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Obesity further contributes to systemic low-grade inflammation, especially via visceral fat accumulation and metabolic dysfunction, leading to increased levels of IL-6, C-reactive protein, and tumor necrosis factor- (TNF-), which can trigger or worsen airway hyperresponsiveness 32

Analyses within each of four US regions (Supplementary Analysis 3) were also generally consistent with the main findings: the Midwest, South, and West showed a clear cigarette shortfall in the post-period that was correlated with ENDS sales (while the Northeast results were inconclusive due to a discrete event in mid-2016 impairing the models ability to detect a significant cigarette shortfall)

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