Measurement of bronchial hyperreactivity: comparison of three Nordic dosimetric methods

Clinical testing of bronchial hyperreactivity (BHR) provides valuable information in asthma diagnostics. Nevertheless, the test results depend to a great extent on the testing procedure: test substance, apparatus and protocol. In Nordic countries, three protocols predominate in the testing field: Per Malmberg, Nieminen and Sovijärvi methods. However, knowledge of their equivalence is limited. We aimed to find equivalent provocative doses (PD) to obtain similar bronchoconstrictive responses for the three protocols. We recruited 31 patients with suspected asthma and health care workers and performed BHR testing with methacholine according to Malmberg and Nieminen methods, and with histamine according to Sovijärvi. We obtained the individual response-dose slopes for each method and predicted equivalent PD values. Applying a mixed-model, we found significant differences in the mean (standard error of mean) response-dose (forced expiratory volume in one second (FEV₁)%/mg): Sovijärvi 7.2 (1.5), Nieminen 13.8 (4.2) and Malmberg 26 (7.3). We found that the earlier reported cut-point values for moderate BHR and marked BHR between the Sovijärvi (PD₁₅) and Nieminen (PD₂₀) methods were similar, but with the Malmberg method a significant bronchoconstrictive reaction was measured with lower PD₂₀ values. We obtained a relationship between slope values and PD (mg) between different methods, useful in epidemiological research and clinical practice.

支气管高反应性（bronchial hyperreactivity, BHR）的临床检测在哮喘诊断中具有重要参考价值。然而，检测结果在很大程度上依赖于检测流程：包括检测试剂、仪器与实验方案。在北欧国家，目前主流的BHR检测方案有三种：Per Malmberg法、Nieminen法与Sovijärvi法，但关于这三种方案等效性的认知仍较为有限。本研究旨在探寻可在三种方案下引发相似支气管收缩反应的等效激发剂量（provocative dose, PD）。本研究共招募31名疑似哮喘患者及医护人员，分别采用Malmberg法与Nieminen法以乙酰甲胆碱（methacholine）、Sovijärvi法以组胺（histamine）开展BHR检测。我们获取了每种方法的个体反应-剂量斜率，并预测了等效PD值。通过混合模型分析，我们发现三种方法的平均（均值标准误）反应-剂量（一秒用力呼气容积（forced expiratory volume in one second, FEV₁）%/mg）存在显著差异：Sovijärvi法为7.2（1.5），Nieminen法为13.8（4.2），Malmberg法为26（7.3）。研究发现，此前报道的中度BHR与重度BHR临界值，在Sovijärvi法（PD₁₅）与Nieminen法（PD₂₀）之间具有相似性；但采用Malmberg法时，较低的PD₂₀值即可引发显著的支气管收缩反应。本研究得到了不同方法间斜率值与PD（mg）的对应关系，该结果可用于流行病学研究与临床实践。