Extent Of Emphysema Research Articles

Assessment of Emphysema on X-ray Equivalent Dose Photon-Counting Detector CT

Objectives The aim of this study was to evaluate the feasibility and efficacy of visual scoring, low-attenuation volume (LAV), and deep learning methods for estimating emphysema extent in x-ray dose photon-counting detector computed tomography (PCD-CT), aiming to explore future dose reduction potentials. Methods One hundred one prospectively enrolled patients underwent noncontrast low- and chest x-ray dose CT scans in the same study using PCD-CT. Overall image quality, sharpness, and noise, as well as visual emphysema pattern (no, trace, mild, moderate, confluent, and advanced destructive emphysema; as defined by the Fleischner Society), were independently assessed by 2 experienced radiologists for low- and x-ray dose images, followed by an expert consensus read. In the second step, automated emphysema quantification was performed using an established LAV algorithm with a threshold of −950 HU and a commercially available deep learning model for automated emphysema quantification. Automated estimations of emphysema extent were converted and compared with visual scoring ratings. Results X-ray dose scans exhibited a significantly lower computed tomography dose index than low-dose scans (low-dose: 0.66 ± 0.16 mGy, x-ray dose: 0.11 ± 0.03 mGy, P < 0.001). Interreader agreement between low- and x-ray dose for visual emphysema scoring was excellent (κ = 0.83). Visual emphysema scoring consensus showed good agreement between low-dose and x-ray dose scans (κ = 0.70), with significant and strong correlation (Spearman ρ = 0.79). Although trace emphysema was underestimated in x-ray dose scans, there was no significant difference in the detection of higher-grade (mild to advanced destructive) emphysema (P = 0.125) between the 2 scan doses. Although predicted emphysema volumes on x-ray dose scans for the LAV method showed strong and the deep learning model excellent significant correlations with predictions on low-dose scans, both methods significantly overestimated emphysema volumes on lower quality scans (P < 0.001), with the deep learning model being more robust. Further, deep learning emphysema severity estimations showed higher agreement (κ = 0.65) and correlation (Spearman ρ = 0.64) with visual scoring for low-dose scans than LAV predictions (κ = 0.48, Spearman ρ = 0.45). Conclusions The severity of emphysema can be reliably estimated using visual scoring on CT scans performed with x-ray equivalent doses on a PCD-CT. A deep learning algorithm demonstrated good agreement and strong correlation with the visual scoring method on low-dose scans. However, both the deep learning and LAV algorithms overestimated emphysema extent on x-ray dose scans. Nonetheless, x-ray equivalent radiation dose scans may revolutionize the detection and monitoring of disease in chronic obstructive pulmonary disease patients.

Application research on asthma-COPD overlap using low-dose CT scan and quantitative analysis

The aim of this study was to assess the proximal airway remodeling, emphysema, and air trapping of asthma-COPD Overlap. 20 ACO patients, 55 mild to moderate COPD patients and 38 non-severe asthma patients were participated in low-dose dual phase CT scanning and pulmonary function test, comparative analysis was performed to identify differences in CT measurements among three groups. (Ⅰ) The average age and smoking index of ACO and mild to moderate COPD were both higher than non-severe asthma. ACO and mild to moderate COPD group had a higher proportion of males than non-severe asthma. (Ⅱ) In terms of pulmonary function test, FEV1 (%Pred), FEV1/FVC%, MEF25% (%Pred), MEF 50% (%Pred), MMEF (%Pred), and PEF (%Pred) in ACO were significantly reduced than those in non-severe asthma. (Ⅲ) On proximal airway parameters, ACO exhibited higher WA% and Pi10 compared to mild to moderate COPD. However, there was no statistically significant difference in WA% and Pi10 between ACO and non-severe asthma. (Ⅳ) On CT lung function, the emphysema index VI-910ex of ACO was significantly higher than non-severe asthma.Additionally, ACO demonstrated higher MLDex and VI-856ex compared to non-severe asthma. Compared with non-severe asthma, ACO is more common in male patients with older age and a longer history of smoking, which had more severe airflow obstruction and airway dysfunction than non-severe asthma.ACO showed more obvious proximal airway remodeling than mild to moderate COPD, and was more similar to non-severe asthma.The extent of emphysema and air trapping in ACO were more pronounced compared to non-severe asthma.

