Degree Of Emphysema Research Articles

427P Quantitative severity of pulmonary emphysema as a prognostic factor for recurrence in patients with surgically resected non-small cell lung cancer

Background Pulmonary emphysema is a major component of chronic obstructive pulmonary disease and lung cancer. However, the prognostic significance of quantitative emphysema severity in patients with lung cancer is unclear. Methods We quantified emphysema severity of whole lung and regional lobe using chest computed tomography-based automatic software in 45 patients (36 males and 9 females; mean age of 68.0) with surgically resected non-small cell lung cancer. Predicting factors for recurrence were investigated using Cox proportional hazards model. The recurrence-free survival was compared after dichotomization of patients according to the whole lung emphysema severity. Results The mean percent ratio of emphysema volume/whole lung volume was 1.21 62.04. Regional lobar emphysema severity was highest in right middle lobe (1.93 6 5.36), followed by right upper (1.35 6 2.50), left upper (1.34 6 2.12), left lower (1.05 6 2.52), and right lower lobe (0.78 6 2.28). Emphysema severity of whole lung (hazard ratio, 1.36; 95% confidence interval, 1.06 - 1.73) and stage III (hazard ratio, 6.17; 95% confidence interval, 1.52 - 25.0) were independent predictors of recurrence after adjustment for age, sex, smoking status, and forced expiratory volume in 1 second. The median recurrence-free survival of low emphysema and high emphysema group were 30.1 months and 22.0 months, respectively. Conclusions Although degree of emphysema was relatively low in this study population, quantitative emphysema severity of whole lung is associated with recurrence in patients with surgically resected non-small cell lung cancer. Legal entity responsible for the study N/A Funding N/A Disclosure All authors have declared no conflicts of interest.

Analysis of Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome Defined on the Basis of Bronchodilator Response and Degree of Emphysema.

Despite the increasing recognition of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) as a clinical entity, it remains poorly characterized due to a lack of agreement on its definition and diagnostic criteria. The aim of this study was to use spirometry and computed tomography (CT) to help better define ACOS as well as to classify subjects with ACOS based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) letter grade. We analyzed 10,192 subjects enrolled in the COPDGene Study. Subjects were non-Hispanic white or African American current or former smokers aged 45-80 years with at least a 10-pack-year smoking history. Subjects were categorized as having either ACOS with a bronchodilator response or chronic obstructive pulmonary disease with emphysema on the basis of spirometry, high-resolution CT, and a history of asthma or hay fever. Subjects with ACOS were younger (60.6 vs. 65.9 years old; P < 0.0001), more likely to be African American (26.8% vs. 14.4%; P < 0.0001), had a higher body mass index (29.6 vs. 25.1 kg/m(2); P < 0.0001), and were more likely to be current smokers (50.9% vs. 20.7%; P < 0.0001). The majority of subjects with ACOS were categorized as GOLD grade B. Despite less severe spirometry and CT findings in subjects with ACOS, there was no significant difference in severe or frequent exacerbations. Bronchodilator responsiveness and degree of emphysema can help define ACOS. When defined on the basis of bronchodilator responsiveness and degree of emphysema, patients with ACOS represent a unique and high-risk group with distinct clinical features.

Lower diffusing capacity with chronic bronchitis predicts higher risk of acute exacerbation in chronic obstructive lung disease.

