Data from The Asthma Report - Curated by EPG Health - Last updated 31 October 2018
A summary of sessions from ERS 2018 covering CRAC antagonists, considering how they may suppress inflammatory responses and may be a new target for anti inflammatory therapy, RV16 induced T2 cytokines but not TSLP and insulin potentiates methacholine induced muscle activation.
Starting the second session of Sunday morning, Urso et al showed that nebulisation of good nanoparticles gives good lung deposition and may be a novel treatment option in lung transplantation.
Viswadanha et al reported on a new molecule, RP3128, which inhibits calcium (CRAC) channels. CRAC channels regulate allergic inflammatory responses and inhibition has shown to suppress inflammation more effectively than Inhaled Corticosteroid (ICS) in Chronic Obstructive Pulmonary Disorder (COPD). Their novel work shows that RP3128 also suppresses inflammatory response in asthmatic mononuclear cells. Another experiment showed an additive effect of RP3128 to steroid therapy with fluticasone. This may therefore represent a novel drug class for use in airway disease in place of or addition to steroid therapy warranting phase 2 study.
Southworth presented data from Manchester showing the results of experimental rhinovirus infection in asthmatic subjects. Previous studies have shown that viral infection results in alarmin response and subsequent upregulation of T2 responses which impairs antiviral cells. Most previous studies enrolled very mild asthma. This study enrolled patients on inhaled steroids and most were taking additional LABA (Long-Acting Beta Agonists).
Three of eleven patients did not become infected following inoculation as shown by bronchoscopy at day five. The remaining eight participants had symptoms of infection and an increase in ACQ score, antiviral response and IL-4, IL-5, IL-13 and IL-25 but no drop in FEV1 or change in IL-33 or Thymic Stromal Lymphopoietin (TSLP) in bronchial lavage. There were strong correlations between IL-25 and T2 cytokines and IL-33/T2 but the same was not true with TSLP.
Proskocil and colleagues investigated asthma with obesity. Previous studies showed that obese rats have significantly higher bronchial hyper responsiveness and Isolated tracheas showed a potentiation effect from insulin in methacholine induced construction. Cell plates were examined for calcium concentration with or without added insulin, and with added agonists. Insulin alone did not increase calcium concentrations, but it potentiated methacholine and serotonin induced calcium flux which may be via L-type calcium channels by which sarcoplasmic reticular stores are replenished.