Single-Breath Simultaneous Measurement of DLNO and DLCO as Predictor of the Emphysema Component in COPD - A Retrospective Observational Study.

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost. To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO). COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC). Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema. When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.

Is Type and Grade of Emphysema Important for Bone Mineral Density and Aortic Calcifications?

Background: Chronic obstructive pulmonary disease has extrapulmonary manifestations, such as cardiovascular diseases and osteoporosis. The purpose of this research was to determine the relationship between the type and extent of emphysema with thoracic aorta calcification (TAC) and bone mineral density (BMD) at Th4, Th8, and L1 vertebrae. Methods: Emphysema was described by computed tomography parameters (both Fleischner classification and low attenuation value percentage, LAV%) and the clinical FEV1/FVC ratio (Tiffeneau-Pinelli index, TI, TI < 0.7; TI > 0.7). Results: Of 200 included patients (median age 64, 33% women), signs of clinical obstruction (TI) were observed in 104 patients, which had significantly lower BMD and more heavy TAC. BMD correlated negatively with LAV%, Rho = -0.16 to -0.23, while a positive correlation of aortic calcification with LAV% was observed, Rho = 0.30 to 0.33. Multiple linear regression showed that age and TI < 0.7 were independent predictors of BMD, β = -0.20 to -0.40, and β = -0.21 to -0.25; age and hypercholesterolemia were independent predictors of TCA, β = 0.61 and β = 0.19. Conclusions: Clinical TI and morphological LAV% parameters correlated with BMD and TAC, in contrast to Fleischer-graded emphysema, which showed no correlation. However, only TI was an independent predictor of BMD, while the morphologically described type and extent of emphysema could not independently predict any extrapulmonary manifestation.

Evaluation of retrieval accuracy and visual similarity in content-based image retrieval of chest CT for obstructive lung disease

The aim of our study was to assess the performance of content-based image retrieval (CBIR) for similar chest computed tomography (CT) in obstructive lung disease. This retrospective study included patients with obstructive lung disease who underwent volumetric chest CT scans. The CBIR database included 600 chest CT scans from 541 patients. To assess the system performance, follow-up chest CT scans of 50 patients were evaluated as query cases, which showed the stability of the CT findings between baseline and follow-up chest CT, as confirmed by thoracic radiologists. The CBIR system retrieved the top five similar CT scans for each query case from the database by quantifying and comparing emphysema extent and size, airway wall thickness, and peripheral pulmonary vasculatures in descending order from the database. The rates of retrieval of the same pairs of query CT scans in the top 1–5 retrievals were assessed. Two expert chest radiologists evaluated the visual similarities between the query and retrieved CT scans using a five-point scale grading system. The rates of retrieving the same pairs of query CTs were 60.0% (30/50) and 68.0% (34/50) for top-three and top-five retrievals. Radiologists rated 64.8% (95% confidence interval 58.8–70.4) of the retrieved CT scans with a visual similarity score of four or five and at least one case scored five points in 74% (74/100) of all query cases. The proposed CBIR system for obstructive lung disease integrating quantitative CT measures demonstrated potential for retrieving chest CT scans with similar imaging phenotypes. Further refinement and validation in this field would be valuable.

Persistence of emphysema following cessation of cigarette smoke exposure requires a susceptibility factor.