This study was designed to evaluate the effect of chronic bronchitis (CB) symptoms and degree of emphysema in a multicenter Korean cohort. From April 2012 to May 2015, patients diagnosed with chronic obstructive lung disease (COPD) who were aged above 40 years at 46 hospitals throughout Korea were enrolled. All of the patients were classified according to CB symptoms and the diffusing capacity of the lung for carbon monoxide (DLCO); demographic data, symptom scores, and the result of lung function tests and exacerbations were then analyzed. A total of 812 patients were enrolled. Among these patients, 285 (35.1%) had CB symptoms. A total of 51% of patients had high DLCO without CB symptoms [CB (-) high DLCO], 24.9% had CB symptoms only [CB (+) high DLCO], 14.2% had low DLCO only [CB (-) low DLCO], and 10.2% had both low DLCO and CB [CB (+) low DLCO]. Patients with CB (+) low DLCO showed a significantly lower post-bronchodilator (BD) forced expiratory volume for 1 second (FEV1) and more severe dyspnea than patients with CB (-) high DLCO. On multivariate analysis, the risk of acute exacerbation was two times higher [odds ratio (OR) 2.06; 95% confidence interval (CI): 1.18-3.62; P=0.01] in the CB (+) low DLCO group than in the CB (-) high DLCO group. In this COPD cohort, patients showed distinct clinical characteristics and outcomes according to the presence of CB and degree of DLCO. CB and low DLCO were associated with the risk of acute exacerbation.

Effect of CD40 knock out on cytotoxic effector function in CD8(+) T cell of mice with cigarette smoke-induced emphysema

To explore the effect of CD40 knock out on the cytotoxic function of CD8(+) T cell of mice with cigarette smoke-induced emphysema. A total of 40 male C57 mice were divided into four groups according to the random number table, including CD40(+ /+) control group, CD40(+ /+) smoke-exposure group, CD40(-/-)control group, CD40(-/-)smoke-exposure group. The smoke-exposure groups were exposed to cigarette smoke for 24 weeks to establish emphysema model. Morphological changes were evaluated by linear intercepts. The percentages of CD8, perforin, granzyme B positive cells were evaluated by immunohistochemistry. The mRNA expressions of perforin, granzyme B, interleukin (IL) -27 were measured by fluorescent real time quantitative polymerase chain reaction (RT-PCR). The IL-27 cytokine level was tested by enzyme-linked immunosorbent assay (ELISA). The mean linear intercepts in CD40(+ /+) smoke-exposure group was significantly higher than CD40(+ /+) control group, CD40(-/-)control group, and CD40(-/-)smoke-exposure group [(37.2±3.6) vs (24.0±3.4), (22.5±2.4), (29.9±1.7) μm] (all P<0.05). CD40(-/-)smoke-exposure group was higher than CD40(+ /+) control group, CD40(-/-)control group (all P<0.05). The percentages of CD8 positive, perforin positive and granzyme B positive cells in CD40(+ /+) smoke-exposure group [(16.3±2.3)%, (11.4±2.1)%, (10.7±1.9)%] were significantly higher than CD40(+ /+) control group [(8.3±1.6)%, (5.1±1.2)%, (4.6±1.0)%], CD40(-/-)control group [ (6.4±1.5)%, (4.3±1.0)%, (4.2±1.0)%] and CD40(-/-)smoke-exposure group [(8.6±1.7)%, (5.6±1.3)%, (5.5±1.3)%] (all P<0.05). RT-PCR results showed that the mRNA expressions of perforin, granzyme B and IL-27 in CD40(+ /+) smoke-exposure group [(20.3±7.3), (18.3±12.3), (2.2±0.7)] were significantly higher than CD40(+ /+) control group [(9.4±4.8), (10.6±3.8), (1.3±0.6)], CD40(-/-)control group [ (8.1±3.1), (7.7±3.5), (1.1±0.5)] and CD40(-/-)smoke-exposure group [(12.9±6.2), (10.4±4.6), (1.5±0.4)] (all P<0.05). ELISA results showed that the level of IL-27 in CD40(+ /+) smoke-exposure group was significantly higher than CD40(+ /+) control group, CD40(-/-)control group and CD40(-/-)smoke-exposure group [(3 242±754) vs (1 627±710), (1 600±680), (1 850±583) ng/L] (all P<0.05). Knockout the CD40 gene can inhibit the cytotoxic effector function in CD8(+) T cells of mice with cigarette smoke-induced emphysema, and alleviate the degree of emphysema.

