• Sejal Saglani and Adnan Custovic.
• 1 National Heart and Lung Institute and.
• Am. J. Respir. Crit. Care Med. 2019 Feb 15; 199 (4): 414-422.

AbstractA paradigm shift brought by the recognition that childhood asthma is an aggregated diagnosis that comprises several different endotypes underpinned by different pathophysiology, coupled with advances in understanding potentially important causal mechanisms, offers a real opportunity for a step change to reduce the burden of the disease on individual children, families, and society. Data-driven methodologies facilitate the discovery of "hidden" structures within "big healthcare data" to help generate new hypotheses. These findings can be translated into clinical practice by linking discovered "phenotypes" to specific mechanisms and clinical presentations. Epidemiological studies have provided important clues about mechanistic avenues that should be pursued to identify interventions to prevent the development or alter the natural history of asthma-related diseases. Findings from cohort studies followed by mechanistic studies in humans and in neonatal mouse models provided evidence that environments such as traditional farming may offer protection by modulating innate immune responses and that impaired innate immunity may increase susceptibility. The key question of which component of these exposures can be translated into interventions requires confirmation. Increasing mechanistic evidence is demonstrating that shaping the microbiome in early life may modulate immune function to confer protection. Iterative dialogue and continuous interaction between experts with different but complementary skill sets, including data scientists who generate information about the hidden structures within "big data" assets, and medical professionals, epidemiologists, basic scientists, and geneticists who provide critical clinical and mechanistic insights about the mechanisms underpinning the architecture of the heterogeneity, are keys to delivering mechanism-based stratified treatments and prevention.

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