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Pollinosis in children with special reference to the development of asthma
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Children with rhinoconjunctivitis and increased bronchial hyperreactivity (BHR) are prone to develop asthma later in life. Eosinophil granule proteins in serum are indirect measures of eosinophil activity and regarded as markers of inflammation. Measurement of eosinophil cationic protein (ECP) has also been evaluated for prediction, diagnosis and monitoring of treatment in children with asthma. In 1992, a multicenter preventive allergy treatment study (PAT-study) was started in order to prevent the development of asthma in children with pollinosis using specific immunotherapy treatment (SIT). Sensitization to cat allergen is common in asthma and up to 50% of children with asthma are sensitized. Exposure to cat allergen can not be avoided because exposure occurs in schools and even in homes without a cat and is a major cause of persisting airway inflammation and asthma in cat sensitized schoolchildren. Data are needed to know the level of allergen maintaining BHR or asthma.

The aims of the thesis were: 1) To assess the relationship between seasonal symptoms of allergy, BHR, PEP-variability and release of markers of inflammation. 2) To investigate the level of markers of inflammation, and PEF variability, in healthy school children. 3) To investigate the diagnostic value of the tests e.g. BHR and mediators of allergic inflammation for diagnosis of asthma in pollinosis. 4) To investigate the efficacy of SIT regarding prevention of asthma, BHR, and polysensitization. 5) To assess, the levels of cat allergens inhaled daily by asthmatic schoolchildren sensitized to cat and relate the levels of allergen to symptoms of asthma and BHR.

The PAT study population comprised 205 birch and/or grass pollen allergic children with pollinosis, from 7 centres in 5 countries in Northern and Central Europe, 28 were enrolled in the Linköping. We recruited 56 healthy school children to study the normal level of inflammatory markers and PEFR variability and 10 asthmatic schoolchildren sensitized to cat to assess the allergen levels in their daily environment.

In the pollinosis children, sensitization status was determined by skin and conjunctival provocation test and RAST. Mediators of allergic inflammation like ECP, EPX, and neutrophil mediators like MPO were measured by RIA methods, non-specific BHR by Methacholine and/or cold air challenge tests and bronchial lability by PEF variability using Mini Wrights Peak-Flow meters. The level of cat allergens in dust samples were measured by ELISA, and in air by amplified ELISA methods. SIT was given by birch and/or grass pollen allergen extracts (Alutard), during a period of 3 years.

In pollinosis children in Linköping, there was no correlation between mediators of allergic inflammation in serum and symptoms and signs of clinical asthma. BHR and PEFR-variability persisted in the autumn, though s-ECP and s-EPX did not, indicating that mediators of inflammation do not reflect asthma. Positive MBPT and IHCA tests were more often found in the children with clinical asthma. The other investigated tests were not useful for screening of asthma in this group of children with pollinosis. In healthy schoolchildren, the mean daily PEF variations were 7.35 and 6.74%, and the 9Sth percentiles were 18 and 14% during the spring and autumn respectively. The 95th percentils for s-ECP were 41 and 38 µg/L, for s-EPX 74 and 62µg/L, for s-MPO 987 and 569 µg/L and for u-EPX tucreatinine 165 and 104 µg/mmol, during spring and autumn, respectively. Our findings for mediator levels in schoolchildren were higher than reported in adults. There was a significant decrease in the levels of the eosinophil and neutrophil mediators from May to November (p ≤ 0.001) and so did the PEF variability (p=0.037) in our healthy children. As normal reference values post seasonal data would be more appropriate. In the environment of cat sensitive children, exposure levels of cat allergen varied from 0.5 µg/g to 751 µg/g dust in homes (median, 36 µg/g) and from 17 µg/g to 378 µg/g in schools (median, 137 µg/g). Airborne allergen levels varied from 13 to 2184 pg/m3 (median, 43 pg/m3 ) in the homes and 68 to 7718 pg/m3 (median 352 pg/m3) in the schools. The inhaled dose was 8 pg to 2336 pg/min. A relation between BHR and exposure level was found. In the PAT-study, children actively treated with SIT had significantly fewer asthma symptoms after 3 years (odds ratio 2.52; p<0.05) and MBPT was improved (p<0.05) compare to the control group. Thus, SIT reduced the development of asthma in our children with pollinosis.

