World Health Business (Who also) estimations that 24% of the global

World Health Business (Who also) estimations that 24% of the global burden of disease is caused by environmental factors that can be averted (1). smoke from solid fuels; secondhand smoke (SHS); and ambient air pollution (1-4). On a typical day children may be exposed to a number of different environmental agents at home in daycare centers and AZD1480 colleges and outdoors. Most study carried out thus far offers focused on the investigation of isolated risk factors. Little is known about the effects on children of concurrent exposures to multiple risk factors and whether they interact with each other to potentiate adverse effects on asthma or whether one element might produce an effect that reduces the effect of another. In this problem of the Journal Rabinovitch and colleagues (pp. 1350-1357) statement novel results from a repeated-measures study of children aged 6 to 15 years that begins to address this space (5). Rather than focusing on individual asthma causes in isolation these investigators used an in-depth panel study of a relatively small group of children with asthma to evaluate the interactive effects of SHS and particulate matter air pollution two common founded environmental risk factors on disease severity. In particular they focused on how SHS exposure modified the effect of ambient pollution on asthma severity. A strength in their analysis is use of objective steps of asthma severity and exacerbations –urinary levels of leukotriene E4 (LTE4 a biological marker associated with airway swelling and bronchoconstriction) and the rate of recurrence of save albuterol inhaler use (logged electronically from the inhaler). Both LTE4 and albuterol use were higher on days with higher outdoor ambient PM2.5 concentrations. However the effects of PM were stronger on days when exposure to SHS measured by same-day urinary cotinine concentrations was low. The effect of PM AZD1480 on asthma severity could not be seen with high SHS exposure. The findings in the study were not as consistent year-to-year and across statistical models as would be preferred but the results are of interest. They suggest that the effects of two common environmental exposures-in this case PM and SHS which might be considered to take action in a AZD1480 similar fashion-do not simply add-on to each other. This finding may be particularly helpful to assess the actual effect of environmental causes of asthma in real-life settings where exposures typically happen in mixtures and mixtures. Aspects of the study design enhance the strength of the work. The repeated-measure design exploits the inherent variability of asthma phenotypes to evaluate time-varying environmental factors. Repeated laboratory assessment of biomarkers of both asthmatic swelling and SHS probably reduces misclassification of both exposure and outcome and hence increases our confidence in the results. Why should exposure to SHS attenuate airway effects of ambient PM? Does tobacco smoke simply overwhelm the effect of PM and create a situation in which our observational methods simply are not sensitive enough to observe the more delicate effect exerted by ambient particles? If the two agents are acting to effect the same biological pathway(s) is definitely one agent actually competing with the additional or is definitely a pathway merely saturated? If the two agents effect different (actually subtly different) pathways then one agent could reduce effect of the additional through a variety of regulatory mechanisms at the cellular and molecular level. Rabinovitch and AZD1480 colleagues explain their findings by relying on the likely nonlinearity of the concentration-response function that includes both SHS and GU2 PM. This explanation is persuasive but is not related to the underlying biological processes that are involved. The finding of an attenuation of the effects of air particles in the presence co-exposure to SHS increases questions concerning the mechanism underlying the cellular and molecular relationships between the two risk factors (Number 1). Both particles and SHS in addition to several additional triggers of child years asthma are inhaled into the airways and initiate cascades that result in local and systemic oxidative stress and swelling. Recent evidence offers helped us to understand that environmental risk factors activate.