Hugo Goulart de Oliveira

Expert Statement: Pneumothorax Associated with Endoscopic Valve Therapy for Emphysema - Potential Mechanisms, Treatment Algorithm, and Case Examples

The use of endoscopically placed unidirectional valves for the treatment of emphysema is increasing. With better patient selection, there is also an increased likelihood of complications associated with the procedure, such as postprocedural pneumothorax. There is, however, little evidence of pneumothorax management in patients with severe COPD and emphysema. This report describes an expert recommendation that has been developed to outline pneumothorax management after valve placement to inform physicians and patients of the risk-benefit profile and to assist them in decision making. Skilled and aggressive pneumothorax management is necessary in this patient population, and by following these recommendations traumatic scenarios, prolonged drainage, extended hospitalizations, and/or surgery might be avoided in many cases.

Improvement of Mycobacterium tuberculosis detection in clinical samples using DNA purified by glass matrix

Abstract A glass matrix was used to purify Mycobacterium tuberculosis DNA from clinical samples before amplification by polymerase chain reaction (PCR). The procedure was established by analysing a subset of 130 clinical samples (70 from patients with tuberculosis and 60 from patients without tuberculosis). The clinical samples included sputum, urine, cerebrospinal fluid, blood and serum. The total number of samples positive by PCR before the glass matrix step was 33 and after the glass matrix step was 58, showing that this purification step improved markedly the detection of M. tuberculosis DNA. The detection limit of the amplified DNA in agarose gels stained with ethidium bromide was 10 CFU for serum and cerebrospinal fluid and 50 CFU for sputum. Once established, the procedure was used in the analysis of 179 additional samples from 133 patients suspected of tuberculosis. In general there was an agreement between the results of PCR and clinical diagnosis for tuberculosis. In the case of sputum samples it was possible to compare the PCR and culture results. When considering all the sputum samples analysed, in general the PCR was slightly less sensitive than the culture test. However, when applied to the analysis of samples from patients suspected of tuberculosis, six samples that were culture negative were positive by PCR. Considering the confirmed results of all clinical samples analysed, the sensitivity of the method described in this work (97.4%) was much higher than culture test (45.5%). This difference was mainly due to the low sensitivity of culture test in cerebrospinal fluid, serum and blood samples. The results presented in this work indicate that the inclusion of the glass matrix step in the preparation of DNA improves the detection of M. tuberculosis in clinical samples.

Combined Bone Marrow‐Derived Mesenchymal Stromal Cell Therapy and One‐Way Endobronchial Valve Placement in Patients with Pulmonary Emphysema: A Phase I Clinical Trial

One‐way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients. However, local inflammation may result and can contribute to worsening of clinical status in these patients. We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients. This initial study sought to investigate the safety of this approach. For this purpose, a phase I, prospective, patient‐blinded, randomized, placebo‐controlled design was used. Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow‐derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one‐way EBVs. Patients were evaluated 1, 7, 30, and 90 days after therapy. All patients completed the study protocol and 90‐day follow‐up. MSC delivery did not result in acute administration‐related toxicity, serious adverse events, or death. No significant between‐group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease. Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes. However, quality‐of‐life indicators were higher in EBV + MSC compared with EBV. EBV + MSC patients presented decreased levels of circulating C‐reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores. Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy. Stem Cells Translational Medicine 2017;6:962–969

Fissure Integrity and Volume Reduction in Emphysema: A Retrospective Study

Background: One-way endobronchial valves (EBVs) relieve symptoms of emphysema, particularly in patients without collateral ventilation between the target and adjacent lobes. Pretreatment knowledge of fissure integrity could serve as an aid in indicating EBV interventions. Objective: This study aimed to investigate the relationship between software-measured lung fissure integrity and clinically relevant lung volume reduction (≥350 ml) in emphysema patients treated with one-way EBVs using a lobar exclusion strategy. Methods: Of 108 patients treated between March 2008 and July 2014, 38 had both baseline and follow-up computed tomography (CT) scans acquired following a specific protocol for quantitative CT analysis and were included in the study (total of 39 treatments, two lungs treated in 1 patient). Outcome measures were fissure integrity measured on baseline CT scans, difference between pre- and postoperative lung volume (considering the lowest measured postoperative volume), and correlation between fissure integrity and volume change. Results: Fissure integrity ≥75% correlated with volume reduction ≥350 ml (Spearman coefficient: -0.65; p < 0.01). The mean and median volume reductions were 1,223.96 ± 907.5 ml and 663 ml, respectively, for lungs with fissure integrity ≥75% (n = 31). The accuracy of fissure integrity ≥75% in predicting a volume reduction was 87.2%. The positive predictive value of fissure integrity ≥75% to predict a volume reduction ≥350 ml was 83.9%, and it was 70% for fissure integrity 75-90% and 90.5% for fissure integrity >90%. Conclusions: A target lobe volume reduction using EBVs is possible with lung fissure integrity ≥75%. For patients with fissure integrity between 75 and 90%, a further evaluation of interlobar ventilation should be performed. A clinically relevant volume reduction following treatment with EBVs is likely with any level of fissure integrity >90%.

Acurácia da mensuração do enfisema pulmonar na tomografia computadorizada: pontos importantes

Some technical aspects should be taken into consideration in order to guarantee the reliability of the assessment of pulmonary emphysema with lung computed tomography densitometry. Changes in lung density associated with variations in lungs inspiratory and expiratory levels, computed tomography slice thickness, reconstruction algorithm and type of computed tomography apparatus make tomographic comparisons more difficult in follow up studies of pulmonary emphysema. Nevertheless, quantitative computed tomography has replaced the visual assessment competing with pulmonary function tests as a sensitive method to measure pulmonary emphysema. The present review discusses technical variables of lung computed tomography and their influence on measurements of pulmonary emphysema.

