Advanced Emphysema Research Articles

Endobronchial Valves for Advanced Emphysema

Lung volume reduction surgery is a therapeutic option for selected patients with advanced emphysema. However, it is an invasive procedure benefitting only a selected group of patients with heterogeneous upper lobe predominant disease and limited exercise capacity. The most widely studied alternatives are endobronchial valves. Hundreds of patients worldwide have undergone endobronchial valve placement. Although short-term outcomes have been described, little is known about the long-term side effects following this treatment, and endoscopic follow-up is virtually nonexistent. The images, biopsies, and microbiologic evidence accrued from this patient are witnesses to the natural evolution of endobronchial valves in the airways and should offer a word of caution with regard to valve placement in patients with life expectancies exceeding those typical of severe chronic obstructive lung disease.

Clinical Applications of Bronchoscopic Lung Volume Reduction for Patients with Severe Emphysema

Emphysema is a category of chronic obstructive pulmonary disease characterized by chronic airflow limitation and hyperinflation. Several decades ago, it was found that the surgical resection of emphysematous lung improved lung function and the long-term survival in patients with severe advanced emphysema. However, it was associated with substantial postoperative morbidity, such as persistent air-leak and mortality. Therefore, bronchoscopic lung volume reduction (BLVR) techniques have been developed to avoid these risks associated with surgery. Of these, endobronchial valves have been subject to the largest number of clinical trials. Endobronchial valves are unidirectional valves placed in the bronchus of the most hyperinflated lobe to block regional inflation, while allowing exhalation, leading to atelectasis of the target lobe. BLVR using endobronchial valves improves lung function, exercise tolerance, and symptoms. To obtain the maximum clinical benefits, it is important to select patients who have a complete lobar fissure and heterogeneous emphysematous lung involvement. Other bronchoscopic approaches are being developed to overcome these limitations. (Korean J Med 2014;86:432-437)

Pulmonary lobe segmentation based on ridge surface sampling and shape model fitting

Performing lobe-based quantitative analysis of the lung in computed tomography (CT) scans can assist in efforts to better characterize complex diseases such as chronic obstructive pulmonary disease (COPD). While airways and vessels can help to indicate the location of lobe boundaries, segmentations of these structures are not always available, so methods to define the lobes in the absence of these structures are desirable. The authors present a fully automatic lung lobe segmentation algorithm that is effective in volumetric inspiratory and expiratory computed tomography (CT) datasets. The authors rely on ridge surface image features indicating fissure locations and a novel approach to modeling shape variation in the surfaces defining the lobe boundaries. The authors employ a particle system that efficiently samples ridge surfaces in the image domain and provides a set of candidate fissure locations based on the Hessian matrix. Following this, lobe boundary shape models generated from principal component analysis (PCA) are fit to the particles data to discriminate between fissure and nonfissure candidates. The resulting set of particle points are used to fit thin plate spline (TPS) interpolating surfaces to form the final boundaries between the lung lobes. The authors tested algorithm performance on 50 inspiratory and 50 expiratory CT scans taken from the COPDGene study. Results indicate that the authors' algorithm performs comparably to pulmonologist-generated lung lobe segmentations and can produce good results in cases with accessory fissures, incomplete fissures, advanced emphysema, and low dose acquisition protocols. Dice scores indicate that only 29 out of 500 (5.85%) lobes showed Dice scores lower than 0.9. Two different approaches for evaluating lobe boundary surface discrepancies were applied and indicate that algorithm boundary identification is most accurate in the vicinity of fissures detectable on CT. The proposed algorithm is effective for lung lobe segmentation in absence of auxiliary structures such as vessels and airways. The most challenging cases are those with mostly incomplete, absent, or near-absent fissures and in cases with poorly revealed fissures due to high image noise. However, the authors observe good performance even in the majority of these cases.

