Full text of DOI:10.1016/S0301-0546(02)79093-9

Pulmonary functions in atopic and nonatopic
asthmatic children
F. Gürkan*, M. Davuto˘glu**, M. Bilici**, N. Sincar**, and K. Haspolat***
*Assoc. Prof. Dr., **Research Assistant Dr., ***Prof. Dr. in Dicle University Medical School, Diyarbakır, Turkey.
to dust mite, cat and dog, were at increase risk of
more severe asthma.
SUMMARY
Background: we examined how lung function and
certain clinical and laboratory characteristics in asth-
matic children were changed according to skin test
positivity to aeroallergens.
Key words: Asthma. Child. Pulmonary function. Skin
test.
Allergol et Immunopathol 2002;30(2):70-73.
Methods: a skin prick test was conducted using
standardized extracts of 10 different allergens in
56 children with bronchial asthma, aged 5-15 years,
in Dicle University Hospital. Lung function was mea-
sured by Microplus spirometer.
INTRODUCTION
Results: among the 56 subjects, asthma was clas-
sified as mild in 16, moderate in 42 and severe in 3.
At least one skin prick test was positive (monosen-
sitized) in 35 subjects (62 %) and positive reactivity
to two or more aeroallergens (polysensitized) was
found in 17 subjects (30%). Positive skin test reac-
tions to aeroallergens were associated with a de-
crease (as percentage of the predicted decrease) in
FEV1, FVC and PEF values. Significant differences
were also found between prick test-positive and -ne-
gative asthmatics in duration of breastfeeding
(8.5 ± 5 months vs 15 ± 7 months, respectively,
p < 0.007), age at which cow’s milk had been started
(5.7 ± 1.6 vs 10.5 ± 5.4, p = 0.004); total serum IgE
concentration (350 ± 221 IU/ml vs 234 ± 164 IU/ml,
p = 0.02), age at onset of asthma symptoms
(2.5 ± 1.9 years vs 4.1 ± 2.2 years) and number of
asthma attacks per year (7.0 ± 3.1 vs 5.2 ± 3.5,
p = 0.012). When one-way ANOVA and a post-Hoc
test were used, asthma attacks were more frequent
and severe and allergic conjunctivitis symptoms
were more frequent in the polysensitized group than
in the nonsensitized and monosensitized groups
(p = 0.03).
Atopy is often regarded as a risk factor for the de-
velopment of asthma, particularly in childhood asth-
ma and occupational asthma (1). Despite increasing
prevalence of childhood asthma, few studies have
quantified the associations between atopy characte-
ristics and pulmonary functions of these patients.
These estudies would supply knowledge of the atopy
characteristics of asthmatic children most at risk.
It was aimed in this study to assess whether
atopy, measured as total IgE level and/or skin prick
test (SPT) reactivity is related to bronchial asthma se-
verity in children by determining the association
of these factors with lung functions. The atopic status
in our study population was also determined.
MATERIAL AND METHOD
The result of SPTs performed between 1995 and
1997 on 61 patients with asthma aged between
5-15 years, in Dicle University Hospital were evalua-
ted considering their pulmonary functions. Skin prick
test was conducted using standardized extracts of dif-
ferent allergens (house dust mite, cat and dog dander,
mixed grass pollens, tree pollens, molds and feat-
hers, ALK laboratories, Denmark) applied to the fore-
Conclusions: children with positive skin prick test
results, especially those with combined sensitivity
Allergol et Immunopathol 2002; 30(2): 70-73

F. Gürkan, M. Davutog˘lu, M Bilici, N. Sincar, K. Haspolat.— PULMONARY FUNCTIONS IN ATOPIC AND NONATOPIC
ASTHMATIC CHILDREN
71
Table I
Skin test positivity and some patient characteristics
Atopic
Characteristics
Nonatopica
Significanceab
Totalb
Monosensitized
Polysensitized
n
26
8
6
35
22
19
18
10
9
17
12
10
FEV1/FVC < %75*
PEF,% predicted < %80*
Total serum IgE (kU/l)
Asthma attacks per year
Duration of breastfeeding (months)
Age onset (years)
Introduction with cow’s milk (months)
Prenteral history of atopy (n)*
0.03
0.03
0.02
234 ± 164
5.2 ± 3.5
14.8 ± 7.0
4.1 ± 2.2
10.5 ± 5.4
2
346 ± 181
7.0 ± 3.1
8.5 ± 5.0
2.5 ± 1.9
5.7 ± 1.6
7
321 ± 177
6.4 ± 3.2
10.5 ± 5.4
1.5 ± 1.7
5.6 ± 1.5
3
395 ± 195
7.7 ± 3.1
8.2 ± 3.8
3.4 ± 3.3
5.1 ± 1.2
4
0.04
0.001
0.004
< 0.001
> 0.05
*p: with Chi-square test, others with Student’s t-test.
