Leukotriene D4 bronchial provocation test: methodology and diagnostic value

Abstract

Background:

Although leukotriene D4 (LTD4) is a potent bronchoconstrictor, little is known about airway responsiveness to LTD4 in asthmatics with different inflammation phenotypes.

Objectives:

To establish the methodology and investigate the distribution characters of airway responsiveness, diagnostic value and safety of LTD4 bronchial provocation test.

Methods:

LTD4 bronchial provocation tests were performed in 62 asthmatics and 21 normal controls. Airway responsiveness was assessed based on the cumulative dosage causing a 20% fall in FEV₁ (PD₂₀FEV₁-LTD4) and was expressed as (median, interquartile range). The fall in spirometric parameters was plotted showing the distribution characters. The diagnostic value was assessed using receiver operation characteristic (ROC) curve. All adverse events were recorded during the test.

Results:

Airway responsiveness to LTD4 was significantly higher in asthmatics (0.410 nmol, 0.808 nmol) as compared with normal controls (5.00 nmol, 0.00 nmol). The decrease in spirometric parameters varied after bronchoprovocation, which was negatively correlated with PD₂₀FEV₁-LTD4, among which FEV₁ had a maximal slope (r = −0.524, P = 0.000). High diagnostic value (AUC: 0.914, 95%CI: [0.855, 0.974]) was revealed by ROC curve. The major adverse events were dyspnea (82.3%), chest tightness (72.6%), wheezing (32.3%) and coughing (25.8%) in asthmatics, which could overall be recovered within 15.0 minutes after inhalation of 200 ∼ 400 mcg salbutamol MDI. No serious adverse event was reported.

Conclusion:

The established procedure of LTD4 bronchial provocation test is effective in the diagnosis of asthma and is well tolerated. Future studies are necessary to provide more evidences in terms of safety and efficacy. This may be helpful upon further application in clinical practice.

Keywords::

• Airway responsiveness
• Asthma
• Bronchial provocation test
• Diagnostic value
• Leukotriene D4

Transparency

Declaration of funding

This study was supported by the Natural Science Foundation of Guangdong Province (No. 915280000100019), Municipal Science and Technology Plan of Guangzhou (No. 2009J1-C321-1), Guangzhou Leading Projects for Medicine and Health (No. 2009-YB-143) and The Science Project of Guangzhou Medical College (2008A02). None of these fundings had any influence on our study.

Declaration of financial/other relationships

W.G., J.Z., Y.G., C.J., J.A., X.Y., and W.L. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors would like to attach their special thanks to Drs. Kefang Lai, Wei Luo and Ruchong Chen (Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease) for their insightful suggestion, and Guangqiao Zeng (Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease) for his linguistic considerations.