Benefit from anti-inflammatory treatment during clinical remission of atopic asthma.
OBJECTIVE
Subjects with atopic asthma often experience a disappearance of symptoms around puberty. However, airway inflammation and remodeling may persist. It is unknown whether those findings warrant prolonged anti-inflammatory treatment despite the absence of symptoms. In this study, we investigated whether a short course of combined anti-inflammatory treatment would, also in this specific patient population, diminish airway inflammation and/or remodeling.


METHODS
A double-blind, randomized placebo-controlled trial was conducted in 28 asymptomatic subjects with a history of atopic asthma, with established bronchial hyperresponsiveness to methacholine (MCh) as non-invasive indicator of ongoing airway pathology.


METHODS
Intervention consisted of the salmeterol/fluticasone propionate combination (SFC) product (50/250 microg bid via the Diskus inhaler) or placebo for 3 months.


METHODS
The change in lung function (FEV1), bronchial response to MCh and adenosine monophosphate (AMP), the fraction of nitric oxide in exhaled air (FENO) and quality of life (QOL) scores were measured. Also, bronchial biopsies were taken and cryo sections immunostained for eosinophils (major basic protein, MBP) and mast cells (tryptase and chymase) before and after treatment. The change in reticular basement membrane (RBM) thickness, one of the parameters of airway remodeling, was also determined.


RESULTS
SFC treatment improved hyperresponsiveness to MCh (P = 0.014) as well as AMP (P = 0.011), and reduced FENO (P < 0.001) significantly as compared with placebo. Lung function tended to improve (NS). Furthermore, SFC treatment reduced tryptase in the subepithelium of bronchial biopsy specimens (P = 0.01), and slightly reduced RBM thickness (P = 0.05). However, eosinophils in (sub)epithelium were not significantly affected; neither were chymase levels, blood eosinophils or QOL scores.


CONCLUSIONS
We found that 3 months of treatment with fluticasone propionate and salmeterol reduced airway hyperresponsiveness, FENO and tryptase density in the airway mucosa as markers of airway inflammation. MBP density in the airway mucosa and QOL were, however, unchanged. The clinical relevance of these findings, especially with respect to the long-term outcome, has not been determined yet.
van den Toorn
Leon M
LM
Department of Pulmonary Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. lvandentoorn@planet.nl
Prins
Jan-Bas
JB
de Jongste
Johan C
JC
Leman
Karolina
K
Mulder
Paul G H
PG
Hoogsteden
Henk C
HC
Overbeek
Shelley E
SE
D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000704:Analysis of Variance; D000730:Androstadienes / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D001944:Breath Tests; D016535:Bronchial Hyperreactivity; D001999:Bronchoscopy; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers; D009569:Nitric Oxide / Q000032:analysis; D012129:Respiratory Function Tests; D000068299:Salmeterol Xinafoate; D016896:Treatment Outcome
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol