Airway responsiveness to methacholine: effects of deep inhalations and airway inflammation

Brusasco, Vito; Crimi, Emanuele; Barisione, Giovanni; Spanevello, Antonio; Rodarte, Joseph R.; Pellegrino, Riccardo

doi:10.1152/jappl.1999.87.2.567

Cited by 110 publications

(109 citation statements)

References 30 publications

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“…Such behaviour is consistent with observations from studies in isolated nonasthmatic ASM or in situ in human asthmatics [21,27,58,60,61]. Such an outcome becomes all the more likely when the ASM mass is increased, when the muscle becomes uncoupled from the lung parenchyma, when expansion of the chest wall is restricted, or when large lung inflations are prohibited during a bronchial challenge [18,62,63], all of which are factors that reduce the stretch experienced by the smooth muscle and circumstances relevant to AHR [49,64]. That being the case, this musclebased molecular mechanism explains not only how the airways can become refractory to the effects of a deep inspiration, but also how it can exhibit a bronchoconstrictor response.…”

Section: Evidence Of Asm Involvement In Asthmasupporting

confidence: 87%

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

An¹,

Bai²,

Bates³

et al. 2007

Eur Respir J

344

298

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Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma.As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling.Anti-inflammatory therapy, however, does not ''cure'' asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM.In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored.

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Section: Evidence Of Asm Involvement In Asthmasupporting

confidence: 87%

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

An¹,

Bai²,

Bates³

et al. 2007

Eur Respir J

344

298

View full text Add to dashboard Cite

show abstract

“…1) could suggest relaxation of airway smooth muscle at E15. DI repetition could have resulted in some degree of bronchoprotection toward the end of the study, as previously documented in different experimental set-ups in healthy adults (35). Significant release of catecholamine in the blood stream has been documented in exercising adult subjects (36) but we are unaware of such data in healthy children during the recovery from exercise.…”

Section: Discussionmentioning

confidence: 67%

Post-Exercise Airway Narrowing in Healthy Primary School Children

Marchal

Werts

Vu³

et al. 2008

Pediatr Res

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Changes in lung function after exercise in healthy primary school children have mostly been described in field studies. More complete description and insight into relevant mechanisms may be provided in lung function laboratory. The aim was to describe airway caliber and response to deep inhalation (DI) after exercise in healthy primary school children. Respiratory resistance (Rrs) by the forced oscillation technique and spirometry were measured before and after exercise in 50 healthy primary school children. The Rrs response to DI was assessed in 31 subjects, assuming a significantly larger decrease in Rrs after exercise would attest relief of exerciseinduced airway smooth muscle contraction. Measurements were taken before, 5 min (E5) and 15 min (E15) after exercise. Significantly larger Rrs and lower forced expiratory volume in 0.5 s were observed at E5 versus baseline or E15 (p Ͻ 0.05). DI induced significant decrease in Rrs (p ϭ 0.01) that was not different between E5 and baseline. Healthy primary school children exhibit changes in Rrs and spirometry after exercise indicating small but significant airway narrowing. The response to DI similar at baseline and E5 suggests airway narrowing from hyperemia in the bronchial wall rather than airway smooth muscle constriction. T here is considerable interest in assessing the airway response to exercise in children because of the clinical impact of exercise triggered asthma attacks (1,2). Field studies in unselected primary school children have described the distribution of lung function changes after exercise (3,4) or tested prevalence of exercise induced bronchoconstriction (EIB) in relation with respiratory symptoms (5,6). In these studies, the response was expressed as largest fall in forced expiratory volume in 1 s (FEV1) within 10 -15 min of exercise cessation (3,4) or considered positive when peak expiratory flow decreased 15% or more (5,6). To the best of our knowledge, whether significant change in airway caliber occurs in healthy children during the recovery from exercise has not been documented. In the context of a lung function laboratory, the airway response to exercise may be characterized more thoroughly and indications obtained relative to potential mechanisms. The respiratory resistance (Rrs) measured by the forced oscillation technique (FOT) is considered a good proxy to airway caliber above a few herz (7). It is particularly relevant to pediatric studies, as it requires minimal cooperation. Forced expiratory volume in 0.5 s (FEV0.5) has been suggested more sensitive than FEV1 to airway caliber in young children because of their high rate of lung emptying (8). FEV0.5 could also prove useful in school children who are known to have higher FEV1 to forced vital capacity ratio than adults. In addition, the tracking of time variations of Rrs has the potential to identifying mechanisms of bronchoconstriction by assessing change induced by a deep inhalation (DI) (9,10). When acute bronchoconstriction has been pharmacologically induced in a context ...

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“…In that study, however, changes in airway caliber were estimated by a parameter that is not totally independent of changes in lung volume. Indeed, similar studies using changes in flow at the same absolute lung volume did not confirm the findings of Skloot et al (39,40). In particular, it was found that airway responsiveness to methacholine was greater in asthmatic than in normal subjects even when deep inhalations were prohibited (Fig.…”

Section: External Modulation Of Airway Narrowingmentioning

confidence: 69%

“…In particular, it was found that airway responsiveness to methacholine was greater in asthmatic than in normal subjects even when deep inhalations were prohibited (Fig. 2), suggesting that the determinants of airway hyperresponsiveness to methacholine in asthma are both the ease of constriction and the limited bronchodilation with deep inspiration (40). Nevertheless, this difference was much greater when repeated deep inspirations had been taken between dose increments.…”

Section: External Modulation Of Airway Narrowingmentioning

confidence: 96%

Methacholine provocation test for diagnosis of allergic respiratory diseases

Brusasco

Crimi

2001

Allergy

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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 ...

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Airway responsiveness to methacholine: effects of deep inhalations and airway inflammation

Cited by 110 publications

References 30 publications

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

Post-Exercise Airway Narrowing in Healthy Primary School Children

Methacholine provocation test for diagnosis of allergic respiratory diseases

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