Late-breaking abstract: Inhaled calcium based dry powder inhibits rhinovirus-induced inflammation and exacerbation in a mouse model of allergic airway inflammation

Acute exacerbations (AE) in asthma are associated with rhinovirus (Rv) infection. AEs drive disease progression and cause loss of lung function, yet no current therapies target this infectious component. Calcium (Ca) based dry powder (DP) formulations were developed as host-targeted therapies that broadly reduce viral infection in vitro , including Rv. Here, a lead Ca-based DP (PUR118) was tested for efficacy against Rv in a mouse model of infection and AE using Rv1B infection in naïve and ovalbumin (OVA)-challenged mice (Bartlett NW et al Nat Med 2008). Mice (Balb/c) were treated with PUR118 or control DP by whole body exposure, twice daily (BID) 2d prior to Rv infection (5×10 6 TCID50) and BID on day of infection. Bronchoalveolar lavage (BAL) inflammation was evaluated 24h post-infection. Additional indices of infection and exacerbation included: viral titers, and expression of relevant cytokines and chemokines. Rv infection caused significant neutrophilic inflammation in naïve mice (7.5×10 5 BAL neutrophils/ml) and exacerbated inflammation in OVA challenged mice (44% increase over control) with increased neutrophils, cytokines and chemokines. In naïve mice, PUR118 treatment reduced neutrophilic inflammation by 38%, which correlated with reduced cytokine and chemokine expression. Similar results were observed in OVA mice where PUR118 treatment reduced neutrophilic inflammation by 40%. The data show Ca-based DP significantly inhibits Rv-induced airway inflammation and Rv-driven exacerbation responses in an asthma-like mouse model. These data support the development of inhaled Ca-based DP to treat infectious causes of AEs in respiratory disease.