ANALYSIS OF FACTORS RELATED TO TOTAL SERUM IgE

DlcLE TIP DERGlsI (JOURNAL OF MEDICAL SCHOOL) C:27 S:3-4
2000
ANALYSIS OF FACTORS RELATED TO TOTAL SERUM IgE LEVELS
IN CHILDREN WITH BRONCHIAL ASTHMA
Ar,.Gor. Dr. Mehmet DAVUToGLU 1 Ar,.Gor. Dr. Meki BiLiCi
Ar,.Go,. Dr. Abdullah DAGLI3
2
Prof. Dr. Kenan HASPOLA T 4
Doe;. Dr. Aydm ECE 5
SUMMARY
The purpose of this study was to evaluate relationship between various risk
factors for allergic diseases and total serum IgE concentrations in asthmatic children.
.
We investigated characteristics of 140 children with asthma (91 males, 49
females) aged 3-15 years in Dicle University Hospital. Information about patient
characteristics were obtained from charts and the parents. Serum totallgE levels were
found significantly correlated with blood eosinophil count (r=O.46,p=O.00 1), intensity of
indoor smoking (r=O.40, p=O.03) and with number of household (r=0.41, p=0.02). We
found no significant relationship between total serum IgE levels and duration of
breastfeeding. feeding with cow's milk and age at onset of asthma symptoms (p>0.05).
With multiple regression analysis, associated symptoms of eczema and allergic
conjunctivitis were found significantly effective on the serum log IgE values (p<:0.05).
Serum totallgE values were normal in 49 asthmatic children (35%) and high in 91
(65%). Males had higher totallgE concentrations than females (geometric mean, 225
IUlml vs 153 IU/ml, p=0.03). Significantly higher totallgE levels were found in children
having positive skin prick test result to aeroallergens than others (geometric mean, 290
IV/ml vs 1871Ulml. p=0.02).
In conclusion, serum totallgE concentrations in asthmatic children were related
to exposure to passive smoking, positive skin prick tests, associated eczema symptoms,
allergic conjunctivitis and allergic rhinitis but not related to duration of breastfeeding and
feeding with cow's milk.
Key Words: asthma, atopy, children, IgE. passive smoking.
INTRODUCTION
Total and specific serum immunoglobulin E (lgE) together with skin prick
tests (SPT) are commonly used to diagnose atopic diseases. Although the
diagnostic value of specific IgE against definite allergens is well accepted, there
are conflicting results about predictive value of total serum IgE levels. Active
cigarette smoking has been found related to elevated levels of totallgE (1, 2).
But inconsistent results have been reported on the association of total serum
IgE and passive smoking (3, 4). In some studies the IgE levels were found to be
higher in males than in females (5, 6), whereas in others there is no age and
sex effect on serum totallgE (7, 8). Bronchial asthma in children may be allergic
(1.2.3,4)DicleOniversitesiTip FakOltesi.Cocuk Saghgl ve Hastahklan AnabilimDaJDlvARBAKIR
22
(extrinsic) or nonatopic (intrinsic). Thus, serum total and specific IgE levels and
positive skin tests may indicate the atopic nature of bronchial asthma (9-11).
Our aim was to evaluate whether gender, age, skin test reactivity, passive
smoking, breast feeding and feeding with cow's milk, the existence of eczema,
allergic rhinitis and allergic conjunctivitis were related to total serum IgE
concentrations in a sample of children with bronchial asthma.
MATERIALS AND METHODS
This study was conducted from May 1998 to September 1998. We
evaluated 140 asthmatic children (male: female ratio, 1.86: 1) aged 3-15 years
(mean age 6.2:t3.4 yrs) at Dicle University Hospital, Diyarbakyr, Turkey, who
followed-up at least one year. Investigation for parasitic diseases and infections
were performed in the study population. We detected parasitosis such as
ascariasis, giardiasis, oxyuriasis, and upper and lower respiratory airway
infections in 43 children during follow-up period. We have taken blood samples
for IgE measurement from these patients after at least 2 months of completion
of anti-parasitic therapy. Blood samples were taken from 8 a.m. to 12 a.m. and
immediately frozen and stored at -20°C until they analyzed together. Serum
totallgE levels of children were measured nephelometrically by a commercial
kit (Dade Behring Marburg, Germany). Serum specific IgE were determined by
Magic Lite sa (CIBA-CORNING, Horsholm, Denmark). IgE values for boys and
girls lower than 230 IU/ml and 170 IU/ml were accepted as normal values (12).