Two-Year Follow-up in Patients Treated With Emphysematous Lung Sealant for Advanced Emphysema

Endoscopic lung volume-reduction therapy for emphysema has been associated with therapeutic responses smaller in magnitude and less durable than surgical volume reduction (LVRS). Bronchoscopic emphysematous lung sealant (ELS) therapy has been shown to produce improvements in pulmonary function similar to surgery at 1 year. This case series summarizes safety and efficacy data of all patients from the initial ELS study out to 2 years. Between 1 and 2 years, there were three all-cause adverse events requiring hospitalization. One patient went on to successful lung transplant. Improvements relative to baseline in spirometry (change in FEV1: + 14.3 ± 33.1%; change in FVC: + 5.8 ± 23.2%) and diffusing capacity (change in diffusing capacity of the lung for carbon monoxide: + 10.6 ± 20.6%) were observed at 2 years. An exponential model fit to FEV₁ data at 6, 12, 18, and 24 months predicted improvements from a baseline of > 5% out to 4.1 years, similar to what has been reported following surgery. This report confirms long-term safety and efficacy following ELS therapy in advanced emphysema. Studies in a larger cohort are needed to define the role of ELS therapy in the treatment algorithm of patients with this condition.

The Glutathione Peroxidase 1–Protein Tyrosine Phosphatase 1B–Protein Phosphatase 2A Axis. A Key Determinant of Airway Inflammation and Alveolar Destruction

Protein phosphatase-2A (PP2A) is a primary serine-threonine phosphatase that modulates inflammatory responses in asthma and chronic obstructive pulmonary disease (COPD). Despite its importance, the mechanisms that regulate lung PP2A activity remain to be determined. The redox-sensitive enzyme protein tyrosine phosphatase-1B (PTP1B) activates PP2A by dephosphorylating the catalytic subunit of the protein at tyrosine 307. This study aimed to identify how the interaction between the intracellular antioxidant glutathione peroxidase-1 (GPx-1) and PTP1B affected lung PP2A activity and airway inflammation. Experiments using gene silencing techniques in mouse lung or human small airway epithelial cells determined that knocking down PTP1B expression blocked GPx-1's activation of PP2A and negated the anti-inflammatory effects of GPx-1 protein in the lung. Similarly, the expression of human GPx-1 in transgenic mice significantly increased PP2A and PTP1B activities and prevented chronic cigarette smoke-induced airway inflammation and alveolar destruction. GPx-1 knockout mice, however, exhibited an exaggerated emphysema phenotype, correlating with a nonresponsive PP2A pathway. Importantly, GPx-1-PTP1B-PP2A signaling becomes inactivated in advanced lung disease. Indeed, PTP1B protein was oxidized in the lungs of subjects with advanced emphysema, and cigarette smoke did not increase GPx-1 or PTP1B activity within epithelial cells isolated from subjects with COPD, unlike samples of healthy lung epithelial cells. In conclusion, these findings establish that the GPx-1-PTP1B-PP2A axis plays a critical role in countering the inflammatory and proteolytic responses that result in lung-tissue destruction in response to cigarette smoke exposure.

Lung emphysema treated successfully using volume reduction with lung sealant (AeriSeal®)

Abstract Emphysema is a progressive and irreversible disease for which there is no cure to date. Endoscopic lung volume reduction with valve implantation or using lung sealant is a treatment option for patients with severe emphysema. A 60-year-old ex-smoker (80 pack years) referred to our center because of severe lung emphysema with progressive worsening of the obstructive ventilator pattern and clinical condition. By our patient we detected collateral channels by using the Chartis system®, which allow airflow into the target lobe and prevent atelectasis and significant lung volume reduction. Thus, we decided to treat the advanced emphysema of our patient with endoscopic volume reduction using lung sealant (AeriSeal®). The foam of lung sealant AeriSeal® is instilled into the peripheral airways and alveoli where it polymerizes and functions as tissue glue, forming a film of material on the lung surface that seals the target region to cause durable absorption atelectasis. Over a period of 16 weeks, the air within the sealed region was absorbed. The follow- up evaluation of this patient showed improved lung function (increased FEV 1, and a reduction of TLC and RV) with improved quality of life. Correlation between changes in primary and secondary outcome measures in the lung function parameters and 6- minute-walking test before and after the application of AeriSealant revealed significant reduction of hyperinflation and improvement both in the flow rates and physical capacity of our patient.

Endobronchial Valve-Induced Pneumatocele: A Case Report

We report a 75-year old female patient with advanced emphysema. After endoscopic lung volume reduction with endobronchial valves (EBV), a huge pneumatocele has occured and resolved spontaneously within a few weeks. Albeit rare, pneumatoceles should be considered in patients with relapsing dyspnoe after EBV treatment.

