Indian J Physiol Pharmacol 1996; 40(3): 267-270

SHORT COMMUNICATION

COMPARISON OF SINGLE BREATH AND STEADY STATEMETHODS FOR MEASUREMENT OF LUNG TRANSFER FACTORFOR CO IN NORMAL SUBJECTS AND SMOKERS

K. K. MAHAJAN*, A. MAHAJAN+ AND N. MISHRA

Departments of Physiology and +Medicine,Pt. B.D. Sharma Postgraduate Institute of Medical Sciences,Rohtak - 124 001

( Received on December 20, 1995 )

Abstract : Pulmonary diffusing capacity (lung transfer factor forcarbon monoxide) has been assessed by the single breath (TLCO

SB)

and steady state (TLCOss) techniques in well matched 90 females,31 non-smoker and 29 smoker males, 18-50 years of age. Both TLCO

SB

and TLCOss are significantly lower in females compared to· non­smoker males (P<O.OOl). Tobacco smoking statistically significantlyreduces TLCOSB as well as TLCOss in smokers as compared to non­smokers. There is a statistically significant correlation of age withTLCO

SBand TLCOss in all the three groups (r = -0.702, -0.360 and

0.300 for TLCOSB

and r =-0.481, -0.355 and 0.380 for TLCOss in non­smoker males, smoker males and females respectively). TLCOSB is30.43±4.89, 27.29±4.54 and 26.13±3.60 ml/mmHg/min, while TLCOssis 19.47±5.26, 16.69±3.27 and 18.24±3.78 ml/mmHg/min in non­smoker males, smoker males and females respectively. A fairly goodcorrelation between the TLCO

SBand TLCOss in male, both non-smoker

and smoker, as well as the female subjects was observed. TLCOss islower than TLCO

SBin all the three groups. Even in smokers of

moderate intensity both of these tests are influenced to a nearlysimilar extent.

Key words : TLCO by single breath methodTLCO by steady state methodTLCO in smokers and non-smokersTLCO in females

INTRODUCTION

Study of lung transfer factor for CO (TLCO)is recommended as a sensitive index ofpulmonary gas exchange to detect structuraland functional lung diseases 0, 2). TLCOmeasurement has been generally made usingeither single breath (TLCOsll) or steady state(TLCOss) methods. Both TLCOsn and TLCOssare influenced by regional non-homogenousdistribution of ventilation and perfusion. Many

*Corresponding Author

authors have reported difficulty of measuringTLCO in patients exhibiting unequal ventilation(1, 3) The single breath method is thought tobe inadequate in such cases. The steady statemethod however gives a more even distributionoftest gas in lung and is therefore less sensitiveto unequal ventilation. Earlier, measurementof TLCO steady state was not much populardue to technical difficulties involved in itsmeasurement and complex calculations.Now recent technical developments have made

268 Mahajan et al

this method more feasible for routinemeasurements.

Smoking is known to affect TLCO adversely,hence needs to be taken into consideration inthe study of TLCO. At present, still there is nounanimity as to which method, TLCOsB orTLCOss' is a more valid index of gaseousdiffusion within the lung (4). To understandthe differences between TLCOsB and TLCOssmeasurement in patients with lung diseases,one needs to have a better understanding ofthe differences obtained when the methods areapplied to healthy subjects. The present studywas undertaken to compare TLCOsB and TLCOssin normal subjects in order to generate thenormal values for subjects in this area. Further,the effect of tobacco smoking on TLCO was alsoassessed.

METHODS

One hundred and fifty normal individuals,60 healthy sedentary male subjects (31 non­smoker and 29 smokers) and 90 females, 18-50years of age, volunteered for this study. Healthysubjects were either healthy relatives of patientsor medical students or employees working atPandit B.D. Sharma PGIMS,Rohtak (India).In the smokers, tobacco consumption amountedto 10-15 pack years (moderate smokers). All ofthem were free from any cardiorespiratorydisease, as assessed by history and dinicalexamination of subjects. The smokers wereasked to abstain from smoking for at least twohours before reporting to the Respiratory

Indian J Physiol Pharmacol 1996; 40(3)

Laboratory at 9 AM in the morning. Smokerswere not allowed to smoke till the study wascompleted on that day. The tests wereperformed in a sitting position between 9-11AM at least one hour after a light breakfast.Subjects with hemoglobin less than 12 grn/dlwere excluded from this study. Routinepulmonary function tests including FVC,FEV1%, PEFR and EFR 2[,.27 were measured ineach subject from flow volume curve usingMorgan Transfer Test Model C and ComputerMagna 88 (P.K. Morgan U.K.) to confirmwhether any significant airway obstruction hadalready set in.

Two measurements of TLCO using singlebreath technique were made at an interval of15 min between them (5). This was followed bymeasurement of transfer factor for CO by steadystate technique (TLCOss) (6), using Rahn andOtis end-tidal sampling device for obtainingalveolar air (7), in the same subjects, on thesame apparatus (Morgan Transfer Test ModelC and Computer Magna 88).

All the results were expressed under STPDconditions. Correlation coefficient between ageand TLCOSR' age and TLCOss were calculatedusing standard statistIcal methods.

RESULTS

Ninety females, 31 non-smoker and 29smoker males, matched for age (±1 year), height(±2 ems), socio-economic status and physicalactivity, completed this study. Mean ± SD of

TABLE I : Ventilatory functions and transfer factor for CO in male. and femals.

