Efficacy and safety of the Spiration Valve System™ for the treatment of severe emphysema in patients with Alpha-1 antitrypsin deficiency (EMPROVE).

OBJECTIVES: Alpha-1 antitrypsin deficiency (AATD) is a hereditary condition associated with emphysema. This study analyzed the efficacy and safety of Spiration Valve System TM (SVS) among AATD patients with severe emphysema. METHODS: This multicenter prospective study included 20 patients demonstrating AATD as assessed by quantitative levels of AAT and genotype containing two ZZ alleles. Most diseased lobe based on high resolution computed tomography was selected for treatment with endobronchial SVS. The change from baseline in forced expiratory volume in 1 s (FEV1) at 6 months (Primary outcome) and at 12 months, quality-of-life (QoL) measured by St. George's Respiratory Questionnaire (SGRQ) as health status, dyspnea scale measured by mMRC, Chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), 36-item Short Form Health Survey (SF-36) physical component summary (PCS) and safety were assessed. RESULTS: Lung function (FEV1) significantly improved at 6 months (P = 0.02); but did not reach statistical significance at 12 months (P = 0.22). Significant improvement was observed in dyspnea (at all time points), QoL measures (3, 6, and 12 months), CAT score and PCS of SF-36 (1, 3 and 6 months). Response rates based on minimal clinically important difference reached 50-80% for all variables. Overall, 4.4 valves/patient were used to isolate the target lobe, with a mean procedure time of 20.3 min. Serious adverse events included COPD exacerbations (5%), pneumonia (10%), pneumothorax (15%) and death (5%), occurring within first three months. CONCLUSION: SVS endobronchial valve treatment showed improvement in lung function, dyspnea, and QoL in AATD patients with severe emphysema.

Sustained Clinical Benefits of Spiration Valve System in Patients with Severe Emphysema: 24-Month Follow-Up of EMPROVE.

Rationale: Follow-up of patients with emphysema treated with endobronchial valves is limited to 3-12 months after treatment in prior reports. To date, no comparative data exist between treatment and control subjects with a longer follow-up. Objectives: To assess the durability of the Spiration Valve System (SVS) in patients with severe heterogeneous emphysema over a 24-month period. Methods: EMPROVE, a multicenter randomized controlled trial, presents a rigorous comparison between treatment and control groups for up to 24 months. Lung function, respiratory symptoms, and quality-of-life (QOL) measures were assessed. Results: A significant improvement in forced expiratory volume in 1 second was maintained at 24 months in the SVS treatment group versus the control group. Similarly, significant improvements were maintained in several QOL measures, including the St. George's Respiratory Questionnaire and the COPD Assessment Test. Patients in the SVS treatment group experienced significantly less dyspnea than those in the control group, as indicated by the modified Medical Research Council dyspnea scale score. Adverse events at 24 months did not significantly differ between the SVS treatment and control groups. Acute chronic obstructive pulmonary disease exacerbation rates in the SVS treatment and control groups were 13.7% (14 of 102) and 15.6% (7 of 45), respectively. Pneumothorax rates in the SVS treatment and control groups were 1.0% (1 of 102) and 0.0% (0 of 45), respectively. Conclusions: SVS treatment resulted in statistically significant and clinically meaningful durable improvements in lung function, respiratory symptoms, and QOL, as well as a statistically significant reduction in dyspnea, for at least 24 months while maintaining an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy: A Prospective Multi-Centre Agreement Clinical Trial (CAN-ICE).

