Pulmonary function test in
Tropical Pulmonary Eosinophilia
Kumar R1, Mourya S2
1Dr Ratan Kumar, Assistant Professor of Pulmonary Medicine, L N Medical
College, Bhopal, MP,2Dr Sudhir Mourya, Associate Professor of
Medicine, Index Medical College, Indore, MP, India,
Address for
correspondence: Dr Ratan Kumar, Email:
ratan_vaish@yahoo.co.in
Abstract
Introduction:
Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever
and eosiniphilia seen predominantly in the Indian subcontinent and
other tropical areas. The syndrome results from immunologic
hyper-responsiveness to human filarial parasites, Wuchereria bancrofti
and Brugia malayi. Absolute eosinophilia counts are usually more than
3,000 cells/mm3. Lung functions are severely compromised. Pulmonary
function tests may show a mixed restrictive and obstructive abnormality
with a reduction in diffusion capacity. The mean values of expiratory
flow rates were significantly decreased. Oral DEC (6 mg/kg per day) for
3 weeks is treatment of choice. Methods:
A total of 61, clinic-radiologically and haematologically suspected
cases of tropical pulmonary eosinophilia were included in study along
with 39 healthy controls. Pulmonary functions, which included forced
vital capacity (FVC), forced expiratory volume in one second (FEV1),
FEV1/FVC Ratio, maximum mid expiratory flow rate (MMEFR) and peak
expiratory flow rate (PEFR) were observed in study cases and control. Results: The mean
values ±S.D. of all spirometric parameters showed low value
in cases in comparison to control. Statistically all parameters showed
highly significant difference (‘p’ value were
<0.001) except in FEV1/FVC ratio (‘p’ value
was >0.05). After the treatment with DEC the mean values
± S.D. of all parameters in cases showed improvement but the
values were remained still below the control value. Conclusion: This
disease, if left untreated or treated late, may lead to long-term
sequelae of pulmonary fibrosis or chronic bronchitis with chronic
respiratory failure.
Key words:
Tropical Pumlonary eosinophilia, Eosinophilia, Pulmonary function test,
Diethylcarbamazepine.
Manuscript received:
22nd Mar 2014, Reviewed:
25th Mar 2014
Author Corrected:
3rd April 2014, Accepted
for Publication: 7th May 2014
Introduction:
Tropical pulmonary Eosinophilia is an occult form of filariasis and is
characterised by paroxysmal cough, breathlessness, nocturnal wheezing,
diffuse reticulonodular infiltrates in chest X-rays and marked
peripheral blood eosinophilia [1-4]. The syndrome results from
immunologic hyper-responsiveness to human filarial parasites,
Wuchereria bancrofty and Brugia malayi [4]. The term tropical pulmonary
eosinophilia (TPE) was first coined by Weingarten in 1943. He described
81 patients with a syndrome of wheezing, fever, eosinophilia and
bilateral mottling of the lungs [5]. Tropical Pulmonary Eosinophilia is
commonly seen in areas endemic for filariasis i.e. in the Indian
subcontinent, South East Asia, South America and Africa [2, 6 ,7]. In
India, it is mostly found around the coastal regions from Maharashtra
to Kerala and West Bengal to Tamil Nadu [2]. The prevalence of TPE in
various settings in India has varied from 0.5 per cent among children
in TamilNadu 10 to 9.9 per cent among jail inmates in Patna [8]. Some
cases are also reported in non endemic countries because of travel to
or immigration from endemic areas. In fact, persons travelling to
endemic areas may be more prone as they lack natural immunity to
filarial antigens [9]. It has been estimated that at least 120 million
persons are infected with mosquito-borne lymphatic filariasis worldwide
[10]. It is seen in less than 1% of filarial infection [11]. The
disease occurs predominantly in males, with male to female ratio of 4:1
and is mainly seen in children and young adults between the age 15
years and 40 years [2-4].
Sputum is usually scanty, viscous and mucoid. Sputum often shows clumps
of eosinophils. Bilateral scattered rhonchi and rales may be heard on
auscultation. Leukocytosis with an absolute increase in eosinophils in
the peripheral blood is the hallmark of TPE. Spontaneous fluctuations
in the eosinophilia count can occur. Absolute eosinophilia counts are
usually more than 3, cells 000 /mm3 and may range from 5,000 to 80,000.