arm. Histamine (10 mg/ml) and saline were used as
positive and negative controls. Fifteen minute after
application of the allergens, wheal size was recorded
as the mean of the long axis and its perpendicular,
and was regarded as positive if 3 mm greater than the
negative control. If there was no reaction to the posi-
tive control or a reaction more than 1 mm to the ne-
gative control, the results were excluded from the
analyses. Children having at least one positive reac-
tion in the SPTs were defined as being atopic.
Lung functions were measured using Micro Plus
spirometer (Micro Medical, England) at symptom free
intervals after provocation with exercise. Subjects per-
forming unsatisfactory forced expiratory maneuvers
were not included in the data analysis. The largest spi-
rometric results were selected from a minimum of th-
ree valid expiratory recordings. Subjects who had ta-
ken a beta-agonist earlier than 6 h before the test
were asked to make another appointment. Each sub-
ject underwent assay for serum total IgE level, mea-
sured nephelometrically using a commercial device
and kit (Dade Behring, Marburg GmbH, Germany).
Statistical analyzes were done by using one-way ANO-
VA and post Hoc Student-Newman-Keuls, unpaired t
test and Chi-square test. P value less than 0.05 was
accepted as significant.
to SPT results was found in 35 (57%) of all children,
and positive reactivity to two or more aeroallergens
(polysensitized) was found in 17 (29%) subjects. Of all
35 positive SPT results, 32 (91.4%) were for
Dermatophagoides
pteronyssimus
and
Dermatophagoides farinae. Positive SPT reactions to
aeroallergens were found to be associated with a de-
crease (as% of predicted) in forced expiratory volume
in one second (FEV1), forced vital capacity (FVC) and
peak expiratory flow (PEF) values as shown in the ta-
ble I.
Significant differences were found between SPT
positive and negative asthmatics in number of asthma
attacks per year (7.0 ± 3.1 vs 5.2 ± 3.5, respectively,
p = 0.04). Duration of breastfeeding (8.5 ± 5.0 months
vs 14.8 ± 7.0 respectively, p < 0.001), and age at in-
troduction of cow’s milk during infancy (5.7 + 1.6 vs
10.5 ± 5.4 respectively, p < 0.001) were statistically
different between the SPT positive and negative asth-
matics. The frequency of positive parental history of
atopy was similar in atopic and non-atopic asthmatic
children (p > 0.05) (table I).
