Structural changes in the COPD lung and related heterogeneity

Copot, Dana; Keyser, Robain De; Derom, Eric; Ionescu, Clara-Mihaela

doi:10.1371/journal.pone.0177969

Cited by 34 publications

(19 citation statements)

References 39 publications

(41 reference statements)

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“…COVID-19 has risen to be one of the biggest killers of 2020, which resulted in 5,817,385 confirmed cases and 362,705 deaths through May 30, 2020 (Stokes et al, 2020). Pulmonary diseases impact tissue structure (Eskandari et al, 2013;Burgstaller et al, 2017;Copot et al, 2017), which in turn modifies respiratory mechanics (Faffe and Zin, 2009;Eskandari et al, 2018) in terms of conducting lung volumes (Broussard et al, 2006;Brown et al, 2006;Limjunyawong et al, 2015a,b;Robichaud et al, 2017), mechanical and viscoelastic properties (Bates et al, 2007;Suki and Bates, 2011) and air flow distribution in the lung (Rouby et al, 2003;Grasso et al, 2008). Understanding each of these changes and how they differ in healthy and diseased patients is necessary to advance diagnosis and treatment strategies in lung disease (Sattari and Eskandari, 2020).…”

Section: Introductionmentioning

confidence: 99%

Introducing a Custom-Designed Volume-Pressure Machine for Novel Measurements of Whole Lung Organ Viscoelasticity and Direct Comparisons Between Positive- and Negative-Pressure Ventilation

Sattari

Mariano

Vittalbabu

et al. 2020

Front. Bioeng. Biotechnol.

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Asthma, emphysema, COVID-19 and other lung-impacting diseases cause the remodeling of tissue structural properties and can lead to changes in conducting pulmonary volume, viscoelasticity, and air flow distribution. Whole organ experimental inflation tests are commonly used to understand the impact of these modifications on lung mechanics. Here we introduce a novel, automated, custom-designed device for measuring the volume and pressure response of lungs, surpassing the capabilities of traditional machines and built to range size-scales to accommodate both murine and porcine tests. The software-controlled system is capable of constructing standardized continuous volume-pressure curves, while accounting for air compressibility, yielding consistent and reproducible measures while eliminating the need for pulmonary degassing. This device uses volume-control to enable viscoelastic whole lung macromechanical insights from rate dependencies and pressure-time curves. Moreover, the conceptual design of this device facilitates studies relating the phenomenon of diaphragm breathing and artificial ventilation induced by pushing air inside the lungs. System capabilities are demonstrated and validated via a comparative study between ex vivo murine lungs and elastic balloons, using various testing protocols. Volumepressure curve comparisons with previous pressure-controlled systems yield good agreement, confirming accuracy. This work expands the capabilities of current lung experiments, improving scientific investigations of healthy and diseased pulmonary biomechanics. Ultimately, the methodologies demonstrated in the manufacturing of this system enable future studies centered on investigating viscoelasticity as a potential biomarker and improvements to patient ventilators based on direct assessment and comparisons of positive-and negative-pressure mechanics.

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Section: Introductionmentioning

confidence: 99%

Introducing a Custom-Designed Volume-Pressure Machine for Novel Measurements of Whole Lung Organ Viscoelasticity and Direct Comparisons Between Positive- and Negative-Pressure Ventilation

Sattari

Mariano

Vittalbabu

et al. 2020

Front. Bioeng. Biotechnol.

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“…The results seen on pulmonary function tests in patients with COPD are evidence of over-in°ation of the lung (Bullae formation), decreased air°ow and abnormalities in gas exchange. 35 The observation that almost all the cardiovascular parameters (DBP, HR and RPP) showed signi¯cant changes in the IS group while the control group showed no signi¯cant change also implies that IS brought about the changes. This positive change could be explained by the fact that respiratory modulation is known to be related to cardiovascular modulation and it plays a vital role in blood pressure control.…”

Section: Discussionmentioning

confidence: 97%

Effects of incentive spirometry on cardiopulmonary parameters, functional capacity and glycemic control in patients with Type 2 diabetes

Aweto

Obikeh

Tella

2020

Hong Kong Physiother. J.