CT-derived Biomechanical Metrics Improve Agreement Between Spirometry and Emphysema

Many patients with chronic obstructive pulmonary disease (COPD) have marked discordance between forced expiratory volume in 1 second (FEV1) and degree of emphysema on computed tomography (CT). Biomechanical differences between these patients have not been studied. We aimed to identify reasons for the discordance between CT and spirometry in some patients with COPD. Subjects with Global initiative for chronic Obstructive Lung Disease stages I-IV from a large multicenter study (The Genetic Epidemiology of COPD) were arranged by percentiles of %predicted FEV1 and emphysema on CT. Three categories were created using differences in percentiles: Catspir with predominant airflow obstruction/minimal emphysema, CatCT with predominant emphysema/minimal airflow obstruction, and Catmatched with matched FEV1 and emphysema. Image registration was used to derive Jacobian determinants, a measure of lung elasticity, anisotropy, and strain tensors, to assess biomechanical differences between groups. Regression models were created with the previously mentioned categories as outcome variable, adjusting for demographics, scanner type, quantitative CT-derived emphysema, gas trapping, and airway thickness (model 1), and after adding biomechanical CT metrics (model 2). Jacobian determinants, anisotropy, and strain tensors were strongly associated with FEV1. With Catmatched as control, model 2 predicted Catspir and CatCT better than model 1 (Akaike information criterion 255.8 vs. 320.8). In addition to demographics, the strongest independent predictors of FEV1 were Jacobian mean (β = 1.60,95%confidence intervals [CI] = 1.16 to 1.98; P < 0.001), coefficient of variation (CV) of Jacobian (β = 1.45,95%CI = 0.86 to 2.03; P < 0.001), and CV of strain (β = 1.82,95%CI = 0.68 to 2.95; P = 0.001). CVs of Jacobian and strain are both potential markers of biomechanical lung heterogeneity. CT-derived measures of lung mechanics improve the link between quantitative CT and spirometry, offering the potential for new insights into the linkage between regional parenchymal destruction and global decrement in lung function in patients with COPD.

Emphysematous lungs do not affect visibility of virtual-assisted lung mapping.

It has recently been suggested that virtual-assisted lung mapping may enable safer and more reliable intraoperative navigation compared to conventional preoperative lung marking strategies. This study aimed to examine the relationship between emphysematous lungs and the intraoperative visibility of virtual-assisted lung mapping markings. We retrospectively analyzed the data of 21 patients who underwent virtual-assisted lung mapping followed by lung resection between October 2013 and May 2015. The visibility of the intraoperative lung markings was graded. The degree of pulmonary emphysema was assessed by the percentage of low attenuation area on computed tomography. We elucidated the associations between the marking grade and other factors such as patient age or sex, pulmonary lobe mapped, marking operator, Brinkman index, and percentage of low attenuation area of the pulmonary lobe. In Spearman rank correlation analysis, there was no correlation between the Brinkman index and the percentage of low attenuation area (n = 26, r = -0.016, p = 0.937). In stepwise multivariate regression analysis, the marking grade correlated with the marking operator (p < 0.001) and the Brinkman index (p = 0.008), but not with patient age or sex, the pulmonary lobe mapped, or degree of pulmonary emphysema. The skill of the marking operator and the patient's smoking history had significant effects on the intraoperative visibility of markings made by virtual-assisted lung mapping, whereas emphysematous lungs did not affect the intraoperative visibility of lung markings.

How Common Is Airflow Limitation in Patients With Emphysema on CT Scan of the Chest?