Chronic obstructive pulmonary disease (COPD) is caused by cigarette smoke (CS) exposure but can often be progressive even in former smokers. Exposure of mice to CS for 22 wk causes emphysema, but whether emphysema persists after cessation of CS exposure is not clear. The purpose of this study was to determine whether emphysema persists in mice following a recovery period of 22 wk and whether a susceptibility factor, such as deficiency in the Bcl-2-interacting killer (Bik), is required for this persistence. Therefore, bik+/+ and bik-/- mice at 6-10 wk of age were exposed to 250 mg/m3 total particulate matter of CS or filtered air (FA) for 3 or 22 wk and were kept in FA for an additional 22 wk. Lungs were lavaged to quantify inflammatory cells, and sections were stained with hematoxylin and eosin to assess severity of emphysema. Exposure to CS for 3 wk increased the number of inflammatory cells in bik-/- mice compared with bik+/+ mice but not at 22 wk of exposure. At 22 wk of CS exposure, extent of emphysema was similar in bik+/+ and bik-/- mice. However, when mice were exposed to CS over the first 22 wk and were kept in FA for an additional 22 wk, emphysema remained similar in bik+/+ mice but was enhanced in bik-/- mice. These findings link increased inflammation with persistent emphysematous changes even after smoking cessation and demonstrate that a preexisting susceptibility condition is required to sustain enhanced emphysema that was initiated by long-term CS exposure.NEW & NOTEWORTHY Exposure of mice to cigarette smoke (CS) for 22 wk causes emphysema, but whether emphysema persists after an additional period of 6 mo after cessation of CS exposure has not been reported. In addition, the role of preexisting susceptibility in enhancing the persistence of CS-induced emphysema after exposure to CS has stopped has not been shown. The present study shows that a preexisting susceptibility must be present to enhance CS-induced emphysema after cessation of CS exposure.

Diffusing capacity as an independent predictor of acute exacerbations in chronic obstructive pulmonary disease

A weak correlation between diffusing capacity of the lung for carbon monoxide (DLCO) and emphysema has been reported. This study investigated whether impaired DLCO in chronic obstructive pulmonary disease (COPD) is associated with increased risk of acute exacerbation independent of the presence or extent of emphysema. This retrospective cohort study included patients with COPD between January 2004 and December 2019. The participants were divided into four groups based on visually detected emphysema and impaired DLCO. Among 597 patients with COPD, 8.5% had no emphysema and impaired DLCO whereas 36.3% had emphysema without impaired DLCO. Among the four groups, patients with impaired DLCO and emphysema showed a higher risk of moderate-to-severe or severe exacerbation than those with normal DLCO. Impaired DLCO was an independent risk factor for severe exacerbation (hazard ratio, 1.524 [95% confidence interval 1.121–2.072]), whereas the presence of emphysema was not. The risk of moderate-to-severe or severe exacerbation increases with the severity of impaired DLCO. After propensity-score matching for the extent of emphysema, impaired DLCO was significantly associated with a higher risk of moderate-to-severe (p = 0.041) or severe exacerbation (p = 0.020). In patients with COPD and heterogeneous parenchymal abnormalities, DLCO can be considered an independent biomarker of acute exacerbation.

A formula for predicting emphysema extent in combined idiopathic pulmonary fibrosis and emphysema

BackgroundNo single pulmonary function test captures the functional effect of emphysema in idiopathic pulmonary fibrosis (IPF). Without experienced radiologists, other methods are needed to determine emphysema extent. Here, we report the development and validation of a formula to predict emphysema extent in patients with IPF and emphysema.MethodsThe development cohort included 76 patients with combined IPF and emphysema at the Royal Brompton Hospital, London, United Kingdom. The formula was derived using stepwise regression to generate the weighted combination of pulmonary function data that fitted best with emphysema extent on high-resolution computed tomography. Test cohorts included patients from two clinical trials (n = 455 [n = 174 with emphysema]; NCT00047645, NCT00075998) and a real-world cohort from the Royal Brompton Hospital (n = 191 [n = 110 with emphysema]). The formula is only applicable for patients with IPF and concomitant emphysema and accordingly was not used to detect the presence or absence of emphysema.ResultsThe formula was: predicted emphysema extent = 12.67 + (0.92 x percent predicted forced vital capacity) – (0.65 x percent predicted forced expiratory volume in 1 second) – (0.52 x percent predicted carbon monoxide diffusing capacity). A significant relationship between the formula and observed emphysema extent was found in both cohorts (R2 = 0.25, P < 0.0001; R2 = 0.47, P < 0.0001, respectively). In both, the formula better predicted observed emphysema extent versus individual pulmonary function tests. A 15% emphysema extent threshold, calculated using the formula, identified a significant difference in absolute changes from baseline in forced vital capacity at Week 48 in patients with baseline-predicted emphysema extent < 15% versus ≥ 15% (P = 0.0105).ConclusionThe formula, designed for use in patients with IPF and emphysema, demonstrated enhanced ability to predict emphysema extent versus individual pulmonary function tests.Trial registrationNCT00047645; NCT00075998.

