Methacholine provocation test for diagnosis of allergic respiratory diseases

Abstract

Airway hyperresponsiveness is regarded as a characteristic feature of bronchial asthma, but it may also be present in other allergic or nonallergic respiratory disorders. The method most widely used to assess airway responsiveness is the methacholine inhalation challenge (1, 2), which mimics the effect of endogenous acetylcholine on airway smooth-muscle muscarinic receptors of the M 3 subtype. The major advantage in using methacholine instead of acetylcholine for bronchial challenge lies in its greater resistance to degradation by cholinesterase, which allows one to obtain cumulative dose-response curves.The molecular mechanism by which methacholine causes airway narrowing is by activating the M 3 -Gq protein coupled receptors and the connected IP 3 pathway, an effect which ultimately results in Ca 2+ release from intracellular stores and contraction. The mechanisms by which methacholine causes the airways of some individuals to constrict more than others are complex and still largely unknown. This complexity may in part explain the relatively low specificity of this test for the diagnosis of bronchial asthma. In this review, the practical relevance of the different determinants of airway response to methacholine will be discussed, with particular attention to those that may account for the presence of airway hyperresponsiveness in diseases other than asthma. Mechanisms of airway narrowingUpon application of a constrictor stimulus, the airway smooth muscle generates a force, the magnitude of which depends on several factors. Among these are the interaction between receptor and agonist, the airway smooth-muscle contractile properties, and the amount of airway smooth muscle in the airway wall. These factors cannot be separated in vivo by analysis of the dose-response curve to methacholine.In vitro, the descriptors of the dose-response curve to a constrictor agonist are the maximal response and the position of the curve, the latter being commonly reflected by the dose causing 50% of maximal response (ED 50 ). Position and maximal response are believed to reflect different mechanisms of response, which are briefly summarized in Table 1. In vivo, a reliable estimate of ED 50 in the methacholine dose-response curve is difficult, as a true maximal response is seldom obtainable. The parameter used in clinical practice to report the response to methacholine is the threshold dose causing a predetermined change in a parameter reflecting airway caliber, most commonly a decrease of FEV 1 by 20% (PD 20 ). This parameter cannot be taken as a surrogate of ED 50 , as it reflects both maximal response and the position of the dose-response curve. The difference between threshold dose and ED 50 is better illustrated in Fig. 1. Therefore, whether airway hyperresponsiveness relies on abnormal transmembrane receptor-mediated response to agonist(s) cannot be determined from in vivo studies. In any case, the similarity of bronchoconstrictor response to different agonists does suggest that airway hyperresponsiveness is not sustained by ...

Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles

“…29 The methacholine challenge was a useful tool in diagnosis of allergic respiratory disorders, which had been widely used in assessing airway responsiveness. 45 In the present study, OVA sensitization and challenge evoked a significant hyperresponsiveness to methacholine challenge in sensitized rats. Curcumin was found to inhibit the airway hyperreactivity.…”

“…The supernatant was filtered through a 0. 45 Transmission electron microscopy and zeta potential measurements…”

Propolis extracts exhibit an immunoregulatory activity in an OVA-sensitized airway inflammatory animal model

“…Experimental evidence indicates that the maximum degree of airway narrowing in response to methacholine is greater in asthmatics than in normal subjects [15]. As shown in Fig.…”

Diagnostic properties of inhaled mannitol in the diagnosis of asthma: A population study

“…However, the direct BPTs lack specificity because a positive test result can be observed in a significant number of nonasthmatic subjects, including those with chronic obstructive pulmonary disease, allergic rhinitis, and respiratory infections, as well as in asymptomatic subjects. [4][5][6] Indirect BPTs, on the other hand, show high specificity in identifying current asthma compared with the direct agents. The indirect tests also correlate better with airway inflammation and severity of disease.…”