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Interest in endoscopic lung volume reduction (ELVR) technologies for emphysema is consistently growing. In the last couple of months, several endoscopic options (e.g., endo- or intrabronchial valves, coil implants, and thermal vapor ablation) that have been evaluated in randomized controlled trials have been reported with the ultimate goal of improving respiratory mechanics and alleviating chronic dyspnea. Patients presenting with severe air trapping and thoracic hyperinflation have the greatest potential to derive benefit from ELVR procedures. Baseline assessment should ideally include cardiological evaluation, high-resolution computed tomography scan and perfusion scintigraphy, full pulmonary function tests, and cardiopulmonary exercise testing. This expert statement updates best practice recommendations regarding patient selection and utilization of these various techniques for the treatment of patients with advanced emphysema.

Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium. Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB. Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George’s Respiratory Questionnaire (SGRQ). Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P

Background: Lung cancer is one of the commonest malignancies with a worldwide incidence of 1.6 million cases each year. Although the main aetiological factor has been identified (cigarette smoking), the progression of lung cancer from early changes such as dysplasia through to cancer is still not fully understood. Furthermore, current research techniques are reliant on obtaining tissue biopsies, a process that alters the natural history of the very process under investigation. Hence, there is a need for developing optical biopsy techniques. Objectives: To prospectively evaluate the feasibility of endocytoscopy and confocal endomicroscopy in the detection of malignant and pre-malignant changes in the airways. Methods: Findings with endocytoscopy and endomicroscopy were compared with conventional biopsies obtained from the same areas in 25 patients undergoing bronchoscopy for evaluation of endobronchial abnormalities and in 5 healthy control subjects. Results: Endocytoscopy was technically more difficult, and interpretable images were only obtained in 21 of the patients evaluated, and hence, complete information including histopathological information was available in 21 patients. Endocytoscopy appeared to correlate with the histopathological findings on tissue biopsy, and was able to distinguish normal epithelium from dysplasia and carcinoma. Confocal endomicroscopy was a more reliable technique with adequate visual information obtained in all patients examined but was unable to distinguish between dysplasia and carcinoma. Conclusion: This feasibility study suggests that endocytoscopy may have the potential to fulfil the role of optical biopsy in the evaluation of the pathogenesis of lung cancer.

Background: No current medication counteracts the excessive mucus secretion or reverses the airway metaplasia of Chronic Bronchitis (CB) in COPD. Metered Cryospray (RejuvenAir® System) is a novel procedure delivering liquid N2 to the bronchial airways to target mucus overproduction, ablate abnormal epithelium, reduce chronic airway inflammation and promote regeneration of a healthy mucosal lining. Methods: This is a prospective, multicenter single-arm study of CB patients with an FEV1 of 30-80% predicted. Primary outcomes were safety and feasibility; secondary outcomes, SGRQ and 6MWT, were measured. Results: We included 35 subjects with Gold Grade II (31.4%) and III (68.6%) COPD (mean age 67.2+7.0 years, FEV1% 50.2±14.5, 54% male). Full treatment was accomplished of intended lobes with median times of 34 (right lower), 30 (left lower) and 41 minutes (upper lobes + trachea) during 3 separate outpatient visits. Approximately 1800 doses of MCS were delivered without inducing pneumothorax or unanticipated device-related serious adverse events (SAEs). Efficacy data showed clinically meaningful improvements of SGRQ-symptom score of -9.5±22.0 (95% CI; -17.7 to -1.3; p=0.025), SGRQ-impact score of -10.2±19.4 (95% CI: -17.5 to -3.0; p=0.007) and SGRQ-total score of -7.9±16.8 (95% CI: -14.2 to -1.6; p=0.008); most pronounced when baseline SGRQ-total ≥50 points (n=19). 6MWT significantly improved by 28 meters (95% CI: 3.0 to 62.0; Wilcoxon signed rank, p=0.034; n=25). Conclusions: These data indicate MCS treatment is safe, feasible and associated with clinically significant improvements in health-related quality of life in COPD patients with CB over 9 months.

Introduction: Bronchoscopic Lung Volume Reduction (BLVR) with the Zephyr® Valve improves lung function, exercise tolerance and quality of life in hyperinflated emphysema patients with little to no collateral ventilation (CV). Here we report further analysis of the impact of BLVR on patient reported outcomes (PROs) in the LIBERATE Study. Methods: 190 severe heterogeneous emphysema subjects were randomized 2:1 (Zephyr Valve to Standard of Care (SOC)) at 24 centers. Subjects were 53% female and had mean forced expiratory volume (FEV1) 27.4% predicted; Residual Volume 225% predicted; St George’s Respiratory Questionnaire (SGRQ) score of 54.5; and COPD Assessment Test (CAT) score of 19.2. Improvements in the total and individual domain scores of the SGRQ, total and individual questions of the CAT and the Focal and individual component scores of the Transitional Dyspnea Index (TDI) at 12-months from baseline were compared between the Zephyr Valve and SOC groups. Results: All three PROs showed statistically significant and clinically meaningful improvements in Zephyr Valve patients compared to SoC patients (SGRQ, -7.05 points; CAT, -3.1 points; TDI Focal score, 4.3 points). The improvement in the SGRQ was driven by the “Impacts” and “Activity” domains (p Conclusion: Data from the LIBERATE trial demonstrates that the Zephyr Valve significantly improves multidimensional measures of dyspnea and quality of life.

