Single breath carbon monoxide diffusing capacity (TLCO) measurements were made

in 50 acute untreated tropical eosinophilia (TE) patients. Forty-four (38%) patients

had a low diffusing capacity (< 85% predicted) which was moderately severe (40-

70% predicted) in 22 (44%) patients. Diffusion per lire of alveolar volume (KCO)

was reduced (< 85% predicted) in 28 (56%) patients. The effective alveolar volume

(VA) was reduced (< 85% predicted) in 30 (60%) patients and there. was highly

signfiicant positive correlation between VA and TLCO (r=0.847, P<0.001). The

reduction in TLCO, therefore, in our patients may be due to a combination of reduction

in the area of membrane available for diffusion and to the involvement of

pulmonary capillaries, as evidenced by low VA and KCO. The reduction in TLCO in

acute TE patients may be due to acute inflammatory changes produced in the lung

parenchyma by eosinophils. However, there was no correlation between peripheral

blood eosinophils and diffusing capacity. Further studies are required to clarify

whether locally accumulated eosinophils in the lung have any relationship with

diffusing capacity

Kuppurao, K V

Prabhakar, R

Sankaran, K

Venkatesan, P

Vijayan, V K

NIRT Institutional Repository

Ind ian J  Chest  D is  & A l l i  Sc iVo l .  30  No .2  pp  71 -77  (1988)DIFFUSING CAPACITY IN ACUTE UNTREATEDTROPICAL EOSINOPHILIAV.K. VIJAYAN , K.V. KUPPU RAO, K. SANKARAN, P. VENKATESAN andR. PRABHAKARCardio-pulmonary Medicine Unit, Tuberculosis Research Centre,Indian Council of Medical Research, MadrasSingle breath carbon monoxide diffusing capacity (TLCO) measurements were madein 50 acute untreated tropical eosinophilia (TE) patients. Forty-four (38%) patientshad a low diffusing capacity (< 85% predicted) which was moderately severe (40-70% predicted) in 22 (44%) patients. Diffusion per lire of alveolar volume (KCO)was reduced (< 85% predicted) in 28 (56%) patients. The effective alveolar volume(VA) was reduced (< 85% predicted) in 30 (60%) patients and there. was highlysignfiicant positive correlation between VA a d TLCO (r=0.847, P<0.001). Thereduction in TLCO, therefore, in our patients may be due to a combination of re-duction in the area of membrane available for diffusion and to the involvement ofpulmonary capillaries, as evidenced by low VA and KCO. The reduction in TLCO inacute TE patients may be due to acute inflammatory changes produced in the lungparenchyma by eosinophils. However, there was no correlation between peripheralblood eosinophils and diffusing capacity. Further studies are required to clarifywhether locally accumulated eosinophils in the lung have any relationship withdiffusing capacity.Tropical eosinophilia (TE) is a systemic disorder involving many organs and tissuesin which the pulmonary manifestations are predominent1. The latter are characterisedby cough, dyspnoea, nocturnal wheezing and diffuse reticulonodular infiltrates on chestradiographs, and pulmonary function tests show a combination of obstructive and rest-rictive ventilatory defect2-10. There is associated with marked peripheral bloodeosinophilia and elevated serum concentrations of filarial specific antibodies4. Thehistopathological observation of dense accumulation of eosinophils in the interstitialtissue; which had shown considerable thickening, suggested that there was a likelihoodof diminished diffusing capacity or transfer factor in tropical eosinophilia2. A decreasein diffusing capacity by steady state end tidal sampling method was reported byPoh11. Because of rarity of published reports of studies on transfer factor for carbonmonoxide (TLCO) in TE, we report our findings of single breath carbon monoxidediffusing capacity in acute tropical eosinophilia.CORRESPONDENCE : Dr V.K. Vijayan, Cardio-pulmonary Medicine Unit, TB Research Centre(ICMR), Madras-600 031.7112 Tropical eosinophiliaAs eosinophils are known to injure normal lung parenchymal cells, alveolarepithelial cells, fibroblasts, pleural mesothelial cells and bronchial epithelial cells12-14,it may be hypothesised that the decrease in diffusing capacity in these patients is due toinflammatory changes produced in the interstitial tissues by the abnormal accumulationof eosinophils and/or