An interferon inducible signature of airway disease from blood gene expression profiling

2021 ◽  
pp. 2100569
Author(s):  
Jeong H. Yun ◽  
Sool Lee ◽  
Pooja Srinivasa ◽  
Jarrett Morrow ◽  
Robert Chase ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Function ◽  
Wall Thickness ◽  
Airway Remodeling ◽  
Gene Expression Signature ◽  
Airway Disease ◽  
Chronic Obstructive ◽  
Airway Wall ◽  
Wall Area ◽  
Airway Wall Thickness

BackgroundThe molecular basis of airway remodeling in chronic obstructive pulmonary disease remains poorly understood. We identified gene expression signatures associated with chest CT scan airway measures to understand molecular pathways associated with airway disease.MethodsIn 2,396 subjects in the COPDGene Study, we examined the relationship between quantitative CT airway phenotypes and blood transcriptomes to identify airway disease-specific genes and to define an airway wall thickness (AWT) gene set score. Multivariable regression analyses were performed to identify associations of the AWT score with clinical phenotypes, bronchial gene expression and genetic variants.ResultsType 1 interferon induced genes were consistently associated with airway wall thickness, Pi10, and wall area percent, with the strongest enrichment in airway wall thickness. A score derived from 18 genes whose expression was associated with AWT was associated with COPD-related phenotypes including reduced lung function (FEV1% predicted −3.4, p<0.05) and increased exacerbations (incidence rate ratio 1.6, p<0.05). The AWT score was reproducibly associated with airway wall thickness in bronchial samples from 23 subjects (beta 3.22, p<0.05). The blood AWT score was associated with genetic variant rs876039, an expression quantitative trait locus (eQTL) for IKZF1, a gene which regulates interferon signaling and is associated with inflammatory diseases.ConclusionA gene expression signature with interferon stimulated genes from peripheral blood and bronchial brushings is associated with CT airway wall thickness, lung function, and exacerbations. Shared genes and genetic associations suggest viral responses and/or autoimmune dysregulation as potential underlying mechanisms of airway disease in COPD.

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

2009 ◽  
Vol 107 (1) ◽  
pp. 185-191 ◽  
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.

Asthma with Irreversible Airway Obstruction in Smokers and Nonsmokers: Links between Airway Inflammation and Structural Changes

Respiration ◽  
2020 ◽  
pp. 1-11
Author(s):  
Louis-Philippe Boulet ◽  
Marie-Eve Boulay ◽  
Harvey O. Coxson ◽  
Cameron J. Hague ◽  
Joanne Milot ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Obstruction ◽  
Airway Inflammation ◽  
Wall Thickness ◽  
Structural Changes ◽  
Smoking History ◽  
Airway Wall ◽  
Tobacco Exposure ◽  
Airway Wall Thickness ◽  
Irreversible Airway Obstruction

<b><i>Background:</i></b> The development of irreversible airway obstruction (IRAO) in asthma is related to lung/airway inflammatory and structural changes whose characteristics are likely influenced by exposure to tobacco smoke. <b><i>Objective:</i></b> To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO. <b><i>Methods:</i></b> We studied asthmatics with IRAO who were further classified according to their smoking history, those with ≥20 pack-years of tobacco exposure (asthmatics with smoking-related IRAO [AwS-IRAO]) and those with &#x3c;5 pack-years of tobacco exposure (asthmatics with nonsmoking-related IRAO [AwNS-IRAO]). In addition to recording baseline clinical and lung function features, all patients had a chest computed tomography (CT) from which airway wall thickness was measured and quantitative and qualitative assessment of emphysema was performed. The airway inflammatory profile was documented from differential inflammatory cell counts on induced sputum. <b><i>Results:</i></b> Ninety patients were recruited (57 AwS-IRAO and 33 AwNS-IRAO). There were no statistically significant differences in the extent of emphysema and gas trapping between groups on quantitative chest CT analysis, although Pi10, a marker of airway wall thickness, was significantly higher in AwS-IRAO (<i>p</i> = 0.0242). Visual analysis showed a higher prevalence of emphysema (<i>p</i> = 0.0001) and higher emphysema score (<i>p</i> &#x3c; 0.0001) in AwS-IRAO compared to AwNS-IRAO and distribution of emphysema was different between groups. Correlations between radiological features and lung function were stronger in AwS-IRAO. In a subgroup analysis, we found a correlation between airway neutrophilia and emphysematous features in AwS-IRAO and between eosinophilia and both airway wall thickness and emphysematous changes in AwNS-IRAO. <b><i>Conclusions:</i></b> Although bronchial structural changes were relatively similar in smoking and nonsmoking patients with asthma and IRAO, emphysematous changes were more predominant in smokers. However, neutrophils in AwS-IRAO and eosinophils in AwNS-IRAO were associated with lung and airway structural changes.

scholarly journals Airway wall thickness associated with forced expiratory volume in 1 second decline and development of airflow limitation

