Airway vascular endothelial function in healthy smokers without systemic endothelial dysfunction.
BACKGROUND
Cigarette smoking can lead to systemic endothelial dysfunction. Since the airway circulation is exposed to a high concentration of cigarette smoke constituents, we reasoned that airway vascular endothelial dysfunction could be present in healthy smokers without systemic endothelial dysfunction.


OBJECTIVE
The purpose of this study was to compare airway and systemic endothelial function and measure markers of systemic inflammation in lung-healthy current smokers. Since endothelial dysfunction in smokers has been related to systemic inflammation, we also investigated its response to an inhaled glucocorticosteroid (ICS).


METHODS
Fifteen healthy, current smokers and 17 healthy, lifetime nonsmokers were enrolled. Smokers were randomly assigned to 3-week treatments with inhaled fluticasone propionate or placebo in a crossover design. Vascular endothelial function was assessed in the airway by the airway blood-flow response to inhaled albuterol (ΔQaw) and in the extrapulmonary circulation by brachial arterial flow-mediated vasodilation (FMD). Venous blood was collected for C-reactive protein and IL-6.


RESULTS
Baseline parameters did not differ between groups except for ΔQaw, which was greater in nonsmokers (45% ± 12%) than smokers (1% ± 12%) (P = .001). In the smokers, ICS treatment increased Qaw to 41% ± 7% (P &lt; .001), but had no effect on FMD or inflammatory markers. There was an inverse relationship between baseline and ICS-induced changes in ΔQaw.


CONCLUSIONS
Healthy smokers with no signs of systemic inflammation or endothelial dysfunction display impaired airway vascular endothelial function, possibly preceding systemic endothelial dysfunction. Airway endothelial function was restored with an ICS, and the response was directly related to the severity of endothelial dysfunction.
Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL. Electronic address: emendes@med.miami.edu.
Eliana S
ES
Mendes
Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL.
Jose Eduardo D
JED
Cancado
Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL.
Patricia
P
Rebolledo
Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL.
Joahna
J
Arana
Behavioral Medicine Research Center, University of Miami Miller School of Medicine, Miami, FL.
Meela
M
Parker
Behavioral Medicine Research Center, University of Miami Miller School of Medicine, Miami, FL.
Alex
A
Gonzalez
Behavioral Medicine Research Center, University of Miami Miller School of Medicine, Miami, FL.
Barry E
BE
Hurwitz
Division of Pulmonary, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL.
Adam
A
Wanner
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage; D000704:Analysis of Variance; D000730:Androstadienes / Q000008:administration & dosage*; D001916:Brachial Artery / Q000000981:diagnostic imaging; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D000068298:Fluticasone; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010919:Placebos; D015203:Reproducibility of Results; D012907:Smoking; D013147:Spirometry; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D000730:Androstadienes; D001993:Bronchodilator Agents; D015850:Interleukin-6; D010919:Placebos; D002097:C-Reactive Protein; D000068298:Fluticasone; D000420:Albuterol