This is what COPD looks like

Despite decades of research, and the growing healthcare and societal burden of chronic obstructive pulmonary disease (COPD), therapeutic COPD breakthroughs have not occurred. Sub-optimal COPD patient phenotyping, an incomplete understanding of COPD pathogenesis and a scarcity of sensitive tools that provide patient-relevant intermediate endpoints likely all play a role in the lack of new, efficacious COPD interventions. In other words, COPD patients are still diagnosed based on the presence of persistent airflow limitation measured using spirometry. Spirometry measurements reflect the global sum of all the different possible COPD pathologies and perhaps because of this, we lose sight of the different contributions of airway and parenchymal abnormalities. With recent advances in thoracic X-ray computed tomography (CT) and magnetic resonance imaging (MRI), lung structure and function abnormalities may be regionally identified and measured. These imaging endpoints may serve as biomarkers of COPD that can be used to better phenotype patients. Therefore, here we review novel CT and MRI measurements that help reveal COPD phenotypes and what COPD really \u27looks\u27 like, beyond spirometric indices. We discuss MR and CT imaging approaches for generating reproducible and sensitive measurements of COPD phenotypes related to pulmonary ventilation and perfusion as well as airway and parenchyma anatomical and morphological features. These measurements may provide a way to advance the development and testing of new COPD interventions and therapies

Longitudinal computed tomography and magnetic resonance imaging of COPD: Thoracic imaging network of Canada (TINCan) study objectives

Although the human and societal burden and cost of COPD is staggering, there are few clinical tools that provide earlier diagnoses or a means to regionally monitor disease in a way that might lead to improved therapies and outcomes. In acknowledgement of the current gaps in COPD therapy, the objective of the Thoracic Imaging Network of Canada (TINCan) is to improve COPD patient phenotyping through imaging, to provide methods and imaging-based intermediate endpoints for the development of new treatments, and to evaluate disease progression and patient-based outcomes in COPD patients and those at risk of COPD. Here we summarize and outline the TINCan study protocol and describe our objectives. TINCan is a prospective study that aims to identify and quantify novel COPD phenotypes from thoracic computed tomography (CT) and thoracic hyperpolarized noble gas magnetic resonance imaging (MRI) in 200 ex-smokers, 50 years of age or greater, including asymptomatic ex-smokers with normal pulmonary function and Global initiative for chronic Obstructive Lung Disease (GOLD) Unclassified (U) , and GOLD stages I-IV patients. Baseline and 2-year follow-up measurements will be acquired using spirometry, plethysmography, diffusing capacity of the lung for carbon monoxide (D

COPD: Do Imaging Measurements of Emphysema and Airway Disease Explain Symptoms and Exercise Capacity?

PURPOSE: To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to-moderate disease. MATERIALS AND METHODS: Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA-compliant protocol and underwent spirometry and plethysmography, completed the St George\u27s Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT). Emphysema was estimated by using the MR imaging apparent diffusion coefficient (ADC) and the relative area of the CT attenuation histogram with attenuation of -950 HU or less (RA950). Airway disease was measured by using the CT airway wall thickness of airways with an internal perimeter of 10 mm and total airway count. Ventilation defect percentage at (3)He MR imaging was used to measure ventilation. Multivariable regression models for the 6MWD and SGRQ symptom subscore were used to evaluate the relationships between physiologic and imaging measurements. RESULTS: Multivariate modeling for the 6MWD in 80 patients with GOLD grade U-II COPD showed that ADC (β = 0.34, P = .04), diffusing capacity of the lung for carbon monoxide (β = 0.60, P = .0008), and residual volume/total lung capacity (β = -0.26, P = .02) were significant variables, while forced expiratory volume in 1 second (FEV1) and airway disease measurements were not. In 36 patients with GOLD grade III or IV disease, FEV1 (β = 0.48, P = .01) was the only significant contributor in a multivariate model for 6MWD. MR imaging emphysema measurements also made the greatest relative contribution to symptoms in patients with milder (GOLD grade U-II) COPD (ADC: β = 0.60, P = .005; RA950: β = -0.52, P = .02; FEV1: β = -0.45, P = .0002) and in grade III or IV disease (ADC: β = 0.95, P = .01; RA950: β = -0.62, P = .07; airway count: β = -0.49, P = .01). CONCLUSION: In patients with mild-to-moderate COPD, MR imaging emphysema measurements played a dominant role in the expression of exercise limitation, while both CT and MR imaging measurements of emphysema explained symptoms

What are ventilation defects in asthma?