Peripheral blood eosinophils were determined by capillary blood smear. Percent
of eosinophil count in peripheral blood smear over 5% was accepted as
eosinophilia. Knowledge about associated atopic eczema, allergic rhinitis,
allergic conjunctivitis, duration of breastfeeding, the time of start feeding with
cow's milk and onset of asthma were obtained from the parents and the charts
of patients. Skin prick tests (SPT) were done using commercially available
skin-test material (ALK Laboratories test kits, Denmark) in 126 children. The
allergen tested were house dust mites (Dermatophagoides pteronyssinus, D.
farinae), grass pollen, cat and dog dander, tree mix, weed mix, mold mixture,
histamine hydrochloride (10 mg/ml) and glycerol (50%) were used as positive
and negative controls respectively. SPT reactivity was evaluated by reading the
maximal diameter of each wheal (mm) after subtracting that of negative control.
The threshold used to consider a positive reaction was three milimeters.
Statistical analysis: Total IgE levels were expressed as arithmetic or
geometric mean and IU/ml. As total serum IgE levels were highly skewed, a
logarithmic transformation (Log10) was performed to obtain a Gaussian shape.
Correlations were made using Spearman's correlation analysis. The difference
of total IgE between two groups was computed using non-parametric Mann
Whitney U test. A multivariate linear regression analysis was used to determine
the effect of different factors on log (lgE). P value less than 0.05 was accepted
as significant. Statistical computations were performed using Statistical
Package for Social Sciences (SPSS).
RESULTS
Of 140 children with bronchial asthma 91 were male, mean age was (SO)
23
6.2:t3.4 years. Some associated characteristics of patients and related serum
total IgE levels were shown in Table 1 and distribution of IgE levels in all
children were shown in figure. Males had higher IgE concentrations than
females (arithmetic means:tSD, 352:t214 IU/ml vs. 240:t164 IU/ml, p=O.03).
Significantly higher IgE levels were found in children with positive skin prick test
results to aeroallergens than in those with a negative prick test (350:t221 IU/ml
vs. 234:t164 IU/ml, p=O.03). Also totallgE values of children who exposed to
environmental tobacco smoke, having symptoms of allergic conjunctivitis and
allergic rhinitis, and positive skin prick test result were higher than others
(p<O.05) (Table 1). Parental smoking habits in the house have found
significantly related to serum totallgE levels (Table 2).
Table 1. Geometric means of IgE values according to some patient
characteristics
n
%
Male
91
65.0
225.6
Female
49
35.0
153.2
Characteristics
Gender
Passive Smoking
Atopic eczema
Allergic conjunctivitis
Allergic rhinitis
Yes
78
No
62
44.3
254.9
28
20.0
281.0
No
112
80.0
174.5
Yes
67
47.9
256.6
No
73
92.1
178.3
63.6
225.6
Yes
Family history of atopy Yes
No
89
51
77
63
Skin prick test
Positive
54
72
Severity of asthma
Negative
Mild
Moderate
Severe
42
P*
0.03
0.01
86.1
Yes
Yes
*With Mann-Whitney
55.7
TotallgE (IU/ml)
0.01
0.02
0.03
76.4
159.2
55.0
206.0
45.0
179.9
NS
42.9
290.7
0.02
57.1
187.4
30.0
176.5
72
51.4
198.0
26
18.6
194.5
NS
U test, NS: not significant
Total IgE levels were found significantly correlated with peripheral
eosinophil count (r=O.46,p=O.OO1),intensity of indoor smoking (r=O.40,p=O.03)
and number of household members (r=O.41, p=O.02). We found no significant
relationship between total serum IgE levels and age, duration of breastfeeding,
feeding with cow's milk and age of first asthma symptom onset (Table 3).
Specific IgE was studied in 54 children and most of them (66.7%) were against
D. pteronyssinus and D. farinea.
24
Table 2. Parental smoking habits in the house and related serum total
IgE levels (geometric mean) in children with bronchial asthma.
n
%
IgE (IU/ml)
Significance*f
Parental smoking habits
Neither parent smoke
62
44.3
86.0
Only father smoke
21
15.0
99.2
Only mother smoke
14
10.0
103.9
Both parents smoke
43
30.7
235.2
*according to Kruskal-Wallis
0.01
ANOVA
With multiple regression analysis, after adjusted for sex and passive
smoking, the existence of eczema symptoms (r=0.37, p=0.02) and allergic
conjunctivitis (r=0.35, p=0.04) were found significantly effective on the serum
log (lgE) levels.
