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.
Edsbruk: Linköpings universitet , 2004. , 95 p.