PULMONARY FUNCTION CHANGES AFTER BRONCHOSCOPIC BIOLOGICAL LUNG VOLUME REDUCTION THERAPY USING AUTOULOGOUS BLOOD

Background: Bronchoscopic lung volume reduction (BLVR) using biological agents is one of the new alternatives to lung volume reduction surgery. Objectives: To evaluate the potential efficacy of bronchoscopic biological lung volume reduction using autologous blood injection in pulmonary emphysema patients. Methods: 7 male patients were enrolled in the study. After determining the targeted emphysematous segment by high resolution computerized tomography (HRCT), 30 ml autologous blood was injected via balloon catheter over 10 to15 seconds into the targeted segment and left in position for 3-6 minutes allowing time for blood to coagulate. The bronchoscope was then repositioned at the following targeted segment. Changes in residual volume (RV), residual volume to total lung capacity ratio (RV/TLC), forced expiratory volume in one second (FEV1) and forced expiratory volume to forced vital capacity ratio (FEV1/FVC) were evaluated at 12-week post procedure as well as for complications. Results: At 12-week post procedure there was statistically significant reduction in RV/TLC (p = 0.038). FEV1 significantly increased (p = 0.018). In addition, there was significant improvement in FEV1/FVC % (p = 0.003). All cases tolerated the procedure with no mortality. There was one case that developed pneumonia at the same side of intervention, and two cases developed mild haemoptysis (blood streaked sputum). There was no life threatening complications e.g (pneumothorax, pulmonary embolism, cardiac ischaemia or myocardial infarction) occurred htoughout the study. Conclusion: Bronchoscopic lung volume reduction using autologous blood injection could be an effective, cheap and relatively safe method to treat advanced emphysema in comparison to other agents used in the clinical trials. Keywords: Emphysema; Bronchoscopy; Lung volume reduction.

Severe Chronic Bronchitis in Advanced Emphysema Increases Mortality and Hospitalizations

Background: Chronic bronchitis in COPD has been associated with an increased exacerbation rate, more hospitalizations, and an accelerated decline in lung function. The clinical characteristics of patients with advanced emphysema and chronic bronchitis have not been well described. Methods: Patients randomized to medical therapy in the National Emphysema Treatment Trial were grouped based on their reports of cough and phlegm on the St. George's Respiratory Questionnaire(SGRQ) at baseline: chronic bronchitis(CB+) and no chronic bronchitis(CB–). The patients were similarly categorized into severe chronic bronchitis(SCB+) or no severe chronic bronchitis (SCB–) based on the above definition plus report of chest trouble. Kaplan-Meier survival analysis was used to determine the relationships between chronic bronchitis and severe chronic bronchitis and survival and time to hospitalization. Lung function and SGRQ scores over time were compared between groups. Results: The CB+(N = 234; 38%) and CB- groups(N = 376; 62%) had similar survival (median 60.8 versus 65.7 months, p = 0.19) and time to hospitalization (median 26.9 versus 24.9 months, p = 0.84). The SCB+ group(N = 74; 12%) had worse survival (median 47.7 versus 65.7 months, p = 0.02) and shorter time to hospitalization (median 18.5 versus 26.7 months, p = 0.02) than the SCB- group (N = 536; 88%). Mortality and hospitalization rates were not increased when chest trouble was analyzed by itself. The CB+ and CB–groups had similar lung function and SGRQ scores over time. The SCB+ and SCB–groups had similar lung function over time, but the SCB+ group had significantly worse SGRQ scores. Conclusions: Severe chronic bronchitis is associated with worse survival, shorter time to hospitalization, and worse health-related quality of life.