its toxic mediators. Since peripheral blood eosinophilia is the hall-mark of TE, the study was also utilised to find out whether there was any relationshipbetween the eosinophils in the peripheral blood and single breath diffusing capacity.Material and MethodsFifty patients with recent onset of symptoms of one week to 6 months duration wereinvestigated. They fulfilled the diagnostic criteria of TE, i.e. residence in the endemic areaof Madras city, respiratory symptoms such as cough, dyspnoea and nocturnal wheezing,chest x-ray infiltrates, peripheral blood eosinophilia of > 2000 cells/cmm, high serumtitres of antifilarial IgG and a positive response to diethyl carbamazine therapy.Clinical evaluation of each patient included detailed history, physical examination,chest x-ray and IgG filarial antibody determinations.The one-second forced expiratory volume (FEV1), forced vital capacity (FVC),FEV1/FVC per cent, total lung capacity (TLC) by helium dilution method, single breathcarbon monoxide diffusing capacity (TLCO) measurements15 were carried outon PK Morgan (U.K.) Transnfer Test Model C using Data Dec computer.A minimum of three consistent readings in the case of spirometry and twoin the case of TLC measurements were obtained. The highest value obtained wasused for analyses and readings were corrected to body temperature, ambientpressure and full saturation with water vapour (BTPS). Epidemiology standardisationproject16 recommendations were followed for the measurement of single breathdiffusing capacity. The patients were seated comfortably and nose clips wereapplied. The patients were instructed to exhale completely to residual volume andon instruction to inhale a volume of test gas (Helium 14%, Carbon monoxide 0-28%,Oxygen 18% and remainder Nitrogen) rapidly and maximally to TLC, to hold the breathfor 10 seconds and finally to exhale rapidly. The inspired volume and breath holdingtime (usually between 9-11 seconds) were noted. In ail tests, the inspired volume wasadjusted to 90% of previously determined FVC. After exhalation of a preset wash outvolume of at least 700 ml, the alveolar sample was collected in an empty sample bag forsubsequent analysis. In all patients, the tests were performed in duplicate withan intervalof at least 4 minutes. The difference between the measurements was less than 5% andthe highest value was used for analysis. The effective alveolar volume (VA) corrected toBTPS was measured by helium dilution during single breath carbon monoxide diffusingcapacity measurements15 and the transfer coefficient, i. . diffusion per litre of alveolarvolume (KCO) was calculated from the ratio of TLCO to VA.Studies had been undertaken in 249 normal subjects, using the PK Morgan (U.K.)Transfer Test Model C, to establish regression equations for predicting normal pul-monary function values in regional subjects. The predicted values of VA, TLCO and KCOV.K. Vijayan et al 73for this study are obtained from these regression-equations (unpublished data). Transferfactor was corrected to a standard haemoglobin concentration of 14.6 G/dl, using thefollowing equation17.TLCO (corrected)=TLCO (observed) x14.6 a + Hb(1 + a) Hbwhere Hb is the actual haemoglobin concentration in G/dl and ‘a’ is 0.7. The KCO (cor-rected) was calculated from the ratio of TLCO (corrected) to VA.The measured values of VA, TLC O and KCO  are considered normal, if they arewithin ± 15% of the predicted value18.ResultsThere were 45 males and 5 females in the study, 21 males and all females were non-smokers and 24 males were smokers. The mean age was 24.1 (SD 7.5) years (range12-48 years) and the mean height was 160.8 (SD 7.6) cm and the mean weight 45.0(SD 8.25) kg.The mean TLCO was 6.24±1.4 mmol/k.pa/mt (72±16% predictedand the mean KCO was 1.88±0.25 mmol/k.pa/mt/L (83.1±12.2% predicted).As there was no significant difference in the mean values of transfer factor andtransfer co-efficient between smokers and non-smokers, the data were pooled foranalysis.Normal TLCO was observed only in 6 (12%) patients and 22 patients (44%) hadmoderately severe diffusion defect (TLCO% predicted ranging between 40-70%). Twenty-eight patients (56%) had a reduction in transfer co-efficient (KCO), ncluding 7 (14%)with moderately