DISCUSSION
Although the prevalence of asthma has risen signifi-
cantly during the last decades, it is not clear whether
this has occurred primarily in persons with a strong
atopy. Much of the increase in asthma prevalence was
found to be associated with specific IgE sensitization
(2). It has long been known that atopy is the strongest
risk factor for the development of asthma, increasing
the risk by 10-20 fold compared with those who are
non-atopic (3). Studies have shown that majority of
RESULTS
Of all 61 children participated in the study group,
16 were classified as having mild asthma, 42 with mo-
derate and 3 with severe. Parenteral history of atopy
and asthma was found to be present in 9 (14.7%) of
all patients and 7 (20.0%) of atopics. Atopy according
Allergol et Immunopathol 2002; 30(2): 70-73

F. Gürkan, M. Davutog˘lu, M Bilici, N. Sincar, K. Haspolat.— PULMONARY FUNCTIONS IN ATOPIC AND NONATOPIC
ASTHMATIC CHILDREN
72
asthmatics have a family history of asthma or atopy
that specific IgE antibody is also present on the mast
cells in the tissue of the clinically affected organ wha-
tever the allergic disorder is. The basic immune me-
diator-induced mucosal injury is similar in both atopic
and nonatopic patients. However atopic patients may
be associated with more easily identified stimuli of
mediator release than nonatopic patients. If there is
an allergic-extrinsic component in the patient, chro-
nic nonspecific stimulation of the mast cell
allergen-induced late-phase immune reactions may
create a prolonged nonspecific airway hyperreactivity,
which can produce broncospasm even in the absense
of identifiable extrinsic factors. On the other hand, po-
sitive skin test does not indicate that the patient will
necessarily have clinical symptoms on exposure to
the allergen. Some atopic individuals may have no
symptoms following natural exposure to allergens
(15).
Short duration of time of breastfeeding and early age
of month at which cow’s milk has been started both
seem to increase the prevalence of atopic status in our
study population. In one of the few studies investiga-
ting the influence of prolongation of breast-feeding and
postponement of introduction of solid food during in-
fancy, no preventive effect of the diet consumed du-
ring infancy was seen on subsequent skin test results
in relation to common allergens (16).
and most of the patients were atopic (3-5). It still re-
mains a question whether atopic asthma patients are
at greater risk to have more severe and frequent asth-
ma attacks. Several investigators have studied the re-
lationship between atopy and childhood asthma; and it
has been claimed that if atopy was a factor in aggrava-
ting asthma, severity of asthma would increase with
increased allergy defined by symptoms and numbers
of positive prick skin tests (6).
There are several studies in due course with our fin-
dings, which show that children with large skin wheal
reactions to certain allergens appear to have more se-
vere illness. Atopic status and increased bronchial res-
ponsiveness were all found to be associated with lo-
wer levels of lung function in a recent study (7). In the
study of Studnicka et al (8), children with a diagnosis
of asthma, those with a positive skin-prick test de-
monstrated increased airway resposiveness as well as
with those reported with exposure to maternal smo-
king. In 81 atopic subjects out of 118 paediatric symp-
tom-free asthma patients, lung functions were found
to be lower than the remaining 37 nonatopic patients
(9). Ulrik and Baker (10) have found that subjects with
new or persistent atopy to house dust mites had sig-
nificantly increased bronchial responsiveness compa-
red with nonatopic subjects; and, moreover, precha-
llenge FEV1 percent predicted was significantly
correlated with bronchial responsiveness. A frequent
positive bronchial response to exercise was reported
to be closely associated with atopy, defined as skin
test positivity to 1 of 7 common aeroallergens (11). In
a cross sectional study carried out in China, the odds
ratios for having respectively slight, mild or moderate,
and severe bronchial hyperresponsiveness were
found to be 5.9, 21.0, and 30.4 for atopy (12).
According to spirometric lung function and skin prick
test results among asthmatic children, atopy, positive
skin test reactions to house dust mite and cat and lo-
wer level (as% of predicted) in FEV1 were associated
with an increased variation in PEF (13).
Atopic individuals were shown to have significantly
more often increased bronchial responsiveness, cu-
rrent asthma, and total asthma than nonatopics, and
the odds ratios of increased bronchial responsiveness
and asthma were found to be increased with the
number of positive skin test reactions (14). In the
study of Zimmerman et al (6), there was an increase
in the number and size of positive skin tests with in-
creasing severity of asthma. Similarly, there was in-
creased reporting of allergic symptoms, such as sen-
sitivity to animals with increasing severity of asthma.