Using Artificial Intelligence Software for Diagnosing Emphysema and Interstitial Lung Disease

Researchers have developed various algorithms utilizing artificial intelligence (AI) to automatically and objectively diagnose patterns and extent of pulmonary emphysema or interstitial lung diseases on chest CT scans. Studies show that AI-based quantification of emphysema on chest CT scans reveals a connection between an increase in the relative percentage of emphysema and a decline in lung function. Notably, quantifying centrilobular emphysema has proven helpful in predicting clinical symptoms or mortality rates of chronic obstructive pulmonary disease. In the context of interstitial lung diseases, AI can classify the usual interstitial pneumonia pattern on CT scans into categories like normal, ground-glass opacity, reticular opacity, honeycombing, emphysema, and consolidation. This classification accuracy is comparable to chest radiologists (70%-80%). However, the results generated by AI are influenced by factors such as scan parameters, reconstruction algorithms, radiation doses, and the training data used to develop the AI. These limitations currently restrict the widespread adoption of AI for quantifying pulmonary emphysema and interstitial lung diseases in daily clinical practice. This paper will showcase the authors' experience using AI for diagnosing and quantifying emphysema and interstitial lung diseases through case studies. We will primarily focus on the advantages and limitations of AI for these two diseases.

Spatial Transcriptomics Resolve an Emphysema-specific Lymphoid Follicle B Cell Signature in COPD.

Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component. To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and COPD patients with varying degrees of emphysema. Lung sections from 40 COPD patients and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin and OCT-fixed lung samples obtained from biopsies or lung explants, were assessed for LF presence. Emphysema measurements were obtained from clinical chest CT scans. High confidence transcriptional (HCT) target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. Overall, 115 LFs from ever-smokers and GOLD 1-2 and GOLD 3-4 patients were analyzed. No LFs were found in never-smokers. Differential gene expression analysis revealed significantly increased expression of LF assembly and B cell markers genes in subjects with severe emphysema. HCT analysis revealed activation of abnormal B cell activity signature in LFs (q-value: 2.56E-111). LFs from GOLD 1-2 COPD patients with emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs from GOLD 1-2 COPD patients without emphysema showed an anti-inflammatory profile. The extent of centrilobular emphysema was significantly associated with genes involved in B cell maturation and antibody production. Protein-RNA network analysis showed that LFs in emphysema have a unique signature skewed towards chronic B cell activation. An off-targeted B cell activation within LFs is associated with autoimmune-mediated emphysema pathogenesis.

Spatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease.

Rationale: Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component. Objectives: To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema. Methods: Lung sections from 40 patients with COPD and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. Measurements and Main Results: Overall, 115 LFs from ever-smokers and Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-2 and GOLD 3-4 patients were analyzed. No LFs were found in never-smokers. Differential gene expression analysis revealed significantly increased expression of LF assembly and B cell marker genes in subjects with severe emphysema. High-confidence transcriptional analysis revealed activation of an abnormal B cell activity signature in LFs (q-value = 2.56E-111). LFs from patients with GOLD 1-2 COPD with emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs from patients with GOLD 1-2 COPD without emphysema showed an antiinflammatory profile. The extent of centrilobular emphysema was significantly associated with genes involved in B cell maturation and antibody production. Protein-RNA network analysis showed that LFs in emphysema have a unique signature skewed toward chronic B cell activation. Conclusions: An off-targeted B cell activation within LFs is associated with autoimmune-mediated emphysema pathogenesis.

Quantitative emphysema on computed tomography imaging of chest is a risk factor for prognosis of esophagectomy: A retrospective cohort study.

