DOI 10.1378/chest.97.6.1386 1990;97;1386-1389Chest

 V Vijayan, K V Kuppurao, P Venkatesan, K Sankaran and R Prabhakar capillary blood volume in tropical eosinophilia.Pulmonary membrane diffusing capacity and

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1386 Diffusing Capacity and Capillary Blood Volume in Tropicai EOSinOPhIIIS (YiJeyan et a!)

Pulmonary Membrane Diffusing Capacityand Capillary Blood Volume in TropicalEosinophilia*Vannan-kandi Vzja�zn, M.B., M.D., F.C.C.P; Kaleker V Kuppurao, M.Sc.;

Perumal Venkatesan, M.Sc., M.Phil; Kameswaran Sankaran B.Sc.; and

Ramachandra Prabhakar, M.B., M.D.

Pulmonary membrane diffusing capacity (Dm) and pulmo-

nary capillary blood volume (Vc) measurements werecarried out in 21 patients with untreated tropical eosino-phuia and 21 healthy controls matched for age, sex, height,and smoking habit. The mean single breath transfer factor(Dee) and the mean membrane diffusing capacity weresignificantly lower (p<O.OOl) in patients with tropical eosin-

ophilia compared with control subjects. However, the meancapillary blood volume was not significantly different(p>O.2). The positive correlations between Dm and transferfactor (r = 0.825), between Dm and effective alveolar vol-ume (VA) (r0.721), and between Dco and VA (r0.774)

were also highly significant (p<O.OOl) in study patients

prior to treatment. These data suggest that reduction insingle breath transfer factor in untreated tropical eosino-

philia may be due to a reduction in membrane diffusing

capacity, which in him may be due to a reduction in area

of membrane available for diffusion, as evidenced by thesignificantly reduced VA (p<O.OO1) in these patients Sincepulmonary capillary blood volume was normal, the pul-monary perfusion was within normal limits. Following threeweeks of treatment with diethylcarbamazine citrate, al-

though there was a significant rise in single breath transferfactor (p<O.OO1) and membrane diffusing capacity(p<o.05), both Dco (p<O.Ol) and Dm (p<O.Ol) continued

to be significantly lower than those of control subjects.

However, pulmonary capillary blood volume did not showany change (p>O.2). (Chest 1990; 97:1386-89)

TE = tropical eosinophflia; Dm pulmonary membrane diffus-ing capacity; Vc = pulmonary capillary blood volume;VA alveolar volume; DL transfer factor

P revious studies”2 have shown that the predominant

pulmonary function abnormality in patients with

untreated tropical eosinophilia (TE) is a reduction in

transfer factor (DL). The studies of Roughton and

Forster�’ have demonstrated that the transfer factor isa function of the diffusing capacity of the alveolar

membrane (Dm), the volume of blood in the alveolar

capillaries (Vc), and the reaction rate of carbon mon-

oxide with oxyhemoglobin (0). Although it had been

reported that the membrane component (Dm) is

mainly reduced in interstitial lung diseases of various

etiologies,4 the occurrence of reduced transfer coeffi-

cient (Dco/VA) in 56 percent ofpatients with untreated

TE2 suggested that there may be changes in pulmonary

capillary blood volume as well. Therefore, a study

was undertaken to evaluate the membrane diffusing

capacity (Dm) and pulmonary capillary blood volume

(Vc) in TE and the effect of treatment on these

parameters. To our knowledge, this study is the first

of its kind in which Dm and Vc measurements were

*From the Cardio-Pulmonary Medicine Unit, Tuberculosis Re-

search Centre, Indian Council of Medical Research, Madras,India.Part ofthe material included in this paper has been submitted byone ofus (VK\T) for a Ph.D. thesis to the University of Madras.

Manuscript received August 4; revision accepted November 13.Reprint requests: Dt� Prabhakar, Directot Thberculosis Research

Centre, Madra� India 600031

carried out in TE.

