Invited Review: Complexity of factors modulating airway narrowing in vivo: relevance to assessment of airway hyperresponsiveness

Abstract

In vivo, the airway response to constrictor stimuli is the net result of a complex array of factors, some facilitating and some opposing airway narrowing, which makes the interpretation of bronchial challenges far from being straightforward. This review begins with a short description of the complex mechanisms of airway smooth muscle activation and force generation as the starting events for airway narrowing. It then focuses on gain factors modulating airway smooth muscle shortening and on the geometric factors determining the magnitude of reduction in airway caliber in vivo. Finally, in light of the evidence that mechanical modulation of airway smooth muscle tone and airway narrowing is at least as important as the inflammatory contractile mediators in the pathogenesis of airway hyper-responsiveness, the implications for the interpretation of bronchial challenges in clinical settings are discussed.

Airway Response to Exercise by Forced Oscillations in Asthmatic Children

“…Altogether, we are unaware of real-life data comparing the impact of these different aspects of the FOT on the routine identification of EIB, but the issue certainly deserves further investigation. This protocol entailed a number of full inspirations before exercising, including those needed for spirometry, which could have induced some degree of bronchoprotection, which has been defined as DI preventing or markedly reducing subsequently induced bronchoconstriction (10,35). The contribution in this study is unclear because the phenomenon has been demonstrated in healthy adults taking deep breaths before histamine or methacholine challenge, is debated in asthma (36), and seems lacking in allergic subjects challenged with inhaled allergen (37).…”

“…Furthermore, the RRS change in relation to volume history, more specifically the bronchomotor alteration that follows a deep inhalation (DI), has potential relevance in identifying the mechanism of EIB (7)(8)(9). Indeed, stretching the acutely contracted bronchial smooth muscle promotes bronchial wall relaxation, which in turn could be taken as an indicator of the magnitude of the airway response (10). To the best of our knowledge, a systematic analysis of diagnostic value of single-frequency RRS has not been performed during case-control identification of EIB in the lung function laboratory at school age.…”

Allergy and the lung

“…AA, together with other forms of asthma (aspirin-and exercise-induced), is defined as a chronic inflammatory disorder of the bronchi [3], characterized by attacks of bronchospasm that revert spontaneously or after bronchodilators. Additional features of asthma are the presence of a non-specific bronchial responsiveness (BHR) [4], the remodelling of the bronchial wall [5] and, possibly, the progressive decline of respiratory function [6]. The characteristics (abrupt onset of wheezing, chest tightness, cough, nocturnal awakenings) make the diagnosis of asthma easy to conduct in a clinical setting.…”

Peristalsis of airway smooth muscle is developmentally regulated and uncoupled from hypoplastic lung growth

“…Furthermore, ASM has been described as "the appendix of the lung," implying it causes only trouble (24). The pivotal role of ASM in reactive airways disease certainly makes this view persuasive (5).…”