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

Background: Chronic 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.Methods: ESI 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.Results: the 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.Conclusions: airflow 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.

Therapeutic Potential of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Recovering From Murine Pulmonary Emphysema Under Cigarette Smoke Exposure

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were shown to have potential for immunoregulation and tissue repair. The objective of this study was to investigate the effects of hUC-MSCs on emphysema in chronic obstructive pulmonary disease (COPD). The C57BL/6JNarl mice were exposed to cigarette smoke (CS) for 4 months followed by administration of hUC-MSCs at 3 × 106 (low dose), 1 × 107 (medium dose), and 3 × 107 cells/kg body weight (high dose). The hUC-MSCs caused significant decreases in emphysema severity by measuring the mean linear intercept (MLI) and destructive index (DI). A decrease in neutrophils (%) and an increase in lymphocytes (%) in bronchoalveolar lavage fluid (BALF) were observed in emphysematous mice after hUC-MSC treatment. Lung levels of interleukin (IL)-1β, C-X-C motif chemokine ligand 1 (CXCL1)/keratinocyte chemoattractant (KC), and matrix metalloproteinase (MMP)-12 significantly decreased after hUC-MSC administration. Significant reductions in tumor necrosis factor (TNF)-α, IL-1β, and IL-17A in serum occurred after hUC-MSC administration. Notably, the cell viability of lung fibroblasts improved with hUC-MSCs after being treated with CS extract (CSE). Furthermore, the hUC-MSCs-conditioned medium (hUC-MSCs-CM) restored the contractile force, and increased messenger RNA expressions of elastin and fibronectin by lung fibroblasts. In conclusion, hUC-MSCs reduced inflammatory responses and emphysema severity in CS-induced emphysematous mice.

Pulmonary Emphysema Regional Distribution and Extent Assessed by Chest Computed Tomography Is Associated With Pulmonary Function Impairment in Patients With COPD

Objective: This study aimed to evaluate how emphysema extent and its regional distribution quantified by chest CT are associated with clinical and functional severity in patients with chronic obstructive pulmonary disease (COPD).Methods/Design: Patients with a post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) &lt; 0.70, without any other obstructive airway disease, who presented radiological evidence of emphysema on visual CT inspection were retrospectively enrolled. A Quantitative Lung Imaging (QUALI) system automatically quantified the volume of pulmonary emphysema and adjusted this volume to the measured (EmphCTLV) or predicted total lung volume (TLV) (EmphPLV) and assessed its regional distribution based on an artificial neural network (ANN) trained for this purpose. Additionally, the percentage of lung volume occupied by low-attenuation areas (LAA) was computed by dividing the total volume of regions with attenuation lower or equal to −950 Hounsfield units (HU) by the predicted [LAA (%PLV)] or measured CT lung volume [LAA (%CTLV)]. The LAA was then compared with the QUALI emphysema estimations. The association between emphysema extension and its regional distribution with pulmonary function impairment was then assessed.Results: In this study, 86 patients fulfilled the inclusion criteria. Both EmphCTLV and EmphPLV were significantly lower than the LAA indices independently of emphysema severity. CT-derived TLV significantly increased with emphysema severity (from 6,143 ± 1,295 up to 7,659 ± 1,264 ml from mild to very severe emphysema, p &lt; 0.005) and thus, both EmphCTLV and LAA significantly underestimated emphysema extent when compared with those values adjusted to the predicted lung volume. All CT-derived emphysema indices presented moderate to strong correlations with residual volume (RV) (with correlations ranging from 0.61 to 0.66), total lung capacity (TLC) (from 0.51 to 0.59), and FEV1 (~0.6) and diffusing capacity for carbon monoxide DLCO (~0.6). The values of FEV1 and DLCO were significantly lower, and RV (p &lt; 0.001) and TLC (p &lt; 0.001) were significantly higher with the increasing emphysema extent and when emphysematous areas homogeneously affected the lungs.Conclusions: Emphysema volume must be referred to the predicted and not to the measured lung volume when assessing the CT-derived emphysema extension. Pulmonary function impairment was greater in patients with higher emphysema volumes and with a more homogeneous emphysema distribution. Further studies are still necessary to assess the significance of CTpLV in the clinical and research fields.