SUBJECTS AND METhODS

Twenty-one patients with TE with symptoms of less than six

months’ duration and 21 healthy control subjects, matched for age,

sex, height, and smoking habits were studied. The diagnosis of TEwas based on the criteria of residence in the filarial endemic area

of Madras city, respiratory symptoms such as cough, dyspnea, andnocturnal wheezing, chest roentgenogram infiltrates; peripheralblood eosinophilia with absolute counts of �2,000 cells/cu mm,high serum titers of antifilarial IgG, and a favorable response todiethylcarabamazine citrate.’ All normal control subjects were of

South Indian ethnic origin. None had respiratory symptoms or

abnormal physical findings. All had normal chest roentgenogramsand normal pulmonary function. None had elevated peripheral

blood eosinophil values and none was taking any medication.

All patients were offered diethylcarbamazine citrate 6 mg/kg ofbody weight per day orally for 21 days and 19 patients consumed

the drug regularly. The transfer factor and its subdivisions wererepeated at one month in these 19 patients who had completed

treatment. Testscould notbe repeated in the remainingtwo patients.

All pulmonary function tests, including single breath carbon

monoxide diffusing capacity (Dco), membrane diffusing capacity(Dm), and pulmonary capillary blood volume (Vc) measurementswere carried out (Transfer Test Model C, P.K. Morgan Ltd.

Chatham, U.K.). All the subjects attended the clinic between 7:30and 8 AM and the single breath measurements were performed after12 noon to make sure that none of the smokers had smoked tobacco

at least four hours preceding the test. All single breath diffusingcapacity measurements in this study were performed by previously

reported methods.’ Initially the single breath Dco and effective

alveolar volume (VA) in each subject were determined, in duplicate,

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RELATIONSHIP BETWEEN OM AND TLCO

.�a.6Jr

.�!

9

7.5

6

4.5

Table 2-Ejfrct OfTreatmen* on Transfer Factor and Its

Subdivialons in Ibtients with 1�opkd Eosinophilia (TE)(Mean ± SEM)

#{149}NS = not significant; TE tropical eosinophilia. *NS = not significant.

CHEST I 97 I 6 I JUNE, 1990 1387

while breathing a mixture of 14 percent helium, 0.288 percent

carbon monoxide, 18 percent oxygen, and the remainder nitrogen.The difference between the measurements was less than 5 percent

and the highest value was used for analysis.’ This was followed by

the determination of Thu and Vc by performing two single breath

Dco measurements at two levels of alveolar oxygen tension: one at

the level obtained during breathing oxygen and the other breathing

alt First, the subject breathes oxygen for five minutes to raise the

alveolar oxygen tension and this is followed by determination ofsingle breath Dco by inhaling a mixture ofl4 percent helium, 0.288

percent carbon monoxide, and the remainder oxygen. The subjectthen breathes air fur ten minutes to wash out the remains of previous

inspiration from the lungs and performs another single breath Dco

maneuver by inhaling a gas mixture of 14 percent helium, 0.288

percent carbon monoxide, 18 percent oxygen, and the remainder

nitrogen. (All gas mixtures in this study were provided by PK.

Morgan Ltd. Chatham, U.K.) Hemoglobin which was measured in

grams per deciliter, was measured in each subject. The Dm and Vc

were then calculated.

We had made serial measurements of Dco, VA, Dm, and Vc in

healthy volunteers at monthly intervals. The coefficients of variation

for Dco and VA were less than 5 percent and for Dm and Vc they

were less than 10 percent.

All data were presented as mean ± SEM. Statistical analysis was

performed using two-tailed Student’s paired t-test. Correlation and

regression coefficients were obtained by the standard linear regres-

sion procedure. A p value of <0.05 was considered significant.

RESULTS

All patients with TE and control subjects were male

and seven subjects in each category were smokers.

The mean (± SEM) age in patients with TE was

24± 1.5 years, height was 166.0± 1.6 cm, and weight

was 47.1 ± 1.4 kg. The mean (± SEM) age in control

subjects was 24.0± 1.6 years, height was 167.0± 1.6

cm, and weight was 51.1 ±2.0 kg. The hemoglobin

level at diagnosis varied from 11.0 to 15.6 g/dl in

patients with it (mean ± SEM, 12.9 ± 0.3 g/dl) and

in control subjects it was 11.0 to 16.9 g/dl (mean ±

SEM, 13.9±0.3 g/dl), and this difference was just

significant statistically (p = 0.04). The mean posttreat-

ment hemoglobin level(13.1 ±0.3 g/dl) was not signif-

icantly different from mean pretreatment level

(12.9±0.3 g/dl, p<O.2) and control values

(13.94±0.37 g/dI; p>O.05) (‘I#{224}ble1).

