Spatial pattern formation in the lung

Journal of Applied Physiology

Elliot

Boser³

et al. 2019

Self Cite

Bronchial thermoplasty is a recent treatment for asthma in which ablative thermal energy is delivered to specific large airways according to clinical guidelines. Therefore, current practice is effectively “blind,” as it is not informed by patient-specific data. The present study seeks to establish whether a patient-specific approach based on structural or functional patient data can improve outcomes and/or reduce the number of procedures required for clinical efficacy. We employed a combination of extensive human lung specimens and novel computational methods to predict bronchial thermoplasty outcomes guided by structural or functional data compared with current clinical practice. Response to bronchial thermoplasty was determined from changes in airway responses to strong bronchoconstrictor simulations and flow heterogeneity after one or three simulated thermoplasty procedures. Structure-guided treatment showed significant improvement over current unguided clinical practice, with a single session of structure-guided treatment producing improvements comparable with three sessions of unguided treatment. In comparison, function-guided treatment did not produce a significant improvement over current practice. Structure-guided targeting of bronchial thermoplasty is a promising avenue for improving therapy and reinforces the need for advanced imaging technologies. The functional imaging-guided approach is predicted to be less effective presently, and we make recommendations on how this approach could be improved. NEW & NOTEWORTHY Bronchial thermoplasty is a recent treatment for asthma in which thermal energy is delivered via bronchoscope to specific airways in an effort to directly target airway smooth muscle. Current practice involves the treatment of a standard set of airways, unguided by patient-specific data. We consider the potential for guided treatments, either by functional or structural data from the lung, and show that treatment guided by structural data has the potential to improve clinical practice.

Section: Methodsmentioning

confidence: 99%

Patient-specific targeted bronchial thermoplasty: predictions of improved outcomes with structure-guided treatment

Journal of Applied Physiology

Elliot

Boser³

et al. 2019

Self Cite

“…If the parameters are such that these curves have multiple intersections, then multiple (static) equilibria are possible. Because much of the physiological range of parameter space does allow multiple equilibria, this bistability has often been used to explain the occurrence of ventilation heterogeneity and clustered ventilation defects (6,7). However, these largely static representations contain incomplete information about how these states may be modulated by ASM dynamics.…”

Section: Motivationmentioning

confidence: 99%

“…There are several distinct, yet related, ideas: static bistability, either in an isolated airway (1) or in a terminal airway unit with coupled parenchymal tethering (2); dynamic coupling of the airway with airway smooth muscle (3)(4)(5); and mechanisms by which spatial organization of airway closure or near closure may lead to clustered ventilation defects (6,7). All are interrelated, but as of yet there is no integrated synthesis of all three mechanisms.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Airway Bistability Is Modulated by Smooth Muscle Dynamics and Length-Tension Characteristics

2016

Biophysical Journal

Airway closure has important implications for lung disease, especially asthma; in particular, the prospect of bistability between open and closed (or effectively closed) airway states has been thought to play a prominent role in airway closure associated with the formation of clustered ventilation defects in asthma. However, many existing analyses of closure consider only static airway equilibria; here we construct, to our knowledge, a new model wherein airway narrowing and closure dynamics are modulated by coupling the airway to cross-bridge models of airway smooth muscle dynamics and force generation. Using this model, we show that important qualitative features of airway pressure-radius hysteresis loops are highly dependent on both airway smooth muscle dynamics, and the length-tension relationship. Furthermore, we show that two recent experimental results from intact bronchial segments are both expressions of the same phenomenon: that a monotonically increasing lengthtension relationship, with sharply higher tension at longer lengths, is needed to drive the observed changes in low-compliance regions of the baseline pressure-radius curve. We also explore the potential implications of this finding for airway closure in coupled airway models.

“…eeThe model Venegas et al has both effects but does not differentiate between their roles; Donovan and Kritter have only the latter.…”

mentioning

confidence: 99%

Systems‐level airway models of bronchoconstriction

WIREs Mechanisms of Disease

2016

Self Cite

Understanding lung and airway behavior presents a number of challenges, both experimental and theoretical, but the potential rewards are great in terms of both potential treatments for disease and interesting biophysical phenomena. This presents an opportunity for modeling to contribute to greater understanding, and here, we focus on modeling efforts that work toward understanding the behavior of airways in vivo, with an emphasis on asthma. We look particularly at those models that address not just isolated airways but many of the important ways in which airways are coupled both with each other and with other structures. This includes both interesting phenomena involving the airways and the layer of airway smooth muscle that surrounds them, and also the emergence of spatial ventilation patterns via dynamic airway interaction. WIREs Syst Biol Med 2016, 8:459-467. doi: 10.1002/wsbm.1349 For further resources related to this article, please visit the WIREs website.