Erythrocyte sedimentation rate is elevated in 90% of cases and returns
to normal following specific treatment [4]. Microfilariae are rarely
seen in the peripheral blood. The chest radiological features of TPE
include reticulonodular shadows predominantly seen in mid and lower
zones and military mottling of 1–3 mm in diameter often
indistinguishable from miliary tuberculosis [2]. Radiologic findings
very often regress on treatment with DEC but many patients may show
residual changes [12].
Lung function changes
Spirometry is usually mixed restrictive and obstruction which may be
mild to moderate in degree [2, 13]. In a study by Kuppurao et al the
mean values of expiratory flow rates were significantly decreased in
untreated TPE and while there was improvement with treatment, it was
still below normal at one months [14]. Udwadia had reported a pure
restrictive pattern on spirometry in 70 per cent patients and mixed
disorder in 30 percent [2]. Vijayan et al also reported a low transfer
factor for carbon monoxide (TLCO) as measured by the single breath
method [15]. The standard treatment recommended by the World Health
Organization for treatment of TPE is oral DEC (6 mg/kg per day) for 3
weeks [16]. One month after the start of the treatment most patient
show marked symptomatic and radiographic improvement and significant
improvement in almost all aspects of lung functions including FEV1,
FVC, TLCO, expiratory flow rates [12,17-19].
Material
& Methods
Present study was carried out in patients attending the Out Patients
Department (O.P.D) and admitted in T.B. and chest ward of S.R.N.
Hospital, Allahabad. The criteria for the selection of patients for
inclusion in the present study were followed as described by Donohugh
(1963).
Major criteria (Donohugh,
1963)
A. Pulmonary symptoms: an insidious dry, paroxysmal cough,
especially nocturnal with breathlessness and wheezing.
B. Peripheral blood eosinophilia count greater then 2000/mm3.
C. Positive filarial complement fixing antibody.
D. Response to specific therapy with diethyl carbamazine, 6mg/kg body
weight (three times a day ) for six days.
Minor criteria (Donohugh,
1963)
A. Recent stay in an endemic area.
B. Age and sex affected (male in second and third decade).
C. Sibilant or sonorous rhonchi on basis.
D. Raised erythrocyte sedimentation rate (ESR)
D. Accompanying non specific symptoms of malaise, fatigue,
anorexia, weight loss.
Selection of the cases
1.Age above 10 years
2.Patients of both sexes
3.Clinico-radiologically and haematologically suspected cases of
tropical pulmonary eosinophillia.
The diagnosis of TPE is considered to be positive if all the four major
criteria or three major and at least three minor criteria are
fulfilled. In our study facility of filarial complement fixing antibody
test, was not available, so those patient who fulfilled at least three
major and three or more minor criteria, were consider as a
case of Tropical Pulmonary Eosinophilia. Patients with a past history
of chronic bronchitis, bronchial asthma, pneumonia, pleurisy, pulmonary
tuberculosis, worm infestation, allergic reaction to drugs and history
of having received DEC during the past six months were excluded from
the study. Detailed clinical history of every patient was taken and
thorough physical examination with special emphasis on respiratory
system was done. Routine investigation like Hb, Stool, Urine, Sputum
for acid fast bacilli, X-ray chest, Pulmonary function test was done.
Because no comparative study is found to be conducted in past few
years, this study is planned with aim to evaluate the disease
pattern and response with standard drug in recent years.
Observation & Results
The present study was carried out in S.R.N. Hospital, Allahabad. A
total of 61, clinic-radiologically and haematologically suspected cases
of tropical pulmonary eosinophilia were included in the study. A total
of 39 healthy control were included in the study. Pulmonary functions,
which included forced vital capacity (FVC), forced expiratory volume in
one second (FEV1), FEV1/FVC Ratio, maximum mid expiratory flow
rate(MMEFR) and peak expiratory flow rate (PEFR) were observed in study
cases and control. All 61 cases were treated with standard dose of
diethylcarbamazine citrate (6 mg/kg/day) in three divided doses for 21
days. Follow up pulmonary function test and haematological test could
be possible only in 13 cases out of 61, after treatment with
diethylcarbamazine.
