Role of add-on zileuton on total exhaled, large airway, and small airway/alveolar nitric oxide in moderate-severe persistent adult asthmatics on fluticasone 250 microg/Salmeterol 50 microg.
BACKGROUND
Measuring non-invasive exhaled biomarkers of inflammation may be important in monitoring asthma therapy.


OBJECTIVE
Evaluate exhaled nitric oxide with add-on leukotriene synthesis inhibitor in moderate-severe persistent asthmatics on combination controllers.


METHODS
In a non-randomized, non-placebo, single-blind, fixed sequence, pilot study, we evaluated 22 non-smoking, stable, moderate-severe adult asthmatics on maintenance inhaled fluticasone 250 microg/salmeterol 50 microg (F/S) via MDI bid> or =1 yr, with add-on oral zileuton 600 mg qid. Exhaled fractional nitric oxide (FENO) gas exchange, large airway NO, small airway/alveolar NO concentration (CANO), Juniper score and lung function were measured. Asthmatics were studied at baseline only on F/S bid (visit 1), on F/S bid pre and 2 h post first dose zileuton 600 mg (visit 2), and post 4 weeks (visit 3) F/S bid plus zileuton 600 mg qid. Values were compared at each visit and to healthy non-smoking age matched healthy controls with normal lung function.


RESULTS
Three asthmatics stopped zileuton prematurely (headache and/or nausea) and 19 (12F) age 55+/-17 yr (mean+/-SD) completed the 4-week study. Baseline forced expiratory lung volume in 1 sec (FEV(1)) was 1.6+/-0.7L (53+/-19% pred) (mean+/-SD), FEV(1) over FVC ratio was 64+/-11% and post 180 microg albuterol FEV(1) was 1.8+/-0.7L (56+/-21% pred), and FEV(1) over FVC ratio was 67+/-12%. Baseline Juniper scores were mild (10+/-10) and similar (p=ns) at all visits. Baseline FENO@50 mL/s was 48+/-27 ppb (mean+/-SD), and FENO@100 mL/s was 29+/-16ppb, and were similar (p=ns) at all visits. Large airway NO flux was 2.0+/-1.3 nL/s (52% asthmatics abnormal) and small airway/alveolar NO was 8.0+/-4.0 ppb (79% asthmatics abnormal) and were similar (p=ns) at all visits. Compared to baseline, post 26+/-6 days Zileuton, mean FEV(1) (L)% predicted increased 3.3% predicted (p=0.03), and FEV(1) over FVC ratio increased 2.2% (p=0.03).


CONCLUSIONS
In stable, moderate-severe persistent adult asthmatics, large airway NO flux, small airway/alveolar CANO, and Juniper airway scores, were not significantly different on F/S bid vs F/S bid plus Zileuton for 4 weeks, despite significant small increase in FEV(1) over FVC ratio and FEV(1)% predicted.
Gelb
Arthur F
AF
Pulmonary Division, Department of Medicine, Lakewood Regional Medical Center, Lakewood, CA 90712, USA. afgelb@msn.com
Taylor
Colleen Flynn
CF
Simmons
Michael
M
Shinar
Chris
C
D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism*; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000502:physiology; D005260:Female; D000068298:Fluticasone; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018653:Juniperus / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011446:Prospective Studies; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000378:metabolism*; D000068299:Salmeterol Xinafoate; D013147:Spirometry
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009569:Nitric Oxide; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; C063449:zileuton; D006918:Hydroxyurea