Rationale: Transbronchial cryobiopsy (TBCB) for the diagnosis of interstitial lung disease (ILD) has shown promising results, but prospective studies with matched surgical lung biopsy (SLB) have yielded conflicting results. Objectives: We aimed to assess within- and between-center diagnostic agreement between TBCB and SLB at both the histopathologic and multidisciplinary discussion (MDD) levels in patients with diffuse ILD. Methods: In a multicenter prospective study, we performed matched TBCB and SLB in patients referred for SLB. After a blinded review by three pulmonary pathologists, all cases were reviewed by three independent ILD teams in an MDD. MDD was performed first with TBCB, then with SLB in a second session. Within-center and between-center diagnostic agreement was evaluated using percentages and correlation coefficients. Measurements and Main Results: Twenty patients were recruited and underwent contemporaneous TBCB and SLB. Within-center diagnostic agreement between TBCB-MDD and SLB-MDD was reached in 37 of the 60 (61.7%) paired observations, resulting in a Cohen's κ value of 0.46 (95% confidence interval [CI], 0.29-0.63). Diagnostic agreement increased among high-confidence or definitive diagnoses on TBCB-MDD (21 of 29 [72.4%]), but not significantly, and was more likely among cases with SLB-MDD diagnoses of idiopathic pulmonary fibrosis than fibrotic hypersensitivity pneumonitis (13 of 16 [81.2%] vs. 16 of 31 [51.6%]; P = 0.047). Between-center agreement for cases was markedly higher for SLB-MDD (κ = 0.71 [95% CI, 0.52-0.89]) than TBCB-MDD (κ = 0.29 [95% CI, 0.09-0.49]). Conclusions: This study demonstrated moderate TBCB-MDD and SLB-MDD diagnostic agreement for ILD, while between-center agreement was fair for TBCB-MDD and substantial for SLB-MDD. Clinical trial registered with www.clinicaltrials.gov (NCT02235779).

A Rare Complication: Development of an Aspergilloma after Endobronchial Coil Placement in a COPD Patient.

Endobronchial coils are a relatively novel endoscopic lung volume reduction modality that aims to increase functional capacity in chronic obstructive pulmonary disease (COPD) patients. Two major trials have studied the safety and efficacy of this therapy, but long-term safety has not been studied. Adverse events reported are mainly periprocedural pneumothoraces and early bacterial infectious complications. We report the case of a patient with severe emphysema (Global Initiative for Chronic Obstructive Lung Disease stage IV COPD) who developed endobronchial coil-associated aspergillomas 3 years after coil placement.

Predictors of Response to Endobronchial Coil Therapy in Patients With Advanced Emphysema.

BACKGROUND: The Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) trial reported improvements in quality of life, pulmonary function, and exercise performance following endobronchial coil treatment. OBJECTIVES: The purpose of this post hoc analysis was to identify baseline predictors, including quantitative CT measures, that identify patients most likely to significantly benefit from endobronchial coil therapy. METHODS: Quantitative CT analysis by an independent radiology laboratory and a qualitative evaluation by five blinded experts of the baseline thoracic CT imaging were performed. Univariate and multivariate logistic regression analyses were performed to elucidate characteristics associated with clinical response. RESULTS: In total, 125 patients underwent coil treatment and had evaluable 12-month follow-up results. Of these, 78 patients received treatment of lobes with the highest emphysematous destruction determined by quantitative CT analysis (quantitative visual match [QVM]+), and 47 received treatment in at least one lobe that was not the most destroyed (QVM-). From the 78 patients with QVM+ treatment, a subgroup of 50 patients (64%) was identified with baseline residual volume > 200% predicted, emphysema score > 20% low attenuation area, and absence of airway disease. In this subgroup, greater lobar residual volume reduction in the treated lobes was achieved, which was associated with significant mean ± SE improvement in FEV1 (15.2 ± 3.1%), St. George's Respiratory Questionnaire (-12 ± 2 points), and residual volume (-0.57 ± 0.13 L). DISCUSSION: This post hoc analysis found that both significant hyperinflation (residual volume ≥ 200% predicted) and CT analysis are critical for patient selection and treatment planning for endobronchial coil therapy. Quantitative CT analysis is important to identify optimal lobar treatment and to exclude patients with insufficient emphysema (< 20% low attenuation area), whereas visual assessment identifies patients with signs of airway disease associated with worse outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01608490; URL: www.clinicaltrials.gov.

Initial Clinical Experience With a Flexible Peripheral 21-G Needle Device.

BACKGROUND: Bronchoscopic techniques can be used to safely sample peripheral lung nodules (PLN), and transbronchial needle aspiration (TBNA) can further increase the diagnostic yield. Current needle devices not necessarily designed for this indication have limitations. We report our initial experience with a new flexible nitinol peripheral TBNA needle specifically designed for such sampling. METHODS: Retrospective case review describing the first clinical cases performed with a commercially available 21-G peripheral TBNA device in 4 centers. RESULTS: Eleven different operators performed 40 procedures for PLNs of a mean size of 35.1 mm (±18), and located 18.8 mm (±18.8) from the pleural surface, with 50% of them being present in the upper lobes. Bronchoscopists rated the use of the needle as good or excellent for reaching the PLN in 27/30 (90%) of cases. The TBNA sample was diagnostic in 18/40 cases (45%) overall and in 18/28 (64.3%) of cases where a diagnosis on bronchoscopy was possible. No episode of pneumothorax, significant bleeding, hypoxemia, escalation of care, or other complications were noted. CONCLUSION: Our initial experience with a novel peripheral TBNA device appears safe and effective, and may offer technical advantages over other available devices. Additional studies will be required to confirm the role of this device in the approach to bronchoscopic sampling of parenchymal lung nodules.

