Severity Of Emphysema Research Articles

Climate-mediated air pollution associated with COPD severity

Air pollution has been reported to be associated with chronic obstructive pulmonary disease (COPD). Our study aim was to examine the mediating effects of air pollution on climate-associated health outcomes of COPD patients. A cross-sectional study of 117 COPD patients was conducted in a hospital in Taiwan. We measured the lung function, 6-min walking distance, oxygen desaturation, white blood cell count, and percent emphysema (low attenuation area, LAA) and linked these to 0–1-, 0–3-, and 0–5-year lags of individual-level exposure to relative humidity (RH), temperature, and air pollution. Linear regression models were conducted to examine associations of temperature, RH, and air pollution with severity of health outcomes. A mediation analysis was conducted to examine the mediating effects of air pollution on the associations of RH and temperature with health outcomes. We observed that a 1 % increase in the RH was associated with increases in forced expiratory volume in 1 s (FEV1), eosinophils, and lymphocytes, and a decrease in the total-lobe LAA. A 1 °C increase in temperature was associated with decreases in oxygen desaturation, and right-, left-, and upper-lobe LAA values. Also, a 1 μg/m3 increase in PM2.5 was associated with a decrease in the FEV1 and an increase in oxygen desaturation. A 1 μg/m3 increases in PM10 and PM2.5 was associated with increases in the total-, right-, left, upper-, and lower-lobe (PM2.5 only) LAA. A one part per billion increase in NO2 was associated with a decrease in the FEV1 and an increase in the upper-lobe LAA. Next, we found that NO2 fully mediated the association between RH and FEV1. We found PM2.5 fully mediated associations of temperature with oxygen saturation and total-, right-, left-, and upper-lobe LAA. In conclusion, climate-mediated air pollution increased the risk of decreasing FEV1 and oxygen saturation and increasing emphysema severity among COPD patients. Climate change-related air pollution is an important public health issue, especially with regards to respiratory disease.

Association between visual emphysema and lung nodules on low-dose CT scan in a Chinese Lung Cancer Screening Program (Nelcin-B3)

ObjectivesThis study aimed to evaluate the association between visual emphysema and the presence of lung nodules, and Lung-RADS category with low-dose CT (LDCT).MethodsBaseline LDCT scans of 1162 participants from a lung cancer screening study (Nelcin-B3) performed in a Chinese general population were included. The presence, subtypes, and severity of emphysema (at least trace) were visually assessed by one radiologist. The presence, size, and classification of non-calcified lung nodules (≥ 30 mm3) and Lung-RADS category were independently assessed by another two radiologists. Multivariable logistic regression and stratified analyses were performed to estimate the association between emphysema and lung nodules, Lung-RADS category, after adjusting for age, sex, BMI, smoking status, pack-years, and passive smoking.ResultsEmphysema and lung nodules were observed in 674 (58.0%) and 424 (36.5%) participants, respectively. Participants with emphysema had a 71% increased risk of having lung nodules (adjusted odds ratios, aOR: 1.71, 95% CI: 1.26–2.31) and 70% increased risk of positive Lung-RADS category (aOR: 1.70, 95% CI: 1.09–2.66) than those without emphysema. Participants with paraseptal emphysema (n = 47, 4.0%) were at a higher risk for lung nodules than those with centrilobular emphysema (CLE) (aOR: 2.43, 95% CI: 1.32–4.50 and aOR: 1.60, 95% CI: 1.23–2.09, respectively). Only CLE was associated with positive Lung-RADS category (p = 0.02). CLE severity was related to a higher risk of lung nodules (ranges aOR: 1.44–2.61, overall p < 0.01).ConclusionIn a Chinese general population, visual emphysema based on LDCT is independently related to the presence of lung nodules (≥ 30 mm3) and specifically CLE subtype is related to positive Lung-RADS category. The risk of lung nodules increases with CLE severity.Key Points• Participants with emphysema had an increased risk of having lung nodules, especially smokers.• Participants with PSE were at a higher risk for lung nodules than those with CLE, but nodules in participants with CLE had a higher risk of positive Lung-RADS category.• The risk of lung nodules increases with CLE severity.