COPD has traditionally been defined by the presence of irreversible airflow limitation on spirometry using either the GOLD (Global Initiative for Chronic Obstructive Lung Disease) or American Thoracic Society/European Respiratory Society criteria (lower limit of normal [LLN]). We have observed that some patients with clinical COPD and emphysema on chest CT scan have no obstruction on spirometry. The purpose of this study was to assess the prevalence of obstruction by GOLD and LLN criteria in patients with emphysema on CT scan and determine which radiographic criteria were associated with a clinical diagnosis of COPD. We retrospectively analyzed the clinical records and spirometry of all patients who had radiographically defined emphysema on chest CT scans completed at the University of Vermont in 2011. We compared spirometric criteria and CT scan factors with the presence of clinical COPD based on chart review. We identified 274 patients with CT scan-defined emphysema. GOLD criteria detected obstruction in 228 patients (83%), and LLN detected obstruction in 206 patients (75%). However, GOLD failed to correctly identify 19 patients (6.9%) and LLN failed to identify 38 patients (13.9%) (average 10.4%) who had radiographic emphysema and a clinical diagnosis of COPD. Obese patients had a lower prevalence of obstruction whether classified by LLN or GOLD. Among patients with spirometric obstruction, there were greater degrees of emphysema and more severely increased airway wall thickness. Factors that were independently associated with clinical COPD were lower FVC % predicted, lower FEV1/FVC ratio, and increasing airway wall thickness. Spirometry missed 10.4% of patients with clinical COPD who have significant emphysema on chest CT scan.

A Retrospective Study of Risk Factors for Radiation Pneumonitis of Definitive Chemoradiotherapy for the Treatment of Locally Advanced Lung Cancer By Emphysema Quantification

ABSTRACT Aim: Radiation pneumonitis (RP) is one of the most crucial adverse events of definitive chemoradiotherapy for the treatment of locally advanced lung cancer. Although chronic obstructive pulmonary disease (COPD) is considered as one of the risk factors of RP, the relationship between RP and pulmonary emphysema (PE) that is a subtype of COPD is not clear. We examined the clinical backgrounds of patients experiencing RP due to concurrent chemodadiotherapy for the treatment of locally advanced lung cancer and evaluated risk factors. Methods: We retrospectively examined patients with locally advanced lung cancer who underwent definitive chemoradiotherapy between Janary 2010 and December 2012. For quantitative assessments of PE, percentage of low attenuation volumes (%LAV) and mean density (MD) were computationally calculated by using AZE Virtual place Fujin (Tokyo). Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 was used to evaluate RP. We evaluated the relationship between clinical backgrounds, the degree of emphysema (%LAV, MD), radiation dose (the percentage of pulmonary volume irradiated to >20Gy (V20), mean lung dose (MLD)) and RP. Results: 33 patients were analyzed, of which 19 (58%) had symptomatic RP (>= Grade2) and 14 (42%) had asymptomatic RP (=Grade1). Age, sex, pathology and stage in patients were similar between both groups. There is no significant difference in forced expiratory volume in 1 second (FEV1) between the symptomatic group and the asymptomatic group (2.23 + -0.60L vs 2.35 + -0.50L, P = 0.296). The symtomatic group had significantly more severe PE (LAV% 10.9 + -8.7% MD -880 ± 21HU) than the asymptomatic group (LAV% 4.4 + -4.0% (P = 0.025), MD -856 + -24 HU (P = 0.002)), respectively. Radiation dose was significantly higher in the symptomatic group (V20 24.6 + -5.1%, MLD 12.9 + -3.4Gy) than the asymptomatic group ((V20 19.9 + -3.3% (P = 0.005), MLD 9.1 + -3.2Gy (P = 0.002)). Conclusions: Severity of emphysma appears to be a factor that can be used to predict RP after concurrent chemoradiotherapy for lung cancer. Disclosure: All authors have declared no conflicts of interest.

Quantitative computed tomography of pulmonary emphysema and ventricular function in chronic obstructive pulmonary disease patients with pulmonary hypertension.

