments 18 DLCO instruments at 13 Intermountain at 13 Intermountain Health Care sites over Health Care sites over 10 months10 months

DLCO instrument DLCO instrument accuracy was accuracy was unacceptable in 22-unacceptable in 22-33%33% of instrumentsof instruments

2011 ATS Abstract

DLCO ValidationDLCO Validation

3.19 units different3.19 units different

DLCO Comparison Old vs New System Same Vendor

0.00

10.00

20.00

30.00

40.00

1 2 3 4 5 6 7 8 9

Bio-QC Technologists

DL

CO

DLCO - EquipmentDLCO - Equipment

DLCO Comparison (High V/Q)

0.00

2.00

4.00

6.00

8.00

10.00

12.00

14.00

16.00

Large VD tubing Small VD Tubing

DLCO (mean of two values)

Un

its

Patient A

Patient B

Patient C

Patient D

Patient E

Patient F

Patient G

Patient H

Patient I

Patient J

Patient K

Patient L

Patient M

Patient N

Patient O

Patient P

Patient Q

Patient R

Comparison of Two Different Size Single Breath Diffusing Capacity Collection Tubes on the Jaeger Masterscope PFT System in Patients with Reduced DLCO and Biological Controls Mottram CD et al. Resp. Care 2002

What is considered What is considered abnormal?abnormal?

20

25

30

35

40

DLC

O

62 64 66 68 70 72 74 76 Height

Crapo Miller Fallat Paoletti ERS

DLCO PREDICTED45 Year old Female

Reference EquationsReference Equations

18 20 22 24 26 28 30 32

DLC

O

20 30 40 50 60 70 80 90Age

Crapo Miller Fallat Paoletti ERS

DLCO PREDICTED64 inch Female

Increase with heightIncrease with height Decrease with ageDecrease with age

Reference EquationsReference Equations

Healthy subjects (498 Healthy subjects (498 male and 474 female) male and 474 female) aged 45–71 years.aged 45–71 years.

Thorax 2008;63:889–893Thorax 2008;63:889–893

Diffusing CapacityDiffusing Capacity - - Clinical CorrelationClinical Correlation

Increased DIncreased DL,COL,CO

Increased blood flow Increased blood flow (exercise, left to right shunt, hyperdynamic state).(exercise, left to right shunt, hyperdynamic state).

Increased HgbIncreased Hgb Increased pulmonary capillary blood volumeIncreased pulmonary capillary blood volume Obesity (secondary to increased blood volume?)Obesity (secondary to increased blood volume?)

Asthma (increased DAsthma (increased Dmm? or increased blood volume?)? or increased blood volume?)

Intrapulmonary hemorrhage.Intrapulmonary hemorrhage.


Isolated low DIsolated low DL,COL,CO

Pulmonary vascular abnormalities (e.g. embolism, Pulmonary vascular abnormalities (e.g. embolism, vasculitis, hypertension)vasculitis, hypertension)

Interstitial lung disease (early disease -> low DInterstitial lung disease (early disease -> low DL,COL,CO

with nml lung volumes)with nml lung volumes)

Anemia [50% reduced Hgb -> 40% reduced DAnemia [50% reduced Hgb -> 40% reduced DL,COL,CO

(Cotes equation)](Cotes equation)] Early emphysemaEarly emphysema


Low DLow DL,COL,CO with other abnormalities: with other abnormalities: Restrictive pattern (low lung volumes): interstitial Restrictive pattern (low lung volumes): interstitial

lung disease.lung disease.

Obstruction: reduced DObstruction: reduced DL,COL,CO, particularly in moderate , particularly in moderate

to severe obstruction combined with increased lung to severe obstruction combined with increased lung volumes (hyperinflation) suggests emphysema. volumes (hyperinflation) suggests emphysema.

Inhomogeneity of gas distribution (bronchitis/asthma) Inhomogeneity of gas distribution (bronchitis/asthma) may cause underestimate of Dmay cause underestimate of DL,COL,CO


DDL,COL,CO/V/VAA

Interpretation of DInterpretation of DL,COL,CO/V/VAA is controversial is controversial

•• May differentiate IPF from other forms of restrictionMay differentiate IPF from other forms of restriction (inflammatory diseases, chest wall, muscle weakness, (inflammatory diseases, chest wall, muscle weakness, pleural disease).pleural disease).

Increased DIncreased DL,COL,CO/V/VAA may be seen in may be seen in

•• Chest wall restrictionChest wall restriction•• pneumonectomy (increased blood flow through remaining pneumonectomy (increased blood flow through remaining lung)lung)


Mottram CD 10th Ed. Ruppel’s Manual of PFT. Chap. 3

A cut point of DLCO < 62% A cut point of DLCO < 62% predicted resulted in 75% predicted resulted in 75% sensitivity and specificity for sensitivity and specificity for exercise desaturationexercise desaturation

Conclusions: Conclusions: The risk of oxygen The risk of oxygen desaturation during submaximal desaturation during submaximal exercise is very high in patients exercise is very high in patients with a low DLCOwith a low DLCO

Diffusing Capacity - Interpretation Diffusing Capacity - Interpretation

Appropriate Reference Equation is essentialAppropriate Reference Equation is essential Understand the measurement variabilityUnderstand the measurement variability Highly sensitive/poor specificityHighly sensitive/poor specificity Must evaluate in context with other testsMust evaluate in context with other tests Consider both absolute value and DL/VA ratio?Consider both absolute value and DL/VA ratio?

Diffusing Capacity - InterpretationDiffusing Capacity - Interpretation

Severity Classification - DLCO

idiopathic idiopathic pulmonary pulmonary fibrosisfibrosis

Alpha - 1Alpha - 1

Alveolar proteinosisAlveolar proteinosis

Diffusing CapacityDiffusing Capacity “ “Carl’s Top List”Carl’s Top List”

1. All equipment is not the 1. All equipment is not the samesame

2. Equipment calibration 2. Equipment calibration

3. QA model should 3. QA model should include Bio-QCinclude Bio-QC

4. Pre-test instructions4. Pre-test instructions

5. 85% of VC in 4 sec.5. 85% of VC in 4 sec.

6. Make appropriate. 6. Make appropriate. adjustments.adjustments.

7. Use Jones-Meade7. Use Jones-Meade

8. Reproducibility 10%, 3 8. Reproducibility 10%, 3 units or 2 units under 10units or 2 units under 10

Questions?Questions?

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