Emphysema severity index (ESI) associated with respiratory death in a large Swedish general population

Recently, it has been shown and validated that presence and severity of emphysema on computed tomography could be estimated by a novel spirometry based index, the emphysema severity index (ESI). However, the clinical relevance of the index has not been established.We conducted cox-regression analyses with adjustment for age, smoking, sex, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) to study whether ESI was associated with all-cause, respiratory and non-respiratory 10-year mortality. Study population was all participants with acceptable spirometry from the Gott Åldrande i Skåne study, a Swedish general population aged 65–102 years old. ESI is expressed as a continuous numeric parameter on a scale ranging from 0 to 10.Out of the 4453 participants in the main study, 3974 was included in the final analysis. Higher age, higher ESI, lower FEV1 and male sex increased hazard of respiratory death. ESI was significantly correlated to respiratory death but not non-respiratory death, while high age, male sex and low FEV1 was associated with non-respiratory as well as respiratory death. Current smoking habits increased the hazard of respiratory death but did not reach significance (p 0.066) One unit increase in ESI increased hazard of all-cause death by 20% (p 0.0002) and hazard of respiratory death by 57% (p < 0.0001). The ESI is a novel clinical marker of emphysema severity that is associated with respiratory death specifically. Since it can be derived from standard spirometry there are potential benefits for clinical practice in terms of more individualised prognosis and treatment alternatives.

CT Attenuation and Cross-Sectional Area of the Pectoralis Are Associated With Clinical Characteristics in Chronic Obstructive Pulmonary Disease Patients.

Purpose: Muscle wasting is associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). Computed tomography (CT) could serve as a method for muscle assessment due to its ability to measure both muscle quantity (e.g., cross-sectional muscle area) and muscle quality (e.g., muscle attenuation). Our study aimed to compare the differences in CT-derived pectoralis muscle cross-sectional area (PMA) and pectoralis muscle attenuation (PMT) between COPD patients and healthy controls and explore the association between PMA and PMT measurements and clinical characteristics in patients with COPD. Methods: A total of 252 participants included in our analysis consisted of 80 healthy controls and 172 patients with COPD. PMA and PMT were measured from a single axial slice of the CT scan above the aortic arch. Linear regression analysis was used to determine the correlation between PMA and PMT measurements and clinical characteristics in patients with COPD. Associations were adjusted for age, sex, BMI, FEV1%pred, smoking pack-years, current smoking status, emphysema percentage, and total airway count (TAC) of the right upper lobe apical bronchus (RB1). Results: PMA and PMT were lower in COPD patients, especially those with acute exacerbation, than in healthy controls. PMA and PMT were significantly associated with the severity of emphysema and the TAC of RB1 (p < 0.05). Patients with stable COPD, who had lower PMA and lower PMT, had significantly worse pulmonary function, poorer exercise tolerance, decreased quality of life, and worse dyspnea scores. In addition, patients with acute COPD exacerbation, who had lower PMA and lower PMT, had a higher risk of respiratory failure on admission. Conclusion: CT-derived measurements of the pectoralis muscle may be helpful in detecting declines in muscle quantity and quality and predicting disease severity in patients with COPD.

Quantitative evaluation of emphysema for predicting immunotherapy response in patients with advanced non-small-cell lung cancer

The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC) might depend on the presence of emphysema, but this association is not established. We aimed to investigate if quantitively and automatically measuring emphysema can predict the effect of ICIs. We retrospectively analyzed 56 patients with NSCLC who underwent immunotherapy at our hospital. We used the Goddard scoring system (GS) to evaluate the severity of emphysema on baseline CT scans using three-dimensional image analysis software. The emphysema group (GS ≥ 1) showed better progression-free survival (PFS) than the non-emphysema group (GS = 0) (6.5 vs. 2.3 months, respectively, p < 0.01). Multivariate analyses revealed that good performance status, GS of ≥ 1, and high expression of PD-L1 were independently associated with better PFS, while smoking status was not. In conclusion, quantitative evaluation of emphysema can be an objective parameter for predicting the therapeutic effects of ICIs in patients with NSCLC. Our findings can be used to generate hypotheses for future studies.