Influence of trainee involvement on procedural characteristics for linear endobronchial ultrasound.

BACKGROUND: Linear endobronchial ultrasound (EBUS) is a safe and effective method for the diagnostic sampling of mediastinal lymph nodes. However, there is a learning curve associated with the procedure and operator experience influences diagnostic yield. We sought to determine if trainee involvement during EBUS influences procedural characteristics, complication rate, and diagnostic yield. METHODS: We performed a retrospective analysis of 220 subjects who underwent an EBUS procedure at our center from December 2012 to June 2013. Procedures were performed by six different interventional pulmonologists with substantial experience with EBUS or by a trainee under their direct supervision. Procedural characteristics and complications were recorded. Diagnostic yield and specimen adequacy were compared between groups. RESULTS: EBUS was performed in 220 patients with a trainee involved (n = 116) or by staff physician alone (n = 104). Patient characteristics, and the number and size of lymph node stations sampled were similar. EBUS duration was longer (16.0 vs. 13.7 minutes; P = 0.002) and the total dose of lidocaine used was higher (322.3 vs. 304.2 mg; P = 0.045) when a trainee was involved. The rate of adequate specimens sampled was comparable between the groups (92.0 vs. 92.0%; P = 0.60). Diagnostic yield was lower when a trainee was involved in the EBUS procedure (52.6 vs. 68.3%; P = 0.02). CONCLUSION: Trainee involvement significantly increased EBUS duration and the dose of local anesthesia used for the procedure. Diagnostic yield was lower when a trainee was involved. Factors accounting for this difference in yield, despite adequate samples being obtained, warrant further investigation.

Approach to Hemoptysis in the Modern Era.

Hemoptysis is a frequent manifestation of a wide variety of diseases, with mild to life-threatening presentations. The diagnostic workup and the management of severe hemoptysis are often challenging. Advances in endoscopic techniques have led to different new therapeutic approaches. Cold saline, vasoconstrictive and antifibrinolytic agents, oxidized regenerated cellulose, biocompatible glue, laser photocoagulation, argon plasma coagulation, and endobronchial stents and valves are amongst the tools available to the bronchoscopist. In this article, we review the evidence regarding the definition, etiology, diagnostic modalities, and treatment of severe hemoptysis in the modern era with emphasis on bronchoscopic techniques.

Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial.

IMPORTANCE: Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. OBJECTIVE: To determine the effectiveness and safety of endobronchial coil treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. INTERVENTIONS: Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. MAIN OUTCOMES AND MEASURES: The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St George's Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. RESULTS: Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs -7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St George's Respiratory Questionnaire score improved -8.9 points (97.5% CI, -∞ to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. CONCLUSIONS AND RELEVANCE: Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01608490.

Evaluation of Pulmonary Nodules Using the Spyglass Direct Visualization System Combined With Radial Endobronchial Ultrasound: A Clinical Feasibility Study.

BACKGROUND: Sampling of peripheral pulmonary nodules with radial endobronchial ultrasound (p-EBUS) increases diagnostic yield of bronchoscopy. However, diagnostic yield is influenced by numerous factors. OBJECTIVE: We evaluated the use of SpyGlass, a one millimeter diameter optic fiber, to obtain images of the distal mucosa and of pulmonary lesions detected with p-EBUS to determine if visual aspect of the distal mucosa was predictive of diagnosis. METHODS: We prospectively recruited subjects investigated for peripheral nodules. Bronchoscopy was performed and p-EBUS was used to locate the lesion through a guide sheath. The Spyglass fiber was introduced in the sheath to obtain images of the distal bronchial mucosa. Tissue sampling was subsequently done. RESULTS: Fifteen patients were enrolled in the study. A final diagnosis of malignancy was confirmed in 80%. All lesions could be located using p-EBUS (100%). Diagnostic sensitivity for p-EBUS was 58.3%. Distal mucosa could be imaged with SpyGlass in 14/15 patients (93.3%). Mucosal appearance was described as abnormal in 7 out of the 15 subjects. Mean SpyGlass procedure time was 6.5 minutes. No direct complication was reported. CONCLUSION: Spyglass can be used in combination with p-EBUS to obtain images of the distal bronchial mucosa and peripheral pulmonary nodules. More patients will be needed to confirm whether mucosal appearance can be predictive of malignancy.