The low attenuation area percentage (LAA%) is gaining popularity. LAA% is an index of quantitative emphysema on computed tomography (CT) imaging of the chest. This study aims to retrospectively investigate whether preoperative LAA% is associated with postoperative prognosis in patients with esophageal cancer who were scheduled for esophagectomy. From January 2016 to March 2020, 105 patients with esophageal cancer underwent esophagectomy via right thoracotomy and neoadjuvant chemotherapy. A Synapse Vincent volume analyzer (Fujifilm Medical, Tokyo, Japan) was used for measurement. The software automatically quantified LAA% using a threshold of less than - 950 Hounsfield units on CT images of lung regions. Cox proportional hazard analyses were performed in univariable and multivariable forms. Estimates of the receiver operating curve are used to determine the cutoff value for death of LAA%, and the binary value is then inserted into Cox proportional hazard analyses. The preoperative LAA% cutoff value was ≥ 6.3%. Patients with a preoperative LAA% ≥6.3% had a significantly worse prognosis than those with a preoperative LAA% of < 6.3%. LAA% ≥6.3% (hazard ratio: 6.76; 95% confidence interval: 2.56-17.90, P < .001) was the most influential preoperative factor for overall survival after esophagectomy in multivariate Cox proportional hazard analyses. LAA% is one of the preoperative risk factors for survival after esophagectomy and an indicator of lung condition using routinely performed preoperative CT images. We quantified the extent of preoperative emphysema in patients with esophageal cancer, who were scheduled for surgery, and for the first time, reported LAA% as one of the preoperative risk factors for survival after esophagectomy.

The impact of emphysema heterogeneity on treatment response after endobronchial valve treatment.

Lung volume reduction with endobronchial valves can significantly improve functional outcomes in patients with advanced emphysema. The extent and spatial distribution pattern of emphysema shows considerable heterogeneity, which might affect response to endobronchial valve treatment. Our aim was to study the effect of emphysema heterogeneity on change in clinical outcomes after endobronchial valve treatment. Data were collected from our national registry of patients who received endobronchial valve treatment between 2016 and 2020. We assessed the association between the heterogeneity index, absolute difference in destruction between the target and ipsilateral lobe, and relative change in forced expiratory volume in 1 s (FEV1), residual volume (RV), St George's Respiratory Questionnaire (SGRQ) and 6-min walk distance (6MWD) at 6-week, 6-month and 12-month follow-up. In total, 236 patients were included. Heterogeneity index was significantly associated with improvements in FEV1, RV and 6MWD at all follow-up visits, and in SGRQ at the 6- and 12-month follow-up visits. The majority of patients, independent of heterogeneity index, showed clinically meaningful improvements based on minimal important difference thresholds. Heterogeneity index influences the degree of clinical improvement after endobronchial valve treatment where in general a more heterogeneous distribution translates to larger improvements. However, patients with a more homogeneous distribution also showed clinically meaningful improvements. Therefore, we believe emphysema heterogeneity alone should not be used as a decisive patient selection criterion, but should be weighed in the context of all other relevant patient and target lobe characteristics when deciding on a patient's treatment eligibility.

Quantitative Computed Tomography Analysis of the Longitudinal Change Between Centrilobular and Paraseptal Emphysema Subtypes: A Retrospective Study.

This study aimed to investigate the difference between the extent of centrilobular emphysema (CLE) and paraseptal emphysema (PSE) on follow-up chest CT scans and their relationship to the cross-sectional area (CSA) of small pulmonary vessels. Sixty-two patients (36 CLE and 26 PSE) who underwent 2 chest CT scans were enrolled in this study. The percentage of low attenuation volume (%LAV) and total CSA of the small pulmonary vessels <5 mm2 (%CSA < 5) were measured at the 2 time points. Analysis of the initial %CSA < 5 and the change in the %LAV and %CSA < 5 on follow-up imaging was performed. The initial %CSA < 5 was not significantly different between the CLE and the PSE groups (CLE, 0.66 vs. PSE, 0.71; P = 0.78). There was no significant difference in the longitudinal change in the %LAV between the 2 groups (CLE, -0.048% vs. PSE, 0.005%; P = 0.26). The longitudinal change in the %CSA < 5 in patients with PSE significantly decreased compared with those with CLE (CLE, 0.025% vs. PSE, -0.018%; P = 0.02). The longitudinal change in the %CSA < 5 was significantly different for patients with CLE and PSE, demonstrating an important pathophysiological difference between the subtypes.