severe reduction (Table 1).Table 1. Severity of diffusion defectPredictedObservedObserved40.0–70.0% 70.1–85.0% >85%TLCO 22 (4%) 6 (12%)KCO 21 (42%) 22 (44%)The mean haemoglobin concentration in 50 patients was 12.84±1.45 G/dl. Whenthe diffusing capacity was corrected to a standard haemoglobin concentration of 14-6G/dl. Low TLCO and KCO persisted in 37 (74%) and 19 (38%) patients. respectively evenafter correction of haemoglobin.As it was observed that the effective alveolar volume (VA) was reduced (<85%predicted) in 30 patients (60%), it was assumed that one of the mechanisms of reducedTLCO in these patients may be due to reduction in the surface area of membrane avail-able for diffusion. When VA was correlated with TLCO (Fig. 1), there was highly signi-ficant positive correlation between VA and TLCO (r= 0.847, P<0.001).74 Tropical cosinophiliaFig. 1. Showing relationship between effective alveolar volume and transfer factor in acute tropicaleosinophilia.Fig. 2. Showing relationship between blood absolute eosinophil count and transfer factor in acutetropical eosinophilia.V.K. Vijayan et al 75The absolute eosinophil count in these patients varied from 3100 to 23500 cells/cumm and most of them (90%) had absolute eosinophil count of > 5000 cells/cumm.As shown in Fig. 2, there was no correlation (r= – 0.164) between peripheral bloodeosinophils and transfer factor (TLCO).DiscussionThe pulmonary manifestations in acute tropical eosinophilia is inflammation of thelung parenchyma in persons highly sensitised immunologically to filarial parasites4.The diffusing capacity is reduced in patients with diseases of the lung parenchyma15,and reduced diffusing capacity in TE by steady state end tidal sampling method wasreported by Poh11. Impairment of diffusion in long standing cases of TE was suggestedby Udwadia3 on the basis of histopathological evidence of dense eosinophil accumu-lation in lung parenchyma. Our findings of reduced transfer factor by single breathmethod in acute untreated tropical eosinophilia corraborates the observation that thereis alveolitis in TE.The transfer factor is the resultant of changes in the diffusing capacity of thealveolar capillary membrane (Dm) and the volume of blood in the alveolar capillaries(VC) under the conditions of measurement15. Th  reduction in diffusing capacity in mostof our patients is not due to anaemia (concentration of haemoglobin range (10.1 to 15.6G/dl). Reduction in the effective accessible gas volume (VA) and reduction in carbonmonoxide transfer per litre of effective accessible gas volume (i.e., transfer coefficient,KCO) are the two mechanisms of reduced diffusing capacity18 and KCO provides someindication of the density of capillaries in the wall of the alveoli. Since we have not measu-red membrane diffusing capacity (Dm) and alveolar capillary blood volume (VC), specificreductions regarding these parameters cannot be made.In interstitial lung disease of various aetiologies, there is a low TLCO and KCO,especially the membrane component, and the mechanism of this reduction is still un-certain19. The highly significant positive correlation of TLCO with VA shows that thereduction in transfer factor in acute TE in our patients may be mainly due to reductionin alveolar volume. As it had been shown previously20,21 that TLCO decreases by 3%for every 8% reduction in TLC and that alveolar surface was related to VA1/3 in the rangeof 40-80% TLC, the reduction in the area of membrane available for diffusion, as evi-denced by low VA, may be mainly responsible for low TLCO in our patients, This maybe due to acute inflammatory changes in the lung parenchyma by the abnormal accumu-lation of eosinophils, which reduces the membrane area for diffusion. The reduction intransfer coefficient(KCO) in 56% of our patients indirectly shows that there are changesin pulmonary capillaries as well, as it had been shown that KCO provides some indi-cation of the density of capillaries in the wall of the alveoli18. Our results in TE are inagreement with the earlier morphometric studies in diffuse interstitial lung diseases22,where it had been shown that the decreased membrane area for diffusion was the mecha-nism for low TLCO and also that a decrease in pulmonary