Inhaled salmeterol and/or fluticasone alters structure/function in a murine model of allergic airways disease.
BACKGROUND
The relationship between airway structural changes (remodeling) and airways hyperresponsiveness (AHR) is unclear. Asthma guidelines suggest treating persistent asthma with inhaled corticosteroids and long acting beta-agonists (LABA). We examined the link between physiological function and structural changes following treatment fluticasone and salmeterol separately or in combination in a mouse model of allergic asthma.


METHODS
BALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by six daily inhalation exposures. Treatments included 9 daily nebulized administrations of fluticasone alone (6 mg/ml), salmeterol (3 mg/ml), or the combination fluticasone and salmeterol. Lung impedance was measured following methacholine inhalation challenge. Airway inflammation, epithelial injury, mucus containing cells, and collagen content were assessed 48 hours after OVA challenge. Lungs were imaged using micro-CT.


CONCLUSIONS
Treatment of allergic airways disease with fluticasone alone or in combination with salmeterol reduced AHR to approximately naüve levels while salmeterol alone increased elastance by 39% compared to control. Fluticasone alone and fluticasone in combination with salmeterol both reduced inflammation to near naive levels. Mucin containing cells were also reduced with fluticasone and fluticasone in combination with salmeterol.


CONCLUSIONS
Fluticasone alone and in combination with salmeterol reduces airway inflammation and remodeling, but salmeterol alone worsens AHR: and these functional changes are consistent with the concomitant changes in mucus metaplasia.
Riesenfeld
Erik P
EP
Vermont Lung Center, University of Vermont, Burlington, Vermont, USA. Erik.Riesenfeld@uvm.edu
Sullivan
Michael J
MJ
Thompson-Figueroa
John A
JA
Haverkamp
Hans C
HC
Lundblad
Lennart K
LK
Bates
Jason H T
JH
Irvin
Charles G
CG
D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000730:Androstadienes; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids; D000420:Albuterol