Table No.1 (A): Age and
Sex wise distribution of cases
|
Age group
(years)
|
Male (n= 49)
|
Female (n= 12)
|
Total (n= 61)
|
|
No
|
%
|
No
|
%
|
No
|
%
|
|
10-20
|
17
|
34.7
|
4
|
33.3
|
21
|
34.4
|
|
21-30
|
21
|
42.9
|
3
|
25.0
|
24
|
39.3
|
|
31-40
|
8
|
16.4
|
1
|
8.3
|
9
|
14.8
|
|
41-50
|
1
|
2.0
|
2
|
16.7
|
3
|
4.9
|
|
>50
|
2
|
4.0
|
2
|
16.7
|
4
|
6.6
|
|
Mean±S.D.
|
25.92±9.96
|
35.20±16.85
|
27.44±11.72
|
Out of 61 cases of TPE, there were 49 males (80.3%) and 12 females
(19.7%), approximately in ratio of 4:1. The maximum number of cases 24
(39.3%) were seen in age group 21-30 years. The maximum number of male
cases 21 (42.9%) and female cases 4 (33.3%) were seen in age groups
of 21-30 and 10-20 years respectively.
Table No.1 (B): Age and
Sex wise distribution of control
|
Age group
(years)
|
Male (n= 30)
|
Female (n= 9)
|
Total (n= 39)
|
|
No
|
%
|
No
|
%
|
No
|
%
|
|
10-20
|
6
|
20.0
|
3
|
33.4
|
9
|
23.1
|
|
21-30
|
15
|
50.0
|
2
|
22.2
|
17
|
43.6
|
|
31-40
|
6
|
20.0
|
1
|
11.1
|
7
|
17.9
|
|
41-50
|
1
|
3.3
|
1
|
11.1
|
2
|
5.1
|
|
>50
|
2
|
6.7
|
2
|
22.2
|
4
|
10.3
|
|
Mean±S.D.
|
25.92±9.96
|
35.20±16.85
|
27.44±11.72
|
Out of 39 control, there were 30 males (77.0%) and 9 females (23.0%).
The maximum number of control was in age group 21-30 years matched with
distribution of cases. The maximum number of male control was in same
age group (also match with male cases age group) and the maximum number
of female control was in age group 10-20 years(same as in female case).
Table No 2: Symptom of 61
cases
|
Symptoms
|
No. of cases (n=61)
|
Frequency (%)
|
|
Cough
|
61
|
100.0
|
|
Dry
cough
|
29
|
47.5
|
|
Productive
cough
|
32
|
52.5
|
|
Breathlessness
|
57
|
93.4
|
|
Wheezing
|
28
|
45.9
|
|
Chest
pain
|
31
|
50.8
|
|
Fever
|
18
|
29.5
|
The commonest symptom was cough found in all cases (100.0%). Dry cough
was found in 29(47.5) while productive cough was found in 32(52.5%).
This was followed by breathlessness 57(93.4%), chest pain 31 (50.8%)
& wheezing 28(45.9%).
Table No 3: Distribution
of cases according to Absolute Eosinophil count level (AEC)
|
ACE level
(/mm3)
|
Male (n=49)
|
Female (n=12)
|
Total (n=61)
|
|
No
|
%
|
No
|
%
|
No
|
%
|
|
2000-
5000
|
14
|
28.6
|
7
|
58.3
|
21
|
34.4
|
|
5000-
10,000
|
14
|
28.6
|
4
|
33.4
|
18
|
29.5
|
|
>
10,000
|
21
|
42.8
|
1
|
8.3
|
22
|
36.1
|
|
Total
|
10,874.82±13,908.41
|
5,561.83±3,098.28
|
9,829.64±12,690.18
|
The maximum number of cases 22 (36.1) had absolute eosinophil count
level more then 10,000/mm3. The maximum number of male cases 21 (42.8%)
had A.E.C. level more then 10,000/mm3 while the maximum number of
female cases 7 (58.3%) had ACE level between 2,000- 5,000/mm3.
