This systematic review gives an overview of the published evidence concerning the association between physical activity and asthma. Our primary research question was aimed at the etiological association between different physical activity levels and subsequent asthma incidence. In an extensive search, we only found 5 longitudinal studies that met the inclusion criteria and could be of use in answering this question. Although the number of longitudinal studies was small, the total accrued number of subjects was considerable (n
85,117). Pooling showed that subjects with higher physical activity levels might have lower risk of developing asthma.
Thirty-four studies were cross-sectional in design. Due to large clinical variability and heterogeneity we had to refrain from further statistical analysis, except for a small group of studies using a motion sensor to measure physical activity. Despite this limitation, however, we can draw some conclusions: a substantial number of included cross-sectional studies, with the largest total study population, did find an association between high physical activity levels and low asthma prevalence. This seems consistent with physical activity being protective against asthma. However, we can not rule out publication bias. Moreover, cross-sectional studies are not suited to give insight into the causal relation between physical activity and subsequent asthma incidence. Besides the hypothesis that subjects with higher physical activity levels have a lower risk of developing asthma (protective), reverse causality is also possible. There are several hypotheses why asthma patients (with asthma as exposure) could have lower physical activity levels (outcome), such as fear for symptoms of shortness of breath, wrongful education, or by asthma that is not well regulated.
In contrast to the studies that were cross-sectional in design, this reverse causality does not play a role in interpreting the results of the 5 longitudinal studies. In all 5 studies physical activity levels were measured before asthma was diagnosed. However, the results could be influenced by protopathic bias (e.g. physical activity restricted by respiratory complaints that precede an asthma diagnosis) or earlier diagnosis of asthma through exercise-induced symptoms. The first would lead to overestimation of the true association between low physical activity levels and subsequent asthma development; whereas the second would lead to an underestimation. Unfortunately, none of the longitudinal studies addressed these biases.
It is important to realize that there are several limitations to this review. First of all, due to the fact that this research is based on published material, publication bias is an important factor. Furthermore, studies showed substantial heterogeneity in different areas such as population (number, age, gender, race, duration of follow-up), exposure variables (physical activity measured by questionnaires, whether or not validated, or measured by motion sensors) and outcome variables (asthma diagnosis as self reported doctor's diagnosis, asthma symptoms or spirometry). Analysis showed borderline statistical heterogeneity. The small number of longitudinal studies prevented us from performing meta-regression or subgroup analysis. Confounding is an important issue, because other risk factors (such as smoking and obesity) could be associated with both low habitual physical activity as well as asthma development. First and second-hand cigarette smoke exposure is already established as an independent risk factor for developing asthma. 
It is suggested that obesity is a risk factor for asthma development. 
In our meta-analysis of longitudinal studies, pooling of results adjusted for confounders was not sensible because only three studies presented such results. However, adjusted odds ratios were never lower than unadjusted odds ratios (see table S3
), so that a pooled effect for the adjusted results would be higher than the odds ratio of 0.88 (95% CI: 0.77–1.01) found for the unadjusted result.
Another limitation might be the fact that the validity of the NOS score recently has been questioned by Stang who believes that the NOS provides a quality score that has unknown validity at best. 
We noted that some methodological pitfalls were not well represented in the NOS scale: reverse causation and protopathic bias or confounding by indication (e.g. advice to remain physically active for children with respiratory complaints).
In conclusion, the results of available published evidence indicate that high physical activity levels are a possible protective factor against asthma development. The heterogeneity suggests that possible relevant effects remain hidden in critical age periods, sex differences, or extremes of levels of physical activity (e.g. sedentary). Future longitudinal studies should address these issues.