A Potent Histone Deacetylase Inhibitor MPT0E028 Mitigates Emphysema Severity via Components of the Hippo Signaling Pathway in an Emphysematous Mouse Model.

BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of chronic mortality. The objective of this study was to investigate the therapeutic potential of a novel potent histone deacetylase (HDAC) inhibitor MPT0E028 on emphysema.Materials and MethodsA mouse model of porcine pancreatic elastase (PPE)-induced emphysema was orally administered 0, 25, or 50 mg/kg body weight (BW) of the MPT0E028 five times/week for 3 weeks. Pulmonary function, mean linear intercept (MLI), chest CT, inflammation, yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), surfactant protein C (SPC), T1-α, p53, and sirtuin 1 (SIRT1) levels were examined.Results50 mg/kg BW of the MPT0E028 significantly decreased the tidal volume in emphysematous mice (p < 0.05). Emphysema severity was significantly reduced from 26.65% (PPE only) to 13.83% (50 mg/kg BW of the MPT0E028). Total cell counts, neutrophils, lymphocytes, and eosinophils significantly decreased with both 25 and 50 mg/kg BW of the MPT0E028 (p < 0.05). Also, 50 mg/kg BW of the MPT0E028 significantly decreased the levels of KC, TNF-α, and IL-6 in lung tissues and serum (p < 0.05). Expressions of p-TAZ/TAZ in lung tissues significantly decreased with 50 mg/kg BW of the MPT0E028 (p < 0.05). Expressions of p53 significantly decreased in alveolar regions with 50 mg/kg BW of the MPT0E028 (p < 0.05), and the expression of SPC increased in alveolar regions with 50 mg/kg BW of the MPT0E028 (p < 0.05).ConclusionsOur study showed that the potent HDAC inhibitor MPT0E028 reduced the severity and inflammation of emphysema with improvement in lung function, which could be regulated by Hippo signaling pathway. The MPT0E028 may have therapeutic potential for emphysema.

Association between Chest CT–defined Emphysema and Lung Cancer: A Systematic Review and Meta-Analysis

Background Given the different methods of assessing emphysema, controversy exists as to whether it is associated with lung cancer. Purpose To perform a systematic review and meta-analysis of the association between chest CT-defined emphysema and the presence of lung cancer. Materials and Methods The PubMed, Embase, and Cochrane databases were searched up to July 15, 2021, to identify studies on the association between emphysema assessed visually or quantitatively with CT and lung cancer. Associations were determined by emphysema severity (trace, mild, or moderate to severe, assessed visually and quantitatively) and subtype (centrilobular and paraseptal, assessed visually). Overall and stratified pooled odds ratios (ORs) with their 95% CIs were obtained. Results Of the 3343 screened studies, 21 studies (107 082 patients) with 26 subsets were included. The overall pooled ORs for lung cancer given the presence of emphysema were 2.3 (95% CI: 2.0, 2.6; I2 = 35%; 19 subsets) and 1.02 (95% CI: 1.01, 1.02; six subsets) per 1% increase in low attenuation area. Studies with visual (pooled OR, 2.3; 95% CI: 1.9, 2.6; I2 = 48%; 12 subsets) and quantitative (pooled OR, 2.2; 95% CI: 1.8, 2.8; I2 = 3.7%; eight subsets) assessments yielded comparable results for the dichotomous assessment. Based on six studies (1716 patients), the pooled ORs for lung cancer increased with emphysema severity and were higher for visual assessment (2.5, 3.7, and 4.5 for trace, mild, and moderate to severe, respectively) than for quantitative assessment (1.9, 2.2, and 2.5) based on point estimates. Compared with no emphysema, only centrilobular emphysema (three studies) was associated with lung cancer (pooled OR, 2.2; 95% CI: 1.5, 3.2; P < .001). Conclusion Both visual and quantitative CT assessments of emphysema were associated with a higher odds of lung cancer, which also increased with emphysema severity. Regarding subtype, only centrilobular emphysema was significantly associated with lung cancer. Clinical trial registration no. CRD42021262163 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Hunsaker in this issue.