ObjectiveThis study strived to evaluate the relationship between degree of pulmonary emphysema and cardiac ventricular function in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH) using electrocardiographic-gated multidetector computed tomography (CT).Materials and MethodsLung transplantation candidates with the diagnosis of COPD and PH were chosen for the study population, and a total of 15 patients were included. The extent of emphysema is defined as the percentage of voxels below -910 Hounsfield units in the lung windows in whole lung CT without intravenous contrast. Heart function parameters were measured by electrocardiographic-gated CT angiography. Linear regression analysis was conducted to examine the associations between percent emphysema and heart function indicators.ResultsSignificant correlations were found between percent emphysema and right ventricular (RV) measurements, including RV end-diastolic volume (R2 = 0.340, p = 0.023), RV stroke volume (R2 = 0.406, p = 0.011), and RV cardiac output (R2 = 0.382, p = 0.014); the correlations between percent emphysema and left ventricular function indicators were not observed.ConclusionThe study revealed that percent emphysema is correlated with RV dysfunction among COPD patients with PH. Based on our findings, percent emphysema can be considered for use as an indicator to predict the severity of right ventricular dysfunction among COPD patients.

Adiponectin is associated with dynamic hyperinflation and a favourable response to inhaled glucocorticoids in patients with COPD

Adipokines are protein mediators first described as products of adipose tissue regulating energy metabolism and appetite. Recently, adipokines have also been found to modulate inflammation and smooth muscle cell responses. Therefore we investigated the association of two adipokines, adiponectin and leptin, with the degree of emphysema, pulmonary function, symptoms and glucocorticoid responsiveness in patients with COPD. Plasma adiponectin and leptin levels, spirometry, body plethysmography and symptoms were measured in 43 male COPD patients with smoking history≥20 pack-years, post bronchodilator FEV1/FVC<0.7 and pulmonary emphysema on HRCT. The measurements were repeated in a subgroup of patients after 4 weeks' treatment with inhaled fluticasone. In patients with COPD, plasma adiponectin levels correlated positively with airway resistance (Raw) (r=0.362, p=0.019) and functional residual capacity (FRC) (r=0.355, p=0.046). Furthermore, the baseline adiponectin concentration correlated negatively with the fluticasone induced changes in St George's Respiratory questionnaire (SGRQ) symptom score (r=-0.413, p=0.040) and in FRC % pred (r=-0.428, p=0.003), i.e. a higher baseline plasma adiponectin level was associated with more pronounced alleviation of symptoms and dynamic hyperinflation. Plasma leptin levels were not related to the measures of lung function, symptoms or glucocorticoid responsiveness. Plasma adiponectin levels were associated with peripheral airway obstruction and dynamic hyperinflation in patients with COPD. A higher adiponectin level predicted more favourable relief of symptoms and hyperinflation during glucocorticoid treatment. Adiponectin may have a role in the COPD pathogenesis; it may also be a biomarker of disease severity and treatment responses in this disease.

Predictors of phase III slope of nitrogen single-breath washout in COPD

The nitrogen (N2) single-breath washout (SBW) test is a measure of ventilation distribution inhomogeneity and also a small airway function that offers complementary information to spirometry; however, the relevance to the forced oscillation technique (FOT) and pulmonary emphysema in COPD is not fully understood. We hypothesized that pulmonary functions, forced oscillatory parameters, and emphysema extent would contribute independently to the results of the SBW test. In this cross-sectional study we assessed the relationship between the phase III slope (delta N2) derived from N2 SBW and these parameters. Spirometry, lung volumes, N2 SBW, and the broadband frequency FOT were performed in 56 patients with COPD. Emphysema extent was measured by high-resolution computed tomography and scored. In multiple regression analyses, the delta N2 was independently predicted by forced vital capacity, resonant frequency, and emphysema score (R2=0.57, p<0.0001). The degree of ventilation inhomogeneity derived from N2 SBW is independently predicted by spirometry, lung mechanics, and the degree of emphysema.

