Increased levels of angiopoietins 1 and 2 in sputum supernatant in severe refractory asthma.
BACKGROUND
Airway and vascular remodeling may play a prominent role in the clinical severity of severe refractory asthma (SRA). Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor.


OBJECTIVE
We aimed to determine the levels of angiopoietins in sputum supernatants of patients with SRA and to investigate the possible associations with mediators and cells involved in both the inflammatory and the vascular remodeling processes.


METHODS
Thirty-eight patients with SRA, 35 patients with moderate asthma, and 20 healthy subjects were studied. All participants underwent lung function tests, bronchial hyperresponsiveness assessment and sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, Cys-LTs, MMP-2, IL-13, ECP, and IL-8 measurement in supernatants. Airway vascular permeability (AVP) index was also assessed.


RESULTS
Ang-1 (ng/ml) and Ang-2 (pg/ml) levels were significantly elevated in patients with SRA compared with patients with moderate asthma and control subjects [median, interquartile ranges: 30 (17-39) vs 7.5 (5-11) vs 4.7 (3.8-5.9) respectively, P < 0.001; and 506 (400-700) vs 190 (146-236) vs 96 (89-120) respectively, P < 0.001]. Regression analysis showed a significant positive association between Ang-2 and AVP index, MMP-2, Ang-1, and VEGF in SRA. A weak association was also observed between Ang-1 and sputum eosinophils% in SRA.


CONCLUSIONS
Our results indicate that both angiopoietins levels are higher in SRA compared with moderate asthma and healthy subjects. In SRA, Ang-2 is associated with mediators involved in both the inflammatory and the vascular remodeling processes.
2nd Respiratory Medicine Department, University of Athens Medical School, 'Attikon' Hospital, Greece.
E
E
Tseliou
P
P
Bakakos
K
K
Kostikas
G
G
Hillas
K
K
Mantzouranis
P
P
Emmanouil
D
D
Simoes
M
M
Alchanatis
S
S
Papiris
S
S
Loukides
D000368:Aged; D056151:Airway Remodeling / Q000502:physiology; D042683:Angiopoietin-1 / Q000032:analysis*; D042702:Angiopoietin-2 / Q000032:analysis*; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity; D002199:Capillary Permeability / Q000502:physiology; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2