Classification based on skeletal muscle mass and the severity of lung emphysema impacts on clinical outcomes after anatomical resection for lung cancer.

Both sarcopenia and lung emphysema are prognostic factors in lung cancer and can be easily assessed using the psoas muscle index and Goddard score, respectively. We investigated the clinical significance of the classification based on psoas muscle index and Goddard score in non-small cell lung cancer. A total of 303 consecutive patients who underwent anatomical resection for non-small cell lung cancer were retrospectively analyzed. The psoas muscle at the level of the third lumbar vertebrae and Goddard score were measured on preoperative computed tomography. The psoas muscle was adjusted by height as the psoas muscle index (cm2/m2). We divided patients into three groups: low-, middle- and high-risk, using cut-off values of psoas muscle index<6.36cm2/m2 for males and 3.92cm2/m2 for females and Goddard score higher than 7. The predictors of postoperative complications and prognosis were examined. High-, middle- and low-risk were present in 30 (10%), 164 (54%) and 109 (36%) patients, respectively. High risk was significantly associated with male sex, low pulmonary function, more comorbidities and increased postoperative complications. High-risk patients showed poorer overall survival than middle- and low-risk patients (P<0.001). Multivariable analysis revealed that high risk was an independent risk factor for postoperative complications and unfavorable prognostic factors (P=0.011, P=0.014, respectively). Classification based on psoas muscle index and Goddard score is significantly associated with short- and long-term outcomes in patients with lung cancer. This method can be easily assessed for patients and may help select patients for nutritional support and rehabilitation before surgery.

Physiological Impairments on Respiratory Oscillometry and Future Exacerbations in Chronic Obstructive Pulmonary Disease Patients without a History of Frequent Exacerbations

Respiratory oscillometry allows measuring respiratory resistance and reactance during tidal breathing and may predict exacerbations in patients with chronic obstructive pulmonary disease (COPD). While the Global Initiative for Chronic Obstructive Lung Disease (GOLD) advocates the ABCD classification tool to determine therapeutic approach based on symptom and exacerbation history, we hypothesized that in addition to spirometry, respiratory oscillometry complemented the ABCD tool to identify patients with a high risk of exacerbations. This study enrolled male outpatients with stable COPD who were prospectively followed-up over 5 years after completing mMRC scale and COPD assessment test (CAT) questionnaires, post-bronchodilator spirometry and respiratory oscillometry to measure resistance, reactance, and resonant frequency (Fres), and emphysema quantitation on computed tomography. Total 134 patients were classified into the GOLD A, B, C, and D groups (n = 48, 71, 5, and 9) based on symptoms on mMRC and CAT and a history of exacerbations in the previous year. In univariable analysis, higher Fres was associated with an increased risk of exacerbation more strongly than other respiratory oscillometry indices. Fres was closely associated with forced expiratory volume in 1 sec (FEV1). In multivariable Cox-proportional hazard models of the GOLD A and B groups, either lower FEV1 group or higher Fres group was associated with a shorter time to the first exacerbation independent of the GOLD group (A vs B) and emphysema severity. Adding respiratory oscillometry to the ABCD tool may be useful for risk estimation of future exacerbations in COPD patients without frequent exacerbation history.