Dose-dependent cardiovascular disorders in a rat model with exacerbated emphysema: Implication of inflammation

Chronic obstructive pulmonary disease (COPD) is currently the third cause of death worldwide. Emphysema is an abnormal enlargement of air spaces in the lungs, with destruction of alveolar parishes. Cardiovascular disorders are the most frequent and serious comorbidities of COPD. Their interconnection is poorly understood but several hypotheses have been proposed, including hyperinflation, oxidative stress, and inflammation. In a rat model with exacerbated elastase (ELA)-induced emphysema that develops heart failure with preserved ejection fraction, our goal is to (1) describe the relationship between exacerbated emphysema and cardiovascular hemodynamic disorders, (2) characterize the inflammation status 24 h and 5 weeks after an exacerbation. The model includes a weekly intra-tracheal instillation of ELA, during four weeks with doses of 4, 6 or 10UI. At week 4, lipopolysaccharide (LPS) was instillated with ELA to mimic an exacerbation and approximate clinical conditions. Experiments were performed 24 hours after the last intra-tracheal instillation (ELA + LPS) and at week 9 just before sacrifice. In vivo, we did a cardiac stress test on metabolic treadmill, whole body plethysmography, echocardiography, arterial pressure, and collected blood samples. Ex vivo, we explanted the heart/lung block to assess pulmonary compliance and histology analyses. We identified a respiratory functional impairment proportional to the dose of elastase instilled. An exercise intolerance appeared after the exacerbation and persisted 5 weeks later. We observed a diastolic dysfunction after the exacerbation and at week 9, with a significantly dose dependent increased E/E’ ratio, correlated with the extent of emphysema. A systolic and diastolic arterial hypertension appeared at week 9, especially in the 10UI elastase group. There was an increased lung compliance and decreased elastance. The characterization of inflammation is under investigation. This ELA-LPS animal model presents a chronic profile of heart failure with preserved ejection fraction linked in a dose-dependent manner to the intensity of the emphysema. Cardiopulmonary changes are accompanied by a reduction in exercise tolerance as well as arterial hypertension. This model seems useful to better understand the mechanisms of cardiac changes induced by emphysema. At length, we aim to develop an inhibition of T1 or T2 inflammation pathway, to determine the part played by this inflammation.

P157 Distinct differences in complement perturbation between scleroderma-related interstitial lung disease with and without emphysema

Abstract Background/Aims Aberrant complement activation is associated with autoimmune diseases including systemic sclerosis (SSc). As a leading cause of death in SSc, interstitial lung disease (ILD) can coexist with emphysema in non-smoking patients, worsening prognosis. It has been suggested that the airway destruction observed in SSc patients may be an exaggerated inflammatory response related to increased complement activation. Methods We analysed 10 complement proteins in plasma samples of 16 non-smoking SSc patients with emphysema (SSc-Emp), 8 SSc no-ILD, 8 SSc-ILD patients and 8 healthy controls (HC) (Table.1) selected from 1800 SSc patients under active follow up at our centre. The extent and distribution of emphysema was evaluated on high resolution computed tomography (HRCT) and enzyme-linked immunosorbent assays (ELISA) were performed for C1q, MASP-2, Factor B, Factor Bb, Factor H, C3, C3a, C4, C5, C5a and TCC (terminal complement complex). One-way ANOVA and post-hoc Tukey test were used for analysis. Results HRCT confirmed that amongst the emphysema cohort, there was a spectrum of mild to severe destruction including both paraseptal and centrilobular emphysema. All 16 SSc-Emp patients had ILD and 9 of the 16 patients demonstrated perivascular emphysema not previously described in SSc. The SSc-ILD group was characterised by extensive lung fibrosis on CT, mean FVC 71% predicted. Across the four groups, C1q was significantly reduced in the SSc-ILD cohort (SSc-Emp 950±404µg/mL, SSc-ILD 355±116µg/mL, SSc-no ILD 1087±206µg/mL, HC 858±210µg/mL, p= 0.0002). In contrast, the ratio of C3a/C3 was significantly increased in the SSc-ILD group compared with the SSc-Emp group (SSc-ILD 0.12±0.07 vs SSc-Emp 0.06±0.03, p= 0.0283). The ratio of Bb/B was significantly increased in the SSc no-ILD group compared with all other groups (SSc-Emp 1.57±0.80µg/mL, SSc-ILD 1.27±0.56µg/mL, SSc-no ILD 3.86±1.12µg/mL, HC 1.89±0.75µg/mL, p&amp;lt; 0.0001). There was a trend towards an increased ratio of C5a/C5 in SSc-ILD and SSc-Emp compared with HC and reduced MASP2 in the SSc groups compared with HC. Conclusion This data demonstrates dysregulated complement levels in three SSc subgroups. Notably, the perturbed C1q and C3a:C3 pathways in SSc-ILD are reversed in SSc-emphysema, supporting complement activation as part of the divergent tissue remodelling responses in these distinct SSc lung phenotypes. Disclosure C. Beesley: Grants/research support; Versus Arthritis [grant number 558800]. A. Cole: None. N. Goldman: None. J. Barnett: None. D. Abraham: None. C. Denton: None. R. Mageed: None. V. Ong: None.

