P246 Glycine attenuates airway hyperresponsiveness associated with T2 asthma

Asthma is a chronic respiratory disease exhibiting circadian rhythmicity and causing significant morbidity and mortality worldwide.1 Current inhaled corticosteroids (ICS) maintenance therapies may not adequately control asthma or treat all sub-types. In addition, side-effects such as adrenal suppression and frequent patient non-compliance highlights the need for alternative treatments (NICE guidelines). Glycine, a non-essential amino acid approved for human use, plays a critical role in cellular metabolism and is significantly reduced in asthma patients.2 We are interested to discover how glycine mediates its anti-inflammatory and immunomodulatory properties and thereby regulating airway hyperresponsiveness (AHR) associated with T2 asthma.

Female C57Bl/6 mice (8 weeks old) were housed under a controlled environment on a 12h light/12h dark cycle with free access to water and lab chow. These mice were subjected to a 5-week regiment of thrice-weekly intranasal house dust mite (HDM) challenges. On a subset of mice after three weeks, Glycine (100 mM in saline) was nebulized thrice weekly on alternate days to HDM administration for 2 weeks synergistically with HDM administration. Another subset of mice underwent saline (vehicle) nebulization on alternate days to HDM administration for a further 2 weeks. After 5 weeks, pulmonary function was measured terminally using Flexivent (SciReq). Lungs were lavaged post-mortem and comprehensive inflammatory cell analysis and lung histopathology were conducted. A lobe of the lung was used for performing single-nulcei RNA sequencing.

We propose that administration of inhaled glycine to the physiological allergen House Dust Mite (HDM) exposed mice for prolonged periods may result in alleviation of airway hyperresponsiveness

Preliminary data shows glycine significantly reduced airway hyperresponsiveness (AHR) as demonstrated by the reduction in airway resistance and improvement in the Pressure-Volume (PV) loops (figure 1A). Furthermore, glycine reduced airway eosinophilia and immune cellular influx (figure 1B). Histopathological analysis revealed glycine targeted airway remodelling by reducing airway epithelial thickness, sub-epithelial collagen and myofibroblast transition. Analysis of single nuclei RNA sequencing to identify key molecular pathway alterations is in progress.