Increased levels of angiopoietin-2 in induced sputum from smoking asthmatic patients.
BACKGROUND
Active cigarette smoking has detrimental effects on asthma morbidity and severity. Angiopoietin-1 has been shown to protect the microvessels against plasma leakage, whereas angiopoietin-2 enhances vascular permeability and subsequently induces airway mucosal oedema. Therefore, it is recently thought that angiopoietin-2 may contribute to the pathophysiology of asthma.


OBJECTIVE
To determine whether angiopoietin-2 levels in the airways are associated with clinical profiles in smoking asthmatics.


METHODS
We measured angiopoietin-1 and -2 levels in induced sputum in 35 normal controls (18 non-smokers and 17 smokers) and 49 asthmatics (24 non-smokers and 25 smokers) before and after inhaled beclomethasone dipropionate (BDP: 800 microg/day) therapy for 12 weeks.


RESULTS
Angiopoietin-1 and -2 levels in induced sputum were significantly higher in asthmatics than in normal controls. Moreover, angiopoietin-2 levels were significantly higher in smoking asthmatics than in non-smoking asthmatics (P=0.0001). The airway vascular permeability index was also higher in smoking asthmatics than in non-smoking asthmatics. Moreover, the angiopoietin-2 level was positively correlated with the airway vascular permeability index (non-smoking asthmatics: r=0.87, P<0.001, smoking asthmatics: r=0.64, P=0.002). After BDP therapy, angiopoietin-1 levels were significantly decreased in non-smoking asthmatics, smoking-cessation asthmatics, and active-smoking asthmatics. In contrast, angiopoietin-2 levels did not differ from before to after BDP therapy in non-smoking asthmatics and active-smoking asthmatics. However, its levels were significantly decreased from before to after BDP therapy in smoking-cessation asthmatics (P=0.002). Although forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) before BDP therapy was comparable in all subgroups, this parameter after BDP therapy was significantly lower in active-smoking asthmatics than in non-smoking and smoking-cessation asthmatics. Moreover, the reduction in angiopoietin-2 levels after BDP therapy in smoking-cessation asthmatics was significantly correlated with an improvement in FEV(1)/FVC.


CONCLUSIONS
Angiopoietin-2 levels were elevated in the airways of smoking asthmatics, and its levels were associated with impaired airway responses.
Kanazawa
H
H
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. kanazawa-h@med.osaka-cu.ac.jp
Asai
K
K
Tochino
Y
Y
Kyoh
S
S
Kodama
T
T
Hirata
K
K
D000328:Adult; D042683:Angiopoietin-1 / Q000032:analysis / Q000378:metabolism; D042702:Angiopoietin-2 / Q000032:analysis / Q000378:metabolism*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D020545:Respiratory Mucosa / Q000378:metabolism / Q000503:physiopathology; D012907:Smoking / Q000378:metabolism* / Q000503:physiopathology; D016540:Smoking Cessation; D013183:Sputum / Q000378:metabolism*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D018927:Anti-Asthmatic Agents; D001507:Beclomethasone