Severity of emphysema predicts location of lung cancer and 5-y survival of patients with stage I non–small cell lung cancer

BackgroundNon–small cell lung cancer (NSCLC) has a predilection to occur in emphysematous lungs. The relation between the regional severity of emphysema and the location of NSCLC as well as long-term survival has been poorly studied. MethodsComputed tomography (CT) scans of 153 patients with biopsy-proven stage I NSCLC diagnosed between 2001 and 2006 were assigned an emphysema severity score in four regions of the lung. The location of the cancer was compared with the severity of emphysema in that region. Survival was also analyzed. ResultsThirty-nine patients had no emphysema documented on CT scan and 114 did. The most common location of cancer was the right upper quadrant with 37% of cancers, followed by the left upper quadrant with 23% of cancers. Twenty-two percent of the cancers occurred in the right lower quadrant, and only 12% were in the left lower quadrant. There is a strong association for cancer being located in the area with the highest degree of emphysema (P < 0.001). Emphysema severity score was also associated with long-term survival (log-rank P = 0.03). ConclusionsThe regional severity of emphysema assessed via a visual scale using CT appears to be associated with the location of lung cancer and is an independent predictor of long-term survival.

Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD.

BackgroundMatrix-metalloproteinase (MMP)-9 has been implicated in the pathogenesis of COPD, although its link to disease severity is unclear. The purpose of the study was to examine the relationship between disease severity assessed by lung function and computed tomography (CT) and sputum MMP-9 expression, concentration and activity in patients with COPD.FindingsIn 53 COPD subjects, smokers and ex-smokers; 46 healthy controls, smokers and never smokers, we measured sputum MMP-9 concentrations (ELISA) and enzyme activity (FRET), sputum MMP-9 mRNA expression, spirometry, diffusing capacity for carbon monoxide (DLco) and CT assessment of emphysema (% low attenuation areas below-950 Hounsfield units).Sputum MMP-9 concentrations and mRNA expression in COPD subjects were significantly greater than in healthy never-smokers (p = 0.007 and p = 0.001 respectively) and similar to those in healthy smokers. Disease severity when assessed by the extent of emphysema measured by CT, but not by spirometry or DLco values, was directly associated with sputum MMP-9 concentrations [r = 0.442 (0.171, 0.634), p = 0.020], and MMP-9 activity [r = 0.447 (0.219, 0.643), p = 0.010]. In moderate to severe COPD, increased MMP-9 mRNA expression levels were associated with reduced post-bronchodilator FEV1 [r = −0.530 (−0.686, -0.327), p < 0.001], FEV1/FVC ratio [r = −0.551 (−0.701, -0.354), p < 0.001] and reduced DLco [r = −0.399 (−539, -0.102), p = 0.048].ConclusionsSputum MMP-9 concentrations in COPD are directly associated with the extent of emphysema measured by CT and MMP-9 expression levels are inversely associated with DLco. These findings support a role for MMP-9 in the pathogenesis of COPD.Electronic supplementary materialThe online version of this article (doi:10.1186/2213-0802-1-11) contains supplementary material, which is available to authorized users.

Comparison of spirometric thresholds in diagnosing smoking-related airflow obstruction

BackgroundDiagnosis of chronic obstructive pulmonary disease is based on detection of airflow obstruction on spirometry. There is no consensus regarding using a fixed threshold to define airflow obstruction versus using...

