Increased levels of angiopoietin-2 in induced sputum from smoking asthmatic patients

Clin Exp Allergy. 2009 Sep;39(9):1330-7. doi: 10.1111/j.1365-2222.2009.03262.x. Epub 2009 Apr 28.

Abstract

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.

Conclusion: Angiopoietin-2 levels were elevated in the airways of smoking asthmatics, and its levels were associated with impaired airway responses.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiopoietin-1 / analysis
  • Angiopoietin-1 / metabolism
  • Angiopoietin-2 / analysis
  • Angiopoietin-2 / metabolism*
  • Anti-Asthmatic Agents / administration & dosage
  • Asthma / drug therapy
  • Asthma / metabolism*
  • Asthma / physiopathology
  • Beclomethasone / administration & dosage
  • Capillary Permeability / drug effects
  • Edema / drug therapy
  • Edema / metabolism
  • Edema / physiopathology
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / physiopathology
  • Smoking / metabolism*
  • Smoking / physiopathology
  • Smoking Cessation
  • Sputum / metabolism*

Substances

  • ANGPT1 protein, human
  • Angiopoietin-1
  • Angiopoietin-2
  • Anti-Asthmatic Agents
  • Beclomethasone