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.
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. kanazawa-h@med.osaka-cu.ac.jp
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H
Kanazawa
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K
Asai
Y
Y
Tochino
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Kyoh
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Kodama
K
K
Hirata
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