Aspirin inhalation treatment for COPD patients: Preliminary studies on PK and inflammatory biomarkers

We are currently investigating if the use of aspirin (ASA), administered via inhalation, can exert a local anti-inflammatory effect, to propose it as a treatment for COPD, an inflammation-related pathology. As little is known on inhaled ASA's PK, a 3-way crossover study was performed on 14 moderate COPD subjects, which were administered 250/500/750mg of ASA's lysine salt via nebulizer, with/without concomitant charcoal intake (all subjects also assumed orally a 500mg dose). The inhalation resulted in a linear PK for ASA and salicylic acid in plasma. Variability appeared important after inhalation, while modest after oral intake. Only approximately 10% of the administered dose was recovered in urine (70% after oral dose). The efficacy of inhaled ASA was investigated in 4-week placebo-controlled clinical trial performed on 59 moderate COPD subjects, who inhaled 250, 500 or 750mg of ASA BID. Functional respiratory parameters were measured together with inflammatory markers in serum and induced sputum. A statistically significant decrease was observed for serum IL6 and IL8 and sputum TNFα (trend test: 0.0004, 0.0144 and 0.0275). The 250mg dose was observed to statistically increase FEV1 and FEV/FVC from T0 to T4 (p=0.02 and 0.008). The same dose also showed important effects, compared to placebo, both on inflammation (reduction of sputum neutrophil elastase, p=0.031) and sputum production (p=0.008). These results are not conclusive to prove the efficacy of the treatment (large intra-patient variation, lack for specific biochemical marker for COPD). However, also considering the good tolerability, they support the opportunity for a larger clinical trial.