Target lobe volume reduction and COPD outcome measures after endobronchial valve therapy

Endobronchial valve (EBV) therapy may be associated with improvements in chronic obstructive pulmonary disease-related outcomes and may therefore be linked to improvements in the body mass index, airflow obstruction, dyspnoea, exercise capacity (BODE) index. Data from 416 patients with advanced emphysema and hyperinflation across Europe and USA, who were randomised to EBV (n=284) or conservative therapy (n=132) were analysed. Quantitative image analysis was used to compare the volume of the targeted lobe at baseline and at 6 months to determine target lobe volume reduction (TLVR). 44% of patients receiving EBV therapy (versus 24.7% of controls) had clinically significant improvements in the BODE index (p<0.001). BODE index was significantly reduced by mean ± sd 1.4 ± 1.8, 0.2 ± 1.3 and 0.1 ± 1.3 points in patients with TLVR >50%, 20%-50% and <20%, respectively (intergroup differences p<0.001), but increased by 0.3 ± 1.2 points in controls. Changes in BODE were predicted by baseline BODE and correlated significantly with lobar exclusion and lung volumes at 6 months. A greater proportion of patients in the treatment group than in the control group achieved a clinically meaningful improvement in BODE index; however, the likelihood of benefit was less than half in both groups. Patients in whom TLVR was obtained had greater improvements in clinical outcomes.

Emphysematous Lung Sealant Therapy Attenuates the Chronic Inflammatory State of Advanced Emphysema

Background: Patients with advanced emphysema often have elevated markers of systemic inflammation, a phenotype associated with greater clinical compromise and increased mortality. We hypothesized that endoscopic lung volume reduction using emphysematous lung sealant therapy might attenuate the state of inflammation in patients with advanced emphysema by eliminating damaged tissue; similar to what has previously been reported following lung volume reduction surgery. Methods: To explore this hypothesis, serum C-reactive protein (CRP) was measured at baseline, 12, 24 and 48 weeks following ELVR therapy with Emphysematous Lung Sealant (ELS) at 5 centers participating in clinical trial NCT00884962 (www.clinicaltrials.gov). Results were correlated with post-treatment changes in BODE Index, systemic white cell count, and vital status out to 3 years. Results: Baseline CRP for the 29 patient cohort was elevated (5.3 ± 8.7 mg/L) compared to normal. Sixteen (16) of 29 patients (55%) had serum levels above the “high risk threshold” (3 mg/L). ELS therapy was associated with a transient increase in CRP followed by a progressive decline. At 48 weeks, the CRP level of the cohort had decreased to 2.2 ± 3.2 mg/L (p=0.041); only 9 of 29 (31%) showed persistently elevation. 3 years post treatment, 28 of 29 patients were alive (3.4% mortality), while 24 and 36 month mortality for this cohort predicted from baseline BODE Index was 12% and 35% respectively. Conclusions: ELS therapy reduces chronic inflammation in patients with advanced emphysema, manifest as a reduction in CRP. Model predictions suggest this is associated with a reduction in long term mortality risk. Larger prospective studies are needed to further evaluate this question.

Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years

BackgroundChronic obstructive pulmonary disease is a major inflammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without significant pulmonary fibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated. ObjectiveThis article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells. MethodsFour patients with advanced pulmonary emphysema were submitted to autologous infusion of bone marrow mononuclear cells. Follow-ups were performed by spirometry up to 3 years after the procedure. ResultsThe results showed that autologous cell therapy in patients having chronic obstructive pulmonary disease is a safe procedure and free of adverse effects. There was an improvement in laboratory parameters (spirometry) and a slowing down in the process of pathological degeneration. Also, patients reported improvements in the clinical condition and quality of life. ConclusionsDespite being in the initial stage and in spite of the small sample, the results of the clinical protocol of cell therapy in advanced pulmonary emphysema as proposed in this study, open new therapeutic perspectives in chronic obstructive pulmonary disease. It is worth emphasizing that this study corresponds to the first study in the literature that reports a change in the natural history of pulmonary emphysema after the use of cell therapy with a pool of bone marrow mononuclear cells.

