The dynamic face of respiratory research: understanding the effect of airway disease on a lung in constant motion

Abstract

The lungs are in a constant state of motion. The dynamic nature of tidal breathing, whereby cycles of pressure changes across the lungs cause the chest wall, lung tissue and airways to repeatedly expand and contract, ventilates the lung tissue and allows respiration to occur. However, these regular cycles of tidal inspirations and expirations are punctuated by breaths of differing volumes, most particularly periodic deep inspirations. In normal, healthy subjects, these deep inspirations have a dual effect in reducing airway responsiveness. Firstly, deep inspirations taken under baseline conditions protect the airways against subsequent bronchoconstriction, termed DI bronchoprotection. Secondly, deep inspirations are able to dramatically reverse bronchoconstriction. The ability for deep inspirations to reverse bronchoconstriction appears to be due to both the ability to dilate the airways with a full inspiration to total lung capacity (TLC) and the rate at which the airways re-narrow once tidal breathing is resumed. Deep inspiration reversal is reduced in subjects with asthma and is due both to a reduced ability to dilate the airways as well as an increase in the rate of re-narrowing. On the other hand, DI bronchoprotection is completely absent in asthma. Although the mechanisms behind these abnormalities remain unclear, the inability for deep inspirations to both protect against and fully reverse bronchoconstriction in patients with asthma appears critical in the development of airway hyperresponsiveness. As such, determining the pathophysiology responsible for the malfunction of deep inspirations in asthma remains critical to understanding the disease and is likely to pave the way for novel therapeutic targets.