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Background: Patients with Type 2 diabetes mellitus (T2DM) suffer cardiopulmonary impairment and may present with weakness of the inspiratory muscles. This study was designed to determine the effects of incentive spirometry (IS) on selected cardiopulmonary parameters, functional capacity and glycemic control in patients with T2DM. Methods: Fifty-nine participants (25 males and 34 females) recruited from the out-patient clinic of the Department of Medicine of two hospitals in Lagos State, Nigeria, who were randomly assigned into two groups, completed the study. In addition to the medical management of T2DM, IS group received incentive spirometry while control group continued with the medical management of T2DM alone. Selected cardiovascular parameters, pulmonary parameters, functional capacity (using 6-min walk test) and fasting blood glucose level were assessed at baseline and at the end of eight weeks intervention period. Data were analyzed using the Statistical Package for Social Sciences (SPSS Version 21). Level of significance was set at [Formula: see text]. Results: There were statistically significant improvements in all the cardiovascular parameters ([Formula: see text]) of IS group except systolic blood pressure. There were significant changes in all the pulmonary parameters, functional capacity and glycemic control ([Formula: see text]) of IS group while there was none in control group. There were significant differences between the mean changes of various selected outcome measures of the two groups ([Formula: see text]) except for diastolic blood pressure and blood glucose level. Conclusion: IS had positive effects in improving cardiopulmonary function, functional capacity and glycemic control in patients with T2DM.

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“…Heterogeneity and anomalous perfusion are observed in post-surgery lung cancer follow up studies [55]. As such, tissue heterogeneity in lungs has been assessed with maneuverless lung function tests in COPD patients [56,57]. The forced oscillation technique can be easily introduced to complement the follow up of NSCLC patients during their treatment as it does not require any forced maneuvers and it only requires tidal breathing measurement.…”

Section: Discussionmentioning

confidence: 99%

A Minimal PKPD Interaction Model for Evaluating Synergy Effects of Combined NSCLC Therapies

Ionescu

Ghita

Copot

et al. 2020

JCM

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This paper introduces a mathematical compartmental formulation of dose-effect synergy modelling for multiple therapies in non small cell lung cancer (NSCLC): antiangiogenic, immuno- and radiotherapy. The model formulates the dose-effect relationship in a unified context, with tumor proliferating rates and necrotic tissue volume progression as a function of therapy management profiles. The model accounts for inter- and intra-response variability by using surface model response terms. Slow acting peripheral compartments such as fat and muscle for drug distribution are not modelled. This minimal pharmacokinetic-pharmacodynamic (PKPD) model is evaluated with reported data in mice from literature. A systematic analysis is performed by varying only radiotherapy profiles, while antiangiogenesis and immunotherapy are fixed to their initial profiles. Three radiotherapy protocols are selected from literature: (1) a single dose 5 Gy once weekly; (2) a dose of 5 Gy × 3 days followed by a 2 Gy × 3 days after two weeks and (3) a dose of 5 Gy + 2 × 0.075 Gy followed after two weeks by a 2 Gy + 2 × 0.075 Gy dose. A reduction of 28% in tumor end-volume after 30 days was observed in Protocol 2 when compared to Protocol 1. No changes in end-volume were observed between Protocol 2 and Protocol 3, this in agreement with other literature studies. Additional analysis on drug interaction suggested that higher synergy among drugs affects up to three-fold the tumor volume (increased synergy leads to significantly lower growth ratio and lower total tumor volume). Similarly, changes in patient response indicated that increased drug resistance leads to lower reduction rates of tumor volumes, with end-volume increased up to 25–30%. In conclusion, the proposed minimal PKPD model has physiological value and can be used to study therapy management protocols and is an aiding tool in the clinical decision making process. Although developed with data from mice studies, the model is scalable to NSCLC patients.

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Structural changes in the COPD lung and related heterogeneity

Cited by 34 publications

References 39 publications

Introducing a Custom-Designed Volume-Pressure Machine for Novel Measurements of Whole Lung Organ Viscoelasticity and Direct Comparisons Between Positive- and Negative-Pressure Ventilation

Introducing a Custom-Designed Volume-Pressure Machine for Novel Measurements of Whole Lung Organ Viscoelasticity and Direct Comparisons Between Positive- and Negative-Pressure Ventilation

Effects of incentive spirometry on cardiopulmonary parameters, functional capacity and glycemic control in patients with Type 2 diabetes

A Minimal PKPD Interaction Model for Evaluating Synergy Effects of Combined NSCLC Therapies

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