ParameterMales P vallie Females P value

Non·smokers (/) Smokers (Il) (I vs. ll) (Ill) (I vs. III

n 31 29 90Age (yrs) 29.54 ± 8.87 30.08 ± 7.74 NS 29.24 ± 9.61 NSFVC(L) 3.90 ± 0.78 3.80 ± 0.62 NS 2.87 ± 0.48 <0.001

FEV, % 88.71 ± 5.30 83.30 ± 6.21 <0.01 82.79 ± 8.50 <0.001PEFR(Usec) 8.76 ± 1.97 7.96 ± 1.62 <0.05 4.79 ± 1.68 <0.001EFR

z5•70 (Usee) 4.00 ± 0.62 3.82 ± 0.58 NS 2.94 ± 0.91 <:0.001

TLCOsu (#) 30.43 ± 4.89 27.29 ± 4.54 <0.01 26.13 ± 3.60 <0.001TLCOs. (#) 19.47 ± 5.26 16.69 ± 3.27 <0.01 18.24 % 3.78 <0.05

Values are Mean ± S.D. Statistical analysis USIng unpaired t-test. # - (mVrnmHg/minJ.

Indian J Physiol Pharmacol 1996; 40(3)

data for age and transfer factor for carbonmonoxide (both TLCO and TLCO ) of

• SB sssubjects under study is shown in Table I.Correlation of age with TLCO and TLCO

SB ss

TLCOSB and TLCOss in Normal Subjects and Smokers 269

DISCUSSION

Measurement of TLCOSB

is commonly usedas a part of diagnostic lung evaluation. A lackof uniform technique and standard values has

TABLE II : Correlation coefficient (r) between different .parameters.

TLCOSB P value TLCOss PValue

-0.70:1 .,U.UOl --Q.4111 _lI,lIl

0.349 <0.05

-0.360 <0.05 -0.355 <0.05

0.383 <0.05

0.300 <0.01 0.380 <0.01

0.340 <0.001

~-g• SMOKERS ,MALES

o NON-SMOKERS

•

Males (n ... 60)Non-smokers (n =31J

AgeTLCOSB

Smokers (n = 2!j)AgeTLCOSB

Females (n = 90)AgeTLCOSB

4000

35.00

c'E 3000a~ 2500

E

1 2000

m1500o':3 1000l-

5.00

FEMALES

10.00 20.00 30.00

TLCO-SS (ml/mmHglmin)

40.00

40.00

35.00

c'E 30.00

a~ 25.00

Ei 2000

ffi 15.00o~ 10.00l-

5.00

0.00

0.00

., . ,. ....,..~.. '.. ." ~~'/ e._ (').. ' ..

... tC..• •

10.00 2000 30.00

TLCO-SS (ml/mmHg/minl

40.00

Fig. 1 : Comparison of TLCOSB

with TLCOss in both male and female subjects.

and between TLCOSlJ

and TLCOss is shown inTable II. Fig 1 shows the correlation of TLCOSB

with TLC0s..<; in female as well as male subjects.We observed that performing TLCO ssby subjects was easier than measurement

of TLCOSB '

led different investigators to recommend thateach lab must establish its own normal values(1, 2, 8). Mahajan et al (9) reported that forsatisfactory inter-laboratory comparison ofvalues of TLCO

SB' it must be measured at

maximal alveolar volume and shouldbe expressed as TLC0 1ZO (at constant p0 2 of

270 Mahl\ian et al

120 mmHg) by using a correction factor. TLCOssis measured during spontaneous breathing atwhatever lung volume the subject adopts underconditions of measurement. Therefore the lattermay be more relevant to normal physiologicalconditions of gas exchange than obtained bysingle breath technique which requires breath­holding at total lung capacity (5, 9).

In this series, diffusion capacity measuredby TLCOSB is statistically greater than TLCOssvalues (Table I). It is well documented thatsmoking promotes unequal ventilation (3); henceincreasing unequal ventilation causes anincreasing underestimation with single breathmethod. This results in TLCO

SBgradually being

equal to TLCOss at vital capacity (10).

FEV1%, PEFR, TLCOSB and TLCOss arestatistically significantly lower in smokers ascompared to non-smokers (Table I) in agreementwith other authors (5, 8). Reduction in transferfactor in smokers is due to the destruction ofinteralveolar septae with consequent reductionin diffusion surface area. In this study, insmokers TLCOSB and TLCOss are lowered by10.3% and 14.2% respectively as compared withnon-smokers. This is statistically significant(P<0.OO1).

Indian J Physiol Pharmacol 1996; 40(3)

In female subjects, both TLCOSB and TLCOssare significantly lower as compared to non­smoker males while TLCOsII is still lower thanthat seen in even smoker males (Table I). TableII shows that in males a statistically significantnegative correlation of age with 'FLCO wasobserved similar to earlier report (11); maximalTLCO was attained at the age of 18-20 yearswhich gradually declined later. On the otherhand, in female subjects a statistically significantpositive correlation of age with TLCO wasobserved, as diffusion functions showeda small rise with age to attain maximal value in31-35 years age group and then started decliningwith advancing age (unpublished observations).In this series, a good correlation was observedbetween two methods measuring TLCO in bothnon-smoker and smoker -males (P<O.05). Infemales, the correlation of two methods wasstill more significant (P<O.OOl, Table II, Fig. 1),

We conclude that TLCOss is lower thanTLCOSB• In agreement with Bore et al (12),both of these measurements of TLCO appearvalid in normal subjects, though TLCOSB

measurement is easier to perform with theadvancement of technology.

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