BACKGROUND: Hyperpolarised (3)He MRI provides a way to visualise regional pulmonary functional abnormalities that in asthma are thought to be related to airway morphological abnormalities. However, the exact aetiology of ventilation defects in asthma is not well understood. OBJECTIVE: To better understand the determinants of ventilation defects in asthma, we evaluated well-established clinical as well as (3)He MRI and X-ray CT airway measurements in healthy subjects and subjects with asthma. METHODS: Thirty-four subjects (n=26 subjects with asthma, n=8 healthy volunteers) underwent MRI, spirometry, plethysmography, fraction of exhaled nitric oxide analysis, methacholine challenge and CT for a region-of-interest proximal to ventilation defects. For subjects who consented to CT (n=18 subjects with asthma, n=5 healthy volunteers), we evaluated 3(rd) to 5th generation airway wall area and wall thickness per cent and lumen area. RESULTS: Seventeen subjects with asthma (17/26=65%) had visually obvious evidence of (3)He ventilation defects prior to bronchoprovocation and nine subjects with asthma had no ventilation defects prior to bronchoprovocation (9/26=35%). Subjects with asthma with defects were older (p=0.01) with worse forced expiratory volume in 1 s (FEV1)/forced vital capacity (p=0.0003), airways resistance (p=0.004), fraction of exhaled nitric oxide (p=0.03), greater bronchoprovocation concentration of methacholine that reduced FEV1 by 20% (p=0.008) and wall thickness per cent (p=0.02) compared with subjects with asthma without defects. There was a moderate correlation for wall area per cent with ventilation defect per cent (r=0.43, p=0.04). CONCLUSIONS: Subjects with asthma with (3)He ventilation defects were older with significantly worse airway hyper-responsiveness, inflammation and airway remodelling but similar FEV1 as subjects with asthma without defects; hyperpolarised (3)He ventilation abnormalities were spatially and quantitatively related to abnormally remodelled airways

Management of COPD:Is there a role for quantitative imaging?

While the recent development of quantitative imaging methods have led to their increased use in the diagnosis and management of many chronic diseases, medical imaging still plays a limited role in the management of chronic obstructive pulmonary disease (COPD). In this review we highlight three pulmonary imaging modalities: computed tomography (CT), magnetic resonance imaging (MRI) and optical coherence tomography (OCT) imaging and the COPD biomarkers that may be helpful for managing COPD patients. We discussed the current role imaging plays in COPD management as well as the potential role quantitative imaging will play by identifying imaging phenotypes to enable more effective COPD management and improved outcomes

On the role of abnormal DL(CO) in ex-smokers without airflow limitation: symptoms, exercise capacity and hyperpolarised helium-3 MRI

BACKGROUND: The functional effects of abnormal diffusing capacity for carbon monoxide (DLCO) in ex-smokers without chronic obstructive pulmonary disease (COPD) are not well understood. OBJECTIVE: We aimed to evaluate and compare well established clinical, physiological and emerging imaging measurements in ex-smokers with normal spirometry and abnormal DLCO with a group of ex-smokers with normal spirometry and DLCO and ex-smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD. METHODS: We enrolled 38 ex-smokers and 15 subjects with stage I COPD who underwent spirometry, plethysmography, St George\u27s Respiratory Questionnaire (SGRQ), 6 min Walk Test (6MWT), x-ray CT and hyperpolarised helium-3 ((3)He) MRI. The 6MWT distance (6MWD), SGRQ scores, (3)He MRI apparent diffusion coefficients (ADC) and CT attenuation values below -950 HU (RA950) were evaluated. RESULTS: Of 38 ex-smokers without COPD, 19 subjects had abnormal DLCO with significantly worse ADC (p=0.01), 6MWD (p=0.008) and SGRQ (p=0.01) but not RA950 (p=0.53) compared with 19 ex-smokers with normal DLCO. Stage I COPD subjects showed significantly worse ADC (p=0.02), RA950 (p=0.0008) and 6MWD (p=0.005), but not SGRQ (p=0.59) compared with subjects with abnormal DLCO. There was a significant correlation for (3)He ADC with SGRQ (r=0.34, p=0.02) and 6MWD (r=-0.51, p=0.0002). CONCLUSIONS: In ex-smokers with normal spirometry and CT but abnormal DLCO, there were significantly worse symptoms, 6MWD and (3)He ADC compared with ex-smokers with normal DLCO, providing evidence of the impact of mild or early stage emphysema and a better understanding of abnormal DLCO and hyperpolarised (3)He MRI in ex-smokers without COPD

MRI ventilation abnormalities predict quality-of-life and lung function changes in mild-to-moderate COPD: Longitudinal TINCan study

