Deep Inspiration-induced Bronchoprotection Is Stronger than Bronchodilation

Scichilone, Nicola; Kapsali, Trisevgeni; Permutt, Solbert; Togias, Alkis

doi:10.1164/ajrccm.162.3.9907048

Cited by 126 publications

(122 citation statements)

References 16 publications

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“…Two recent studies (10,21) reported that a series of five deep breaths taken before the inhalation of a single dose of MCh dramatically and exclusively protected healthy humans from airway narrowing. The conclusion was based on the fact that the decrements of FEV 1 and FVC after a bolus of MCh were significantly less when the constrictor agent was preceded by deep breaths than when it was not.…”

Section: Discussionmentioning

confidence: 99%

“…RECENT STUDIES HAVE SHOWN that deep breaths taken immediately before inhalation of methacholine (MCh) greatly modulate the bronchoconstrictor response in normal (10,12,21) but not in asthmatic (10) subjects. This would suggest that the shortening capacity of airway smooth muscle is reduced by previous lung stretching in healthy subjects, and the lack of such a bronchoprotective mechanism may be responsible for airway hyperresponsiveness in asthma.…”

mentioning

confidence: 99%

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Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects

Crimi

Pellegrino

Milanese

et al. 2002

Journal of Applied Physiology

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Crimi, Emanuele, Riccardo Pellegrino, Manlio Milanese, and Vito Brusasco. Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects. J Appl Physiol 93: 1384-1390, 2002. First published June 21, 2002 10.1152/japplphysiol.00209.2002Deep breaths taken before inhalation of methacholine attenuate the decrease in forced expiratory volume in 1 s and forced vital capacity in healthy but not in asthmatic subjects. We investigated whether this difference also exists by using measurements not preceded by full inflation, i.e., airway conductance, functional residual capacity, as well as flow and residual volume from partial forced expiration. We found that five deep breaths preceding a single dose of methacholine 1) transiently attenuated the decrements in forced expiratory volume in 1 s and forced vital capacity in healthy (n ϭ 8) but not in mild asthmatic (n ϭ 10) subjects and 2) increased the areas under the curve of changes in parameters not preceded by a full inflation over 40 min, during which further deep breaths were prohibited, without significant difference between healthy (n ϭ 6) and mild asthmatic (n ϭ 16) subjects. In conclusion, a series of deep breaths preceding methacholine inhalation significantly enhances bronchoconstrictor response similarly in mild asthmatic and healthy subjects but facilitates bronchodilatation on further full inflation in the latter.forced expiratory volume in 1 s; specific airway conductance; partial flow-volume curve; functional residual capacity; residual volume RECENT STUDIES HAVE SHOWN that deep breaths taken immediately before inhalation of methacholine (MCh) greatly modulate the bronchoconstrictor response in normal (10, 12, 21) but not in asthmatic (10) subjects. This would suggest that the shortening capacity of airway smooth muscle is reduced by previous lung stretching in healthy subjects, and the lack of such a bronchoprotective mechanism may be responsible for airway hyperresponsiveness in asthma. A mechanistic interpretation of the above studies is, however, limited by the use of forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC), measurements that are highly and variably affected by the full lung inflation preceding the forced expiratory maneuver. During induced bronchoconstriction, a full inflation transiently increases airway caliber, and the magnitude of this increase depends on the relative magnitude of the distending force of lung parenchyma and the constrictor force of airway smooth muscle (17). Therefore, any parameter derived from a full forced expiratory maneuver, including FEV 1 and FVC, will depend on both airway smooth muscle shortening capacity and airway wall response to a deep breath.It is reasonable to postulate that, if the lack of a bronchoprotective effect by multiple deep breaths taken before inhaling a constrictor agent in asthma is due to the inability to reduce the shortening capacity of airway smooth muscle, then the different effects of the deep breaths on airway response to MCh between asthmati...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects

Crimi

Pellegrino

Milanese

et al. 2002

Journal of Applied Physiology

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“…The third possible answer stems from studies in which the protective effect of deep inspirations taken before experimentally induced bronchoconstriction is examined [18,27,60,[65][66][67][68]. MALMBERG et al [65] were the first to notice that if a deep inspiration was taken shortly before (,6 min) acutely induced bronchoconstriction, the extent of airway narrowing during the induced constriction was reduced.…”

Section: Evidence Of Asm Involvement In Asthmamentioning

confidence: 99%

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

An¹,

Bai²,

Bates³

et al. 2007

European Respiratory Journal

342

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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“…Furthermore, they showed that this effect was greater when deep inspirations were taken before than after inhalation of methacholine. More recent work (44) has confirmed this finding and also shown that the bronchoprotective effect increases with the number of deep inspirations in normal subjects, but is totally absent in asthma (45). The limitation of these studies is that the changes in airway caliber were assessed by FEV 1 , which needs a deep inhalation to be measured.…”

Section: External Modulation Of Airway Narrowingmentioning

confidence: 83%

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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Deep Inspiration-induced Bronchoprotection Is Stronger than Bronchodilation

Cited by 126 publications

References 16 publications

Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects

Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects

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

Methacholine provocation test for diagnosis of allergic respiratory diseases

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