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Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signaling pathways, to mitigate allergen and obesity-induced lung function decline in a murine model of asthma. Bile acids were measured in the plasma of healthy subjects and individuals with asthma and serum and lung tissue of mice with and without allergic airway disease (AAD). Lung function, indices of inflammation and hepatic bile acid enzyme expression were measured in obese mice with house dust mite-induced AAD treated with vehicle or NO2-OA. Serum levels of glycocholic acid and glycoursodeoxycholic acid clinically correlate with body mass index and airway hyperreactivity whereas murine levels of β-muricholic acid and tauro-β-muricholic acid were significantly increased and positively correlated with impaired lung function in obese mice with AAD. NO2-OA reduced murine bile acid levels by modulating hepatic expression of bile acid synthesis enzymes, with a concomitant reduction in small airway resistance and tissue elastance. Bile acids correlate to body mass index and lung function decline and the signaling actions of nitroalkenes can limit AAD by modulating bile acid metabolism, revealing a potential pharmacologic approach to improving the current standard of care.

Vocal cord dysfunction (VCD) is a functional disorder of the vocal cords characterized by exaggerated adduction of vocal cords during inspiration and/or expiration causing respiratory and laryngeal symptoms. VCD can exist in isolation and coexist with asthma, or it can mimic asthma. The missteps during the VCD and asthma diagnostic process and subsequent faulty clinical conclusions can lead to mistreatment and increased health care utilization that can last for years. Therefore, diagnostic precision in conjunction with optimal therapeutics is a prerequisite for the best patient outcomes in this patient population. An integrated approach is frequently required using multiple diagnostic modalities to make a correct diagnosis. The treatment options, usually applied in a step-wise progression, depend on the severity of presentation and the underlying type of VCD. Future studies should address the better identification of specific phenotypes of VCD and their corresponding treatments.