Effects of low dose fluticasone/salmeterol combination on surrogate inflammatory markers in moderate persistent asthma.
BACKGROUND
Noninvasive surrogate markers provide valuable information on the asthmatic inflammatory process. We wished to examine the effects of low dose fluticasone/salmeterol combination on different commonly used inflammatory markers in moderate persistent asthma.


METHODS
Twenty-five moderate persistent atopic asthmatics were enrolled of whom 20 completed an open label study. Following an initial 4 week steroid washout period in which patients took salmeterol 50 microg dry powder inhaler 1 puff BD, they received the addition of fluticasone as fluticasone 100 microg/salmeterol 50 microg combination dry powder inhaler 1 puff BD for the next 2 weeks. Exhaled nitric oxide, spirometry, methacholine PD20, sputum/blood eosinophils and sputum/serum eosinophil cationic protein (ECP) were measured following the salmeterol only and fluticasone/salmeterol combination treatment periods.


RESULTS
Compared to salmeterol alone (i.e. after the steroid washout), the use of fluticasone/salmeterol combination conferred significant improvements (P < 0.05) in all surrogate markers of inflammation apart from serum ECP. Geometric mean fold changes were 4.3-fold/1.3-fold for sputum/blood eosinophils, 2.2-fold/1.2-fold for sputum/serum ECP, 2.3-fold for methacholine PD20 and 1.8-fold for exhaled nitric oxide.


CONCLUSIONS
Surrogate markers apart from serum ECP may be used as a guide to evaluate the anti-inflammatory effects of low dose inhaled corticosteroids. Sputum markers tend to be more sensitive than blood when assessing the anti-inflammatory response.
Currie
G P
GP
Asthma & Allergy Research Group; Department of Pathology, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, UK.
Syme-Grant
N J
NJ
McFarlane
L C
LC
Carey
F A
FA
Lipworth
B J
BJ
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; 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; D001507:Beclomethasone / Q000008:administration & dosage; D015415:Biomarkers / Q000032:analysis; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage; D017402:Chlorofluorocarbons / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D000068298:Fluticasone; D005540:Forced Expiratory Flow Rates / Q000187:drug effects; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D011237:Predictive Value of Tests; D012260:Ribonucleases / Q000187:drug effects / Q000378:metabolism; D000068299:Salmeterol Xinafoate; D012720:Severity of Illness Index; D013147:Spirometry; D013183:Sputum / Q000737:chemistry / Q000378:metabolism; D016896:Treatment Outcome
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D001798:Blood Proteins; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D017402:Chlorofluorocarbons; D047091:Eosinophil Granule Proteins; D016210:Methacholine Chloride; D019819:Budesonide; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D012260:Ribonucleases; D001507:Beclomethasone; D000420:Albuterol