2015 ◽  
Vol 45 (3) ◽  
pp. 644-651 ◽  
Author(s):  
Firdaus A.A. Mohamed Hoesein ◽  
Pim A. de Jong ◽  
Jan-Willem J. Lammers ◽  
Willem P.T.M. Mali ◽  
Michael Schmidt ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Forced Expiratory Volume ◽  
Airflow Limitation ◽  
Airway Wall ◽  
Lung Function Decline ◽  
Wall Area ◽  
Percentile Method ◽  
Airway Wall Thickness ◽  
Fev1 Decline

Airway wall thickness and emphysema contribute to airflow limitation.We examined their association with lung function decline and development of airflow limitation in 2021 male smokers with and without airflow limitation. Airway wall thickness and emphysema were quantified on chest computed tomography and expressed as the square root of wall area of a 10-mm lumen perimeter (Pi10) and the 15th percentile method (Perc15), respectively. Baseline and follow-up (median (interquartile range) 3 (2.9–3.1) years) spirometry was available.Pi10 and Perc15 correlated with baseline forced expiratory volume in 1 s (FEV1) (r= −0.49 and 0.11, respectively (p<0.001)). Multiple linear regression showed that Pi10 and Perc15 at baseline were associated with a lower FEV1 after follow-up (p<0.05). For eachsdincrease in Pi10 and decrease in Perc15 the FEV1 decreased by 20 mL and 30.2 mL, respectively. The odds ratio for developing airflow limitation after 3 years was 2.45 for a 1-mm higher Pi10 and 1.46 for a 10-HU lower Perc15 (p<0.001).A greater degree of airway wall thickness and emphysema was associated with a higher FEV1 decline and development of airflow limitation after 3 years of follow-up.

Chronic Obstructive Pulmonary Disease: Thin-Section CT Measurement of Airway Wall Thickness and Lung Attenuation

Radiology ◽  
2005 ◽  
Vol 234 (2) ◽  
pp. 604-610 ◽  
Author(s):  
Ilaria Orlandi ◽  
Chiara Moroni ◽  
Gianna Camiciottoli ◽  
Maurizio Bartolucci ◽  
Massimo Pistolesi ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Thin Section ◽  
Wall Thickness ◽  
Chronic Obstructive ◽  
Airway Wall ◽  
Obstructive Pulmonary Disease ◽  
Airway Wall Thickness ◽  
Ct Measurement

scholarly journals Small Airway Wall Thickening Assessed by Computerized Tomography Is Associated With Low Lung Function in Chinese Carbon Black Packers

2020 ◽  
Vol 178 (1) ◽  
pp. 26-35
Author(s):  
Xue Cao ◽  
Li Lin ◽  
Akshay Sood ◽  
Qianli Ma ◽  
Xiangyun Zhang ◽  
...  
Keyword(s):  
Lung Function ◽  
Carbon Black ◽  
Elemental Carbon ◽  
Airway Remodeling ◽  
Forced Expiratory Volume ◽  
Small Airway ◽  
Wall Thickening ◽  
Dependent Manner ◽  
Airway Wall ◽  
Wall Area

Abstract Nanoscale carbon black as virtually pure elemental carbon can deposit deep in the lungs and cause pulmonary injury. Airway remodeling assessed using computed tomography (CT) correlates well with spirometry in patients with obstructive lung diseases. Structural airway changes caused by carbon black exposure remain unknown. Wall and lumen areas of sixth and ninth generations of airways in 4 lobes were quantified using end-inhalation CT scans in 58 current carbon black packers (CBPs) and 95 non-CBPs. Carbon content in airway macrophage (CCAM) in sputum was quantified to assess the dose-response. Environmental monitoring and CCAM showed a much higher level of elemental carbon exposure in CBPs, which was associated with higher wall area and lower lumen area with no change in total airway area for either airway generation. This suggested small airway wall thickening is a major feature of airway remodeling in CBPs. When compared with wall or lumen areas, wall area percent (WA%) was not affected by subject characteristics or lobar location and had greater measurement reproducibility. The effect of carbon black exposure status on WA% did not differ by lobes. CCAM was associated with WA% in a dose-dependent manner. CBPs had lower FEV1 (forced expiratory volume in 1 s) than non-CBPs and mediation analysis identified that a large portion (41–72%) of the FEV1 reduction associated with carbon black exposure could be explained by WA%. Small airway wall thickening as a major imaging change detected by CT may underlie the pathology of lung function impairment caused by carbon black exposure.

scholarly journals Association of Obesity with Quantitative Chest CT Measured Airway Wall Thickness in WTC Workers with Lower Airway Disease

Lung ◽  
2019 ◽  
Vol 197 (4) ◽  
pp. 517-522 ◽  
Author(s):  
Rafael E. de la Hoz ◽  
Xiaoyu Liu ◽  
Juan C. Celedón ◽  
John T. Doucette ◽  
Yunho Jeon ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Airway Disease ◽  
Chest Ct ◽  
Lower Airway ◽  
Airway Wall ◽  
Airway Wall Thickness
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