Table No 4(A):
Distribution of mean values ± S.D. of pulmonary functions in
total cases according to different age groups
|
Age group
(years)
|
No.
|
FVC(lit)
|
FEV1(lit)
|
FEV1/FVC
(%)
|
MMEFR
(lit/sec)
|
PEFR
(lit/sec)
|
|
10-20
|
21
|
2.70±0.69
|
2.19±0.66
|
82.24±12.50
|
2.60±1.34
|
5.47±1.11
|
|
21-30
|
24
|
3.41±0.95
|
2.72±0.73
|
81.59±11.53
|
3.49±1.99
|
6.49±2.11
|
|
31-40
|
9
|
2.74±0.82
|
1.89±0.56
|
68.79±9.56
|
1.45±0.52
|
4.12±1.82
|
|
41-50
|
3
|
2.67±0.70
|
2.09±0.46
|
79.79±0.46
|
2.50±1.10
|
5.25±1.19
|
|
>50
|
4
|
2.20±1.17
|
1.66±0.76
|
79.30±15.34
|
1.41±0.38
|
4.01±3.39
|
|
Total
|
61
|
2.95±0.91
|
2.31±0.75
|
79.69±12.41
|
2.64±1.68
|
5.57±2.25
|
The mean values ± S.D. of FVC, FEV1, FEV1/FVC, MMFER and
PEFR of all cases were 2.95±0.91; 2.31±0.75;
79.69±12.41; 2.64±1.68 and 5.57±2.25
respectively.
Maximum mean values ± S.D. of FVC, FEV1, MMFER and PEFR were
observed in age group 21-30 years while maximum mean value ±
S.D. of FEV1/FVC ratio was found in 10-20 years age group.
Table No 4(B):
Distribution of mean values ± S.D. of pulmonary functions in
total control according to different age groups
|
Age group (years)
|
No.
|
FVC(lit)
|
FEV1(lit)
|
FEV1/FVC (%)
|
MMEFR
(lit/sec)
|
PEFR (lit/sec)
|
|
10-20
|
9
|
3.64±0.87
|
3.23±0.69
|
86.45±2.61
|
3.54±0.74
|
6.96±2.04
|
|
21-30
|
17
|
4.49±0.54
|
3.85±0.44
|
82.79±0.66
|
4.17±0.42
|
9.02±0.96
|
|
31-40
|
7
|
3.94±0.70
|
3.32±0.57
|
80.71±0.62
|
3.55±0.47
|
8.25±1.17
|
|
41-50
|
2
|
3.68±0.62
|
3.08±0.41
|
79.94±1.68
|
3.30±0.29
|
7.52±1.31
|
|
>50
|
4
|
2.63±0.60
|
2.15±0.46
|
77.15±0.78
|
2.28±0.20
|
6.24±1.13
|
|
Total
|
39
|
3.96±0.86
|
3.40±0.72
|
82.54±3.08
|
3.68±0.75
|
8.05±1.64
|
The mean values ± S.D. of FVC, FEV1, FEV1/FVC, MMEFR and
PEFR were 3.96±0.86, 3.40±0.72,
82.54±3.08, 3.68±0.75 and 8.05±1.64
respectively.
Maximum mean values ±SD of FVC, FEV1, MMEFR and
PEFR observed in age group of 21-30 years while maximum mean value
± SD of FEV1/FVC ratio was found in age group 10-20 years.
Table No 5:Comparison of
mean values ± S.D. of pulmonary functions between total
control and cases
|
Subject
|
FVC
|
FEV1 (lit)
|
FEV1/FVC(%)
|
MMEFR(lit/sec)
|
PEFR(lit/sec)
|
|
Total
control(n=39)
|
3.96±0.86
|
3.40±0.72
|
82.54±3.08
|
3.68±0.75
|
8.05±1.64
|
|
Total
cases (n=61)
|
2.95±0.91
|
2.32±0.75
|
79.69±12.41
|
2.64±1.68
|
5.57±2.25
|
|
‘t’
value
|
5.54
|
7.14
|
1.40
|
3.62
|
5.93
|
|
‘p’
value
|
<0.001
|
<0.001
|
>0.05
N.S.
