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Response–Dose Ratio is a Surrogate of Cumulative Provocative Dosage for Bronchial Provocation Tests in Asthma

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Abstract

Background

Response–dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma.

Objectives

To compare the diagnostic value of RDR and PD, by conducting leukotriene D4 (LTD4-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels.

Methods

Healthy subjects and asthmatic patients underwent LTD4-BPT and MCh-BPT, at 2–14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20 % fall in forced expiratory volume in one second (PD20FEV1) and the RDR, defined as FEV1 fall (%) at the final step divided by the corresponding provocative dosage.

Results

Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. Log10RDR was positively correlated with log10PD20FEV1 in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower PD20FEV1 and higher RDR (both P < 0.05). The differences in PD20FEV1 and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with log10PD20FEV1, the log10RDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR (≤25th percentile) was associated with higher baseline FEV1 (P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and PD20FEV1 led to an increased diagnostic value compared with either parameter alone.

Conclusions

RDR is a surrogate of PD20FEV1 for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants.

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Abbreviations

RDR:

Response–dose ratio

FVC:

Forced vital capacity

FEV1 :

Forced expiratory volume in one second

PEF:

Peak expiratory flow

LT:

Leukotriene

LTD4-BPT:

Leukotriene D4 bronchial provocation test

MCh-BPT:

Methacholine bronchial provocation test

PD20FEV1-LTD4 :

Cumulative dose of leukotriene D4 causing a 20 % fall in FEV1

PD20FEV1-MCh:

Cumulative dose of methacholine causing a 20 % fall in FEV1

ROCC:

Receiver operation characteristic curve

UC:

Uncontrolled

PC:

Partly controlled

CC:

Controlled

μmol:

Micromole

nmol:

Nanomoles

UC-PD:

Provocative dosage in uncontrolled asthma group

UC-RDR:

Response–dose ratio in uncontrolled asthma group

PC-PD:

Provocative dosage in partly controlled asthma group

PC-RDR:

Response–dose ratio in partly controlled asthma group

CC-PD:

Provocative dosage in controlled asthma group

CC-RDR:

Response–dose ratio in controlled asthma group

HS-PD:

Provocative dosage in healthy subjects

HS-RDR:

Response–dose ratio in healthy subjects

Log10RDRMCh :

Logarithm of the RDR in MCh-BPT

Log10RDRLTD4 :

Logarithm of the RDR in LTD4-BPT

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Acknowledgments

The authors would like to thank Drs. Ke-fang Lai, Ru-chong Chen, and Wei Luo (State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University) for their useful comments. This work is supported by the Provincial Nature Science Foundation of Guangdong 915280000100019 (Dr. J. Zheng), Municipal science and technology plan of Guangzhou 2009J1-C321-1 (Dr. Y. Gao), Guangzhou leading project for medicine and health 2009-YB-143 (Dr. Y. Gao) and the Scientific Project of Guangzhou Medical College 2008A02 (Dr. Y. Gao), Changjiang Scholars and Innovative Research Team in University ITR0961 (Dr. J. Zheng), and the National Key Technology R&D Program of the 12th National Five-year Development Plan (2012BAI05B01 and 2013BAI09B09) (Dr. J. Zheng).

Conflict of interest

Dr. Zheng and Gao received the Provincial Nature Science Foundation of Guangdong 915280000100019 (Dr. J. Zheng), Municipal science and technology plan of Guangzhou 2009J1-C321-1 (Dr. Y. Gao), Guangzhou leading project for medicine and health 2009-YB-143 (Dr. Y. Gao) and the Scientific Project of Guangzhou Medical College 2008A02 (Dr. Y. Gao), Changjiang Scholars and Innovative Research Team in University ITR0961 (Dr. J. Zheng), and the National Key Technology R&D Program of the 12th National Five-year Development Plan (2012BAI05B01 and 2013BAI09B09) (Dr. J Zheng). None of these funding had any influence on data collection or interpretation.

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Authors and Affiliations

  1. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, China

    Wei-jie Guan, Jin-ping Zheng, Xu Shi, Yan-qing Xie, Cai-yu Jiang, Yi Gao, Zheng Zhu, Jia-ying An, Xin-xin Yu & Wen-ting Liu

  2. Sichuan People’s Hospital, Chengdu, Sichuan, China

    Cai-yu Jiang

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  1. Wei-jie Guan
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  2. Jin-ping Zheng
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  3. Xu Shi
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  7. Zheng Zhu
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Corresponding author

Correspondence to Jin-ping Zheng.

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Guan, Wj., Zheng, Jp., Shi, X. et al. Response–Dose Ratio is a Surrogate of Cumulative Provocative Dosage for Bronchial Provocation Tests in Asthma. Lung 192, 701–709 (2014). https://doi.org/10.1007/s00408-014-9612-7

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  • DOI: https://doi.org/10.1007/s00408-014-9612-7

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