The Percentage of Low Attenuation Area on Computed Tomography to Detect Chronic Lung Allograft Dysfunction After Bilateral Lung Transplantation

<h3>Purpose</h3> Lung emphysematous changes may develop in patients with chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). To evaluate the severity of lung emphysema, the percentage of low attenuation area (LAA%) of the bilateral lungs calculated on computed tomography has been shown to be a useful index. This study aimed to investigate whether the LAA% was associated with the development of CLAD after bilateral LT. <h3>Methods</h3> We conducted a single-center retrospective study of 75 recipients who underwent bilateral LT from May 2008 to August 2015. The LAA% on computed tomography were calculated and compared between the CLAD group (N = 30) and the non-CLAD group (N = 45) from 2 years before to 4 years after the diagnosis of CLAD. The LAA% at 5 years after bilateral LT was designated as the control value in the non-CLAD group. The Pearson product-moment correlation coefficient was calculated between the LAA% and the percent baseline values of the forced expiratory volume in 1 s (FEV1), the forced vital capacity (FVC), and the total lung capacity (TLC) at the diagnosis of CLAD after bilateral LT. <h3>Results</h3> The median observation period after LT was 3277 (380-7691) days. The LAA% in the CLAD group was significantly higher than that in the non-CLAD group from even 2 years before the diagnosis of CLAD to 2 years after the diagnosis of CLAD (P < 0.05) (Figure 1). The difference in the LAA% between the CLAD group and the non-CLAD group tended to increase after the onset of CLAD. Furthermore, the LAA% was significantly correlated with the percent baseline values of the FEV1, the FVC, and the TLC (FEV1, r = -0.36, P = 0.0031; FVC, r = -0.27, P = 0.027; TLC, r = -0.40, P < 0.001) (Figure 2). <h3>Conclusion</h3> The LAA% was associated with the development of CLAD and increased after the diagnosis of CLAD. Moreover, the LAA% was associated with declines in the FEV1, FVC and TLC at the time of CLAD diagnosis. The LAA% appears to have the potential to predict CLAD after bilateral LT.

Association of air pollution exposure with exercise-induced oxygen desaturation in COPD

BackgroundThere is a link between exposure to air pollution and the increased prevalence of chronic obstructive pulmonary disease (COPD) and declining pulmonary function, but the association with O2 desaturation during exercise in COPD patients with emphysema is unclear. Our aims were to estimate the prevalence of O2 desaturation during exercise in patients with COPD, and determine the association of exposure to air pollution with exercise-induced desaturation (EID), the degree of emphysema, and dynamic hyperinflation (DH).MethodsWe assessed the effects of 10-year prior to the HRCT assessment and 7 days prior to the six-minute walking test exposure to particulate matter with an aerodynamic diameter of < 10 µm (PM10) or of < 2.5 µM (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in patients with emphysema in this retrospective cohort study. EID was defined as a nadir standard pulse oximetry (SpO2) level of < 90% or a delta (△)SpO2 level of ≥ 4%. Ambient air pollutant (PM2.5, PM10, O3, and NO2) data were obtained from Taiwan Environmental Protection Administration (EPA) air-monitoring stations, usually within 10 km to each participant’s home address.ResultsWe recruited 141 subjects with emphysema. 41.1% of patients with emphysema exhibited EID, and patients with EID had more dyspnea, worse lung function, more severe emphysema, more frequent acute exacerbations, managed a shorter walking distance, had DH, and greater long-term exposure to air pollution than those without EID. We observed that levels of 10-year concentrations of PM10, PM2.5, and NO2 were significantly associated with EID, PM10 and PM2.5 were associated with the severity of emphysema, and associated with DH in patients with emphysema. In contrast, short-term exposure did not have any effect on patients.ConclusionLong-term exposure to ambient PM10, PM2.5 and NO2, but not O3, was associated with EID.

