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

Abstract

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...

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

“…Radial strain increased ASM length, whereas under the experimental conditions applied, axial distension reduced ASM length. These in vitro findings are, however, in agreement with those reported in vivo by CRIMI et al [70], showing that in both asthmatic and healthy humans, multiple deep inspirations taken prior to inhaling a constrictor agent led to airway narrowing rather than dilatation, thus arguing against the existence of an in vivo bronchoprotective mechanism.…”

“…It was postulated by KING et al [26] that this post-oscillation refractoriness of resting ASM was responsible for the bronchoprotective effect of deep inspiration taken before bronchoprovocation seen in nonasthmatics, and that in asthmatics, this refractoriness might be absent. CRIMI et al [70], however, found that this effect was only evident when lung function parameters preceded by a full inflation were used, such as FEV1 or forced vital capacity. Using parameters not preceded by full inflation, (e.g.…”

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“…Most notably, expiratory flow derived from maximal expiration (i.e. FEV1) is differentially altered compared with flow during expiration from a submaximal expiration (partial expiration) [7,15]. The FEV1 necessitates a DI, which is significant in that potential bronchoprotective effects become intertwined with the bronchodilatory effects of DI.…”

“…Notably, when manoeuvres other than maximal expiration are used to assess the effects of DI prior to challenge; for example, in expiration from a submaximal lung volume (i.e. partial exhalation), bronchoprotection is not observed [7,15].…”

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