Seasonal variation in total and pollen‐specific immunoglobulin E levels in the European Community Respiratory Health Survey

Several small-scale studies limited to allergic patients have reported higher IgE sensitization rates or higher specific IgE (sIgE) level to pollens during or following the pollen season compared to out of pollen season 1-4 . However, to the best of our knowledge, such studies have not been conducted in larger, more representative populations. Evidence shows that climate change may lead to changes in the pollen seasons for both grass and birch (earlier start and higher counts) 5 but the likely impact of such changes on sensitisation to these pollens is unknown.


Seasonal variation in total and pollen-specific immunoglobulin E levels in the European Community Respiratory Health Survey
To the Editor, Several small-scale studies limited to allergic patients have reported higher IgE sensitization rates or higher specific IgE (sIgE) level to pollens during or following the pollen season compared to out of pollen season. [1][2][3][4] However, to the best of our knowledge, such studies have not been conducted in larger, more representative populations. Evidence shows that climate change may lead to changes in the pollen seasons for both grass and birch (earlier start and higher counts) 5 but the likely impact of such changes on sensitization to these pollens is unknown.
This analysis provides some indirect information on the potential impact of changes in pollen levels on serum markers of allergy in the general population. We examined seasonality of total and pollen-specific (Timothy grass and birch) sIgE levels in blood samples taken on one occasion from 13673 participants aged 20-44 years from 35 centres in 15 countries (Australia, Belgium, France, Germany, Iceland, Ireland, Italy, New Zealand, the Netherlands, Norway, Spain, Sweden, Switzerland, UK and USA) enrolled in the European Community Respiratory Health Survey from 1991-3. 6 The lower limit of detection of the assay used for sIgE was 0.35 kU/L. Seasonality was examined by comparing the expected IgE levels in blood samples that were taken in spring, summer and autumn to that in winter using gamma generalized linear models (GLM) and tobit models with adjustment for age and sex. Season was defined on a 3-month basis (eg spring was March-May in northern hemisphere and September-November in southern hemisphere). Country-level estimates were pooled to obtain regional estimates using random effect meta-analysis. Four regions (Australasia, Northern Europe (NE), Southern Europe (SE) and the USA) were considered for total and grass-specific IgE. Birch-specific IgE was pooled from seven European countries (Belgium, Germany, Norway, the Netherlands, Sweden, UK and Switzerland). Our analyses assessed whether IgE levels were higher in those tested during spring or summer or in the probable pollen seasons compared to winter for each country based on literature. Ethical permission for each centre was granted by local ethics committees, and all participants signed informed consent.
When there was sufficient data, we repeated the GLMs using bimonthly periods (Jan/Feb, Mar/April etc). We further adjusted GLMs for self-reported allergies in sensitivity analysis to account for any differences in proportion of allergic participants included in each season and applied logistic regression models to examine the seasonal variations of proportion of participants sensitized to grass and birch and proportion of participants reporting allergies. Interaction between season and self-reported allergies was examined.
Two countries, Iceland and Ireland, were excluded from sIgE analysis due to data sparsity.
There was little evidence that those with allergic diseases were more likely to have their blood samples taken at a particular time of year (data not shown).
There was no significant variation in total IgE or pollen-specific IgE by season overall (Figure 1). However, the pattern of pollenspecific IgE in some regions was consistent with previous reports of increases during or after the relevant pollen season. The sIgE level to grass pollen was significantly higher in those tested in spring and autumn compared to winter in SE, but not in NE, Australasia or USA. Although the statistical significance of associations reported here varies, overall the data are consistent with the hypothesis that sIgE to grass and birch pollen is higher during or in the month after the relevant pollen season. We did not identify any convincing evidence that total IgE levels change by season or month. This is consistent with findings of some but not all previous small studies. A panel study of 17 allergic rhinitis/asthma patients in Germany reported an increase in geometric mean sIgE level to grass during the grass pollen season. 4 However, a panel study of 15 seasonal allergic rhinitis and/or asthma patients in Turkey found

Key Messages
• Previous work in populations found higher specific IgE levels in the relevant pollen season.
• We evaluated total and pollen-specific IgE levels in a cross-sectional survey of 13,673 adults.
• Our data support the concept that pollen-specific IgE increases during the relevant season.

F I G U R E 1 Ratio of expected IgE level by season in comparison to winter. A, total
IgE level, B, sIgE level to Timothy grass pollen and C, sIgE level to birch pollen. Regional and overall-pooled result from GLMs with the adjustment of age and sex. Remarks: Aus: Australasia. NEu: Northern Europe. SEu: Southern Europe Despite these limitations, our data suggest that expected levels of sIgE to grass and birch pollen rose by 45-55% in spring compared to winter. The clinical significance of this level of change in sIgE level is uncertain although we know that higher sIgE levels to grass were associated with a higher frequency of reporting symptoms on exposure to pollen, 9 and seasonal variations in allergic disease are well described.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study may be available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.