Right Ventricular and Pulmonary Computed Tomography Assessments in Paradoxical Low-Flow Low-Gradient Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

BackgroundPatients with paradoxical low-flow low-gradient aortic stenosis (pLFLG AS) have high mortality and a high degree of transcatheter aortic valve replacement (TAVR) futility. Computed tomography (CT) enables accurate simultaneous right ventricular (RV) and parenchymal lung disease evaluation, which may provide useful objective markers of AS severity, concomitant pulmonary comorbidities, and TAVR improvement. However, the prevalence of RV dysfunction and its association with pulmonary disease in pLFLG AS are unknown. The study objective was to test the hypothesis that pLFLG AS patients undergoing TAVR have decreased RV function without a significant parenchymal lung disease. MethodsBetween August 2016 and March 2020, 194 consecutive AS patients completed high-resolution CT imaging for TAVR evaluation. Subjects were stratified based on echocardiographic criteria as the study group, pLFLG (n = 27), and 2 consecutive control groups: classic severe, normal-flow, high-gradient (n = 27) and normal-flow, low-gradient (NFLG) (n = 27) AS. Blinded biventricular function and lung parenchymal disease assessments were obtained by high-resolution CT imaging. ResultsPatient demographics were similar between groups. pLFLG AS had a lower RV ejection fraction (49 ± 10%) than both classic severe (58 ± 7%, p < 0.001) and NFLG AS (55 ± 65%, p = 0.02). There were no significant differences on lung emphysema (p = 0.19), air fraction (p = 0.58), or pulmonary disease presence (p = 0.94) and severity (p = 0.67) between groups. ConclusionspLFLG AS patients have lower RV ejection fraction than classic severe and NFLG AS patients in the absence of significant parenchymal lung disease on CT imaging. These findings support the direct importance of RV function in the pathophysiology of aortic valve disease.

Dark-field chest x-ray imaging: first experience in patients with alpha1-antitrypsin deficiency

BackgroundSpirometry and conventional chest x-ray have limitations in investigating early emphysema, while computed tomography, the reference imaging method in this context, is not part of routine patient care due to its higher radiation dose. In this work, we investigated a novel low-dose imaging modality, dark-field chest x-ray, for the evaluation of emphysema in patients with alpha1-antitrypsin deficiency.MethodsBy exploiting wave properties of x-rays for contrast formation, dark-field chest x-ray visualises the structural integrity of the alveoli, represented by a high signal over the lungs in the dark-field image. We investigated four patients with alpha1-antitrypsin deficiency with a novel dark-field x-ray prototype and simultaneous conventional chest x-ray. The extent of pulmonary function impairment was assessed by pulmonary function measurement and regional emphysema distribution was compared with CT in one patient.ResultsWe show that dark-field chest x-ray visualises the extent of pulmonary emphysema displaying severity and regional differences. Areas with low dark-field signal correlate with emphysematous changes detected by computed tomography using a threshold of -950 Hounsfield units. The airway parameters obtained by whole-body plethysmography and single breath diffusing capacity of the lungs for carbon monoxide demonstrated typical changes of advanced emphysema.ConclusionsDark-field chest x-ray directly visualised the severity and regional distribution of pulmonary emphysema compared to conventional chest x-ray in patients with alpha1-antitrypsin deficiency. Due to the ultra-low radiation dose in comparison to computed tomography, dark-field chest x-ray could be beneficial for long-term follow-up in these patients.

Association between plasma sRAGE and emphysema according to the genotypes of AGER gene

