PURPOSE: Evaluate the addition of Zileuton 600mg qid in clinically stable, non-smoking, non-atopic, adult asthmatics (<10 pk yr smoking history)with moderate to severe persistent illness despite treatment with Salmeterol 250 ug/ Fluticasone 50ug bid.
METHODS: Open label non-randomized pilot study. Spirometry, Juniper asthma symptom score (Juniper EF et al AJRCCM 2000;162:1330-34) and nitric oxide gas exchange (Tsoukias NM and George SC JAP 1998;85:653=666) with normal values (Gelb AF et al AJRCCM 2004;170:737-741) were measured at baseline, and 2hr post first dose of 600 mg Zileuton and 25 days post Zileuton 600mg qid. Salmeterol 250ug/Fluticasone50ug was withheld 48hr and albuterol MDI 8hr prior to testing.
RESULTS: Value for baseline, 2hr post first dose Zileuton 600mg and 24±6 day (mean±SD) post Zileuton 600mg qid in 9 asthmatics for FEV 1: 1.4±0.5L, 1.4±0.4L, 1.4±0.5L (mean±SD); FEV1%pred:54±18%, 54±18%, 52±19%; total exhaled nitric oxide (FENO) at 50ml/s: 39±24ppb, 41±26ppb, 37±21ppb (nl value, 20±11ppb); FENO at 100ml/s: 24±13ppb, 24±14ppb, 22±13ppb (nl value, 12± 5ppb); bronchial NO flux: 1.6±1. 1nL/s, 1.6±1.1nL/s, 1.5±1. 0nL/s (nl value 0.85±0.55nL/s); alveolar NO: 7.0±2.7ppb, 8.3± 4.1 ppb, 6.4±3.8 ppb (nl value 3.2±2. 0ppb); Juniper: 11±10, 11±10, 8.0±10 (nl value 0). No significant change from baseline in any parameter when Zileuton added.
CONCLUSION: Asthmatics had increased nitric oxide gas exchange despite Salmeterol 250ug/Fluticasone 50ug. Addition of Zileuton did not result in significant improvement in spirometry, Juniper score and nitric oxide gas exchange.
CLINICAL IMPLICATIONS: Inflammation as reflected by nitric oxide gas exchange is still present in clinically stable, moderate to severe persistent,non-atopic,adult asthmatics despite baseline Salmeterol 250ug/Fluticasone 50ug and addition of Zileuton.
DISCLOSURE: Arthur Gelb, Grant monies (from industry related sources) Critical Therapeutics, Boston, Mass.