Effect of fluticasone 250 microg/salmeterol 50 microg and montelukast on exhaled nitric oxide in asthmatic patients.
BACKGROUND
Monitoring noninvasive biomarkers of inflammation is an important adjunct in asthma therapy.


OBJECTIVE
The goal of the present study was to identify airway and alveolar site(s) of inflammation using exhaled nitric oxide (NO) as a marker in asthmatic patients, and to evaluate the NO response to maintenance fluticasone 250 microg/salmeterol 50 microg (F/S) and add-on montelukast 10 mg (M).


METHODS
Thirty (24 women) nonsmoking, mild to moderate asthmatic patients were studied, mean age (+/- SD) 43+/-9 years, treated with F/S for more than one year. All were clinically stable for longer than eight weeks and had not taken oral corticosteroids and/or leukotriene antagonists for eight weeks before the present study. Spirometry, Juniper asthma symptom score, fractional exhaled NO (FENO) 100 mL/s, bronchial NO and alveolar NO concentration (CANO) were measured in a single-blind, nonrandomized crossover study.


METHODS
Visit 1: baseline F/S; visit 2: after four weeks of F/S plus M; visit 3: after four weeks of S plus M; and visit 4: after four weeks of S only. Values in asthmatic patients were also compared with 34 nonsmoking age-matched healthy controls with normal lung function.


RESULTS
After 180 microg aerosolized metered dose inhaler albuterol, the forced expiratory volume in 1 s at baseline was 2.6+/-0.8 L (86%+/-16% of the predicted value) and the forced expiratory volume in 1 s over the forced vital capacity was 77%+/-9% (mean +/- SD), and was similar at visits 2 to 4. Juniper scores were mildly abnormal at visits 1 to 3, but significantly worse (P=0.03) at visit 4 versus visits 1 to 3. FENO values at visits 1 to 3 were similar but significantly increased (P=0.007) at visit 4. Bronchial NO was higher (P=0.03) at visit 4, versus visits 1 and 2, and was no different at visit 3. Compared with the healthy subjects, FENO and bronchial NO values were abnormal (greater than the normal mean plus 2 SD) in 33% of asthmatic patients at visits 1 to 3. CANO was similar for visits 1 to 4. CANO was abnormal (greater than the normal mean + 2 SD) in 20% of asthmatic patients.


CONCLUSIONS
In clinically stable asthmatic patients, despite controller treatment including moderate-dose inhaled corticosteroids and add-on M, 33% of mild to moderate asthmatic patients have ongoing nonsuppressed bronchial sites of increased NO production, compared with healthy control subjects. These controllers have no effect on CANO, which was abnormal in 20% of the asthmatic patients studied. The addition of add-on M to baseline moderate-dose inhaled corticosteroid did not further reduce total exhaled, bronchial and/or alveolar NO production.
Division of Pulmonary Services, Department of Medicine, Lakewood Regional Medical Center, Lakewood, Los Angeles, USA. afgelb@msn.com
Arthur F
AF
Gelb
Colleen Flynn
CF
Taylor
Chris M
CM
Shinar
Carlos A
CA
Gutierrez
Noe
N
Zamel
D000085:Acetates / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001944:Breath Tests; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011804:Quinolines / Q000008:administration & dosage*; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D009569:Nitric Oxide; C093875:montelukast; D000420:Albuterol