Airway hyperresponsiveness: mechanisms and relevance

Airway provocation tests such as the methacholine inhalation test or histamine inhalation test are commonly used for the quantitation of the airway hyperresponsiveness characteristic of asthma. The reduced provocation concentration of methacholine (PC 20 M) or histamine (PC 20 H) required to produce a 20% fall in FEV 1 may be due to a number of underlying mechanisms, particularly airway mucosal inflammation. The characteristic eosinophilic mucosal inflammation of asthma apparently contributes to hyperresponsiveness through an enhancement of neuromuscular responses to methacholine and histamine in addition to increased responses to various stimuli through the release of inflammatory mediators. Methacholine airway hyperresponsiveness and airway mucosal inflammation usually are both present in asthma, but these findings do not always coexist. Patients with chronic cough and a normal PC 20 M may have eosinophilic airway inflammation; treatment with inhaled steroid can reduce the cough, sputum production and the number of eosinophils and mast cells in the sputum. Airway responses in provocation tests with histamine or methacholine seem to depend, at least in part, upon direct stimulation of airway smooth muscle and have been referred to as direct tests of airway responsiveness. In contrast, tests with stimuli such as allergen or adenosine, which elicit mediator release, have been referred to as indirect tests of airway hyperresponsiveness. There are complex interrelationships and an interdependence between methacholine airway hyperresponsiveness and airway inflammation; progress in the assessment of underlying mechanisms has been greatly enhanced by biochemical, immunologic and pathologic‐type measurements in various types of specimens from the airways to directly assess the pathogenetic processes. Some features of asthma such as exercise and nocturnal symptoms correlate well with the level of methacholine airway hyperresponsiveness. Conversely, the occurrence of cough or the occurrence of asthmatic attacks are not predicted accurately by a measurement of methacholine airway hyperresponsiveness. The assessment of asthma severity seems to require the consideration of a number of types of parameters including the level of ongoing symptoms, need for inhaled B 2 ‐agonist, frequency and severity of acute attacks, level of treatment required to maintain control of asthma, baseline airflow rates and tests of variability of airflow such as serial measurements of variability of PEF or of PC 20 M. Measurement of the PC 20 M is a sensitive test of changes in airway responsiveness and can be useful in serial measurements. In some instances, airway reactions can be identified by serial measurements of PC 20 M but not by serial measurement of airway calibre such as the FEV 1 .