Strengths and limitations
Besides the modest sample size and somewhat limited external validity due to loss to follow-up, primarily of families with low school education, the largest limitation of our study is that it is based on a single study area. Therefore, our findings cannot be generalized to other areas. Future studies should further investigate our observed associations in urban, suburban and rural contexts across different climates and countries. Moreover, we cannot exclude residual confounding of our findings by allergenic shrubs and herbs and even by trees on private grounds, as these were not part of the tree registry. We co-adjusted our models with tree exposures for general vegetation degree, but this is not sufficient to rule out potential impacts of other allergenic vegetation. Limited sample size together with relatively low prevalence of asthma and AR precluded us from testing more effect modifiers, in particular, socioeconomic status. Nevertheless, LISA is an established cohort study meant to explore various risk factors of allergic diseases. All allergic outcomes were collected by using state-of-the-art methods at many timepoints. Repeated measurements analysis provides enough power to detect even small associations. The impact of confounding was reduced by controlling for many perinatal and early postnatal allergy risk factors. Finally, we were able to classify all tree genera into allergenic vsnon-allergenic by several different criteria, something that was never done before in epidemiological analyses.