BackgroundHigher soluble receptor for advanced glycation end product (sRAGE) levels are considered to be associated with severe emphysema. However, the relationship remains uncertain when the advanced glycation end-product specific receptor (AGER) gene is involved. We aimed to analyse the association between sRAGE levels and emphysema according to the genotypes of rs2070600 in the AGER gene.MethodsWe genotyped rs2070600 and measured the plasma concentration of sRAGE in each participant. Emphysema was quantified based on the chest computed tomography findings. We compared sRAGE levels based on the presence or absence and severity of emphysema in each genotype. Multiple logistic and linear regression models were used for the analyses.ResultsA total of 436 participants were included in the study. Among them, 64.2% had chronic obstructive pulmonary disease and 34.2% had emphysema. Among the CC-genotyped participants, the sRAGE level was significantly higher in participants without emphysema than in those with emphysema (P < 0.001). In addition, sRAGE levels were negatively correlated with emphysema severity in CC-genotyped patients (r = − 0.268 P < 0.001). Multiple regression analysis revealed that sRAGE was an independent protective factor for the presence of emphysema (adjusted odds ratio, 0.24; 95% confidence interval (CI) 0.11–0.51) and severity of emphysema (β = − 3.28, 95% CI − 4.86 to − 1.70) in CC-genotyped participants.ConclusionPlasma sRAGE might be a biomarker with a protective effect on emphysema among CC-genotyped patients of rs2070600 on the AGER gene. This is important in determining the target group for the future prediction and treatment of emphysema.

Plasma sRAGE levels strongly associate with centrilobular emphysema assessed by HRCT scans

BackgroundThere is a strong need for biomarkers to better characterize individuals with COPD and to take into account the heterogeneity of COPD. The blood protein sRAGE has been put forward as promising biomarker for COPD in general and emphysema in particular. Here, we measured plasma sRAGE levels using quantitative LC–MS and assessed whether the plasma sRAGE levels associate with (changes in) lung function, radiological emphysema parameters, and radiological subtypes of emphysema.MethodsThree hundred and twenty-four COPD patients (mean FEV1: 63%predicted) and 185 healthy controls from the COPDGene study were selected. Plasma sRAGE was measured by immunoprecipitation in 96-well plate methodology to enrich sRAGE, followed by targeted quantitative liquid chromatography-mass spectrometry. Spirometry and HRCT scans (inspiration and expiration) with a 5-year follow-up were used; both subjected to high quality control standards.ResultsLower sRAGE values significantly associated with the presence of COPD, the severity of airflow obstruction, the severity of emphysema on HRCT, the heterogeneous distribution of emphysema, centrilobular emphysema, and 5-year progression of emphysema. However, sRAGE values did not associate with airway wall thickness or paraseptal emphysema.ConclusionsRather than being a general COPD biomarker, sRAGE is especially a promising biomarker for centrilobular emphysema. Follow-up studies should elucidate whether sRAGE can be used as a biomarker for other COPD phenotypes as well.

Quantitative measurements of emphysema in ultra-high resolution computed tomography using model-based iterative reconstruction in comparison to that using hybrid iterative reconstruction.

The percentage of low attenuation volume ratio (LAVR), which is measured using computed tomography (CT), is an index of the severity of emphysema. For LAVR evaluation, ultra-high-resolution (U-HR) CT images are useful. To improve the image quality of U-HRCT, iterative reconstruction is used. There are two types of iterative reconstruction: hybrid iterative reconstruction (HIR) and model-based iterative reconstruction (MBIR). In this study, we physically and clinically evaluated U-HR images reconstructed with HIR and MBIR, and demonstrated the usefulness of U-HR images with MBIR for quantitative measurements of emphysema. Both images were reconstructed with a slice thickness of 0.25mm and an image matrix size of 1024 × 1024 pixels. For physical evaluation, the modulation transfer function (MTF) and noise power spectrum (NPS) of HIR and MBIR were compared. For clinical evaluation, LAVR calculated from HIR and MBIR were compared using the Wilcoxon matched-pairs signed-rank test. In addition, the correlation between LAVR and forced expiratory volume in one second (FEV1%) was evaluated using the Spearman rank correlation test. The MTFs of HIR and MBIR were comparable. The NPS of MBIR was lower than that of HIR. The mean LAVR values calculated from HIR and MBIR were 19.5 ± 12.6% and 20.4 ± 11.7%, respectively (p = 0.84). The correlation coefficients between LAVR and FEV1% that were taken from HIR and MBIR were 0.64 and 0.74, respectively (p < 0.01). MBIR is more useful than HIR for the quantitative measurements of emphysema with U-HR images.

