WS06.5 Validation of automated airway-artery method to diagnosis of cystic fibrosis-related bronchiectasis and airway wall thickening

ObjectivesLumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). This study aimed to assess lung structural changes after one year of lumacaftor-ivacaftor treatment, and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor.MethodsAdolescents and adults with CF from the French multicenter real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pretherapeutic and follow-up chest computed tomography (CT)-scans available. CT scans were visually scored using a modified Bhalla score. A k-mean clustering method was performed based on 120 radiomics features extracted from unenhanced pretherapeutic chest CT scans.ResultsA total of 283 patients were included. The Bhalla score significantly decreased after 1 year of lumacaftor-ivacaftor (−1.40±1.53 points compared with pretherapeutic CT; p<0.001). This finding was related to a significant decrease in mucus plugging (−0.35±0.62 points; p<0.001), bronchial wall thickening (−0.24±0.52 points; p<0.001) and parenchymal consolidations (−0.23±0.51 points; p<0.001). Cluster analysis identified 3 morphological clusters. Patients from cluster C were more likely to experience an increase in percent predicted forced expiratory volume in 1 sec (ppFEV1) ≥5 under lumacaftor–ivacaftor than those in the other clusters (54% of responders versus 32% and 33%; p=0.01).ConclusionOne year treatment with lumacaftor-ivacaftor was associated with a significant visual improvement of bronchial disease on chest CT. Radiomics features on pretherapeutic CT scan may help in predicting lung function response under lumacaftor-ivacaftor.

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Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo

Journal of Applied Physiology ◽

10.1152/jappl.1997.83.2.366 ◽

1997 ◽

Vol 83 (2) ◽

pp. 366-370 ◽

Cited By ~ 26

Author(s):

Robert H. Brown ◽

Wayne Mitzner ◽

Elizabeth M. Wagner

Keyword(s):

Dose Response ◽

Lung Volume ◽

Bronchial Artery ◽

Wall Thickening ◽

Airway Wall ◽

Lung Inflation ◽

Wall Area ◽

Airway Edema ◽

Airway Constriction

Brown, Robert H., Wayne Mitzner, and Elizabeth M. Wagner.Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo. J. Appl. Physiol. 83(2): 366–370, 1997.—Inflammatory changes and airway wall thickening are suggested to cause increased airway responsiveness in patients with asthma. In five sheep, the dose-response relationships of individual airways were measured at different lung volumes to methacholine (MCh) before and after wall thickening caused by the inflammatory mediator bradykinin via the bronchial artery. At 4 cmH2O transpulmonary pressure (Ptp), 5 μg/ml MCh constricted the airways to a maximum of 18 ± 3%. At 30 cmH2O Ptp, MCh resulted in less constriction (to 31 ± 5%). Bradykinin increased airway wall area at 4 and 30 cmH2O Ptp (159 ± 6 and 152 ± 4%, respectively; P < 0.0001). At 4 cmH2O Ptp, bradykinin decreased airway luminal area (13 ± 2%; P< 0.01), and the dose-response curve was significantly lower ( P = 0.02). At 30 cmH2O, postbradykinin, the maximal airway narrowing was not significantly different (26 ± 5%; P = 0.76). Bradykinin produced substantial airway wall thickening and slight potentiation of the MCh-induced airway constriction at low lung volume. At high lung volume, bradykinin increased wall thickness but had no effect on the MCh-induced airway constriction. We conclude that inflammatory fluid leakage in the airways cannot be a primary cause of airway hyperresponsiveness.

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Effects of lung volume, bronchoconstriction, and cigarette smoke on morphometric airway dimensions

Journal of Applied Physiology ◽

10.1152/jappl.1988.64.3.913 ◽

1988 ◽

Vol 64 (3) ◽

pp. 913-919 ◽

Cited By ~ 26

Author(s):

A. L. James ◽

P. D. Pare ◽

J. C. Hogg

Keyword(s):

Smooth Muscle ◽

Cigarette Smoke ◽

Lung Volume ◽

Muscle Tone ◽

Cigarette Smoke Exposure ◽

Wall Thickening ◽

Airway Wall ◽

Lung Inflation ◽

Wall Area ◽

Airway Dimensions

To examine the role of airway wall thickening in the bronchial hyperresponsiveness observed after exposure to cigarette smoke, we compared the airway dimensions of guinea pigs exposed to smoke (n = 7) or air (n = 7). After exposure the animals were anesthetized with urethan, pulmonary resistance was measured, and the lungs were removed, distended with Formalin, and fixed near functional residual capacity. The effects of lung inflation and bronchoconstriction on airway dimensions were studied separately by distending and fixing lungs with Formalin at total lung capacity (TLC) (n = 3), 50% TLC (n = 3), and 25% TLC (n = 3) or near residual volume after bronchoconstriction (n = 3). On transverse sections of extraparenchymal and intraparenchymal airways the following dimensions were measured: the internal area (Ai) and internal perimeter (Pi), defined by the epithelium, and the external area (Ae) and external perimeter (Pe), defined by the outer border of smooth muscle. Airway wall area (WA) was then calculated, WA = Ae - Ai. Ai, Pe, and Ae decreased with decreasing lung volume and after bronchoconstriction. However, WA and Pi did not change significantly with lung volume or after bronchoconstriction. After cigarette smoke exposure airway resistance was increased (P less than 0.05); however, there was no difference in WA between the smoke- and air-exposed groups when the airways were matched by Pi. We conclude that Pi and WA are constant despite changes in lung volume and smooth muscle tone and that airway hyperresponsiveness induced by cigarette smoke is not mediated by increased airway wall thickness.

