Relationship between airway narrowing, patchy ventilation and lung mechanics in asthmatics

Abstract

Bronchoconstriction in asthma results in patchy ventilation forming ventilation defects (VDefs). Patchy ventilation is clinically important because it affects obstructive symptoms and impairs both gas exchange and the distribution of inhaled medications. The current study combined functional imaging, oscillatory mechanics and theoretical modelling to test whether the degrees of constriction of airways feeding those units outside VDefs were related to the extent of VDefs in bronchoconstricted asthmatic subjects.Positron emission tomography was used to quantify the regional distribution of ventilation and oscillatory mechanics were measured in asthmatic subjects before and after bronchoconstriction. For each subject, ventilation data was mapped into an anatomically based lung model that was used to evaluate whether airway constriction patterns, consistent with the imaging data, were capable of matching the measured changes in airflow obstruction.The degree and heterogeneity of constriction of the airways feeding alveolar units outside VDefs was similar among the subjects studied despite large inter-subject variability in airflow obstruction and the extent of the ventilation defects. Analysis of the data amongst the subjects showed an inverse relationship between the reduction in mean airway conductance, measured in the breathing frequency range during bronchoconstriction, and the fraction of lung involved in ventilation defects.The current data supports the concept that patchy ventilation is an expression of the integrated system and not just the sum of independent responses of individual airways.

Update on the roles of distal airways in asthma

“…This method is particularly attractive in children as it requires only passive cooperation from the subject, who breathes quietly at tidal volume during the test. A predominant increase of Rrs at low frequencies (,10-15 Hz) called frequency dependence has been shown to reflect obstruction in distal airways in various obstructive lung diseases, including asthma [87][88][89][90][91]. Low frequency Rrs were increased in asthmatic children with mild airway obstruction (FEV1 .80% pred and FEF25-75% ,80% pred) [92].…”

Airway Contractility in the Precision-Cut Lung Slice after Cryopreservation

“…Assessment in the living animal offers the advantage of studying the airway in its native microenvironment (1), but because responses of individual airways are innately and dramatically heterogeneous (2)(3)(4)(5), inference of airway behavior is indirect, complex, and often ambiguous (6,7) and is costly in terms of time and money. The ASM strip (8)(9)(10) or ASM cell (4, 11-13) isolated from trachea or major bronchi provides a direct and unambiguous assessment of muscle contractility, but results so obtained may not be representative of responses of muscle from smaller airways.…”

Bronchoconstriction in Response to Deep Inhalation During Spirometry Testing

“…In fact, the asthmatic response is one of dynamic heterogeneous bronchoconstriction and bronchodilation, which are accompanied by patchy zones of parenchymal hypo-expansion and hyper-expansion, respectively. [16][17][18][19][20] These zones of constricted airways and hypo-expanded parenchyma are referred to as ventilation defects (Fig. 3).…”