The amino acid glycine attenuates airway hyperresponsiveness associated with T2 asthma

Asthma is a chronic respiratory disease exhibiting circadian rhythmicity and causing significant morbidity and mortality worldwide. Current inhaled corticosteroids (ICS) maintenance therapies may not adequately control asthma or treat all sub-types in addition to side-effects such as adrenal suppresion and frequent patient non-compliance. Glycine, a non-essential amino acid, plays a critical role in metabolism and is reduced in asthma patients. We hypothesize that glycine can alleviate airway hyperresponsiveness associated with asthma. Female C57Bl/6 mice (8 wks) were challenged with thrice-weekly house dust mite (HDM) i.n for 5-weeks. On a subset of mice, Glycine (100mM) was nebulized thrice weekly synergistically with HDM administration for 2 weeks while another subset underwent saline (vehicle) nebulization. After 5 weeks, lung function was measured terminally using Flexivent, lungs lavaged, comprehensive inflammatory cell analysis and lung histopathology was conducted while a lobe of the lung was used for single-nuclei RNA sequencing. <fig><object-id>erj;66/suppl_69/PA2121/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> Preliminary data shows glycine significantly reduced airway hyperresponsiveness (AHR) as demonstrated by the reduction in airway resistance (Fig 1A) and improvement in the Pressure-Volume (PV) loops (Fig 1B). Furthermore, inflammatory cellular infiltration in the lavaged lungs, histopathological analysis and single-nuclei RNA sequencing is in progress to determine how glycine can reduce AHR.