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Longitudinal CT Assessment Of Airway Wall Thickening In Severe Asthma

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a3721 ◽

2011 ◽

Author(s):

Chad Witt ◽

David Gierada ◽

James Kozlowski ◽

Eric A. Hoffman ◽

Janice Cook-Granroth ◽

...

Keyword(s):

Severe Asthma ◽

Wall Thickening ◽

Airway Wall

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Role of nitric oxide in airway remodelling

Clinical Science ◽

10.1042/cs0980291 ◽

2000 ◽

Vol 98 (3) ◽

pp. 291-294 ◽

Cited By ~ 7

Author(s):

Esteban C. GABAZZA ◽

Osamu TAGUCHI ◽

Shigenori TAMAKI ◽

Shuichi MURASHIMA ◽

Hiroyasu KOBAYASHI ◽

...

Keyword(s):

Nitric Oxide ◽

Causative Factor ◽

Wall Thickening ◽

No Production ◽

Airway Remodelling ◽

Pathophysiological Mechanism ◽

Airway Wall ◽

High Resolution Computed Tomography ◽

Bronchial Wall ◽

Nitrite Nitrate

Airway remodelling, which is manifested by thickening of bronchial wall, is an important causative factor of bronchial hyper-responsiveness in asthma. The pathophysiological mechanism of airway remodelling is not clear. In the present study we evaluated the relationship between nitric oxide (NO) generation and airway wall thickening in patients with chronic asthma. As a marker of NO production, the levels of nitrite/nitrate were measured in induced sputum, and bronchial wall thickening was measured by high-resolution computed tomography. Sputum concentrations of nitrite/nitrate were significantly increased in asthmatic patients compared with controls. The ratio of airway wall thickness to lumen diameter was significantly correlated with the sputum concentration of nitrite/nitrate. Although statistical correlation does not prove causation, this finding suggests that NO may play a key role in the pathogenesis of airway remodelling.

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A comparative study of matrix remodeling in chronic models for COPD; mechanistic insights into the role of TNF-α

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00116.2014 ◽

2014 ◽

Vol 307 (7) ◽

pp. L557-L565 ◽

Cited By ~ 23

Author(s):

Irene M. J. Eurlings ◽

Mieke A. Dentener ◽

Evi M. Mercken ◽

Rafael de Cabo ◽

Ken R. Bracke ◽

...

Keyword(s):

Two Dimensions ◽

Small Airway ◽

Wall Thickening ◽

Suitable Model ◽

Matrix Remodeling ◽

Airway Wall ◽

Copd Patients ◽

Tnf Α ◽

Chronic Models ◽

Airway Walls

Remodeling in chronic obstructive pulmonary disease (COPD) has at least two dimensions: small airway wall thickening and destruction of alveolar walls. Recently we showed comparable alterations of the extracellular matrix (ECM) compounds collagen, hyaluoran, and elastin in alveolar and small airway walls of COPD patients. The aim of this study was to characterize and assess similarities in alveolar and small airway wall matrix remodeling in chronic COPD models. From this comparative characterization of matrix remodeling we derived and elaborated underlying mechanisms to the matrix changes reported in COPD. Lung tissue sections of chronic models for COPD, either induced by exposure to cigarette smoke, chronic intratracheal lipopolysaccharide instillation, or local tumor necrosis factor (TNF) expression [surfactant protein C (SPC)-TNFα mice], were stained for elastin, collagen, and hyaluronan. Furthermore TNF-α matrix metalloproteinase (MMP)-2, -9, and -12 mRNA expression was analyzed using qPCR and localized using immunohistochemistry. Both collagen and hyaluronan were increased in alveolar and small airway walls of all three models. Interestingly, elastin contents were differentially affected, with a decrease in both alveolar and airway walls in SPC-TNFα mice. Furthermore TNF-α and MMP-2 and -9 mRNA and protein levels were found to be increased in alveolar walls and around airway walls only in SPC-TNFα mice. We show that only SPC-TNFα mice show changes in elastin remodeling that are comparable to what has been observed in COPD patients. This reveals that the SPC-TNFα model is a suitable model to study processes underlying matrix remodeling and in particular elastin breakdown as seen in COPD. Furthermore we indicate a possible role for MMP-2 and MMP-9 in the breakdown of elastin in airways and alveoli of SPC-TNFα mice.

