Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma.
BACKGROUND
Airway hyperresponsiveness, induced sputum eosinophils, and exhaled nitric oxide (NO) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma. The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study.


METHODS
In a randomised, double blind, placebo controlled, parallel study 25 patients with mild asthma (19-34 years, forced expiratory volume in one second (FEV1) >75% predicted, concentration of histamine provoking a fall in FEV1 of 20% or more (PC20) <4 mg/ml) inhaled fluticasone propionate (500 microg twice daily) for four weeks. PC20 to histamine, sputum eosinophil numbers, and exhaled NO levels were determined at weeks 0, 2, and 4, and two weeks after completing treatment. Sputum was induced by inhalation of hypertonic (4.5%) saline and eosinophil counts were expressed as percentage non-squamous cells. Exhaled NO levels (ppb) were measured by chemiluminescence.


RESULTS
In the steroid treated group there was a significant increase in PC20, decrease in sputum eosinophils, and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment. Subsequently, each of these variables showed significant worsening during the two week washout period compared with week 4. These changes were significantly different from those in the placebo group, except for the changes in sputum eosinophils and exhaled NO levels during the washout period. There were no significant correlations between the changes in the three markers in either group at any time.


CONCLUSIONS
Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine, eosinophil counts in induced sputum, and exhaled nitric oxide levels. The results suggest that these markers may provide different information when monitoring anti-inflammatory treatment in asthma.
van Rensen
E L
EL
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Straathof
K C
KC
Veselic-Charvat
M A
MA
Zwinderman
A H
AH
Bel
E H
EH
Sterk
P J
PJ
D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000276:immunology; D001985:Bronchial Provocation Tests; D004311:Double-Blind Method; D004804:Eosinophils / Q000276:immunology; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006632:Histamine; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D013183:Sputum / Q000276:immunology
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D005938:Glucocorticoids; D009569:Nitric Oxide; D006632:Histamine; D000068298:Fluticasone