Treatment of Severe Advanced Emphysema With Volume Reduction Using Lung Sealant

Emphysema is a progressive and irreversible disease for which there is no cure to date. The patients experience debilitating shortness of breath with repetitive exacerbations and poor quality of daily life. At present, patients with severe emphysema have limited treatment options. Endoscopic lung-volume reduction with valve implantation or using lung sealant is a treatment option for patients with severe emphysema. By our patients, we detected collateral channels, which allow airflow into the target lobe and prevent atelectasis and significant lung-volume reduction. Thus, we decided to treat the advanced emphysema of our patients with endoscopic volume reduction using lung sealant (AeriSeal). Lung-volume reduction surgery reduces hyperinflation and improves lung function by removal of emphysematous lung tissue. However, lung-volume reduction surgery is also associated with significant short-term morbidity and mortality. Results from recently published Endobronchial Valve for Emphysema Palliation Trail (VENT) and Exhale Airway Stents for Emphysema (EASE) trial showed that treatment was substantially less effective and did not consistently reduce hyperinflation or improve lung function mostly likely due to collateral ventilation present in majority of patients. There is a volume reduction therapy in case of detection of collateral flow; use of a lung sealant is a possible alternative. A novel endoscopic tissue sealant (AeriSeal; Aeris Therapeutics, Woburn, MA) is a liquid foam sealant that collapses hyperinflated lung areas destroyed by emphysema. The foam of lung sealant AeriSeal is instilled into the peripheral airways and alveoli where it polymerizes and functions as tissue glue, forming a film of material on the lung surface that seals the target region to cause durable absorption atelectasis. Two patients with advanced emphysema and hyperinflation underwent endoscopic volume reduction with endoscopic tissue sealant (AeriSeal); collateral flow was confirmed by using the Chartis System. Both patients experienced transient fever, malaise, chest discomfort, and shortness of breath for about 3 days after the procedure. Over a period of 8 and 12 weeks, the air within the sealed region was absorbed and the treated area showed atelectasis on computed tomography scan. The follow-up evaluations of those 2 patients showed improved lung function (increased FEV1, and a reduction of TLC and RV) with improved quality of life of both patients. Correlation and comparisons between changes in primary and secondary outcome measures in the lung function parameters and 6-minute walking test before and after the application of AeriSealant revealed significant reduction of hyperinflation and improvement both in the flow rates and physical capacity of our patients.

Comment on: Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years

Stem cells are undifferentiated cells present in the tissues of embryos, fetuses and adults that give rise to differentiated cells. The major characteristics of stem cells are the ability to proliferate extensively (self-renewal capacity) even from a single cell (clonality), and the ability to differentiate into different cell types (potency)(1). The idea of organ regeneration is very old in the history of mankind, as can be concluded by myths such as that of Prometheus, the Greek titan punished by Zeus to have part of his liver eaten by an eagle everyday which then regenerates. Cell therapy has now been investigated in almost every degenerative disorder. Mesenchymal stem cells are the most extensively evaluated cells for clinical cell-based therapy(2). Promising results have already been described in several diseases, such as diabetes mellitus, chronic myeloid leukemia, cirrhosis, pulmonary fibrosis, Crohn's disease, heart failure, and nervous system disorders(3). The lung is a complex organ composed of more than 40 different types of cells. Its primary function is gas exchange and, for this reason, it could be defined as being composed by alveoli surrounded by a capillary network. Lung disease is one of the main causes of death in the world. Several toxic compounds contained in air pollution, cigarette smoke, and pathogens can reach the alveoli and damage alveolar epithelial cells as well as bronchial epithelial cells. Damaged epithelia should be repaired but lung cell turnover is slow compared to other tissues and organs(4). The lung matrix is also important. Unless the lung structure is destroyed, damaged alveolar epithelia can be replaced with progenitor cells that migrate to the injured area(5). Chronic obstructive pulmonary disease (COPD) is a common disease. It is characterized by progressive airflow limitations caused by chronic small airway disease and lung parenchymal destruction (emphysema), resulting in chronic respiratory failure. Several protocols using mesenchymal stem cells in COPD have been described, including in phase II clinical trials(6). Endothelial progenitor cells are another candidate for cell therapy in COPD due to their capacity of endothelia repair(7). In a paper in the current issue of the Revista Brasileira de Hematologia e Hemoterapia, Stessuk et al. provide the first Brazilian description of the follow-up of up to 3 years of COPD patients with advanced pulmonary emphysema(8). The follow-up was performed after the beginning of a phase I clinical trial with the autologous infusion of bone marrow mononuclear cells. In spite of the small number of patients enrolled in this protocol, the procedure was shown to be safe. Moreover, disease progression apparently slowed down as shown by laboratory and clinical parameters. The results are really opening good perspectives for the use of bone marrow mononuclear cells in the clinical treatment of COPD.

