Respiratory sensation during bronchial challenge testing with methacholine, sodium metabisulphite, and adenosine monophosphate

Background - There is some evidence that the perception of bronchoconstriction may vary according to the nature of the provoking stimulus. The aims of this study were, firstly, to develop a method for measuring dyspnoea during induced bronchoconstriction in patients with asthma and, secondly, to apply this method to testing differences between directly and indirectly acting bronchoconstricting stimuli. Methods - Descriptive terms suitable for quantifying respiratory discomfort due to bronchoconstriction in patients with asthma were identified in a preliminary investigation. The relation between reduction in forced expiratory volume in one second (FEV(1)) and respiratory discomfort, measured using a visual analogue scale (VAS), was then studied during challenges with three different inhaled stimuli: methacholine (MCH), sodium metabisulphite (MBS), and adenosine monophosphate (AMP). Three indices were calculated to describe the relation: the VAS value associated with a 20% fall in FEV(1) (FEV(20) VAS); the ratio of the final VAS value to the final percentage fall in FEV1( )(VAS-FEV(1) ratio); and the regression coefficient for predicting VAS from the percentage fall in FEV1( )within each challenge (beta VAS FEV(1)). Results - ''Difficulty in breathing'' and ''chest tightness'' were selected as suitable terms for quantifying respiratory discomfort. There were no differences between the three agonists in the qualitative aspects of the respiratory sensation. In paired challenges with the same agonist the three indices were all found to be reproducible for both sensations measured. MCH induced less intense difficulty in breathing and chest tightness for a given fall in FEV(1) than did AMP. There was a trend in the same direction for the comparison between MCH and MBS. There were no differences between AMP and MBS. FEV(20) VAS was less powerful in discriminating between agonists than the two slope indices. Conclusions - The relation between induced reduction in FEV(1) and the intensity of respiratory discomfort can be measured reliably. The indirectly acting bronchoconstricting agonists AMP and MBS induced more intense respiratory discomfort for a given fall in FEV, than the direct agonist MCH. This may be due to differences in unmeasured mechanical changes in the lungs or to an additional action on airway sensory nerves.