Is low dose inhaled corticosteroid therapy as effective for inflammation and remodeling in asthma? A randomized, parallel group study.
BACKGROUND
While most of the clinical benefits of inhaled corticosteroid (ICS) therapy may occur at low doses, results of dose-ranging studies are inconsistent. Although symptom/lung function response to low and high dose ICS medication is comparable, it is uncertain whether low dose ICSs are as effective as high dose in the treatment of inflammation and remodeling.


METHODS
22 mild or moderate asthmatic adult subjects (corticosteroid free for > 2 months) participated in a randomized, parallel group study to compare effects of fluticasone propionate (FP) 200 mcg/day and 1000 mcg/day. Alveolar macrophage (AM)-derived cytokines and basement membrane thickness (BMT) were measured at baseline and after 7 weeks treatment while symptoms, spirometry, exhaled nitric oxide (eNO) and airway hyperresponsiveness (AHR) to mannitol at baseline and 6 weeks.


RESULTS
FP improved spirometry, eNO, symptoms and AHR with no difference between low and high dose FP. Both high and low dose FP reduced GM-CSF, TNF-alpha and IL-1ra, with no change in BMT and with no differences between low and high dose FP.


CONCLUSIONS
200 μg/day of FP was as effective as 1000 μg/day in improving asthma control, airway inflammation, lung function and AHR in adults in the short term. Future studies should examine potential differential effects between low and high dose combination therapy (ICS/long acting beta agonist) on inflammation and airway remodeling over longer treatment periods.
Woolcock Institute of Medical Research, Sydney, NSW, Australia. melissa.baraket@sswahs.nsw.gov.au
Melissa
M
Baraket
Brian G G
BG
Oliver
Janette K
JK
Burgess
Sam
S
Lim
Gregory G
GG
King
Judith L
JL
Black
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D056151:Airway Remodeling / Q000187:drug effects* / Q000502:physiology; D000730:Androstadienes / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001485:Basement Membrane / Q000503:physiopathology; D001944:Breath Tests; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D000068298:Fluticasone; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008353:Mannitol; D009569:Nitric Oxide / Q000032:analysis; D012129:Respiratory Function Tests; D055815:Young Adult
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D016207:Cytokines; D009569:Nitric Oxide; D008353:Mannitol; D000068298:Fluticasone