Quantitative lung SPECT applied on simulated early COPD and humans with advanced COPD

BackgroundReduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), reflected as inhomogeneities in the single-photon emission computed tomography (SPECT) lung image, is correlated to disease advancement. An analysis method for measuring these inhomogeneities is proposed in this work. The first aim was to develop a quantitative analysis method that could discriminate between Monte Carlo simulated normal and COPD lung SPECT images. A second aim was to evaluate the ability of the present method to discriminate between human subjects with advanced COPD and healthy volunteers.MethodsIn the simulated COPD study, different activity distributions in the lungs were created to mimic the healthy lung (normal) and different levels of COPD. Gamma camera projections were Monte Carlo simulated, representing clinically acquired projections of a patient who had inhaled 125 MBq 99mTc-Technegas followed by a 10-min SPECT examination. Reconstructions were made with iterative ordered subset expectation maximisation. The coefficient of variance (CV) was calculated for small overlapping volumes covering the 3D reconstructed activity distribution. A CV threshold value (CVT) was calculated as the modal value of the CV distribution of the simulated normal. The area under the distribution curve (AUC), for CV values greater than CVT, AUC(CVT), was then calculated. Moreover, five patients with advanced emphysema and five healthy volunteers inhaled approximately 75 MBq 99mTc-Technegas immediately before the 20-min SPECT acquisition. In the human study, CVT was based on the mean CV distribution of the five healthy volunteers.ResultsA significant difference (p < 0.001) was found between the Monte-Carlo simulated normal and COPD lung SPECT examinations. The present method identified a total reduction of ventilation of approximately 5%, not visible to the human eye in the reconstructed image. In humans the same method clearly discriminated between the five healthy volunteers and five patients with advanced COPD (p < 0.05).ConclusionsWhile our results are promising, the potential of the AUC(CVT) method to detect less advanced COPD in patients needs further clinical studies.

Severe Emphysema Treated by Endoscopic Bronchial Volume Reduction with Lung Sealant (AeriSeal)

Endoscopic lung volume reduction using lung sealant is a very new and innovative treatment option for patients with severe progressive and irreversible lung emphysema. A 55-year-old ex-smoker (60 pack years) referred to our center because of severe lung emphysema with progressive worsening of the obstructive ventilator pattern and clinical condition. We detected collateral channels of this patient by using the Chartis system. Therefore, we decided to treat the advanced emphysema of our patient with endoscopic volume reduction using lung sealant (AeriSeal). The foam of lung sealant AeriSeal is instilled into the peripheral airways and alveoli where it polymerizes and functions as tissue glue on the lung surface in order to seal the target region to cause durable irreversible absorption atelectasis. The follow-up evaluation 12 weeks later showed improved lung function (increased FEV 1/partial oxygen pressure/peripheral oxygen saturation and a reduction of TLC and RV) with improved quality of life. Correlation between changes in primary and secondary outcome measures in the lung function parameters and 6-minute-walking test before and 12 weeks after the application of lung sealant revealed significant reduction of hyperinflation and improvement both in the flow rates and in the physical capability of this patient.

Bilateral Endoscopic Sealant Lung Volume Reduction Therapy for Advanced Emphysema

A clinical study was performed to assess the safety and efficacy of bilateral AeriSeal Emphysematous Lung Sealant System (ELS) treatment in patients with advanced emphysema out to 1 year. Twenty patients received treatment at four subsegments, two in each upper lobe. Tenhad upper lobe disease, and 10 had homogeneous disease. Treatments were administered under moderate sedation. Efficacy was assessed at 3, 6, and 12 months. Procedure times were short (15.2 ± 9.6 min), and hospital length of stay averaged 1.1 days. The study was successful in reaching its primary end point of a reduction at 3 months in upper lobe lung volume assessed by quantitative CT scan analysis ( - 895 ± 484 mL, P < .001). Treatment was associated with improvements in spirometry ( Δ FEV 1 at 6 months = 31.2% ± 36.6%, 12 months = 25.0% ± 33.4%), gas trapping ( Δ residual volume/total lung capacity at 6 months = 2 7.2% 12.7%, 12 months = - 10.9% 14.0%), diffusing capacity of lung for carbonmonoxide (6 months = 12.7% ± 16.4%, 12 months = 12.3% ± 21.1%), symptom scores ( Δ Medical Research Council dyspnea score at 6 months = median 0, range - 2 to 1, 12 months = median - 1, range - 3 to 0), and health-related quality of life ( Δ St. George Respiratory Questionnaire at 6 months = 8.0 ± 17.2 U, 12 months = 7.0 ± 15.8 U). There was one serious procedural complication and seven all-cause significant respiratory adverse events over 17 patient-years of follow-up. Bilateral ELS treatment administered under conscious sedation in patients with advanced emphysema is associated with short procedure time and length of hospital stay and produces physiologic and functional improvement out to 1 year.