capillary blood volume maybe an additional contributory factor23. Our findings of high positive correlation of76 Tropical eosinophiliaTLCO with VA, along with reductions in VA and KCO in 60% and 56% of patients suggestthat both reductions in membrane area and pulmonary capillary blood volume contri-bute to the reduction in transfer factor in acute TE.There was no correlation between peripheral blood eosinophils and transferfactor (TLCO). It will be worthwhile to study whether the transfer factor is related tothe abnormally accumulated eosinophils in interstitial tissue, as shown histopathologi-cally2. We are continuing the study on these lines utilising bronchoalveolar lavage.AcknowledgementWe are grateful to Mrs Annamma Joy for nursing assistance and also to Sri R.S. Senand Mrs Shantha Sri Raghavan for secretarial assistance.References1. UDWADIA FE, JOSHI VV. A study of tropical eosinophilia. Thorax 1964; 19 : 548-554.2. UDWADIA FE. Tropical eosinophilia:  correlation of clinical, histopathologic and lung functionstudies. Dis Chest 1967; 52 : 531-538.3. UDWADIA FE. Tropical eosinophilia. In : Pulmonary Eosinophilia. Progress in Respiration Research.S. Karger, Basel, 1975; 35-155.4. NEVA FA, OTTESAN EA. Tropical (Filaria) eosinophilia. N Engl J Med 1970; 298 : 1129-11315. AZAD KHAN AK, PATRA RW, BANU SA, RABEE MF. Spirometry in tropical pulmonary eosino-philia. Br J Dis Chest 1970; 65 : 107-109.6. NASARAIAH MS. Pulmonary function in tropical eosinophilia. Thorax 1972; 27 : 85-187.7. RAY  D. Lung function in tropical eosinophilia. Ind Chest Dis 1974; 16 : 368-373.8. KAMAT SR, PIMPARKAR SD, STORE SD, WARRIER NVU, FAKEY  YC. Study of clinical, radiologicaland pulmonary function pattern and response to treatment in pulmonary eosinophilia. Ind J ChestDis and All Sci 1970; 12 : 91-101.9. ABDULLAH AK, SIDDIQUI MA, QUERESHI MA, AZIZ KHAN. Ventilatory impairment in tropicaleosinophilia and its comparison with asthma. Ind J Chest Dis and All Sci 1977 ; 19 : 82-87.10. MATHUR KS, NASRATH SP, KISHORE B, RASTOGI SP. A study of ventilatory function and arterialblood gases in tropical eosinophilia. Ind J Chest Dis and All Sci 1969 ; 11 : 1-4.11. POH SC. The course of lung function in treated tropical pulmonaryeosin philia. Thorax 1974; 29 :710-712.12. DAVIS WB, FELLS GA, SUN X GADEK JE, VENET A, CRYSTAL RG. Eosinophil mediated injury tolung parenchymal cells and interstitial matrix. J Clin Invest 1984; 74 : 269-278.13. WALLER PF, GOETZL EJ The human eosinophil: Roles in host defense and tissue injury. Am JPathol 1980; 100 : 793-820.14. GLEICH GJ, LOEGERING DA. Immunobiology of eosinophils. Ann Rev Immunol 1984; 2 : 429-459.15. COTES JE. Lung function at different stages in life including reference values. In : Lung Function.Assessment and Application in Medicine. Black Well Scientific Publication, Oxford, 3rd Edition;1975; -pp 233-234, 243-245, 356-360, 384-391.16. FERRIS BG. Epidemiology standardisation project (Editorial). Am Rev Respir Dis 1978; 118 (Part 2):62-72.V.K. Vijayan et al 7717. COTES JE, DABBS JM, ELWOOD PC, HALL AM, MCDONALD A, SAUNDERS MJ. Iron deficiencyanema, its effects on transfer factor for the lung (diffusing capacity) and ventilation and cardiacfrequency during sub-maximal exercise. Clin Sci 1972; 42 : 325-335.18. Denison DM. Physiology. In : Clinical Investigation of Respiratory Disease. T.J.H. Clarke, Chapmanand Hall, London, 1981; pp 33-94.19. DAVIES NJH, DENISON DM. What does the transfer of carbon monoxide mean ? Br J Dis Chest1982; 76 : 105-124.20. LIPSCOMB DJ, PATEL K, HUGHES JMB. Interpretation of increases in the transfer coefficient forcarbon monoxide (TLCO/VA or KCO). Thorax 1978; 33 : 728-733.21. GIL J, BACHOFEN H, GEHR P, WEIBEL ER. Alveolar volume-surface area in air and saline filledlungs fixed by vascular perfusion. J Appl Physiol 1979; 47 : 990-1001.22. DIVERTIC MB, CASSAN SM, O’BRIEN PC et al. Fine structural morphometry of diffuse lungdisease with abnormal blood-air gas transfer. M yo Clin Proc 1976; 51 : 42-47.23. WEINBERGER SE, JOHNSON TS, WEISS ST. Use and interpretation of the single breath diffusing capa-city. Chest 1980; 78 : 483-488.

Diffusing capacity in acute untreated tropical eosinophilia

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