Charles Hugo Marquette

A Randomized Study of Endobronchial Valves for Advanced Emphysema

BACKGROUND Endobronchial valves that allow air to escape from a pulmonary lobe but not enter it can induce a reduction in lobar volume that may thereby improve lung function and exercise tolerance in patients with pulmonary hyperinflation related to advanced emphysema. METHODS We compared the safety and efficacy of endobronchial-valve therapy in patients with heterogeneous emphysema versus standard medical care. Efficacy end points were percent changes in the forced expiratory volume in 1 second (FEV1) and the 6-minute walk test on intention-to-treat analysis. We assessed safety on the basis of the rate of a composite of six major complications. RESULTS Of 321 enrolled patients, 220 were randomly assigned to receive endobronchial valves (EBV group) and 101 to receive standard medical care (control group). At 6 months, there was an increase of 4.3% in the FEV1 in the EBV group (an increase of 1.0 percentage point in the percent of the predicted value), as compared with a decrease of 2.5% in the control group (a decrease of 0.9 percentage point in the percent of the predicted value). Thus, there was a mean between-group difference of 6.8% in the FEV1 (P=0.005). Roughly similar between-group differences were observed for the 6-minute walk test. At 12 months, the rate of the complications composite was 10.3% in the EBV group versus 4.6% in the control group (P=0.17). At 90 days, in the EBV group, as compared with the control group, there were increased rates of exacerbation of chronic obstructive pulmonary disease (COPD) requiring hospitalization (7.9% vs. 1.1%, P=0.03) and hemoptysis (6.1% vs. 0%, P=0.01). The rate of pneumonia in the target lobe in the EBV group was 4.2% at 12 months. Greater radiographic evidence of emphysema heterogeneity and fissure completeness was associated with an enhanced response to treatment. CONCLUSIONS Endobronchial-valve treatment for advanced heterogeneous emphysema induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation. (Funded by Pulmonx; ClinicalTrials.gov number, NCT00129584.)

Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study

BACKGROUND Talc is the most effective chemical pleurodesis agent for patients with malignant pleural effusion. However, concerns have arisen about the safety of intrapleural application of talc, after reports of development of acute respiratory distress syndrome in 1-9% of treated patients. Our aim was to establish whether use of large-particle-size talc is safe in patients with malignant pleural effusion. METHODS We did a multicentre, open-label, prospective cohort study of 558 patients with malignant pleural effusion who underwent thoracoscopy and talc poudrage with 4 g of calibrated French large-particle talc in 13 European hospitals, and one in South Africa. The primary endpoint was the occurrence of acute respiratory distress syndrome after talc pleurodesis. FINDINGS No patients developed acute respiratory distress syndrome (frequency 0%, one-sided 95% CI 0-0.54%). 11 (2%) patients died within 30 days. Additionally, seven patients had non-fatal post-thoracoscopy complications (1.2%), including one case of respiratory failure due to unexplained bilateral pneumothorax. INTERPRETATION Use of large-particle talc for pleurodesis in malignant pleural effusion is safe, and not associated with the development of acute respiratory distress syndrome.

A proposed classification system of central airway stenosis

Tracheobronchial stenosis, a serious problem in adults and children, has multiple causes and has been treated in many ways. While developing an international multicentre study to evaluate efficacy of airway stents, it was realised that no adequate description of central airway stenosis regarding type, location and degree has been published. Thus, comparing results of different treatment modalities in different centres has been difficult due to a lack of uniformity of classification. Reports are typically descriptive and precise classification schemes have not adequately addressed either for the trachea or the main bronchi. A standardised classification scheme was proposed with descriptive images and diagrams for rapid and uniform classification of central airway stenosis. The present authors’ system divides stenosis into structural and dynamic types and further classifies the disease by degree of stenosis, location and transition zone. Multiple sites can be described and each is transformed into a simple numerical scoring system prompted by a diagram, which can be easily captured for subsequent uniform analysis across sites. A pilot validation of the system, with 18 pulmonologists of varying training background, showed strong precision and agreement between observers. Such a system will enhance the ability to study the effectiveness of treatment modalities for central airway stenosis.

Lung Volume Reduction Coil Treatment vs Usual Care in Patients With Severe Emphysema: The REVOLENS Randomized Clinical Trial