|
<0.001
|
<0.001
|
The mean values ±S.D. of all spirometric parameters showed
low value in cases in comparison to control. Statistically all
parameters showed highly significant difference
(‘p’ value were <0.001 ) except in FEV1/FVC
ratio (‘p’ value was >0.05)
Table No 6:Comparison of
mean values ± S.D. of different haematological and lung
functions values between before and after treatment with diethyl
carbamazine therapy
|
Treatment
Status
|
AEC
(/mm3)
|
FVC
(lit)
|
FEV1
(lit)
|
FEV1/FVC
(%)
|
MMEFR
(lit/sec)
|
PEFR
(lit/sec)
|
|
Before
Treatment
(n=13)
|
12,154.08
±4,285.06
|
2.81
±0.66
|
2.30
±0.69
|
81.01
±9.91
|
2.23
±0.87
|
5.13
±2.04
|
|
After
Treatment
(n=13)
|
690.46
±225.90
|
2.87
±0.84
|
2.53
±0.73
|
81.22
±7.96
|
2.44
±0.85
|
5.78
±2.21
|
|
‘t’
value
|
9.63
|
0.18
|
0.84
|
0.06
|
0.60
|
0.77
|
|
‘p’value
|
<
0.001
|
>0.10
N.S.
|
>0.10
N.S.
|
>0.10
N.S.
|
>0.10
N.S.
|
>0.10
N.S.
|
Treatment given with standard doses of diethylcarbamazine citrate
(6mg/kg/day) in three divided dosage for 21 days. After treatment, improvement was observed in all parameters of
haematological and lung functions but statistically, highly significant
difference (‘p’ <0.001) was observed in
haematological parameters that is in AEC, while non significant
difference (‘p’ > 0.10) was observed in all
parameters of lung functions.
Table No 7-Comparison of
mean values ± S.D. of pulmonary functions between normal
healthy control and TPE cases after treatment
|
|
FVC
(lit)
|
FEV1
(lit)
|
FEV1/FVC
(%)
|
MMEFR
(lit/sec)
|
PEFR
(lit/sec)
|
|
After
treatment
(n=13)
|
2.87±
0.84
|
2.53±0.73
|
81.22±7.96
|
2.44±0.85
|
5.78±2.21
|
|
Control
(n=39)
|
3.96±
0.86
|
3.40±0.72
|
82.54±3.08
|
3.68±0.75
|
8.05±1.64
|
|
‘t’
value
|
4.01
|
3.73
|
0.87
|
4.99
|
3.95
|
|
‘p’
value
|
<0.001
|
<0.001
|
>0.10
N.S.
|
<0.001
|
<0.001
|
Statistically, on comparison between after treatment and control showed
highly significant difference in all parameters
(‘p’ value <0.001), except in FEV1/FVC ratio
(‘p’>0.10).
After the treatment, the mean values ± S.D. of all
parameters in cases showed improvement but the values were still below
the control value.
Discussion
The present study was undertaken to assess the pulmonary functions in
cases of tropical pulmonary eosinophilia .Pulmonary function test were
carried out in 100 subjects; 61were cases and 39 were controls. In the
present study, out of 61 cases of TPE, 49(80.3%) were males and 12
(19.7%) were females. The male to female ratio was approximately 4:1.
Almost similar male preponderance was reported by Kamat et al [20];
Udwadia [2]; Vijayan et al [17]; Rom et al [21] and Sandhu et al [22].
In the present study, the mean age ± SD of cases was
27.44±11.72 (ranged from 14 to 62 years). 74% of total cases
were below 30 years, with only four (6.5%) cases were above 48 years of
age. The mean age ± SD of male and female cases were
25.92±9.96 and 35.20±16.85 years respectively.
The finding of the present study showed correlation with studies done
by Vijayan et al that studied 50 cases of tropical pulmonary
eosinophilia with mean age ± SD of 24.1 ± 7.5
years (ages ranged from 12 to 48 years)[17]. Rom et al studied 23 cases
of tropical pulmonary eosinophilia. The mean age of their cases was 26
± 2 years [21]. Vijayan et al studied 50 cases of tropical
pulmonary eosinophilia, with ages ranging from 14 to 48 years, with 84%
of their cases were below 30 years of age[12].