Under the light of these literatures, the issue is that
why those atopic children may have more severe and
frequent asthma attacks. Positive skin test indicates
We conclude that the two markers of atopy stu-
died (serum total IgE and SPT) were related to lung
functions and severity of bronchial asthma. Our fin-
dings support the concept that children with positive
skin prick test results may have more frequent and
severe asthma attacks. So as not to reduce the pul-
monary functions of atopic asthmatic children, it is
imperative that we design interventions for the domi-
nant allergens.
ACKNOWLEDGEMENTS
This paper was presented in part [Allergy
54 (suppl. 51) 1999: 44] at the Joint meeting of
European Respiratory Society Paediatric Assembly
and European Society of Pediatric Allergy and Clinical
Immunology in Berlin, Germany in 26-29 May 1999.
RESUMEN
Antecedentes: examinamos cómo se modificaban
las funciones pulmonares y algunas características
clínicas y de laboratorio en niños asmáticos en fun-
ción de su reacción positiva a los aeroalergenos en
las pruebas cutáneas.
Allergol et Immunopathol 2002; 30(2): 70-73

F. Gürkan, M. Davutog˘lu, M Bilici, N. Sincar, K. Haspolat.— PULMONARY FUNCTIONS IN ATOPIC AND NONATOPIC
ASTHMATIC CHILDREN
73
Palabras clave: Asma. Niños. Función pulmonar.
Pruebas cutáneas.
Métodos: se realizó una prueba de punción cutánea
(prick test) utilizando extractos estandarizados de
10 alergenos distintos en 56 niños con asma bron-
quial, de edades comprendidas entre 5 y 15 años en el
hospital de la Universidad de Dicle. Las funciones pul-
monares se midieron con un espirómetro Microplus.
Resultados: el asma de 16 de dichos sujetos se
clasificó como leve, en 42 de los casos, como mode-
rada, y en 3 de grave. Por lo menos una prueba de
punción cutánea fue positiva (monosensibilizados) en
35 sujetos (62%), y se detectó una reacción positiva
a dos o más alergenos (polisensibilizados) en 17 sus-
jetos (30%). Reacciones positivas a los aeroalerge-
nos asociadas con una disminución en los valores de
volumen espiratorio forzado en el primer segundo
(VEMS/FEV1), capacidad vital forzada (CVF/FVC) y flu-
jo espiratorio máximo (FEM/PEF). También se detec-
taron diferencias significativas entre los asmáticos
con prueba de punción cutánea positiva y negativa
en la duración de la lactancia materna (8,5 ± 5 meses
vs 15 ± 7 respectivamente, p < 0,007); en los meses
de vida a los que se comenzó a tomar leche de vaca
(5,7 ± 1,6 vs 10,5 ± 5,4, p = 0,004); en concentración
total en suero de inmunoglobulina E (350 ± 221 IU/ml
vs 234 ± 164 IU/ml, p = 0,02); en la edad de la apari-
ción de los síntomas asmáticos (2,5 ± 1,9 años vs
4,1 ± 2,2 años); y en el número de ataques de asma
anuales (7,0 ± 3,1 vs 5,2 ± 3,5, p = 0,012). Los análisis
de varianza unidireccional ANOVA y post-Hoc mos-
traron que el grupo de polisensibilizados sufría ata-
ques de asma más frecuentes y graves y síntomas
frecuentes de conjuntivitis alérgica que los grupos no
sensibilizados y monosensibilizados (p = 0,03).
REFERENCES
1. Grainger DN, Stenton SC, Avery AJ, Duddridge M, Walters EH,
Hendrick DJ. The relationship between atopy and non-speci-
fic bronchial responsiveness. Clin Exp Allergy 1990;20(2):
181-7.
2. Christie GL, Helms PJ, Godden DJ, Ross SJ, Friend JA, Legge
JS, Haites NE, Douglas JG. Asthma, wheezy bronchitis, and
atopy across two generations. Am J Respir Crit Care Med
1999;159(1):125-9.