Quantitative CT Evaluation of Emphysema Progression over 10 Years in the COPDGene Study.

Background Long-term studies of chronic obstructive pulmonary disease (COPD) can evaluate emphysema progression. Adjustment for differences in equipment and scanning protocols of individual CT examinations have not been studied extensively. Purpose To evaluate emphysema progression in current and former smokers in the COPDGene cohort over three imaging points obtained at 5-year intervals accounting for individual CT parameters. Materials and Methods Current and former cigarette smokers enrolled between 2008 and 2011 from the COPDGene study were prospectively followed for 10 years between 2008 and 2020. Extent of emphysema as adjusted lung density (ALD) from quantitative CT was measured at baseline and at 5- and 10-year follow-up. Linear mixed models adjusted for CT technical characteristics were constructed to evaluate emphysema progression. Mean annual changes in ALD over consecutive 5-year study periods were estimated by smoking status and baseline emphysema. Results Of 8431 participants at baseline (mean age, 60 years ± 9 [SD]; 3905 female participants), 4913 were at 5-year follow-up and 1544 participants were at 10-year follow-up. There were 4134 (49%) participants who were current smokers, and 4449 (53%) participants had more than trace emphysema at baseline. Current smokers with more than trace emphysema showed the largest decline in ALD, with mean annual decreases of 1.4 g/L (95% CI: 1.2, 1.5) in the first 5 years and 0.9 g/L (95% CI: 0.7, 1.2) in the second 5 years. Accounting for CT noise, field of view, and scanner model improved model fit for estimation of emphysema progression (P < .001 by likelihood ratio test). Conclusion Evaluation at CT of emphysema progression in the COPDGene study showed that, during the span of 10 years, participants with pre-existing emphysema who continued smoking had the largest decline in ALD. Adjusting for CT equipment and protocol factors improved these longitudinal estimates. Clinical trial registration no. NCT00608764 © RSNA, 2023 Supplemental material is available for this article. See the editorial by Parraga and Kirby in this issue.

Pulmonary Vascular Volume by Quantitative CT in Dyspneic Smokers with Minor Emphysema

Reduced lung diffusing capacity for carbon monoxide (DLCO) at rest and increased ventilation (⩒ E)-carbon dioxide output (⩒CO2) during exercise are frequent findings in dyspneic smokers with largely preserved FEV1. It remains unclear whether low DLCO and high ⩒ E-⩒CO2 are mere reflections of alveolar destruction (i.e. emphysema) or impaired pulmonary perfusion in non-emphysematous tissue contributes to these functional abnormalities. Sixty-four smokers (41 males, FEV1= 84 ± 13%predicted) underwent pulmonary function tests, an incremental exercise test, and quantitative chest computed tomography. Total pulmonary vascular volume (TPVV) was calculated for the entire segmented vascular tree (VIDA Vision™). Using the median % low attenuation area (-950 HU), participants were dichotomized into “Trace” or “Mild” emphysema (E), each group classified into preserved versus reduced DLCO. Within each emphysema subgroup, participants with abnormally low DLCO showed lower TPVV, higher ⩒ E-⩒CO2, and exertional dyspnea than those with preserved DLCO (p < 0.05). TPVV (r = 0.34; p = 0.01), but not emphysema (r = −0.05; p = 0.67), correlated with lower DLCO after adjusting for age and height. Despite lower emphysema burden, Trace-E participants with reduced DLCO had lower TPVV, higher dyspnea, and lower peak work rate than the Mild-E with preserved DLCO (p < 0.05). Interestingly, TPVV (but not emphysema) correlated inversely with both dyspnea-work rate (r = −0.36, p = 0.004) and dyspnea-⩒ E slopes (r = −0.40, p = 0.001). Reduced pulmonary vascular volume adjusted by emphysema extent is associated with low DLCO and heightened exertional ventilation in dyspneic smokers with minor emphysema. Impaired perfusion of non-emphysematous regions of the lungs has greater functional and clinical consequences than hitherto assumed in these subjects.

