Modelling structural determinants of ventilation heterogeneity: a perturbative approach

Abstract

We have developed a computational model of gas mixing and ventilation in the human lung represented as a bifurcating network. We have simulated multiple-breath washout (MBW), a clinical test for measuring ventilation heterogeneity in patients with obstructive lung conditions. By applying airway constrictions inter-regionally, we have predicted the response of MBW indices to obstructions and found that they detect a narrow range of severe constrictions that reduce airway radius to between 10% -30% of healthy values. These results help to explain the success of the MBW test to distinguish obstructive lung conditions from healthy controls. Further, we have used a perturbative approach to account for intra-regional airway heterogeneity that avoids modelling each airway individually. We have found, for random airway heterogeneity, that the variance in MBW indices is greater when largemagnitude constrictions are already present, and that the indices become more sensitive to structural heterogeneity when already elevated. This method is a computationally efficient way to probe the lung's sensitivity to structural changes, and to quantify uncertainty in predictions due to random variations in lung mechanical and structural properties. Author summaryThe multiple-breath washout (MBW) test is a clinical test of lung function that measures the efficiency of gas transport and mixing within the lung, and which has proven very sensitive in detecting early disease in cystic fibrosis (CF). In this paper we have developed a computational model of lung function to simulate air movement and gas transport in the lungs and generate MBW outcomes. We have used this to show why MBW is so sensitive to airway blockages similar to those encountered in CF. Importantly, the model incorporates a new and computationally-efficient method that also allows us to account for uncertainty and randomness in lung structure and mechanical properties. This has been used to show how variability of MBW outcomes increases in disease states. The model provides a framework for modelling clinical data, where accounting for uncertainties in inputs is crucial in making clinically meaningful predictions.

Investigation of tracer gas transport in a new numerical model of lung acini

“…The authors were able to show how the molecular diffusion properties of the gases influenced gas transport at branches in lung regions where diffusion plays a dominant role in gas transport. More recently, Whitfield et al [27] presented a new approach to investigate the influence of the asymmetry in a bronchial tree on ventilation inhomogeneities and thus on the parameters determined with MBW. The model developed by Hasler et al [28] considered both the asymmetric structure of the air conducting airways and the compliance of the peripheral airways and alveoli.…”

“…In the past, several numerical lung models were conceived for the prediction of the effects of VI on the characteristic shapes in washout curves in healthy individual lungs [19][20][21][22][23][24][25]. In addition, models were presented which analyzed the mechanisms that lead to increased VI in OLD [26][27][28].…”

Spectral graph theory efficiently characterizes ventilation heterogeneity in lung airway networks

“…Therefore, this provides a method for efficient prediction and characterization of poorly ventilated regions of the lung based on the geometry and topology of the airway tree. The method has significant advantages over previous approaches of dimensionality reduction in airway models, which involve replacing parts of the tree with symmetric models [ 39 , 40 ] based on ‘trumpet’ models [ 41 ] of the airway geometry. These methods remove the asymmetry of the smaller airways, and sacrifice some of the complexity of the system to reduce dimensionality, which is not the case for the spectral graph theory methods used here.…”

Effect of intermittent inspiratory leaks on measurement of lung clearance index using nitrogen and sulfur hexafluoride

“…Whitfield and colleagues assumes a simple, symmetrically branching, trumpet airway. The interpretation is limited, as the data from the lung model seem preliminary [ 3 ]. It remains unclear if the model accounts for uneven gas mixing and validation in vivo is required.…”