Potential Value of Expiratory CT in Quantitative Assessment of Pulmonary Vessels in COPD

Objective: To investigate the associations between intrapulmonary vascular volume (IPVV) depicted on inspiratory and expiratory CT scans and disease severity in COPD patients, and to determine which CT parameters can be used to predict IPVV.Methods: We retrospectively collected 89 CT examinations acquired on COPD patients from an available database. All subjects underwent both inspiratory and expiratory CT scans. We quantified the IPVV, airway wall thickness (WT), the percentage of the airway wall area (WA%), and the extent of emphysema (LAA%−950) using an available pulmonary image analysis tool. The underlying relationship between IPVV and COPD severity, which was defined as mild COPD (GOLD stage I and II) and severe COPD (GOLD stage III and IV), was analyzed using the Student's t-test (or Mann-Whitney U-test). The correlations of IPVV with pulmonary function tests (PFTs), LAA%−950, and airway parameters for the third to sixth generation bronchus were analyzed using the Pearson or Spearman's rank correlation coefficients and multiple stepwise regression.Results: In the subgroup with only inspiratory examinations, the correlation coefficients between IPVV and PFT measures were −0.215 ~ −0.292 (p < 0.05), the correlation coefficients between IPVV and WT3−6 were 0.233 ~ 0.557 (p < 0.05), and the correlation coefficient between IPVV and LAA%−950 were 0.238 ~ 0.409 (p < 0.05). In the subgroup with only expiratory scan, the correlation coefficients between IPVV and PFT measures were −0.238 ~ −0.360 (p < 0.05), the correlation coefficients between IPVV and WT3−6 were 0.260 ~ 0.566 (p < 0.05), and the correlation coefficient between IPVV and LAA%−950 were 0.241 ~ 0.362 (p < 0.05). The multiple stepwise regression analyses demonstrated that WT were independently associated with IPVV (P < 0.05).Conclusion: The expiratory CT scans can provide a more accurate assessment of COPD than the inspiratory CT scans, and the airway wall thickness maybe an independent predictor of pulmonary vascular alteration in patients with COPD.

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

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.

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

<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.

Extracellular matrix remodelling in COPD

The extracellular matrix (ECM) of the lung plays several important roles in lung function, as it offers a low resistant pathway that allows the exchange of gases, provides compressive strength and elasticity that supports the fragile alveolar–capillary intersection, controls the binding of cells with growth factors and cell surface receptors and acts as a buffer against retention of water.COPD is a chronic inflammatory respiratory condition, characterised by various conditions that result in progressive airflow limitation. At any stage in the course of the disease, acute exacerbations of COPD may occur and lead to accelerated deterioration of pulmonary function. A key factor of COPD is airway remodelling, which refers to the serious alterations of the ECM affecting airway wall thickness, resistance and elasticity. Various studies have shown that serum biomarkers of ECM turnover are significantly associated with disease severity in patients with COPD and may serve as potential targets to control airway inflammation and remodelling in COPD. Unravelling the complete molecular composition of the ECM in the diseased lungs will help to identify novel biomarkers for disease progression and therapy.

Effect of smoking cessation on CT imaging in patients with Chronic Obstructive Pulmonary Disease: A systematic review

BackgroundSmoking cessation is the only intervention known to affect disease progression in patients with COPD as measured by the rate of change in forced expiratory volume/1s (FEV1) over time. The need for new drugs to modify the progression of COPD is well recognised. We hypothesised that changes on CT in relation to smoking cessation may relate to changes in response to disease-modifying drugs, and therefore as a novel quantitative biomarker of drug efficacy. CT biomarkers of emphysema and airway wall thickness are increasingly used in research, but there has not been a systematic appraisal of the evidence to assess how these biomarkers evolve with a change in smoking exposure in COPD patients.MethodsWe searched MEDLINE, Embase, the Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL)), and Web of Science to 10th September 2019. We included longitudinal studies of smoking COPD patients who had CT scans before and after smoking cessation. Two review authors (DC, SA) independently screened studies, extracted outcome data and assessed the risk of bias, with a third reviewer (JRH) arbitrating conflicts.ResultsFour studies were included in the final analysis. Three studies measured CT markers of lung density, which all, perhaps counter-intuitively, showed a significant decrease with smoking cessation. One study measured CT markers of airway wall thickness, which also significantly decreased with smoking cessation.Authors’ conclusionsSmoking cessation in COPD patients causes a fall in lung density, but the magnitude of the effect has not been rigorously assessed. One study has reported a decrease in airway wall thickness with smoking cessation. The number of studies is small, with some risk of bias. This question remains important for COPD researchers and requires further studies, in particular to assess whether changes with smoking cessation may model changes in response to novel pharmaceutical agents, and how to handle change in smoking status in relation to longitudinal observational imaging studies in COPD.

Airway wall thickness and airflow limitations in asthma assessed in quantitative computed tomography

Background: Asthma is a frequent chronic disease of the airways. In spite of the fact that symptoms of asthma are well known, the pathogenesis has not yet been fully understood. Quantitative computed tomography (qCT) of the lung allows for the measurment of a set of parameters. The aim of this study was to evaluate the usefulness of quantitative computed tomography in the assessment of airway wall thickness in asthma. Methods: The prospective study was performed on a group of 83 patients with well-defined, long-term asthma between 2016 and 2018. The control group was composed of 30 healthy volunteers. All examined subjects were non-smokers. All computed tomography (CT) studies were performed using a 128 multi-slice CT scanner with no contrast, following a chest scanning protocol in the supine position, at full inspiration and breath-holds. Results: Quantitative bronchial tree measurements were obtained from the third up to the ninth generation of the posterior basal bronchi (B10) of the right lung in a blinded fashion. The value of the wall thickness in patients with asthma was significantly higher in all measured generations of the bronchial tree (third to ninth generation). The lumen area and the inner diameter significantly correlated with the lung function tests and were substantially smaller in the examined group from the seventh to the ninth generation of the bronchi ( p < 0.05). Conclusions: We conclude that airway remodelling occurs in most patients with long-term asthma and is associated mainly with the medium and small airways. Imaging techniques, especially qCT can be useful in the diagnosis and management of asthma. The reviews of this paper are available via the supplemental material section.