Impact of Marijuana Smoking on COPD Progression in a Cohort of Middle-Aged and Older Persons.

Limited data are available regarding marijuana smoking's impact on the development or progression of chronic obstructive pulmonary disease (COPD) in middle-aged or older adults with a variable history of tobacco cigarette smoking. We divided ever-tobacco smoking participants in the SubPopulations and InteRmediate Outcomes In COPD Study (SPIROMICS) into 3 groups based on self-reported marijuana use: current, former, or never marijuana smokers (CMSs, FMSs or NMSs, respectively). Longitudinal data were analyzed in participants with ≥2 visits over a period of ≥52 weeks. We compared CMSs, FMSs, and NMSs, and those with varying amounts of lifetime marijuana use. Mixed effects linear regression models were used to analyze changes in spirometry, symptoms, health status, and radiographic metrics; zero-inflated negative binomial models were used for exacerbation rates. All models were adjusted for age, sex, race, baseline tobacco smoking amount, and forced expiratory volume in 1 second (FEV1) %predicted. Most participants were followed for ≥4 years. Annual rates of change in FEV1, incident COPD, respiratory symptoms, health status, radiographic extent of emphysema or air trapping, and total or severe exacerbations were not different between CMSs or FMSs versus NMSs or between those with any lifetime amount of marijuana use versus NMSs. Among SPIROMICS participants with or without COPD, neither former nor current marijuana smoking of any lifetime amount was associated with evidence of COPD progression or its development. Because of our study's limitations, these findings underscore the need for further studies to better understand longer-term effects of marijuana smoking in COPD.

Effect of Chest Computed Tomography Kernel Use on Emphysema Score in Severe Chronic Obstructive Pulmonary Disease Patients Evaluated for Lung Volume Reduction

Background: Chest computed tomography (CT) emphysema quantification is a vital diagnostic tool in patient evaluation for bronchoscopic lung volume reduction (BLVR). Smooth kernels for CT image reconstruction are generally recommended for quantitative analyses. This recommendation is not always followed, which may affect quantification of emphysema extent and eventually, treatment decisions. Objective: The main goal is to demonstrate the influence of CT reconstruction kernels on emphysema quantification in patients with severe COPD, considered for BLVR. Methods: Chest CT scans were acquired with one multi-detector CT system and reconstructed using three different kernels: smooth, medium smooth, and sharp. Other parameters were kept constant. Emphysema scores (ESs), meaning the percentage of voxels below −950 Hounsfield units, were calculated and compared to the smooth reference kernel using paired t tests. Bland-Altman plots were made to assess the biases and limits of agreement between kernels. Results: Ninety-eight COPD patient CT scans were analyzed. The sharp kernel had a systematic bias of 6.2% and limits of agreement of 16.6% to −4.2% compared to the smooth kernel. The medium smooth kernel had a systematic bias of 5.7% and limits of agreement of 9.2% and 2.2% compared to the smooth kernel. The ES differed, for a single patient, up to 18% for different kernels. Conclusions: Chest CT kernel reconstruction can lead to a significant difference in emphysema severity quantification. This may cause invalid treatment selection in COPD patients evaluated for BLVR. Standardization of a smooth CT kernel setting and/or normalization to a standard kernel is strongly recommended.