We followed the pollinosis children in Linköping in our centre for 11 years. Our findings were: I) there was a trend of diminishing in sensitivity to MBPT and in PEF variation with age. 2) Pollen counts in different years influenced MBPT results in that particular year. 3) MBPT in 1992 could predict the development of asthma in 1994.

Place, publisher, year, edition, pages
Edsbruk: Linköpings universitet , 2004. , 95 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 842
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-22415Local ID: 1630ISBN: 91-7373-809-3 (print)OAI: oai:DiVA.org:liu-22415DiVA: diva2:242728
Public defence
2004-11-30, Eken, Hälsouniversitetet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-30Bibliographically approved
List of papers
1. Clinical characteristics of school children with birch and/or grass pollen hay-fever (The PAT-Study)
Open this publication in new window or tab >>Clinical characteristics of school children with birch and/or grass pollen hay-fever (The PAT-Study)
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: To describe the clinical characteristics of school children with hay-fever based on baseline data from the PAT-Study.

Material: Two hundred and five children, 6-15 years, mean 10.7 years, with birch and or grass pollen hay-fever, without known asthma were recruited by six pediatric allergy centers in Northern and Central Europe.

Methods: Bronchial hyperresponsiveness (BHR) to methacholine tested by methacholine bronchial provocation test (MBPT) expressed in PC20 was registered during the birch and grass pollen seasons. During the winter symptoms of conjunctivitis, rhinitis and asthma were graded by visual analogue scale (VAS), conjunctival provocation test with birch and or timothy pollen extracts, skin tests with a panel of allergen extracts and MBPT were done and a questionnaire was filled in. Differences of p <0.01 level or less were considered significant.

Results: Despite the children were included because of seasonal hay-fever without known asthma, 42/205 children (21 %) got doctor diagnosed asthma (DDA) after the first season. During the three seasons, between 60 and 73 % of the children had a PC20 to methacholine ≤ 8 mg/ml, about 30 % to ≤ 2 mg/ml and 7-10% even to ≤ 0.5 mg/ml. Most children had both rhinitis and conjunctivitis. Furthermore, 119/201 children (59%) were regularly exposed to furred animals.

There was an association between DDA and the sum of VAS for asthma during the pollen seasons.

The BHR was significantly more pronounced in those with than those without DDA during all three seasons: Using the three cut offs, the difference was most pronounced during the winter season but reached also significance using the cut off limit 0.5 mg/ml during the birch pollen season.

Doctor diagnosed asthma correlated to PC20 during the seasons for most of the cut off limits for PC20 and in general there was an association in PC20 between the seasons independent of cut off limits.

Furthermore, DDA, but not BHR, correlated to exposure to traffic and there was an association between exposure to traffic and industrial pollution, but not to ETS or duration of breastfeeding.

Conclusion: The most striking feature of school children with uncomplicated hay-fever was the high frequency of DDA and BHR, most pronounced during the winter, the high frequency of exposure to living animals and sensitization to indoor allergens. Hay-fever is a generalized disease. Even without obvious asthma, BHR is common and most children have symptoms from both the eyes and the airways. Diagnosis of asthma in children with hay-fever and early anti-inflammatory treatment may improve the prognosis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85000 (URN)
Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2012-10-30
2. Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis: ECP and EPX levels are not related to bronchial hyperreactivity
Open this publication in new window or tab >>Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis: ECP and EPX levels are not related to bronchial hyperreactivity
1997 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 27, no 5, 530-539 p.Article in journal (Refereed) Published
Abstract [en]

Background Symptoms of allergic asthma are triggered by allergen exposure inducing allergic inflammation and hyperreactivity of the bronchi.