Mortality by Level of Emphysema and Airway Wall Thickness

There is limited knowledge of the prognostic value of quantitative computed tomography (CT) measures of emphysema and airway wall thickness (AWT) on mortality. To examine 8-year mortality in relation to CT-measured emphysema and AWT, and assess if potential impact of these predictors remained after adjustment for lung function. In the Norwegian GenKOLS study of 2003-2005, 947 ever-smokers (49% with COPD) aged 40-85 years performed spirometry and CT examination. Mortality data from 2003-2011 were gathered from the Norwegian Cause of Death Registry. CT emphysema % low-attenuation areas (%LAA) and standardized measure for AWT (AWT-Pi10) were main predictors. We performed Laplace regression for survival data, estimating survival time for specified population percentiles within each emphysema category. Models were adjusted for sex, FEV1, COPD status, age, body mass index, smoking, and inflation level. During 8-year follow-up all-cause mortality rate was 15%. Although 4% of the subjects with %LAA less than 3 died, 18% with %LAA 3-10 and 44% with %LAA greater than or equal to 10 died. After adjustment, the comparable percentile subjects with medium and high emphysema had 19 months shorter survival than subjects who died in the lowest emphysema category. Subjects with %LAA greater than or equal to 10 had 33 and 37 months shorter survival than the lowest emphysema category with regard to respiratory and cardiovascular mortality, respectively. No significant associations were found between %LAA and cancer and lung cancer mortality. AWT did not predict mortality independently, but a positive interaction with emphysema was observed. AWT affected mortality with increasing degree of emphysema, whereas CT measure of emphysema was a strong independent mortality predictor.

Vitamin A, Vitamin E, Lutein and &amp;lt;i&amp;gt;β&amp;lt;/i&amp;gt;-Carotene in Lung Tissues from Subjects with Chronic Obstructive Pulmonary Disease and Emphysema

Vitamin A (VA) and its active metabolites play an essential role in lung airway function. Patients with moderate to severe chronic obstructive pulmonary disease (COPD) have a lower serum retinol concentration, and improvement of their 1-second Forced Expiratory Volume (FEV1) is achieved with VA supplementation. In order to test our hypothesis that the VA signaling pathway is compromised in COPD, we obtained 20 lung samples from COPD patients differing in the degree of emphysema as judged by their FEV% values. All were smokers or were exposed to secondhand smoke. Levels of VA (retinol/retinyl ester), tocopherols and carotenoids (lutein, beta-carotene) in these samples were determined using HPLC. Additional analytes beside VA were included for their known roles as antioxidants and modulators of VA-action. VA levels (retinol/retinyl ester) decreased significantly with the increase in severity of emphysema. Among other analytes, α-tocopherol levels fell by 25.8% in the severe emphysema group in comparison to the mild emphysema group, and lutein levels similarly decreased in severe compared to moderate emphysema groups. However, beta-carotene levels remained unchanged. Thus there is a significant linear correlation between lung VA-levels and the severity of emphysema. There was also a significant reduction in the levels of α-, δ-tocopherol and lutein in the severe emphysema group of COPD patients who either smoked or were exposed to smoke.

İki Farklı Tespit Yönteminin Akciğer Morfolojisine Etkilerinin Karşılaştırılması: Deneysel Bir Çalışma

Objective: Enlargement of the alveoli is considered to be the most important parameter to assess the degree of emphysema and expansion. Alveolar enlargement is primarily defined by morphological criteria. Lung morphology can be of considerable forensic interest and it may contribute to the differentiation of drowning from other types of asphyxiation. Level of alveolar expansion is critical to differentiate between stillborn infants and those born alive but died shortly after birth. A detailed morphological analysis on the state of lung expansion may be interfered by the collapse of the lung, which usually occurs after opening the thoracic cage at autopsy resulting in loss of negative pleural pressure. Material and Methods: The degree of alveolar expansion and distortion of alveolar shape were analyzed morphometrically on samples of rat lungs which were fixed and dissected by different methods. This study comprised three groups including the control group, with 10 rats in each group. Some shape descriptors for the alveoli were measured using an image processing and analysis algorithm. Results: The median alveolar area was 0.062 mm² in the control group, 0.10 mm² in the drowning group, and 0.088 mm² in the in situ fixed group, respectively. In this experimental study, when fixation was completed before dissection, the morphometric measurements regarding the alveolar shape descriptors, especially in the alveolar area, major-minor alveolar axis and circularity variables were significantly different between groups (p<0.05). Conclusion: We conclude that in situ fixation of the lungs may provide important data in selected cases in terms of diagnosis.

