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Seasonal variation in serum eosinophilic cationic protein (S-ECP) in a general population sample
RESPIRATORY
MEDICINE
(1997)
91, 347-349
Seasonal variation in serum eosinophilic protein (S-ECP) in a general population C. JANSON”+*, E. BjoRNSSON”t,
cationic sample
I. ENANDER’ AND L. HAKANSON~
“Department of Lung Medicine, Akademiska Sjukhuset, Uppsala, Sweden ‘Asthma Research Centre, Uppsala University, Sweden *Department of Public Health Medicine, UMDS, St Thomas’s Hospital, London, ‘Phaumacia Diagnostics, Uppsala, Sweden 7Depavtment of Clinical Chemistry, Akademiska Sjukhuset, Uppsala, Sweden
UK
The aim of this investigation was to study the seasonal variation in the serum levels of eosinophil cationic protein (S-ECP). The study population comprised a general population sample of 379 individuals (range: 2045 years) who were investigated with blood sample for the measurement of S-ECP, skin prick test and methacholine challenge. The examination took place between May and October 1991. Of the 379 subjects investigated, 137 (36%) were atopic. A significant seasonal variation in S-ECP was found in the group of birch-pollen-positive subjects (P
MED.
(1997)
91,
347-349
Introduction
Materials
The inflammatory activity of the airways of asthmatics can be assessedby means of bron-
The
choscopy (1,2), but less invasive methods are needed for monitoring airway inflammation clinically or in epidemiological studies. Measuring the serum levels of eosinophil degranulation products such as eosinophil cationic protein (S-ECP) is thought to be valuable for monitoring asthma (3-5). However, the usefulnessof peripheral blood markers is dependent on how factors other than the diseaseinfluence blood levels. The purpose of this investigation was to determine whether there is seasonalvariation in S-ECP. If present, this sort of variation should be taken into account when using the marker clinically or in epidemiologic research. Received 18 November 1995 and accepted in revised form 25 July 1996. Correspondence should be addressed to: C. Janson, Department of Lung Medicine, Akademiska Sjukhuset, S-751 85 Uppsala, Sweden. 0954-6111/97/060347+03
$12.00/O
study
and Methods population
comprised
a general
population sample of 379 individuals from the municipality of Uppsala, Sweden [mean age (range): 32 (2045) years]. These subjects were participants in the European Community Respiratory Health Survey (6). The study was conducted between April 1991 and February 1992. This investigation was limited to subjects who were studied in May (n=73), June (n=42), August (n=65), September (n= 86) and October (n= 114), as the number of subjects examined during the other months was low (~40). The study included a structured interview, skin prick tests, lung function measurements, methacholine challenge and blood sampling for the measurement of S-ECP. The concentration of S-ECP was assayed by means of double antibody radioimmunoassay at Pharmacia Diagnostics in Uppsala (5). Atopy was defined as a positive prick test (Phazet, Pharmacia Diagnostics, Uppsala, Sweden) with a mean diameter of 0
1997 W. B. SAUNDERS
COMPANY
LTD
348
C. JANSON ET AL.
2 3 mm. Bronchial hyper-responsiveness(BHR) was defined as a fall of 220% in forced expiratory volume in 1 s (FEV,) after the inhalation of 2 mg or less of methacholine using a dosimeter (Mefar, Brescia, Italy) (5,6).
-*30 1
STATISTICS
Differences in S-ECP in subjects with and without atopy and BHR were analysed using unpaired t-test, and the combined effect of these variables was studied using multiple linear regression. ANOVA was used to analyse seasonal variation. In order to achieve an approximately normal distribution, S-ECP values were log transformed. A P value of
0 May
JLlIle
August
September
October
1. Seasonal variation in serum eosinophilic cationic protein (S-ECP) in non-atopic (7~~242, open bars) and atopic subjects with a negative skin prick test to birch (n=72, hatched bars), and subjects with a positive skin prick test to birch (n=65, solid bars) (mean and SE). “WO.05. FIG.