CT biomarkers of emphysema (15th percentile of the CT density histogram, HU15%) and airways disease (wall thickness of airways with 10 mm internal perimeter, Pi10) have shown promise for providing prognostic information.2 Although recent data3 showed that the change in CT emphysema may be used to estimate the efficacy of therapy in patients with α-1-antitrypsin-deficiency, thus far none of the currently developed CT biomarkers have been shown to reflect changes in outcomes that are important to patients with COPD. MRI with inhaled noble gases provide highly sensitive and unique microstructural and functional information in COPD.4 MRI biomarkers of COPD are highly reproducible,5 are associated with COPD outcomes6 and detect changes with greater sensitivity and before disease-related changes can be detected by CT or FEV1. Here we evaluated longitudinal changes in both CT and MRI measurements of COPD. Based on previous longitudinal results,8 ,10 we hypothesised that 3He MRI biomarkers would predict quality-of-life and FEV1 changes in COPD, and that longitudinal changes in MRI biomarkers would be correlated with changes in COPD quality-of-life measures

Free-breathing Pulmonary (1)H and Hyperpolarized (3)He MRI: Comparison in COPD and Bronchiectasis.

RATIONALE AND OBJECTIVES: In this proof-of-concept demonstration, we aimed to quantitatively and qualitatively compare pulmonary ventilation abnormalities derived from Fourier decomposition of free-breathing (1)H magnetic resonance imaging (FDMRI) to hyperpolarized (3)He MRI in subjects with chronic obstructive pulmonary disease (COPD) and bronchiectasis. MATERIALS AND METHODS: All subjects provided written informed consent to a protocol approved by a local research ethics board and Health, Canada, and they underwent MRI, computed tomography (CT), spirometry, and plethysmography during a single 2-hour visit. Semiautomated segmentation was used to generate ventilation defect measurements derived from FDMRI and (3)He MRI, and these were compared using analysis of variance and Pearson correlations. RESULTS: Twenty-six subjects were evaluated including 12 COPD subjects (67 ± 9 years) and 14 bronchiectasis subjects (70 ± 11 years). For COPD subjects, FDMRI and (3)He MRI ventilation defect percent (VDP) was 7 ± 6% and 24 ± 14%, respectively (P \u3c .001; bias = -16 ± 9%). In COPD subjects, FDMRI was significantly correlated with (3)He MRI VDP (r = .88; P = .0001), (3)He MRI apparent diffusion coefficient (r = .71; P \u3c .05), airways resistance (r = .60; P \u3c .05), and RA950 (r = .80; P \u3c .01). In subjects with bronchiectasis, FDMRI VDP (5 ± 3%) and (3)He MRI VDP (18 ± 9%) were significantly different (P \u3c .001) and not correlated (P \u3e .05). The Dice similarity coefficient (DSC) for FDMRI and (3)He MRI ventilation was 86 ± 7% for COPD and 86 ± 4% for bronchiectasis subjects (P \u3e .05); the DSC for FDMRI ventilation defects and CT RA950 was 19 ± 20% in COPD and 2 ± 3% in bronchiectasis subjects (P \u3c .01). CONCLUSIONS: FDMRI and (3)He MRI VDP were strongly related in COPD but not in bronchiectasis subjects. In COPD only, FDMRI ventilation defects were spatially related with (3)He ventilation defects and emphysema

Reproducibility of optical coherence tomography airway imaging

Optical coherence tomography (OCT) is a promising imaging technique to evaluate small airway remodeling. However, the short-term insertion-reinsertion reproducibility of OCT for evaluating the same bronchial pathway has yet to be established. We evaluated 74 OCT data sets from 38 current or former smokers twice within a single imaging session. Although the overall insertion-reinsertion airway wall thickness (WT) measurement coefficient of variation (CV) was moderate at 12%, much of the variability between repeat imaging was attributed to the observer; CV for repeated measurements of the same airway (intra-observer CV) was 9%. Therefore, reproducibility may be improved by introduction of automated analysis approaches suggesting that OCT has potential to be an in-vivo method for evaluating airway remodeling in future longitudinal and intervention studies. (C) 2015 Optical Society of Americ

Quantitative CT: Associations between Emphysema, Airway Wall Thickness and Body Composition in COPD

The objective of the present study was to determine the association between CT phenotypes—emphysema by low attenuation area and bronchitis by airway wall thickness—and body composition parameters in a large cohort of subjects with and without COPD. In 452 COPD subjects and 459 subjects without COPD, CT scans were performed to determine emphysema (%LAA), airway wall thickness (AWT-Pi10), and lung mass. Muscle wasting based on FFMI was assessed by bioelectrical impedance. In both the men and women with COPD, FFMI was negatively associated with %LAA. FMI was positively associated with AWT-Pi10 in both subjects with and without COPD. Among the subjects with muscle wasting, the percentage emphysema was high, but the predictive value was moderate. In conclusion, the present study strengthens the hypothesis that the subgroup of COPD cases with muscle wasting have emphysema. Airway wall thickness is positively associated with fat mass index in both subjects with and without COPD