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.
Highlights
Bronchial challenge testing with inhaled methacholine and histamine diphosphate may provoke bronchoconstriction
We found that the response-dose relationship in the assessment of bronchial hyperreactivity (BHR) was different between the methods when analysing the fixed effects
The Malmberg method produced the greatest reduction in forced expiratory volume in one second (FEV1) per milligram, followed by the Nieminen method, both employing methacholine as the test substance
Summary
Bronchial challenge testing with inhaled methacholine (chloride or bromide) and histamine diphosphate may provoke bronchoconstriction. This transient alteration of pulmonary function is expressed as a reduction of the forced expiratory volume in one second (FEV1). In two Nordic countries, three dosimetric protocols employed in clinical settings possess noteworthy methodological differences: methacholine testing with a nebuliser and a drying device developed by Per Malmberg et al [2], methacholine testing with a jet dosimeter according to Nieminen et al [3] and histamine testing with the same dosimeter according to Sovij€arvi et al [4]. Comparison of the aforementioned protocols is a challenging task, considering that the endpoint level (provocative dose) varies between protocols and there are inherent differences in the testing substances, such as molecular mass and pharmacodynamics.
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