Results
Of the 379 subjects investigated, 137 (36%) were atopic. Of these, 65 and 72 had positive prick tests to birch and timothy, respectively. In addition, positive skin prick tests to Dermatophagoides pteronyssinus (n =28), cat (n = 57), dog (n=43), mugworth (n=24), Cladopsorium hevbatum (n=4) and Alternaria alternata (72~7) were found. Levels of S-ECP were significantly higher in atopic subjects than in nonatopic subjects (15.7 f 9.5 vs. 13.0 f 7.3 pg I- ’ (PcO.05). Levels of S-ECP were also significantly higher in the 42 subjects with BHR than in those with no BHR (17.1 f 10.8 vs. 13.6f 7.9 pg - ‘) (PcO.05). When the S-ECP level in the whole population was studied, a significant seasonalvariation was found with a peak mean value in June (PcO.01). When comparing atopic and non-atopic subjects, there was a significant seasonalvariation in S-ECP in the atopic (P
In atopic individuals with a positive skin prick test to timothy, there was no significant relationship between the month of investigation and S-ECP levels. Discussion
The main finding of this analysis in a general population sample was that there was a significant seasonal variation in S-ECP levels. This variation was, however, only seenin birch-pollen atopic subjects, where the mean level of ECP in June was about twice as high as in birch atopic subjects examined during any of the other months. The correlation between the month of investigation and S-ECP remained significant when adjusting for BHR as a possible confounder. The main birch pollen season in 1991 in the Uppsala region started on 28 April and ended on 31 May. The pollen counts were considerably lower than is normally found in the region (mean count: l-325 vs. 7.360 birch pollen m - 3, (7). Despite this, in accordance with previous studies, the present study found seasonal variation in S-ECP in birch-pollen atopic subjects, with peak levelsjust after the birch pollen season had ended (8,9). The most important new information obtained from this investigation is that the magnitude, even during a mild birch pollen
SEASONALVARIATION Iiv S-ECP
season, was sufficient to affect the results for a general population. No investigations were made during the peak of the grass pollen season due to the summer holidays in Sweden in July. If S-ECP in grasspositive atopics had varied as it did in birch-pollen-sensitive subjects, the authors would have expected peak levels of S-ECP in August. This was not, however, found in the present study. It is concluded that in northern Europe, seasonal variation in birch-pollen-positive subjects is an additional factor that must be taken into account when using S-ECP for the monitoring of asthma clinically or in epidemiological research. Acknowledgements
This study was supported financially the Swedish Heart and Lung Foundation, Swedish Medical Research Council, Swedish Association against Asthma Allergy, The Bror Hjerpstedt Foundation the County Council of Uppsala.
by the the and and
References 1. Laitinen LA, Heino M, Laitinen A, Kava T, Haashtela T. Damage of airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis 1985; 131: 599-606.
349
2. Adelroth E, Rosenhall L, Johansson S-A, Linden M, Venge P. Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage: the effect of treatment with budesonide or terbutaline. Am Rev Respir Dis 1990; 142: 91-99. 3. Griffin E, Hakansson L, Formgren H, Jorgenson K, Peterson C, Venge P. Blood eosinophil number and activity in relation to lung function in patients with asthma and with eosinophilia. J Allergy Clin Immunol 1991; 87; 548-556. 4. Zimmerman B. Clinical experience with the measurement of ECP: usefuhress in the management of children with asthma. Clin Exp Allergy 1993; 23 (Suppl 2): S-12. 5. Bjiirnsson E, Janson C, Hakansson L, Enander I, Venge P, Boman G. Serum Eosinophil Cationic Protein in relation to bronchial asthma in a young Swedish population. Allergy 1994; 49: 730-736. 6. Burney PGJ, Luczynska CM, Chinn S, Jarvis D. The European Community Respiratory Health Survey. Eur Respir J 1994; 7: 954-960. 7. Berggren B, Nilsson S. Pollensiisongen 1991 (in Swedish). Skarholmen: Fisons Pharmaceuticals, 1992. 8. Rak S, Liivhagen 0, Venge P. The effect of immunotherapy on bronchial hyperresponsiveness and eosinophil cationic protein in pollen allergic patients. J Allergy Clin Immunol 1988; 82: 470480.
9. Carlsson M, Hakansson L, Kampe M, Stalenheim G, Peterson C, Venge P. Degranulation of eosinophils from pollen atopic patients with asthma is increased during the pollen season. J Allergy Clin Immunol1992; 89: 131-139.