Longitudinal study of spatially heterogeneous emphysema progression in current smokers with chronic obstructive pulmonary disease.

BackgroundCigarette smoke is the main risk factor for emphysema, which is a key pathology in chronic obstructive pulmonary disease (COPD). Low attenuation areas (LAA) in computed tomography (CT) images reflect emphysema, and the cumulative size distribution of LAA clusters follows a power law characterized by the exponent D. This property of LAA clusters can be explained by model simulation, where mechanical force breaks alveolar walls causing local heterogeneous lung tissue destruction. However, a longitudinal CT study has not investigated whether continuous smoking causes the spatially heterogeneous progression of emphysema.MethodsWe measured annual changes in ratios of LAA (LAA%), D and numbers of LAA clusters (LAN) in CT images acquired at intervals of ≥3 years from 22 current and 31 former smokers with COPD to assess emphysema progression. We constructed model simulations using CT images to morphologically interpret changes in current smokers.ResultsD was decreased in current and former smokers, whereas LAA% and LAN were increased only in current smokers. The annual changes in LAA%, D, and LAN were greater in current, than in former smokers (1.03 vs. 0.37%, p = 0.008; −0.045 vs. −0.01, p = 0.004; 13.9 vs. 1.1, p = 0.007, respectively). When LAA% increased in model simulations, the coalescence of neighboring LAA clusters decreased D, but the combination of changes in D and LAN in current smokers could not be explained by the homogeneous emphysema progression model despite cluster coalescence. Conversely, a model in which LAAs heterogeneously increased and LAA clusters merged somewhat in relatively advanced emphysematous regions could reflect actual changes.ConclusionsSusceptibility to parenchymal destruction induced by continuous smoking is not uniform over the lung, but might be higher in local regions of relatively advanced emphysema. These could result in the spatially heterogeneous progression of emphysema in current smokers.

Lung Volume Reduction Surgery After Lung Transplantation for Emphysema—Chronic Obstructive Pulmonary Disease

Lung Volume Reduction Surgery (LVRS) has become a palliative treatment for patients with advanced emphysema and disabling dyspnea. After single lung transplantation in chronic obstructive pulmonary disease, LVRS may be indicated to improve graft dysfunction caused by native lung hyperinflation compressing the grafted lung. This common complication is the subject of our study, which showed LVRS to be helpful to manage this situation. We performed an observational retrospective and descriptive study using the data of 293 patients transplanted in our center between January 1996 and October 2011. Some of the patients who underwent a single lung transplantation developed native lung hyperinflation years after the transplantation, interfering with respiratory function due to graft compression.

Multicentre European study for the treatment of advanced emphysema with bronchial valves

This multicentre, blinded, sham-controlled study was performed to assess the safety and effectiveness of bronchial valve therapy using a bilateral upper lobe treatment approach without the goal of lobar atelectasis. Patients with upper lobe predominant severe emphysema were randomised to bronchoscopy with (n = 37) or without (n = 36) IBV Valves for a 3-month blinded phase. A positive responder was defined as having both a ≥ 4-point improvement in St George's Respiratory Questionnaire (SGRQ) and a lobar volume shift as measured by quantitative computed tomography. At 3 months, there were eight (24%) positive responders in the treated group versus none (0%) in the control group (p = 0.002). Also, there was a significant shift in volume in the treated group from the upper lobes (mean ± SD -7.3 ± 9.0%) to the non-treated lobes (6.7 ± 14.5%), with minimal change in the control group (p<0.05). Mean SGRQ total score improved in both groups (treatment: -4.3 ± 16.2; control: -3.6 ± 10.7). The procedure and devices were well tolerated and there were no differences in adverse events reported in the treatment and control groups. Treatment with bronchial valves without complete lobar occlusion in both upper lobes was safe, but not effective in the majority of patients.