Brief Report: HIV Is Associated With Impaired Pulmonary Diffusing Capacity Independent of Emphysema.

Background:HIV is associated with accelerated decline in lung function and increased risk for chronic obstructive pulmonary disease (COPD). Recently, there has been growing attention toward the impairment in the diffusing capacity of the lungs for carbon monoxide (DLCO), a marker of pulmonary gas exchange, observed among persons living with HIV. Although increased emphysema can contribute to the DLCO impairment observed, other factors may drive this association.Methods:Using cross-sectional data from the Study of HIV in the Etiology of Lung Disease, we studied the association between HIV and DLCO independent of emphysema. We also analyzed the joint influence of HIV and COPD on DLCO impairment. An analysis was conducted among 339 participants (229 with HIV) with lung function and chest CT imaging data. Multivariable regression models were generated with percent predicted DLCO and odds of DLCO impairment as outcomes.Results:After adjusting for confounders, including emphysema severity, HIV was associated with lower DLCO (β −4.02%; P = 0.020) and higher odds of DLCO impairment (odds ratio 1.93; P = 0.017). Even among those without COPD, HIV was independently associated with lower DLCO (β −3.89%; P = 0.049). Compared with HIV-uninfected participants without COPD, those with both HIV and COPD experienced the greatest impairment in DLCO (β −14.81; P < 0.001).Conclusions:HIV is associated with impaired pulmonary gas exchange independent of emphysema severity. Our data also suggest a potentially additive influence between HIV and COPD on DLCO impairment. Further studies should investigate the other factors, including pulmonary vascular disease, which may contribute to DLCO impairment among persons living with HIV.

Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort.

Forced expiratory volume in 1 second (FEV1) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD. To determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD. The SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease. Lower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC). The %predFEF25-75% provides additional information about disease manifestation beyond FEV1. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF25-75% helps link the anatomic pathology and deranged physiology of COPD.

Emphysema Severity Index (ESI) Predicts Respiratory Death in a Large Swedish General Population

Emphysema Severity Index (ESI) Predicts Respiratory Death in a Large Swedish General Population

Standard spirometry to assess emphysema in patients with chronic obstructive pulmonary disease: the Emphysema Severity Index (ESI).

BackgroundChronic obstructive pulmonary disease (COPD) is a generic term identifying a condition characterized by variable changes in peripheral airways and lung parenchyma. Standard spirometry cannot discriminate the relative role of conductive airways inflammatory changes from destructive parenchymal emphysema changes. The aim of this study was to quantify the emphysema component in COPD by a simple parameter (the Emphysema Severity Index - ESI), previously proved to reflect CT-assessed emphysema.MethodsESI was obtained by fitting the descending limb of MEFV curves by a fully automated procedure providing a 0 to 10 score of emphysema severity. ESI was computed in COPD patients enrolled in the CLIMA Study.ResultsThe vast majority of ESI values ranged from 0 to 4, compatible with no-to-mild/moderate emphysema component. A limited proportion of patients showed ESI values >4, compatible with severe-to-very severe emphysema. ESI values were greatly dispersed within each GOLD class indicating that GOLD classification cannot discriminate emphysema and conductive airways changes in patients with similar airflow limitation. ESI and diffusing capacity (DLCO) were significantly correlated (p<0.001). However, the great dispersion in their correlation suggests that ESI and DLCO reflect partially different anatomo-functional determinants in COPD.ConclusionsAirflow limitation has heterogenous determinants in COPD. Inflammatory and destructive changes may combine in CT densitometric alterations that cannot be detected by standard spirometry. ESI computation from spirometric data helps to define the prevailing pathogenetic mechanism underlying the measured airflow limitation. ESI could be a reliable advancement to select large samples of patients in clinical or epidemiological trials, and to compare different pharmacological treatments.