Randomized Trial Comparing Patient Comfort Between the Oral and Nasal Insertion Routes for Linear Endobronchial Ultrasound.

BACKGROUND: Linear endobronchial ultrasound (EBUS) is a safe and accurate sampling method for mediastinal adenopathy. The transnasal approach has been proposed to improve patient comfort, but no data compare the oral and nasal routes. The objective was to compare patient comfort during linear EBUS under conscious sedation between the oral and the nasal routes. METHODS: An open-label randomized study comparing the 2 insertion routes for linear EBUS was conducted. Standardized protocols for sedation and topical anesthesia were used. Primary outcome was subjects' comfort measured by a 10-point scale filled 2 hours after the procedure. Willingness to return for a repeat examination, procedural characteristics, complications, and diagnostic yields were also compared. RESULTS: A total of 220 subjects were randomized and allocated to the nasal (n=110) or oral (n=110) route. Twenty-seven subjects in the nasal group (24.5%) had a failed nasal insertion but were analyzed in the nasal group. Procedural characteristics were similar (EBUS duration, doses of sedatives and lidocaine, number of stations sampled, complications). There was no difference between the nasal and oral groups in subjects' comfort (8.3 vs. 8.3, respectively, P=0.99), overall patient satisfaction (8.9 vs. 9.1, respectively, P=0.34), subjects' willingness to return (96% vs. 97%, P=1.00), and physician-reported subject comfort. Rates of adequate specimens and diagnostic yields did not differ significantly between the groups. CONCLUSIONS: For linear EBUS, the nasal and oral approaches confer a similarly high degree of patient comfort with similar complication rates and diagnostic yield. Patient and physician preferences should dictate the route of insertion.

Diagnostic yield of non-guided flexible bronchoscopy for peripheral pulmonary neoplasia.

BACKGROUND: The role of conventional bronchoscopy for peripheral pulmonary neoplasia remains controversial. We aimed to assess the diagnostic yield and the added value of non-guided bronchial aspiration, bronchoalveolar lavage (BAL), and brushing for the diagnosis of pulmonary neoplasia not visible endoscopically. METHODS: We retrospectively assessed 207 consecutive patients with a final diagnosis of peripheral lung malignancy who underwent bronchoscopy with non-guided aspiration, brushing, and BAL as their initial evaluation. The influence of clinical and radiological factors on diagnostic yield was assessed using univariate logistic regression analyses. RESULTS: The overall sensitivity of non-guided bronchoscopy was 25.6%, whereas sensitivities for bronchial aspiration, BAL, and brushing were 14.2%, 11.6%, and 16.5%, respectively. Younger age, larger lesion, central/intermediate distance from the hilum, presence of a bronchus sign, and higher standardized uptake value (SUV) on positron emission tomography scan were predictors of a higher diagnostic yield. Conversely, forced expiratory volume in one second, fellow implication in the procedure, and tumor histology did not influence sensitivity. The overall sensitivity of bronshoscopy was >40% for tumors >4 cm, located in the central/intermediate thirds of the lung, showing a bronchus sign, with an SUV >12 or occurring in patients <50 years of age. Conversely, the sensitivity was <10% for tumors <2 cm, located peripherally or with an SUV <4. CONCLUSION: Neoplasia characteristics may help targeting situations in which conventional bronchoscopy could be used as the initial diagnostic procedure when advanced techniques are unavailable. However, advanced diagnostic tools should probably be proposed as the initial modality for the diagnosis of peripheral malignant lesions when available.

Feasibility of using the nasal route for linear endobronchial ultrasound.