Objectives To investigate the possible relationship between clinical symptoms and signs of asthma, i.e. bronchial variability as measured by peak expiatory flow rate (PEFR). bronchial hyperreactivity (BHR) and mediators of allergic inflammation.

Methods Twenty-eight children with pollinosis. but no obvious history of asthma, were studied at three occasions, i.e. before, during and after (autumn) the birch pollen season. Twelve children sensitive to birch pollen were considered as the case group. Sixteen children, who were only clinically sensitive to grass pollen, served as controls. Subjective symptoms of asthma were recorded by visual analogue scale, BHR was estimated by methacholine bronchial provocation tests, bronchial variability PEFR and circulating mediators of inflammation, i.e. eosinophil cationic protein, eosinophil protein X, myeloperoxidase and tryptase in serum.

Results Bronchial hyperreactivity and by PEFR was more pronounced after than during the season (P < 0.01), whereas eosinophil mediators and the peak expiratory flow rate increased during the season (P < 0.05). Except for between PEFR variability and BHR in the autumn (r= 0.45; P= 0.014). no correlations were found. However, in the autumn, the majority of children were still hyperreactive in the bronchi and showed PEFR variability but the levels of eosinophil mediators in serum had returned to normal levels.

Conclusion Signs and symptoms of asthma did not correlate with serum levels of mediators of allergic inflammation. Bronchial hyperreactivity and PEFR variability persisted after the pollen season when signs of bronchial inflammation had disappeared. We hypothesize that eosinophil mediators and other markers of allergic inflammation disappear after the late-phase reaction, whereas BHR persists. This would explain the lack of correlation between the levels of eosinophil mediators in serum and symptoms of asthma and BHR.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85002 (URN)10.1111/j.1365-2222.1997.tb00741.x (DOI)
Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2017-12-07
3. Seasonal differences of peak expiratory flow rate variability and mediators of allergic inflammation in non-atopic adolescents
Open this publication in new window or tab >>Seasonal differences of peak expiratory flow rate variability and mediators of allergic inflammation in non-atopic adolescents
2001 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 5, 238-246 p.Article in journal (Refereed) Published
Abstract [en]

Variations in peak expiratory flow (PEF) and serum eosinophil mediators were studied in healthy adolescents. Twenty-five boys and 31 girls, 11–16 years of age (mean age 14.3 years), were selected and investigated during the birch pollen season of 1995; 45 were also investigated during the autumn of the same year. The PEF was measured twice daily and eosino-phil mediators in serum and in urine were measured by radioimmunoassay (RIA) once during the birch pollen season and once in autumn. The type values of the daily PEF variation, expressed in amplitude percentage mean, were 6.4 and 3.9%, mean values were 7.35 and 6.74%, and the 95th percentiles were 18 and 14%, during the birch pollen season and autumn, respectively. The 95th percentiles were 41 and 38 µg/l for serum eosinophil cationic protein (s-ECP), 74 and 62 µg/l for serum eosinophil protein X (s-EPX), 987 and 569 µg/l for serum myeloperoxidase (s-MPO), and 165 and 104 µg/mmol for urinary eosinophil protein X/urinary creatinine (u-EPX/u-creatinine), during the birch pollen season and autumn, respectively. The levels of the eosinophil mediators decreased significantly from May (n = 56) to November (n = 45), for s-ECP from a median value of 14 µg/l to 7 µg/l (p= 0.001), for s-EPX from a median value of 28 µg/l to 20 µg/l (p= 0.001), and for the neutrophil mediator, s-MPO, from a median value of 440 g/l to 292 g/l (p< 0.001). The PEF variability decreased significantly (p= 0.037), from spring (n = 55; median 8%, 95% confidence interval [CI] 7.8–10.19) to autumn (n = 44; median 6%, 95% CI 6.1–8.9). A significant correlation was found between the levels of s-ECP and s-EPX (rs = 0.7, p< 0.001), between s-ECP and s-MPO (rs = 0.6, p< 0.001), between s-EPX and s-MPO (rs = 0.4, p< 0.005), and between s-EPX and u-EPX/u-creatinine (rs = 0.6, p< 0.0001), in the birch pollen season (n = 56) and in the autumn (n = 45). There was a positive correlation found in PEF variability between the two seasons (n = 43; rs = 0.5, p= 0.0006). No other correlation was found between PEF variability and any other parameters. The difference in the levels of eosinophil mediators between seasons in non-atopic, healthy children is unexplained. Normal limits for mediators were higher and PEF variability was almost the same as has been reported in adults. When using normal values, seasonal influences should be considered.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25880 (URN)10.1034/j.1399-3038.2001.00024.x (DOI)10320 (Local ID)10320 (Archive number)10320 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
4. Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever
Open this publication in new window or tab >>Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever
2005 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 16, no 6, 478-486 p.Article in journal (Refereed) Published
Abstract [en]