The single-breath Dco, VA, Dm, and Vc measure-

ments in patients and control subjects are given in

Table 1. The mean Dco (‘FE, 7.0 ± 0.3 mmol/kpa/min;

control, 9.4±0.5 mmol/kpa/min; p<O.OOl) and mean

Table 1-lbansfrr Factor and its Subdivisions in Thtientaat Diagnosis and Control Subjects (Mean ± SEM)*

Control

Subjects

(n=21)

Patients with TB

at Diagnosis

(n21) Significance

Dco, mmol/kpa/min 9.4±0.5 7.0±0.3 p<O.OOl

VA, L 4.4±0.2 3.6±0.2 p<O.Ol

Dm, mmol/lcpa/min 13.4±0.6 9.4±0.6 p<O.001Vc, ml 78.0±4.5 74.8±4.8 NS

PuLmonary membrane diffusing capacity (Dm11rn . mol./k. poimt.j

FIGURE 1. Relationship between Dm and TLCO.

VA (FE, 3.6±0.2 L; control, 4.4±0.2 L; p<O.Ol)

were significantly lower in patients with TE compared

with control subjects. The mean membrane diffusing

capacity was also significantly lower in untreated TE

(TE, 9.4±0.6 mmol/kpa/min; control, 13.4±0.6

mmol/kpa/min; p<O.OOl). However, the mean pul-

monary capillary blood volume was not significantly

different from control subjects (TE, 74.8 ± 4.8 ml;

control, 78.0±4.5 ml; p>O.2).

In study patients, before treatment, there was

significant correlation between Dm and Dco

(r=0.825, p<O.00l, Fig 1) between Dm and VA

(r = 0.721, p<O.OO1), and between Dco and VA

(r = 0.774, p<O.OOl). However, there was no correla-

tion between Vc and Dco (r = - 0.086) and between

Vc and VA (r = - 0.060) (Table 2).

All patients had shown remarkable clinical response

to three weeks oftreatment with diethylcarbamazine.

There was also a significant fall (p<0.001) in the mean

peripheral blood eosinophil value from 11,540± 1,389

cells/cu mm (range, 3,100 to 26,475 cells/cu mm) to

2, 160 ± 429 cells/cu mm (range, 150 to 7,830 cells/cu

mm) following treatment. On comparison with paired

observation in 19 patients who had completed treat-

ment successfully, the mean Dco (pretreatment,

6.8±0.4; one month, 7.8±0.4; p<O.OOl), the mean

VA (pretreatment, 3.7 ± 0.2; one month, 4.0 ± 0.2;

p<O.OOl), and the mean Dm (pretreatment 9.6 ± 0.6;

Patients with Patients with

TEat TEat

Diagnosis One Month

(n = 19) (n 19) Significance

Dco, mmol/kpa/min 6.8±0.4 7.8±0.4 p<O.OOl

VA, L 3.7±0.2 4.0±0.2 p<O.OOl

Dm, mmol/kpa/min 9.6±0.6 11.3±0.7 p<O.05

Vc, ml 70.2±3.3 73.1±4.5 NS

 © 1990 American College of Chest Physicians by guest on July 10, 2011chestjournal.chestpubs.orgDownloaded from

1388 Diffusing Capacity and Capillary Blood Volume in TrOpical Eosinophllia (V!jayan eta!)

one month, 11.3±0.7; p<O.05) had shown a signifi-

cant rise following treatment (l#{224}ble2). However, there

was no difference in mean values of Vc following

treatment (pretreatment, 70.2 ± 3.3; one month,

73. 1 ± 4.5; p>O.2). The mean posttreatment values of

Dco, VA, and Dm continued to be significantly lower

than those ofcontrols (p<O.Ol for each comparison).