Association Between Air Pollution and Lung Lobar Emphysema in COPD

The development of emphysema has been linked to air pollution; however, the association of air pollution with the extent of lobar emphysema remains unclear. This study examined the association of particulate matter &lt;2.5 μm in aerodynamic diameters (PM2.5) (≤2.5 μm), nitrogen dioxide (NO2), and ozone (O3) level of exposure with the presence of emphysema in 86 patients with chronic obstructive pulmonary disease (COPD). Exposure to the air pollution estimated using the land-use regression model was associated with lung function, BODE (a body mass index, degree of obstruction, dyspnea severity, and exercise capacity index) quartiles, and emphysema measured as low-attenuation areas on high-resolution CT (HR-CT) lung scans. Using paraseptal emphysema as the reference group, we observed that a 1 ppb increase in O3 was associated with a 1.798-fold increased crude odds ratio of panlobular emphysema (p &lt; 0.05). We observed that PM2.5 was associated with BODE quartiles, modified Medical Research Council (mMRC) dyspnea score, and exercise capacity (all p &lt; 0.05). We found that PM2.5, NO2, and O3 were associated with an increased degree of upper lobe emphysema and lower lobe emphysema (all p &lt; 0.05). Furthermore, we observed that an increase in PM2.5, NO2, and O3 was associated with greater increases in upper lobe emphysema than in lower lobe emphysema. In conclusion, exposure to O3 can be associated with a higher risk of panlobular emphysema than paraseptal emphysema in patients with COPD. Emphysema severity in lung lobes, especially the upper lobes, may be linked to air pollution exposure in COPD.

Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers

BackgroundPentraxin 3 (PTX3) influences innate immunity and inflammation, host defence, the complement cascade and angiogenesis. PTX3 expression in lung and blood of subjects with tobacco exposure, and its potential relationship with disease pattern and clinical outcome are poorly understood.MethodsUsing independent platforms and cohorts, we identified associations of PTX3 gene expression in lung tissue and plasma from current and former tobacco smokers (with and without chronic obstructive pulmonary disease, COPD) to disease phenotypes including quantitative CT determined emphysema, lung function, symptoms and survival. Two putative regulatory variants of the PTX3 gene were examined for association with COPD manifestations. The relationship between plasma PTX3 and hyaluronic acid levels was further examined.ResultsPTX3 gene expression in lung tissue was directly correlated with emphysema severity (p<0.0001). Circulating levels of PTX3 were inversely correlated with FEV1 (p=0.006), and positively associated with emphysema severity (p=0.004) and mortality (p=0.008). Two PTX3 gene regulatory variants were associated with a lower risk for emphysema and expiratory airflow obstruction, and plasma levels of PTX3 and hyaluronic acid were related.ConclusionsThese data show strong and overlapping associations of lung and blood PTX3 levels, and PTX3 regulatory gene variants, with the severity of airflow obstruction, emphysema and mortality among smokers. These findings have potential implications regarding the pathogenesis of smoking-related lung diseases and warrant further exploration for the use of PTX3 as a predictive biomarker.

Associations of CT evaluations of antigravity muscles, emphysema and airway disease with longitudinal outcomes in patients with COPD

Multiple CT indices are associated with disease progression and mortality in patients with COPD, but which indices have the strongest association remain unestablished. This longitudinal 10-year observational study (n=247) showed that the emphysema severity on CT is more closely associated with the progression of airflow limitation and that a reduction in the cross-sectional area of erector spinae muscles (ESMCSA) on CT is more closely associated with mortality than the other CT indices, independent of patient demographics and pulmonary function. ESMCSA is a useful CT index that is more closely associated with long-term mortality than emphysema and airway disease in patients with COPD.