IMPORTANCE Therapeutic options for severe emphysema are limited. Lung volume reduction using nitinol coils is a bronchoscopic intervention inducing regional parenchymal volume reduction and restoring lung recoil. OBJECTIVE To evaluate the efficacy, safety, cost, and cost-effectiveness of nitinol coils in treatment of severe emphysema. DESIGN, SETTING, AND PARTICIPANTS Multicenter 1:1 randomized superiority trial comparing coils with usual care at 10 university hospitals in France. Enrollment of patients with emphysema occurred from March to October 2013, with 12-month follow-up (last follow-up, December 2014). INTERVENTIONS Patients randomized to usual care (n = 50) received rehabilitation and bronchodilators with or without inhaled corticosteroids and oxygen; those randomized to bilateral coil treatment (n = 50) received usual care plus additional therapy in which approximately 10 coils per lobe were placed in 2 bilateral lobes in 2 procedures. MAIN OUTCOMES AND MEASURES The primary outcome was improvement of at least 54 m in the 6-minute walk test at 6 months (1-sided hypothesis test). Secondary outcomes included changes at 6 and 12 months in the 6-minute walk test, lung function, quality of life as assessed by St Georges Respiratory Questionnaire (range, 0-100; 0 being the best and 100 being the worst quality of life; minimal clinically important difference, ≥4), morbidity, mortality, total cost, and cost-effectiveness. RESULTS Among 100 patients, 71 men and 29 women (mean age, 62 years) were included. At 6 months, improvement of at least 54 m was observed in 18 patients (36%) in the coil group and 9 patients (18%) in the usual care group, for a between-group difference of 18% (1-sided 95% CI, 4% to ∞; P = .03). Mean between-group differences at 6 and 12 months in the coil and usual care groups were +0.09 L (95% CI, 0.05 L to ∞) (P = .001) and +0.08 L (95% CI, 0.03 L to ∞) (P = .002) for forced expiratory volume in the first second, +21 m (95% CI, -4 m to ∞) (P = .06) and +21 m (95% CI, -5 m to ∞) (P = .12) for 6-minute walk distance, and -13.4 points (95% CI, -8 points to ∞) and -10.6 points (95% CI, -5.8 points to ∞) for St Georges Respiratory Questionnaire (1-sided P < .001 for both). Within 12 months, 4 deaths occurred in the coil group and 3 in the usual care group. The mean total 1-year per-patient cost difference between groups was

From normal respiratory mucosa to epidermoid carcinoma: Expression of human mucin genes

47,908 (95% CI,

Experimental models of tracheobronchial stenoses: a useful tool for evaluating airway stents.

47,879-

A randomised trial of lung sealant versus medical therapy for advanced emphysema

48,073) (P < .001); the incremental cost-effectiveness ratio was

Protected Specimen Brush in the Assessment of Ventilator-Associated Pneumonia: Selection of a Certain Lung Segment for Bronchoscopic Sampling Is Unnecessary

782,598 per additional quality-adjusted life-year. CONCLUSIONS AND RELEVANCE In this preliminary study of patients with severe emphysema followed up for 6 months, bronchoscopic treatment with nitinol coils compared with usual care resulted in improved exercise capacity with high short-term costs. Further investigation is needed to assess durability of benefit and long-term cost implications. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01822795.

Effect of fissure integrity on lung volume reduction using a polymer sealant* in advanced emphysema

Mucous cells in the respiratory tract contribute to the maintenance of the normal epithelial cell population via mechanisms of cell proliferation and differentiation. Mucous cell hyperplasia often occurs as a basic response to injury in the tracheobronchial epithelium. These cells are also thought to be involved in the histogenesis of epidermoid metaplasia. A typical biochemical feature of these cells is mucus secretion. Aberrant glycosylation or under‐glycosylation of mucins is well known in cancer; however, the specific role played by mucin genes is at present unclear. To provide information regarding the expression of these genes in squamous metaplasia and squamous cell carcinoma, we analyzed and compared the expression of MUC1‐MUC7 genes by in situ hybridization in control respiratory mucosa and lesions associated with neoplasia (hyperplasia, metaplasia and dysplasia) and squamous cell carcinomas. MUC4 was expressed independently of mucus secretion since it was expressed weakly by basal cells and probably by ciliated cells as well as collecting ducts, epidermoid metaplasia with complete squamous cell differentiation, and most of epidermoid carcinomas even well differentiated and keratinized. In squamous metaplasia and dysplasia, MUC4 gene expression was diffuse and less intense than in normal epithelium. MUC5AC was overexpressed in dysplasia as well as in mucous cell and basal cell hyperplasia and undetectable when squamous differentiation was achieved. Int. J. Cancer 86:162–168, 2000.

Conservative treatment of tracheal rupture

BACKGROUND Stent implantation is a conservative alternative to open operation for treating benign tracheobronchial strictures. Most of the presently available stents were primarily designed for endovascular use. Their respiratory use entails a risk of iatrogenic complications. From a scientific and from an ethical point of view these risks justify preclinical evaluation of new respiratory stents in experimental models of central airway stenoses. Therefore, an attempt was made to develop such models in piglets and adult minipigs. METHODS Tracheal stenoses were obtained by creating first a segmental tracheomalacia through extramucosal resection of cartilaginous arches. The fibrous component of the stenoses was then obtained through bronchoscopic application of a caustic agent causing progressive deep mucosal and submucosal injury. Stenoses of the main bronchi were created by topical application of the caustic agent only. RESULTS These models demonstrated the typical features of benign fibromalacic tracheobronchial stenoses with constant recurrence after mechanical dilation. Preliminary experiments showed that short-term problems of tolerance of stent prototypes are easily demonstrable in these models. CONCLUSIONS These experimental models, which simulate quite realistically human diseases, offer the opportunity to perfect new tracheobronchial stents specifically designed for respiratory use and to evaluate their long-term tolerance before their use in humans.