PURPOSE: Linear endobronchial ultrasound (EBUS) is a safe and accurate diagnostic test for mediastinal adenopathy. Its feasibility through the nasal route has not been reported. The objective of this study was to document the feasibility of linear EBUS using the nasal route and compare its accuracy and safety with the oral route. METHODS: A retrospective analysis of consecutive subjects who underwent an EBUS procedure under conscious sedation at our center was conducted. Nasal insertion of the bronchoscope was attempted in all subjects; the oral route was used in case of failed nasal insertion. Characteristics of the procedure and the diagnostic accuracy of EBUS were compared between the two insertion routes. RESULTS: From May to October 2012, 209 subjects underwent an EBUS. Complete data were available for 196 subjects. Nasal insertion of the EBUS bronchoscope was possible in 73.5 %. There was no difference between the two insertion routes in the location and number of stations sampled per subject. Procedure duration and complications (epistaxis, bronchial bleeding, desaturation, and pneumothorax) were similar between the two groups (2.1 % for nasal group vs 1.9 % for oral group). Minor epistaxis occurred in one subject in the nasal group. Comparing the nasal and oral groups, rates of adequate specimens were similar (90.5 vs 88.9 %, respectively; p = 0.68), and proportions of diagnostic specimens were not statistically different (51.4 vs 42.3 %, respectively; p = 0.26). CONCLUSION: Linear EBUS can be performed safely and with high accuracy via the nasal route. Controlled studies are required to determine which insertion route provides best patient comfort.

Diagnostic utility of peripheral endobronchial ultrasound with electromagnetic navigation bronchoscopy in peripheral lung nodules.

BACKGROUND AND OBJECTIVE: This study aimed to investigate the diagnostic utility of peripheral endobronchial ultrasound (pEBUS) followed by as-needed electromagnetic navigation bronchoscopy (ENB) for sampling peripheral lung nodules. METHODS: The study was a single-arm, prospective cohort study of patients with peripheral lung nodules. Peripheral lung lesion localization was initially performed using a pEBUS probe with guide sheath. If localization failed with pEBUS alone, ENB was used to help identify the lesion. Transbronchial biopsy, bronchial brush, transbronchial needle aspiration and bronchial washings were performed. RESULTS: Sixty patients were enrolled with average lesion size of 27 mm and mean pleural distance of 20 mm. Lesions were found with pEBUS alone in 75% of cases. The addition of ENB improved lesion localization to 93%. However, diagnostic yield for pEBUS alone and pEBUS with ENB were 43% and 50%, respectively. Factors predicting need for ENB use included smaller lesion size and absence of an air bronchus sign on computed tomography. CONCLUSIONS: ENB improves localization of lung lesions after unsuccessful pEBUS but is often not sufficient to ensure confirmation of a specific diagnosis. Technical improvements in sampling methods could improve the diagnostic yield.

Cryptogenic hemoptysis in chronic obstructive pulmonary disease: characteristics and outcome.

BACKGROUND: Hemoptysis is a common presenting symptom and cause of hospitalization in the department of respiratory diseases. In a number of patients with chronic obstructive pulmonary disease (COPD) presenting with this symptom, investigations fail to reveal a precise etiology. Little data are available regarding characteristics and outcome of COPD patients presenting with cryptogenic hemoptysis (CH). OBJECTIVES: Our study goal was to assess the functional characteristics of these subjects, the risk factors for CH and the severity of hemoptysis, as well as long-term outcome. METHODS: For more than 1 year, we enrolled and followed a group of 39 consecutive COPD patients admitted to our center with CH. RESULTS: Between 1988 and 2003, 39 patients with COPD were admitted for CH in which investigation failed to reveal an etiology. The mean age was 51.3 years. All subjects were active smokers. Twenty-one patients (54%) had at least 1 risk factor for prolonged bleeding. Patients with more severe airflow obstruction tended to have more severe bleeding. Bronchoscopy appeared as useful as a computed tomography in locating the bleeding site. Arterial embolization succeeded in controlling bleeding in all patients who underwent angiography. One patient experienced a relapse in bleeding at 2 months. One developed lung cancer after 1 year. Thirty-four patients were followed for an average of 5 years. Only 2 subjects experienced recurrent hemoptysis. None died. CONCLUSIONS: CH in patients with COPD is associated with a favorable short- and long-term outcome when managed with timely angiographic embolization. Long-term incidence of lung cancer was uncommon after an episode of CH, and recurrences of hemoptysis were rare.