-' Table 3. Spearman's coefficients of correlation for serum total IgE to
some characteristics
r
p
Blood eosinophilia
0.46
0.001
Age of asthma onset
0.11
0.43
Number of household
0.41
0.02
Indoor smoking
0.40
0.03
Duration of breastfeeding
- 0.09
0.49
FeedingwithCow'smilk
0.08
0.72
Of all our asthmatic children 42 (30%) had mild asthma, 72 (51%)
moderate and severe 26 (19%). There was no significant differences between
serum totallgE levels of mild moderate and severe asthma (p>O.05)(Table 1).
The highest frequencies of positive skin prick test results were observed
for house dust mites (D. pteronyssinus 57%, D. farinae 50%). The frequency
for pollens was 32%, for molds 25% and for animal danders was 17%.
Polysensitized asthmatic children consisted 27.9% of all children whereas
29.5% of them were monosensitized and 42.6 % were nonsensitized. The mean
serum total IgE levels of children who non-sensitized, mono and poly-sensitized
were 230:t164 IU/ml, 325:t157 IU/ml and 395:t192 IU/ml, respectively
(p=0.014).
?I;
50
40
f/)
13
Q)
:er
::]
f/)
'5
0
Z
30
20
10
0
450
50
250
1250
850
650
1050
TotallgE (kU/L)
Figure: The distribution of total serum IgE concentrations in children with
bronchial asthma.
DISCUSSION
In the present study we have shown in a group of asthmatic children that
total serum IgE levels are significantly higher in male, in passive smokers, in
those having positive skin prick test, having more crowded families. peripheral
blood eosinophili, having symptoms of allergic rhinitis, conjunctivitis and
eczema. But levels of total serum IgE were found not related to age, duration of
breastfeeding, age at start feeding with cow's milk and severity of asthma.
Childhood asthma is often associated with atopy manifested by positive
skin prick tests, concomitant eczema or allergic rhinitis (13). It is generally
accepted that there are both allergic (extrinsic) and non-allergic (intrinsic) forms
of asthma, and the distinction is usually based on the presence and the
absence of skin test reactivity to aeroallergens. Extrinsic asthma appears to be
the predominant form of the disease among children and young adults, and
intrinsic asthma is considered to be more common among older sUbjects (14).
Although serum IgE reaches its peak level during childhood, there is no
agreement about the levels of serum IgE that exceeds the normal limit (14). In
addition serum IgE levels have been shown to be effected by sex and by
smoking habits (15) . In some previous studies elevated levels of total serum
IgE were found correlated with airway hyperresponsiveness in asthmatic
children (16, 17) but in others (18-20) totallgE was not found correlated with
any special feature of asthma, so this topic is in debate.
The mean overall total serum IgE levels of study population exceeded
26
100 IU/ml, although 57.2% of our asthmatic children had negative SPT results.
In a general population study, the prevalence of asthma was closely related to
serum IgE levels. Those with low IgE levels reported no asthma, whereas 28%
of those with the highest IgE levels reported having the asthma. In that study,
however the diagnosis of asthma was based solely on a questionnaire and not
validated by objective criteria (14). These findings were interpreted to indicate a
probable allergic basis for all asthma, even in apparently nonatopic persons
with negative skin tests. In a randomized large adult study Tschopp et al. (21)
found that to diagnose current allergic asthma and current allergic rhinitis, the
sensitivity of serum total IgE was 68.4% and that of SPT was 77.1%. Positive
predictive value for current allergic asthma was 5.2% for SPT and 4.6% for total
IgE. The negative predictive value for totallgE was 88.1% .
In presented study meanSEM value for total asthmatic children was
348.0:t:124.2 IU/ml (geometric mean, 192.3 IU/ml). In the previously described
birth cohort of New Zealand children, the presence of asthma reported by
physician correlated with serum IgE, and those with previously diagnosed
asthma no longer had intermediate IgE levels (mean, 169.8 IU/mL) and those
with current asthma had the highest level (456.6 IU/mL) (17).
We found a significant correlation between serum total IgE and passive
smoking and with positive skin prick test results. Sapigni et al. (15) found that
peak IgE concentration at 8-14 years in a general population (8-73 years). At
that study, higher serum IgE levels were shown in subjects with a positive skin
prick test and passive smoking was significantly related to increased IgE values.