Novel Silicone Stent to Treat Tracheobronchial Lesions: Results of 35 Patients

We describe a case series of 35 patients with either benign (14) or malignant (21) tracheal stenosis who were treated using a novel silicone stent, the HCPA-1, designed to prevent migration. Between March 2001 and September 2008, 13 women and 22 men received 41 HCPA-1 stents. The median duration of stenting in benign cases was 457 days (range, 4–2, 961 days). Successful stent removal with curative results was accomplished in 2 patients with tracheomalacia and 1 with post-intubation stenosis. In malignant cases, the median duration of stenting was 162 days (range, 1–1, 279 days). Five patients had tumor progression with obstruction requiring repeated laser resection, dilatation, or additional stents. Two patients died due to airway obstruction despite bronchoscopic intervention. Twelve patients with malignant lesions died with the stent in place. At the end of the study, 3 patients with malignant disease remained alive; 2 were lost to follow-up. The HCPA-1 stent proved to be safe, with no severe complications during the study period, and effective in improving quality of life with relief of dyspnea.

A Multicenter RCT of Zephyr® Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE)

Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. Methods: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the &Dgr;EBV‐SoC of subjects with a post‐bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post‐bronchodilator FEV1, 6‐minute‐walk distance, and St. Georges Respiratory Questionnaire scores. Measurements and Main Results: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a &Dgr;FEV1 greater than or equal to 15% (P < 0.001). &Dgr;EBV‐SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6‐minute‐walk distance, +39.31 m (P = 0.002); and St. Georges Respiratory Questionnaire, −7.05 points (P = 0.004). Significant &Dgr;EBV‐SoC were also observed in hyperinflation (residual volume, −522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (−0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (−1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. Conclusions: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

Non-answered questions in patients with endobronchial valve placement for lung volume reduction

Endoscopic lung volume reduction is a minimally invasive procedure performed to reduce the space occupied by the emphysemas’ lobes. This procedure has been demonstrated to be beneficial for patients with advanced chronic obstructive pulmonary disease and severe hyperinflation. The use of endobronchial valves is increasing, as well as the number of reports of adverse events. The most common complications after the procedure are a pneumothorax, bleeding, infections, the need for valve removal, and valve expulsion. We have recently treated a patient who achieved immediate left upper lobe atelectasis but developed a pneumothorax on the 6th day and near-fatal kinking of the left lower lobe bronchus. This patient had asphyctic episodes probably due to a functional left pneumonectomy. We should consider this unusual complication in patients undergoing endoscopic lung volume reduction whose condition worsens after achieving complete lobar atelectasis.

Bronchoscopic Lung Volume Reduction with Endobronchial Valves

In the past 12 years, advancements in the treatment of lung emphysema have been intrinsically linked to interventional bronchoscopy. The present chapter will focus on the most studied bronchoscopic lung volume reduction (BLVR) technique, the endobronchial valve (EBV). The definition of the ideal candidate for BLVR with EBV has evolved to include aspects of fissure integrity (≥90%) in addition to emphysema gradient >15 pp. Collateral ventilation is currently recognized as a crucial factor directly linked to lung volume reduction. Together, dynamic air trapping and the absence of collateral ventilation indicate the cases in which valve treatment is more likely to succeed. Emphysema is a complex condition, and much remains to be learned regarding pathophysiology, phenotypes, pulmonary vascular bed, interlobar airflow, exercise, nutrition, and other aspects, including the quality of sleep in emphysema patients. In addition, efforts must be made to devise interventions that underscore the biopsychosocial well-being of these patients.

Offene Fragen zur endoskopischen Lungenvolumen- reduktion mit Endobronchialventilen

Die endoskopische Lungenvolumenreduktion ist ein minimalinvasiver Eingriff bei Lungenemphysem mit dem Ziel, dass die überblähten Lungenanteile weniger Raum einnehmen. Der Nutzen dieses Verfahrens bei Patientinnen und Patienten mit fortgeschrittener chronisch-obstruktiver Lungenerkrankung und hochgradiger Überblähung ist nachgewiesen. Immer häufiger kommen dabei Endobronchialventile zum Einsatz, und immer häufiger wird auch über unerwünschte Ereignisse berichtet. Als häufigste Komplikationen nach diesem Eingriff treten Pneumothorax, Blutungen und Infektionen auf, und Ventile müssen entfernt werden oder werden ausgestoßen. Wir behandelten kürzlich einen Patienten, bei dem zunächst eine sofortige Atelektase im linken Oberlappen eintrat, dann jedoch am 6. Tag ein Pneumothorax und eine Abknickung des linken Unterlappenbronchus, die beinahe fatal verlaufen wäre. Der Patient erlitt Erstickungsanfälle, vermutlich infolge einer funktionellen linksseitigen Pneumektomie. Diese ungewöhnliche Komplikation sollte künftig bedacht werden, wenn sich der Zustand einer Patientin oder eines Patienten verschlechtert, bei dem zuvor mit einer endoskopischen Lungenvolumenreduktion eine komplette lobäre Atelektase herbeigeführt wurde. Übersetzung aus Respiration 2018;95:269-272 (DOI: 10.1159/000484252)