In the present study commonest symptom found was cough in 100% cases
(dry, 47.5% and productive, 52.5%) followed by breathlessness (93.4%),
wheezing(45.9%),chest pain(50.8%).The frequency of symptoms found in
present study showed correlation with frequency of previous study done
by Udwadia found cough in 90% of cases followed by breathlessness in
70%, fever 35%, wheezing (28%), chest pain(10%)[2]. Rom et al found
both cough and dyspnoea in 100% cases, followed by nocturnal wheezing
(70%) and chest pain (39%)[21]. Vijayan et al also described symptoms
on presentation were cough in 100% cases followed by dyspnoea(94%),
wheezing(54%), chest pain (34%) and fever (16%)[12]. In the present
study, the mean AEC ±SD of total cases was 9,829.64
± 12,690.18/mm3 (ranged from 2,550 to 26,488). 36.1% of
these cases had AEC level above 10,000/mm3, which shows similarities
with studies done by Vijayan et al that found the mean AEC
±SD was 9.18 ± 0.66 ×109/L (ranged from
3.1 to 23.5 × 109/L). 90% of their cases had AEC level more
than 5.0 × 109/L[12]. Sharma et al found that the mean AEC
± SD was 14,880±18,710/mm3 (ranged from 8,142 to
21,618)[23]. Sandhu et al found that the mean ± SD was
9,401±8,556/mm3 (ranged from 2,500 to 30,750)[22].
In this study the mean values ± SD of FVC; FEV1;
MMEFR and PEFR of cases were significantly lower than that of controls.
The findings of present study showed correlation with various studies.
Panda et al found that the mean values ± SD of VC;
FEV1 and maximal expiratory flow rate (MMEFR) were significantly
reduced in cases as compared to control (‘p’
< 0.01).[24]. Singh et al found that the mean values
± SD of VC; FEV1; FEV1/FVC ratio; PEFR and MMEFR were
significantly lower in the diseased group in comparison to
control.[25]. Sharma et al found mild reduction in FVC, PEFR and MMEFR
in cases [23]. In the present study, after treatment, improvement was
observed in all parameters of haematological and lung functions but
statistically, highly significant difference (‘p’
< 0.001) was observed in all haematological parameters, while no
significant difference (‘p’ > 0.10) was
observed in all parameters of lung functions. The mean values
± SD of AEC was fell significantly from 12,154.08
± 4,285.06/mm3 to 690.46 ±
225.90/mm3.Statistically on comparison between after treatment and
control showed highly significant difference in all lung functions
parameters (‘p’ < 0.001), except in FEV1/FVC
ratio (‘p’ > 0.10).
These findings are comparable with various studies done previously by
kamat et al observed significant improvement for FEV1 and PEFR after
therapy with diethylcarbamazine, but for FVC the increase was not
significant [26]. Panda et al observed significant increase in the VC,
FEV1, and MMEFR after treatment with diethylcarbamazine [24]. Pinkston
et al observed peripheral blood eosinophilia fell significantly after
therapy from 8.7±1.2 × 103/µl to
2.2±0.5/µl (‘p’<
0.05).pulmonary function tests demonstrate decreased VC and
FEV1.[27].Singh et al observed after treatment diethylcarbamazine,
significant improvement (‘p’< 0.05) for FEV1
in patients having duration of symptoms for less then 3 months; other
parameters however, did not show a significant improvement. Highly
significant improvement (‘p’< 0.01) was
found in fell in absolute eosinophil counts [25]. Rom et al observed
after therapy with diethylcarbamazine, FEV1 although improved but found
lower than normal group [21]. Vijayan et al observed after therapy with
diethylcarbamazine, peripheral eosinophil count fell from
3.1±23.5×109/L to
2.82±0.36×109/L(‘p’<
0.001) [12]. Patients of tropical pulmonary eosinophilia cases showed
significant improvement clinically, haematologically and
spirometrically after treatment with standard dose of
diethylcarbamazine for three weeks but some lung function abnormality
persisted even after therapy.
Conclusion
On comparison between after treatment and control, significant
improvement was observed in lung functions but the values were still
below the control values. Patients of tropical pulmonary eosinophilia
cases showed significant improvement clinically, hematologically and
spirometrically after treatment with standard dose of diethyl
carbamazine for three weeks but some lung function abnormality
persisted even after therapy.
Funding: Nil, Conflict of interest:
Nil
Permission from IRB:
Yes
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How to cite this article?
Kumar R, Mourya S. Pulmonary function test in Tropical Pulmonary
Eosinophilia. Int J Med Res Rev 2014;2(4):283- 290.doi:10.17511/ijmrr.2014.i04.03