Baldacci et al. (18) evaluated skin prick test (SPT) reactivity and total serum IgE
in a general population sample in Italy. They found that asthma, asthma
symptoms and rhinitis were significantly associated with SPT reactivity. But,
Strachan and Cook (19) conducted a systematic review of the effects of
parental smoking on immunoglobulin E (lgE) levels, skin prick test positivity
allergic rhinitis and eczema in children and they concluded that parental
smoking is unlikely to increase the risk of allergic sensitization in children.
Although the distribution of IgE levels is extremely wide in age-defined groups,
no single level of IgE clearly distinguishes atopic from nonatopic individuals
(22).
Also we found the number of household members related to serum total
IgE. In the study of Wjst et al. (3) serum total IgE of 703 children and urinary
cotinine in a subsample of 244 children were analyzed. Passive smoking was
found as one of the most important effective factor on total serum IgE level and
totallgE increased with the number of persons living in the crowded household,
independent of indoor smoking. Frequent upper respiratory infections may be
responsible for allergic sensitization in crowded families. In one study,
increased total IgE was found more affected by factors increasing the risk of
intercurrent infection and non-specific airway inflammation such as
environmental tobacco smoke and the use of gas cooker in infancy (22).
In presented study population serum total IgE level of males was
significantly higher than females. The study of Johnson et al. (23) compared
total and allergen specific IgE by gender from birth through 4 years of age and
27
found that total IgE increased with age for boys and girls and was higher in
boys. They suggested that differences in IgE development between young boys
and girls may partially account for the higher prevalence of asthma in boys than
in girls.
Longer duration of breastfeeding and late onset of feeding with cow's milk
were suggested that a preventive measures for developing allergic diseases.
But we found no relationship between totallgE and feeding practices of children
in infancy.
We found no relationship between the severity of asthma and the total
IgE and high IgE levels were associated with blood eosinophilia. Our results
were resembling to the study of Rosario and Vilela (20). In that study significant
eosinophili and elevated serum IgE levels were found correlated with the
presence of asthma but no relation to severity of the disease.
In conclusion presented results confirm that in asthmatic children total
serum IgE concentrations are related not only to skin-prick test reactivity to
aeroallergens but also to other risk factors for allergic diseases such as gender,
passive smoking and crowded family.
OZET
BRON~iYAL ASTIMLI COCUKLARDA TOTAL SERUM IGE
DOZEYLERi ilE iLi~KiLi FAKTORLERiN DEGERLENDiRiLMESi
Bu yall~manln amacl astlmll yocuklarda allerjik hastallklar iyin risk
olu~turan ye~itli faktorler ile total serum IgE dOzeyleri araslndaki ili~kiyi
degerlendirmektir.
Ya~lan 3-15 y'l araslnda degi~en 91'i erkek toplam 140 astlmll yocuk
ara~tlnldl. Hastalarla ilgili bilgiler ailelerinden ve hasta takip kartlanndan elde
edildi.
Serum total IgE dOzeyi, kan eozinofil say'sl (r=0.46, p=0.001), evde
sigara iyilmesi (r=0.40, p=0.03) ve aym evde oturan ki~i say's' (r=0.41, p=0.02)
ile anlamll iIi~kili bulundu. Serum total IgE dOzeyi ile anne s010veya inek s010
ile beslenme sOresi ve astlm semptomlanmn ba~ladlgl ya~ araslnda anlamh bir
iIi~ki saptanmadl (p>O.05). Multipl regresyon analizi ile ast.mla birlikte egzema
ve allerjik konjonktivit semptomlanmn bulunmasl serum log IgE degerleri
Ozerinde etkili bulundu (p<0.05). Total IgE dOzeyi 91 yocukta (%65) yOksek
bulundu. Erkekler klzlardan daha yOksek total IgE dOzeylerine sahipti
(geometrik ortalama, 225 IU/ml ve 153 IU/ml, p=0.03). Aeroallerjenlere kar~1
pozitif deri testi sonucu bulunan yocuklar digerlerine gore anlamh yOksek total
IgE dOzeylerinesahipti (290 IU/ml ve 187 IU/ml, p=0.02).
Sonuy olarak astlmh yocuklardaki total serum IgE dOzeyleri pasif sigara
iyimi, pozitif deri testi sonuylan, beraberinde egzema, allerjik konjonktivit ve
allerjik rinit semptomlanmn bulunmasl ile ili~kili bulunurken, anne s010 veya
inek s010ile beslenme sOresiile iIi~kili bulunmadl.
Anahtar Kelimeler: Astlm, atopi, yocuklar, IgE, pasif sigara iyimi.
28
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