In children with mild asthma, symptoms are not always apparent. Therefore, results of tests play an important role for the diagnosis. First, to investigate whether children with bronchial hyper-responsiveness (BHR) but no symptoms of asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim was to find out the diagnostic properties of tests for asthma/allergic inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to diagnose asthma in a group of children with hay fever. Twenty-eight children with pollinosis, 12 of them with a history of asthma for the first time during the season 1992, were studied during the birch pollen season and in the autumn of 1994. During both periods, the bronchial hyper-reactivity was estimated by methacholine bronchial provocation tests (MBPT), bronchial variability by peak expiratory flow rate variability, subjective symptoms of asthma by visual analogue scale (VAS) and bronchial inflammation by serum and urine levels of inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16 children with BHR but without clinical asthma in 1992 had developed asthma in 1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992 had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in 1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28 hay-fever children had a positive IHCA tests and 24 had positive MBPT. In relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was high, but the specificity low, whereas the specificity of most other tests was high, but based on few individuals. In relation to DDA both the IHCA test (65–80%) and the MBPT test (79–85%) had a high sensitivity and it was three to six times more likely to find a positive test among asthmatics than in non-asthmatics. Children with hay fever without clinical asthma have a high risk of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and the MBPT showed a high sensitivity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-36346 (URN)10.1111/j.1399-3038.2005.00296.x (DOI)31085 (Local ID)31085 (Archive number)31085 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
5. Cat allergen exposure in Swedish schools is high enough to maintain continuous bronchial hyperreactivity and to cause symptoms in children with asthma who are sensitized to cat
Open this publication in new window or tab >>Cat allergen exposure in Swedish schools is high enough to maintain continuous bronchial hyperreactivity and to cause symptoms in children with asthma who are sensitized to cat
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Exposure to indoor allergens play a major role for development of sensitization and induction of allergic inflammation, bronchial hyperreactivity and symptoms in sensitized individual.

Objective: fu this study, we investigated the individual exposure levels of cat allergen, Fel d1, among asthmatic schoolchildren sensitized to cats. We studied the exposure relationship with symptoms, medication, lung functions, bronchial hyperreactivity (BHR) and mediators of allergic inflallrmation.

Methods: Ten school children with known allergy to cats were selected from 5 schools in Linköping, Sweden. All children had positive skin test to cats. We collected dust samples from homes and schools. All children carried a portable air-sampler in the schools during the period of 4-6 weeks. Air was also sampled fi·om the bedroom. The children performed lung function (PEF) twice daily using a digital Peak flow meter. They maintain symptom and medication chart once in a week. We performed methacholine bronchial provocation test (PD20) and analyzed mediators of allergic inflammation (s-ECP, EPX and MPO) iu blood and urine at the beginning and at the end of the study period. Dust and air samples were analyzed for major cat allergen (Fel d1) using ELISA.

