Bronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing

Abstract

Bronchial hyperresponsiveness is currently defined as an increase in sensitivity to a wide variety of airway narrowing stimuli. Most patients with asthma and chronic obstructive pulmonary disease (COPD) exhibit such an enhanced sensitivity. In asthma, in particular, this hypersensitivity is accompanied by excessive degrees of airway narrowing. This raises the question as to whether measures of sensitivity, e.g. the provocative concentration or dose producing 20% fall in FEV1 (PC20 or PD20), comprise all the relevant information in bronchial hyperresponsiveness. In adjunct to model studies, there is experimental evidence in man that the potential mechanisms of bronchial hyperresponsiveness can be divided into those causing hypersensitivity and those responsible for the increase in the maximal attainable degree of airway narrowing. The recognition and distinction of these components of hyperresponsiveness have clinical implications in the diagnosis and therapy of asthma and COPD. Bronchial hyperresponsiveness is a composite functional disorder, which requires treatment of each of its components.

Inhaled steroids modify bronchial responses to hyperosmolar saline

“…On the basis of the PD 20 values to histamine and methacholine the patients included in this group would be assessed clinically as having moderate to severe bronchial hyperresponsiveness before treatment and mild to moderate bronchial hyperresponsiveness after treatment [29]. The findings in this study that airways of these asthmatics remained responsive with continued exposure to the inciting stimulus supports the contention by STERK and BEL [21] that there is a need to distinguish between changes in sensitivity and airway narrowing in response to treatment. The suggestion by WooccocK et al [30] that the demonstration of a plateau may be the important feature determining a reduction in risk from severe asthma is also supported by the findings in this study.…”

“…Thus, these indices give information about both the position and the slope of the dose-response curve and are both important in assessing bronchial responsiveness [21).…”

The effect of an inhaled corticosteroid (budesonide) on exercise-induced asthma in children. Dutch CNSLD Study Group

“…The underlying mechanisms which determine airway responsiveness and the reaction of airways to triggers are complex [29]. Exercise is likely to have its primary point of action at the epithelial level [11], histamine on neural control and smooth muscle [30], and methacholine on smooth muscle [30], whereas PEF variation is the expression of the spontaneous changes in smooth muscle contractility as the result of these interacting factors.…”

Comparison of PD20 with two alternative measures of response to histamine challenge in epidemiological studies

“…Sigmoid shaped curves have been found in normal subjects at doses higher than can be given in epidemiological studies [3,8,18]. WooLCOCK et al [18] gave equations for the dose-response curve in 10 normal subjects, from which it can be calculated that the dose producing a fall of 90% of the maximum fall achieved, ranged from 9.4 J.Unol histamine to 16.7 J.tmol in nine subjects, with the tenth having an outlying value of 51.8 J.Unol.…”

“…Whilst provocation testing has become established in studies of airway disease [1,2], there has been continued debate over how the results should be expressed. Complete description of the histamine or methacholine doseresponse curve requires at least two parameters, one for position and one for maximal response, and may require a third paran1eter for "slope" [3]. However, estimation of maximal response, or plateau, requires higher doses of drug than can be administered in a community setting.…”