3. Kalyoncu AF, Türkats¸ H. Etiology and pathogenesis of asthma.
In: National Asthma Data. Ankara, 1999;66.
4. Mungan D, Demirel Y, Kalpaklıog˘lu F, Sin B, Bavbek S, Mısırlıgil
Z, Gürbüz L. Skin test reactivity of asthmatic patients in Turkey.
Madrid: XVI European Congress of Allergology and Clinical Im-
munology, 1995.
5. Tükenmez F, Barlan I, Bakır M, Bas¸aran M. Uçyüzyetmis¸altı
atopik hastanın klinik özellikleri. XXXIX Milli Pediatri Kongresi
1995.
6. Zimmerman B, Feanny S, Reisman J, Hak H, Rashed N,
McLaughlin FJ, Levison H. Allergy in asthma. I. The dose rela-
tionship of allergy to severity of childhood asthma. J Allergy
Clin Immunol 1988;81(1):63-70.
7. Bremner PR, de Klerk NH, Ryan GF, James AL, Musk M, Mu-
rray C, Le. Respiratory symptoms and lung function in aborigi-
nes from tropical Western Autralia. Am J Respir Crit Care Med
1998;158(6):1724-9.
8. Studnicka M, Roithner B, Gartner C, Weiss ST, Neumann M,
Frischer T. Longitudinal predictors of airway responsiveness
to distilled water: the role of atopy and maternal smoke expo-
sure. Eur Respir J 1998;12(1):75-81.
9. Gruber W, Eber E, Steinbrugger B, Modl M, Weinhandl E,
Zach MS. Atopy, lung function and bronchial responsiveness
in symptom-free paediatric asthma patients. Eur Respir J
1997.
10. Ulrik CS, Backer V. Longitudinal determinants of bronchial
responsiveness to inhaled histamine. Chest 1998;113(4):
973-9.
11. Frischer T, Meinert R, Karmaus W, Urbanek R, Kuehr. Rela-
tionship between atopy and frequent bronchial response to
exercise in school children. Pediatr Pulmonol 1994;17(5):
320-5.
Conclusión: los niños con resultados positivos a
las pruebas de punción cutánea, especialmente los
que muestran sensibilidad combinada a los ácaros
del polvo, perros y gatos, presentaban un riesgo ma-
yor de padecer asma más grave.
12. Zhong NS, Chen RC, O-yang M, Wu JY, Fu WX, Shi LJ. Bron-
chial hyperresponsiveness in young students of southern Chi-
na: relation to respiratory symptoms, diagnosed asthma, and
risk factors. Thorax 1990;45(11):860-5.
13. Timonen KL, Nielsen J, Schwartz J, Gotti A, Vondra V, Grat-
ziou C, Giaever P, Roemer W, Brunekreef B. Chronic respira-
tory symptoms, skin test results, and lung function as predic-
tors of peak flow variability. Am J Respir Crit Care Med
1997;156:776-82.
14. Helenius IJ, Tikkanen HO, Sarna S, Haahtela T. Asthma and in-
creased bronchial responsiveness in elite athletes: atopy and
sport event as risk factors. J Allergy Clin Immunol 1998;
101(5):646-52.
Correspondence:
Dr. Fuat Gürkan
Dicle University
Medical School
Dept. of Pediatrics
Diyarbakır, Turkey
E-mail: fuatgurkan@hotmail.com
15. Sly RM. Allergic disorders. In: Behrman RE, Kliegman RM,
Jenson HB, eds. Nelson Textbook of Pediatrics. Philadelphia:
WB Saunders, 2000;645-95.
16. Poysa L. Atopy in children with and without a family history of
atopy. II. Skin reactivity. Acta Paediatr Scand 1989;78(6):
902-6.
Allergol et Immunopathol 2002; 30(2): 70-73