MiR-638 regulates gene expression networks associated with emphysematous lung destruction

BackgroundChronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by varying degrees of emphysematous lung destruction and small airway disease, each with distinct effects on clinical outcomes. There is little known about how microRNAs contribute specifically to the emphysema phenotype. We examined how genome-wide microRNA expression is altered with regional emphysema severity and how these microRNAs regulate disease-associated gene expression networks.MethodsWe profiled microRNAs in different regions of the lung with varying degrees of emphysema from 6 smokers with COPD and 2 controls (8 regions × 8 lungs = 64 samples). Regional emphysema severity was quantified by mean linear intercept. Whole genome microRNA and gene expression data were integrated in the same samples to build co-expression networks. Candidate microRNAs were perturbed in human lung fibroblasts in order to validate these networks.ResultsThe expression levels of 63 microRNAs (P < 0.05) were altered with regional emphysema. A subset, including miR-638, miR-30c, and miR-181d, had expression levels that were associated with those of their predicted mRNA targets. Genes correlated with these microRNAs were enriched in pathways associated with emphysema pathophysiology (for example, oxidative stress and accelerated aging). Inhibition of miR-638 expression in lung fibroblasts led to modulation of these same emphysema-related pathways. Gene targets of miR-638 in these pathways were amongst those negatively correlated with miR-638 expression in emphysema.ConclusionsOur findings demonstrate that microRNAs are altered with regional emphysema severity and modulate disease-associated gene expression networks. Furthermore, miR-638 may regulate gene expression pathways related to the oxidative stress response and aging in emphysematous lung tissue and lung fibroblasts.

Syndrome emphysème – fibrose pulmonaire : histoire naturelle de la maladie. Évolution chronologique clinique, fonctionnelle respiratoire et scanographique

The syndrome of combined basal pulmonary fibrosis and apical emphysema (CPFE) is characterised by severe dyspnoea not fully explained by pulmonary function tests that show subnormal lung volumes and expiratory flows while CT imaging reveals varying degrees of emphysema and interstitial fibrosis. A man presented with chronic obstructive pulmonary disease associated with severe emphysema. Airflow obstruction was associated with early over-inflation. Five years later he developed interstitial fibrosis with CT appearances compatible with non-specific interstitial pneumonitis. Simultaneously, the decreased expiratory flows due to emphysema had become normal and the pulmonary distension had resolved. When CPFE develops, the reduced expiratory flows and thoracic distension due to emphysema can resolve. These changes may be explained by the late development of interstitial changes, which balance the functional consequences of emphysema by an increase in elastic recoil and reduction in volume. This is the first case report that describes the evolutionary profile in a single patient. It reinforces the pathophysiological hypothesis that explains the normal pulmonary volumes and expiratory flows in CPFE.

Levels of Components of the Urokinase-Type Plasminogen Activator System are Related to Chronic Obstructive Pulmonary Disease Parenchymal Destruction and Airway Remodelling

Retrospective study to investigate levels of components of the urokinase-type plasminogen activator (uPA) system in patients with chronic obstructive pulmonary disease (COPD). Peripheral lung tissue was obtained from patients who underwent surgical resection for benign lung diseases: 16 patients with COPD, 10 controls without lung function impairment who were smokers, and 10 controls without lung function impairment who were nonsmokers. Immunohistochemical staining for uPA, uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) was quantified. Airway remodelling (collagen; detected by Sirius red staining), lung function (determined by spirometry) and emphysema (alveolar destruction; percentage of low attenuation areas on computed tomography scan) were evaluated. uPA, uPAR and PAI-1 were significantly different in structural lung cells and pulmonary macrophages from patients with COPD compared with controls. There were significant positive correlations between collagen levels and uPA and PAI-1, and between uPA and degree of emphysema. There were significant inverse correlations between lung function and uPA, uPAR and PAI-1. Correlations between components of the uPA system and lung function, small airway fibrosis and emphysema indicate a role for the uPA system in COPD.