Measurement of bronchial hyperreactivity: comparison of three Nordic dosimetric methods

Abstract

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.

Keywords:

• Histamine
• methacholine
• asthma
• response–dose slope
• provocative dose

Acknowledgments

The authors thank staff members from the Skin and Allergy Hospital and the Laboratory of Clinical Physiology at the Meilahti Hospital, particularly Pia Saarenkoski, Helena Punkari and Elina Voutilainen for performing the challenge tests. The authors also thank Anna But, PhD from the Faculty of Medicine, University of Helsinki for providing statistical counselling, Alyce Whipp, MPH for the language revision and Pia Saarenkoski for giving permission to reproduce Figure 1.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study

Author contributions

AS, PLK, and PP conceived and designed the research. PM and PP supervised the experiments. BMS contributed with experimental tools. PLK analysed the data and wrote the manuscript, under the tutelage of PP. AS, BMS, PM and PP reviewed the manuscript. All authors read and approved the manuscript.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the Nummela Sanatorium Foundation [PP 2017], The Research Foundation of the Pulmonary Diseases [PLK], Tampere Tuberculosis Foundation: Eero Hämäläinen [PLK], Väinö and Laina Kivi Foundation [PLK], Ida Montin Foundation [PLK], the Nordic Council of Ministers: NordForsk (Nordic EpiLung Study), and the University of Helsinki.