DISCUSSION

The significant reduction in membrane diffusing

capacity without a reduction in pulmonary capillary

blood volume suggests that the reduction in Dco in

TE may be due mainly to a reduction in membrane

diffusing capacity. The significant correlation of Dm

with Dco and VA further suggests that the reduction

in the area of membrane available for diffusion as

evidenced by a significantly reduced VA may he

responsible for the lower Dco and Dm in untreated

TE . These findings are in agreement with the previous

studies of components of the transfer factor in which

it had been shown that there is a significant correlation

between Dm and VA; and Dco is dependent on lung

volume and Dm.7

As our study subjects are not anemic or polycythe-

mic, there may not he any abnormal influence of

hemoglobin on 08 Similarly, all smokers in this study

were light smokers (smoking less than five cigarettes

per day for less than two years) and none had smoked

for at least four hours preceding the test. Since smoking

produces mainly a reduction in pulmonary capillary

blood volume,8 the observation of normal pulmonary

capillary blood volume in these patients suggests that

a mild degree of smoking by a proportion of patients

did not influence the results of the study.

A significant reduction in Dm alone, without a

reduction in Vc, had been reported in patients with

systemic sclerosis without chest roentgenographic

changes9 and in patients with submassive pulmonary

embolism . ‘#{176}However, in patients with systemic scle-

rosis with an evident pulmonary localization as shown

by chest roentgenographic changes,9 there was a

reduction in both Dm and Vc. Thus, a reduction in

both Dm and Vc was observed in patients with

systemic sclerosis as the disease progressed to have

radiologic localization. The demonstration of degen-

erating microfilariae in pulmonary parenchyma” and

also the histopathologic observation of mild to mod-

erate thickening ofboth pulmonary arteries and veins

in a patient with a TE with a three-year duration of

symptoms’ suggested that there might be changes in

pulmonary capillary blood volume that might have

contributed to the reduction in Dco. Therefore, a

reduction in membrane diffusing capacity alone, with-

out a significant reduction in pulmonary blood volume

in our patients with TE with symptoms less than sixmonths’ duration, may suggest that the disease might

not have progressed to produce reductions in both

DmandVc.

The reduction in Dm in our study may be due to

the inflammatory changes produced by the abnormally

accumulated eosinophils in the lower respiratory

tract’2 and the eosinophils have been shown to produce

toxic mediators injurious to pulmonary parenchyma.’3

All our patients had symptoms less than six months’

duration at diagnosis and hence the “injury” that may

result from eosinophilic alveolitis’2”4”5 may not be

severe enough to have any deleterious effect on the

pulmonary capillary blood volume, although it had

produced a signfficant reduction in Dm.

There was a remarkable clinical response to a

standard three weeks of treatment with diethylcar-

bamazine citrate and this had resulted in a significant

rise in Dco, VA, and Dm. However, these values did

not return to normal despite treatment and the reason

for the persisting abnormality is not immediately

apparent. Since all our study patients had their first

episode of TE of less than six months’ duration, the

persisting abnormality at one month was not due to

the development of some degree of permanent abnor-

mal pulmonary function from a previous episode of

this disorder. It has been shown previously that there

was a signfficant reduction in lung eosinophils even

with 6 to 12 days of treatment with diethylcarbama-

zine,’2 and there was a signfficant reduction in periph-

eral blood eosinophils at one month in this study. The

suppression ofthe eosinophilic inflammatory process’s

in the lower respiratory tract, therefore, might have

resulted in an improvement in Dco and Dm.

In summary, patients with TE presenting with

shorter duration ofsymptoms at diagnosis (<6 months)

had a significant reduction in both Dco and Dm. The

pulmonary perfusion was normal, as evidenced by a

normal pulmonary capillary blood volume. Thus, the

reduction in transfer factor in TE may be due to a

reduction in membrane diffusing capacity. Treatment

with diethylcarbamazine citrate resulted in a signifi-

cant improvement in Dco and Dm, but these param-

eters did not return to normal despite treatment.

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DOI 10.1378/chest.97.6.1386 1990;97; 1386-1389Chest

V Vijayan, K V Kuppurao, P Venkatesan, K Sankaran and R Prabhakartropical eosinophilia.

Pulmonary membrane diffusing capacity and capillary blood volume in

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