MEDICINE
(1997)
91, 347-349
Seasonal variation in serum eosinophilic protein (S-ECP) in a general population C. JANSON”+*, E. BjoRNSSON”t,
cationic sample
I. ENANDER’ AND L. HAKANSON~
“Department of Lung Medicine, Akademiska Sjukhuset, Uppsala, Sweden ‘Asthma Research Centre, Uppsala University, Sweden *Department of Public Health Medicine, UMDS, St Thomas’s Hospital, London, ‘Phaumacia Diagnostics, Uppsala, Sweden 7Depavtment of Clinical Chemistry, Akademiska Sjukhuset, Uppsala, Sweden
UK
The aim of this investigation was to study the seasonal variation in the serum levels of eosinophil cationic protein (S-ECP). The study population comprised a general population sample of 379 individuals (range: 2045 years) who were investigated with blood sample for the measurement of S-ECP, skin prick test and methacholine challenge. The examination took place between May and October 1991. Of the 379 subjects investigated, 137 (36%) were atopic. A significant seasonal variation in S-ECP was found in the group of birch-pollen-positive subjects (P
MED.
(1997)
91,
347-349
Introduction
Materials
The inflammatory activity of the airways of asthmatics can be assessedby means of bron-
The
choscopy (1,2), but less invasive methods are needed for monitoring airway inflammation clinically or in epidemiological studies. Measuring the serum levels of eosinophil degranulation products such as eosinophil cationic protein (S-ECP) is thought to be valuable for monitoring asthma (3-5). However, the usefulnessof peripheral blood markers is dependent on how factors other than the diseaseinfluence blood levels. The purpose of this investigation was to determine whether there is seasonalvariation in S-ECP. If present, this sort of variation should be taken into account when using the marker clinically or in epidemiologic research. Received 18 November 1995 and accepted in revised form 25 July 1996. Correspondence should be addressed to: C. Janson, Department of Lung Medicine, Akademiska Sjukhuset, S-751 85 Uppsala, Sweden. 0954-6111/97/060347+03
$12.00/O
study
and Methods population
comprised
a general
population sample of 379 individuals from the municipality of Uppsala, Sweden [mean age (range): 32 (2045) years]. These subjects were participants in the European Community Respiratory Health Survey (6). The study was conducted between April 1991 and February 1992. This investigation was limited to subjects who were studied in May (n=73), June (n=42), August (n=65), September (n= 86) and October (n= 114), as the number of subjects examined during the other months was low (~40). The study included a structured interview, skin prick tests, lung function measurements, methacholine challenge and blood sampling for the measurement of S-ECP. The concentration of S-ECP was assayed by means of double antibody radioimmunoassay at Pharmacia Diagnostics in Uppsala (5). Atopy was defined as a positive prick test (Phazet, Pharmacia Diagnostics, Uppsala, Sweden) with a mean diameter of 0
1997 W. B. SAUNDERS
COMPANY
LTD
348
C. JANSON ET AL.
2 3 mm. Bronchial hyper-responsiveness(BHR) was defined as a fall of 220% in forced expiratory volume in 1 s (FEV,) after the inhalation of 2 mg or less of methacholine using a dosimeter (Mefar, Brescia, Italy) (5,6).
-*30 1
STATISTICS
Differences in S-ECP in subjects with and without atopy and BHR were analysed using unpaired t-test, and the combined effect of these variables was studied using multiple linear regression. ANOVA was used to analyse seasonal variation. In order to achieve an approximately normal distribution, S-ECP values were log transformed. A P value of
0 May
JLlIle
August
September
October
1. Seasonal variation in serum eosinophilic cationic protein (S-ECP) in non-atopic (7~~242, open bars) and atopic subjects with a negative skin prick test to birch (n=72, hatched bars), and subjects with a positive skin prick test to birch (n=65, solid bars) (mean and SE). “WO.05. FIG.