Results: Exposure levels of cat allergen varied from 0,5 µg/g to 751 µg/g dust in homes (median, 36 µg/g) and from 17 µg/g to 378 µg/g in schools (median, 137 µg/g). Airborne allergen levels varied from 13 to 2184 pg/m3 (median, 43 pg/m3) in the homes and 68 to 7718 pg/m3 (median 352 pg/m3) in the schools. The mediators of allergic inflammation ranged from 4 to 57 µg/L for ECP, from 12 to 73 µg/L for EPX and from 148 to 581 µg/L for MPO. All children had bronchial hyperreactivity and all but one child used asthma/allergy medicine during the entire study period. A significant relationship (p<0.05) was found between the peak allergen exposure and symptoms, airborne allergens and BHR of the children.

Conclusions: Our study suggests, that school is an important source of cat allergen exposure, that cat sensitized asthmatic children inhale a substantial amount of cat allergen in the schools, that despite treatment of asthma including regular use of inhaled corticosteroids, 8 pg to 2336 pg of cat allergen inhaled per minute is sufficient enough to maintain a continuous airway hyper-responsiveness among this group of children.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85007 (URN)
Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2012-10-30
6. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)
Open this publication in new window or tab >>Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)
Show others...
2002 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 109, no 2, 251-256 p.Article in journal (Refereed) Published
Abstract [en]

Background: Children with allergic rhinitis are likely to develop asthma.

Objective: The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis.

Methods: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean age, 10.7 years) with grass and/or birch pollen allergy but without any other clinically important allergy were randomized either to receive specific immunotherapy for 3 years or to an open control group. All subjects had moderate to severe hay fever symptoms, but at inclusion none reported asthma with need of daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by peak flow. Methacholine bronchial provocation tests were carried out during the season(s) and during the winter.

Results: Before the start of immunotherapy, 20% of the children had mild asthma symptoms during the pollen season(s). Among those without asthma, the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P < .05). Methacholine bronchial provocation test results improved significant in the active group (P < .05).

Conclusion: Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis.

Keyword
prevention, specific immunotherapy, bronchial hyperresponsiveness, asthma, rhinitis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-47894 (URN)10.1067/mai.2002.121317 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
7. Asthma and allergy in pollinosis children: an 11-year follow-up of specific immunotherapy
Open this publication in new window or tab >>Asthma and allergy in pollinosis children: an 11-year follow-up of specific immunotherapy
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Pollen immunotherapy is effective in hay fever and asthma in children, although there are few studies on the long-term benefit.

Methods: We conducted a longitudinal follow up for 11 years of specific immunotherapy (SIT) for birch and or grass pollen allergy in children (n=28) who took part in the preventive allergic treatment (PAT) study. Bronchial hyperresponsiveness (BHR.) to methacholine, conjunctival provocation tests (CPT), and the skin sensitivity to common allergens-(SPT) were done. A matched group of patients who had not received immunotherapy served as controls.

Results: Eight years after of discontinuation of IT, 11 children with and 11 children without IT could be investigated. In the SIT group 2 had asthma compared to 7 in the control group. The skin and conjunctival sensitivity in the SIT group decreased more (n.s.). Birch pollen counts were measured dming the pollen seasons in every year from 1992 to 1995 and in the year 1997. The years 1993 and 1995 had high levels of birch pollen counts compared to the other years.

When all the children were considered, scores for asthma symptoms and BHR was higher in these years.

PEF variation decreased with age in both groups.

Conclusions: SIT for hay fever for three years induced a clinical remission 8 years after discontinuation of immunotherapy accompanied by a reduction in the degree of BHR, conjunctival sensitivity, number of allergen sensitizatlons, and occurrence of asthma symptoms.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85009 (URN)
Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2012-10-30

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