ORCID Profile
0000-0001-5903-5484
Current Organisation
The University of Auckland
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Publisher: European Respiratory Society (ERS)
Date: 12-10-2023
Publisher: American Thoracic Society
Date: 11-2019
Publisher: Wiley
Date: 24-01-2023
DOI: 10.1111/RESP.14454
Publisher: American Physiological Society
Date: 12-2021
Publisher: American Physiological Society
Date: 03-2019
DOI: 10.1152/JAPPLPHYSIOL.00951.2018
Abstract: 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.
Publisher: American Physiological Society
Date: 12-2022
DOI: 10.1152/JAPPLPHYSIOL.00493.2022
Abstract: Bronchial thermoplasty is a treatment for asthma that targets the airway smooth muscle directly. We demonstrate the feasibility and constraints of predicting patient-specific response to thermoplasty using a computational model informed by pretreatment CT scans at different lung volumes. Predictions are compared with functional outcomes and posttreatment CT scans. This has the potential to form the basis for improved clinical practice.
Publisher: American Thoracic Society
Date: 15-02-2023
Publisher: European Respiratory Society (ERS)
Date: 03-2023
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.RESP.2015.09.006
Abstract: Length adaptation is a phenomenon observed in airway smooth muscle (ASM) wherein over time there is a shift in the length-tension curve. There is potential for length adaptation to play an important role in airway constriction and airway hyper-responsiveness in asthma. Recent results by Ansell et al., 2015 (JAP 2014 10.1152/japplphysiol.00724.2014) have cast doubt on this role by testing for length adaptation using an intact airway preparation, rather than strips of ASM. Using this technique they found no evidence for length adaptation in intact airways. Here we attempt to resolve this apparent discrepancy by constructing a minimal mathematical model of the intact airway, including ASM which follows the classic length-tension curve and undergoes length adaptation. This allows us to show that (1) no evidence of length adaptation should be expected in large, cartilaginous, intact airways (2) even in highly compliant peripheral airways, or at more compliant regions of the pressure-volume curve of large airways, the effect of length adaptation would be modest and at best marginally detectable in intact airways (3) the key parameters which control the appearance of length adaptation in intact airways are airway compliance and the relaxation timescale. The results of this mathematical simulation suggest that length adaptation observed at the level of the isolated ASM may not clearly manifest in the normal intact airway.
Publisher: European Respiratory Society (ERS)
Date: 17-10-2019
DOI: 10.1183/13993003.00857-2019
Abstract: Epidemiological studies report that overweight or obese asthmatic subjects have more severe disease than those of a healthy weight. We postulated that accumulation of adipose tissue within the airway wall may occur in overweight patients and contribute to airway pathology. Our aim was to determine the relationship between adipose tissue within the airway wall and body mass index (BMI) in in iduals with and without asthma. Transverse airway sections were s led in a stratified manner from post mortem lungs of control subjects (n=15) and cases of nonfatal (n=21) and fatal (n=16) asthma. The relationship between airway adipose tissue, remodelling and inflammation was assessed. The areas of the airway wall and adipose tissue were estimated by point count and expressed as area per mm of basement membrane perimeter (Pbm). The number of eosinophils and neutrophils were expressed as area densities. BMI ranged from 15 to 45 kg·m −2 and was greater in nonfatal asthma cases (p .05). Adipose tissue was identified in the outer wall of large airways (Pbm mm), but was rarely seen in small airways (Pbm mm). Adipose tissue area correlated positively with eosinophils and neutrophils in fatal asthma (Pbm mm, p .01), and with neutrophils in control subjects (Pbm mm, p=0.04). These data show that adipose tissue is present within the airway wall and is related to BMI, wall thickness and the number of inflammatory cells. Therefore, the accumulation of airway adipose tissue in overweight in iduals may contribute to airway pathophysiology.
Publisher: American Physiological Society
Date: 12-2021
Publisher: American Physiological Society
Date: 04-2021
DOI: 10.1152/JAPPLPHYSIOL.00959.2020
Abstract: CT scanning was used to evaluate the response of in idual airways in patients undergoing bronchial thermoplasty. Airways dilated after treatment by 6.4% on average with substantial heterogeneity and a greater response in the most distal airways measured.