Results
Of the 379 subjects investigated, 137 (36%) were atopic. Of these, 65 and 72 had positive prick tests to birch and timothy, respectively. In addition, positive skin prick tests to Dermatophagoides pteronyssinus (n =28), cat (n = 57), dog (n=43), mugworth (n=24), Cladopsorium hevbatum (n=4) and Alternaria alternata (72~7) were found. Levels of S-ECP were significantly higher in atopic subjects than in nonatopic subjects (15.7 f 9.5 vs. 13.0 f 7.3 pg I- ’ (PcO.05). Levels of S-ECP were also significantly higher in the 42 subjects with BHR than in those with no BHR (17.1 f 10.8 vs. 13.6f 7.9 pg - ‘) (PcO.05). When the S-ECP level in the whole population was studied, a significant seasonalvariation was found with a peak mean value in June (PcO.01). When comparing atopic and non-atopic subjects, there was a significant seasonalvariation in S-ECP in the atopic (P
In atopic individuals with a positive skin prick test to timothy, there was no significant relationship between the month of investigation and S-ECP levels. Discussion
The main finding of this analysis in a general population sample was that there was a significant seasonal variation in S-ECP levels. This variation was, however, only seenin birch-pollen atopic subjects, where the mean level of ECP in June was about twice as high as in birch atopic subjects examined during any of the other months. The correlation between the month of investigation and S-ECP remained significant when adjusting for BHR as a possible confounder. The main birch pollen season in 1991 in the Uppsala region started on 28 April and ended on 31 May. The pollen counts were considerably lower than is normally found in the region (mean count: l-325 vs. 7.360 birch pollen m - 3, (7). Despite this, in accordance with previous studies, the present study found seasonal variation in S-ECP in birch-pollen atopic subjects, with peak levelsjust after the birch pollen season had ended (8,9). The most important new information obtained from this investigation is that the magnitude, even during a mild birch pollen
SEASONALVARIATION Iiv S-ECP
season, was sufficient to affect the results for a general population. No investigations were made during the peak of the grass pollen season due to the summer holidays in Sweden in July. If S-ECP in grasspositive atopics had varied as it did in birch-pollen-sensitive subjects, the authors would have expected peak levels of S-ECP in August. This was not, however, found in the present study. It is concluded that in northern Europe, seasonal variation in birch-pollen-positive subjects is an additional factor that must be taken into account when using S-ECP for the monitoring of asthma clinically or in epidemiological research. Acknowledgements
This study was supported financially the Swedish Heart and Lung Foundation, Swedish Medical Research Council, Swedish Association against Asthma Allergy, The Bror Hjerpstedt Foundation the County Council of Uppsala.
by the the and and
References 1. Laitinen LA, Heino M, Laitinen A, Kava T, Haashtela T. Damage of airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis 1985; 131: 599-606.
349
2. Adelroth E, Rosenhall L, Johansson S-A, Linden M, Venge P. Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage: the effect of treatment with budesonide or terbutaline. Am Rev Respir Dis 1990; 142: 91-99. 3. Griffin E, Hakansson L, Formgren H, Jorgenson K, Peterson C, Venge P. Blood eosinophil number and activity in relation to lung function in patients with asthma and with eosinophilia. J Allergy Clin Immunol 1991; 87; 548-556. 4. Zimmerman B. Clinical experience with the measurement of ECP: usefuhress in the management of children with asthma. Clin Exp Allergy 1993; 23 (Suppl 2): S-12. 5. Bjiirnsson E, Janson C, Hakansson L, Enander I, Venge P, Boman G. Serum Eosinophil Cationic Protein in relation to bronchial asthma in a young Swedish population. Allergy 1994; 49: 730-736. 6. Burney PGJ, Luczynska CM, Chinn S, Jarvis D. The European Community Respiratory Health Survey. Eur Respir J 1994; 7: 954-960. 7. Berggren B, Nilsson S. Pollensiisongen 1991 (in Swedish). Skarholmen: Fisons Pharmaceuticals, 1992. 8. Rak S, Liivhagen 0, Venge P. The effect of immunotherapy on bronchial hyperresponsiveness and eosinophil cationic protein in pollen allergic patients. J Allergy Clin Immunol 1988; 82: 470480.
9. Carlsson M, Hakansson L, Kampe M, Stalenheim G, Peterson C, Venge P. Degranulation of eosinophils from pollen atopic patients with asthma is increased during the pollen season. J Allergy Clin Immunol1992; 89: 131-139.