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Automatic airway-artery analysis on lung CT to quantify airway wall thickening and bronchiectasis

Medical Physics ◽

10.1118/1.4963214 ◽

2016 ◽

Vol 43 (10) ◽

pp. 5736-5744 ◽

Cited By ~ 21

Author(s):

Adria Perez-Rovira ◽

Wieying Kuo ◽

Jens Petersen ◽

Harm A. W. M. Tiddens ◽

Marleen de Bruijne

Keyword(s):

Wall Thickening ◽

Airway Wall ◽

Lung Ct

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Airway wall attenuation: a biomarker of airway disease in subjects with COPD

Journal of Applied Physiology ◽

10.1152/japplphysiol.00216.2009 ◽

2009 ◽

Vol 107 (1) ◽

pp. 185-191 ◽

Cited By ~ 44

Author(s):

George R. Washko ◽

Mark T. Dransfield ◽

Raúl San José Estépar ◽

Alejandro Diaz ◽

Shin Matsuoka ◽

...

Keyword(s):

Lung Function ◽

Wall Thickness ◽

Airway Disease ◽

Wall Thickening ◽

Chronic Obstructive ◽

Airway Wall ◽

Wall Area ◽

Computer Based ◽

Structure Density ◽

Contrast Reduction

The computed tomographic (CT) densities of imaged structures are a function of the CT scanning protocol, the structure size, and the structure density. For objects that are of a dimension similar to the scanner point spread function, CT will underestimate true structure density. Prior investigation suggests that this process, termed contrast reduction, could be used to estimate the strength of thin structures, such as cortical bone. In this investigation, we endeavored to exploit this process to provide a CT-based measure of airway disease that can assess changes in airway wall thickening and density that may be associated with the mural remodeling process in subjects with chronic obstructive pulmonary disease (COPD). An initial computer-based study using a range of simulated airway wall sizes and densities suggested that CT measures of airway wall attenuation could detect changes in both wall thickness and structure density. A second phantom-based study was performed using a series of polycarbonate tubes of known density. The results of this again demonstrated the process of contrast reduction and further validated the computer-based simulation. Finally, measures of airway wall attenuation, wall thickness, and wall area (WA) divided by total cross-sectional area, WA percent (WA%), were performed in a cohort of 224 subjects with COPD and correlated with spirometric measures of lung function. The results of this analysis demonstrated that wall attenuation is comparable to WA% in predicting lung function on univariate correlation and remain as a statistically significant correlate to the percent forced expiratory volume in 1 s predicted when adjusted for measures of both emphysema and WA%. These latter findings suggest that the quantitative assessment of airway wall attenuation may offer complementary information to WA% in characterizing airway disease in subjects with COPD.

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Longitudinal shape irregularity of airway lumen assessed by CT in patients with bronchial asthma and COPD

Thorax ◽

10.1136/thoraxjnl-2014-206651 ◽

2015 ◽

Vol 70 (8) ◽

pp. 719-724 ◽

Cited By ~ 14

Author(s):

Tsuyoshi Oguma ◽

Toyohiro Hirai ◽

Motonari Fukui ◽

Naoya Tanabe ◽

Satoshi Marumo ◽

...

Keyword(s):

Bronchial Asthma ◽

Ct Images ◽

Wall Thickening ◽

Airway Remodelling ◽

Healthy Controls ◽

Airway Wall ◽

Cross Sectional ◽

Airway Lumen ◽

Luminal Area ◽

Shape Irregularity

BackgroundAirway remodelling in bronchial asthma (BA) and COPD has been quantitatively assessed by analysing the airway wall area and the luminal area on cross-sectional CT images. To date, there have been no reports on assessment of the longitudinal structure of the airway lumen.MethodsQuantitative airway analysis using CT was performed on three groups consisting of 29 patients with BA, 58 patients with COPD and 59 healthy controls. To assess the longitudinal shape irregularity of the airway lumen, new quantitative CT parameters, validated by a phantom study, were established. The internal radii of imaginary inscribed spheres in the airway lumen were measured as a function of distance from the level of the carina to the fifth-order branches of the right posterior basal bronchus. The gaps of these radii from the regression line were calculated as parameters to reflect the longitudinal airway lumen shape irregularity. These new parameters were compared among the study groups as well as with the conventional parameters of airway wall thickening and luminal area.ResultsLongitudinal airway lumen shape irregularity was significantly greater in patients with COPD than in those with BA and healthy controls. Wall thickening was significantly greater, and luminal area smaller, in patients with BA than in those with COPD and healthy controls. These results were consistent even among the BA and COPD subgroups with similar airflow limitation.ConclusionsThe combination of cross-sectional and longitudinal airway structure analyses using CT images may suggest differences in the characteristics of airway remodelling between COPD and asthma.

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