Publisher: European Respiratory Society (ERS)
Date: 10-2019
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.RESP.2022.103884
Abstract: Clinical visualization and quantification of the amount and distribution of airway smooth muscle (ASM) in the lungs of in iduals with asthma has major implications for our understanding of airway wall remodeling as well as treatments targeted at the ASM. This paper theoretically investigates the feasibility of quantifying airway wall thickness (focusing on the ASM) throughout the lung in vivo by means of bronchoscopic polarization-sensitive optical coherence tomography (PS-OCT). Using extensive human biobank data from subjects with and without asthma in conjunction with a mathematical model of airway compliance, we define constraints that airways of various sizes pose to any endoscopic imaging technique and how this is impacted by physiologically relevant processes such as constriction, inflation and deflation. We identify critical PS-OCT system parameters and pinpoint parts of the airway tree that are conducive to successful quantification of ASM. We further quantify the impact of breathing and ASM contraction on the measurement error and recommend strategies for standardization and normalization.
Publisher: Wiley
Date: 06-2020
DOI: 10.14814/PHY2.14451
Publisher: American Thoracic Society
Date: 09-2018
Publisher: European Respiratory Society (ERS)
Date: 10-2020
DOI: 10.1183/23120541.00300-2020
Abstract: Bronchial thermoplasty induces atrophy of the airway smooth muscle layer, but the mechanism whereby this improves patient health is unclear. In this study, we use computed tomography (CT) to evaluate the effects of bronchial thermoplasty on airway volume 12 months post-procedure. 10 consecutive patients with severe asthma were evaluated at baseline by the Asthma Control Questionnaire (ACQ), and high-resolution CT at total lung capacity (TLC) and functional residual capacity (FRC). The CT protocol was repeated 4 weeks after the left lung had been treated by bronchial thermoplasty, but prior to right lung treatment, and then again 12 months after both lungs were treated. The CT data were also used to model the implications of including the right middle lobe (RML) in the treatment field. The mean patient age was 62.7±7.7 years and forced expiratory volume in 1 s (FEV 1 ) 42.9±11.5% predicted. 12 months post-bronchial-thermoplasty, the ACQ improved, from 3.4±1.0 to 1.5±0.9 (p=0.001), as did the frequency of oral steroid-requiring exacerbations (p=0.008). The total airway volume increased 12 months after bronchial thermoplasty in both the TLC (p=0.03) and the FRC scans (p=0.02). No change in airway volume was observed in the untreated central airways. In the bronchial thermoplasty-treated distal airways, increases in airway volume of 38.4±31.8% at TLC (p=0.03) and 30.0±24.8% at FRC (p=0.01) were observed. The change in distal airway volume was correlated with the improvement in ACQ (r=−0.71, p=0.02). Modelling outputs demonstrated that treating the RML conferred no additional benefit. Bronchial thermoplasty induces long-term increases in airway volume, which correlate with symptomatic improvement.
Publisher: Wiley
Date: 17-05-2017
DOI: 10.1111/RESP.13071
Abstract: Intrauterine growth restriction (IUGR) is associated with asthma development. We hypothesized that IUGR disrupts airway development leading to postnatal structural abnormalities of the airway that predispose to disease. This study therefore examined structural changes to the airway and lung in a rat model of maternal hypoxia-induced IUGR. Pregnant rats were housed under hypoxic conditions (11.5% O IUGR offspring were lighter at birth compared with control, but not at 7 weeks. While there was no difference in mean airway dimensions or lung volume, there was greater anatomical variation in airway lumen area in the IUGR group. A mathematical model of the human lung was used to show that greater heterogeneity in lumen area in IUGR-affected in iduals increases bronchoconstriction during simulated bronchial challenge. More macrophages were identified in the BALF of IUGR offspring. The rat model demonstrates that IUGR leads to a more heterogeneous distribution of airway lumen calibre in adulthood with potential implications for bronchoconstriction in human subjects. Together with increased lung macrophages, these findings support a phenotypic shift after IUGR that may impact disease susceptibility.
No related grants have been discovered for Graham Donovan.