Background: Endobronchial coil treatment is effective in selected emphysema patients, however, the exact underlying mechanism of action is unknown. Objective: To investigate the role of lung compliance, respiratory muscle strength and dynamic hyperinflation after coil treatment and to identify predictors of response. Methods: Prospective evaluation of severe emphysema patients who were bilaterally treated with coils (PneumRx, USA) in the UMCG hospital (NCT02179125). Testing was performed at baseline and 3 months after coil treatment including lung compliance, MIP/MEP, metronome paced dynamic hyperinflation tests and cycle ergometry. Results: Twenty-four patients were included (11M/13F, mean age 62y, residual volume (RV) 230%pred). Patients significantly improved in static lung hyperinflation, exercise capacity and quality of life. Changes in RV and exercise capacity were significantly associated with a change in dynamic compliance, airway resistance and maximal expiratory pressure. Furthermore, the change in exercise capacity was significantly associated with change in dynamic hyperinflation (Table 1). At baseline, higher RV, higher airtrapping (difference TLC-helium and Bodyplethysmography) and lower functional status (steps/day and Wmax) were predictors of response in RV. Conclusions: Next to decreasing static hyperinflation, improvement of airway resistance and dynamic lung compliance could be underlying mechanisms of action of the endobronchial coil treatment.

Background: Bronchial Thermoplasty (BT) is a treatment for severe uncontrolled asthma patients. Although studies have shown clinical improvement after BT, not all patients respond equally well. Identifying optimal candidates for BT treatment is needed. Aim: To identify patient characteristic differences between BT responders and non-responders. Methods: Patients from the multicenter TASMA trial were included in this analysis. Before BT, a set of clinical, functional, inflammatory and airway biopsy data were collected (Table 1). A positive BT response was defined as a minimal clinically important change of >0.5 on asthma control questionnaire (ACQ) score, 6 months after BT. Results: 30 patients were analyzed. ACQ improved from 2.66 (±0.68) to 2.09 (±1.07) (p Conclusion: IgE and blood eosinophils before BT were higher in BT responders compared to non-responders and might therefore contribute in optimizing patient selection for BT.

Background: Endobronchial Ultrasound guidance allows lymph nodes in the mediastinum to be sampled under direct vision. The currently available EBUS-TBNA needles usually provide adequate samples for cytological assessment, but do not always contain sufficient material for the preparation of a cell block, thereby precluding histological assessment. Larger core tissue biopsy specimens are more likely to establish a diagnosis in suspected lung cancer patients. It can also improve the diagnostic yield of EBUS-TBNA for lymphoma and sarcoidosis. Objectives: This study that aims to determine the efficacy of the Flex 19G EBUS-TBNA (Olympus) compared to a standard 21G needle in patients with enlarged mediastinal and hilar lymph nodes. We evaluated the adequacy of the samples obtained with a modified Mair score. Methods: We completed a prospective randomised diagnostic clinical study of all cases performed at two study sites. Results: A total of 500 subjects underwent an EBUS procedure. 453 lesions with a mean lymph node size of 19.2mm (+/- SD 9.97) were sampled using Flex 19G & 480 lesions with a mean lymph node size of 17.8mm (+/- 8.15) were obtained using the standard needle. The Mair score did not differ between the two needles with a mean of 4.52 (+/- 2.28) for the Flex 19G & 4.40 (+/- 2.44) for the standard needle (p= 0.468). The complication rates were: 3.2% (19G) & 3.6% (21G). The sensitivity was 77% & specificity 100% with both needles. Conclusion: The Flex 19G EBUS-TBNA needle was safely used in this study. However, the efficacy was similar to the 21G needle.

Background: BT is an endoscopic treatment for uncontrolled asthma. The long-term efficacy and safety of BT beyond 5 years is not known. Objective: To evaluate the efficacy and safety of BT at 10+ years follow-up. Methods: BT10+ is an international, multi-center, ≥10yrs follow-up study on subjects who were previously enrolled in the AIR, RISA and AIR2 trials. Demographics, quality of life, lung function, severe exacerbations (SE, defined as exacerbations requiring systemic corticosteroids) and healthcare utilisation for the previous year were collected. Results: Of the 429 subjects enrolled in the previous studies, 192 subjects had a follow-up at 10.6-15.8 years (12.1 median) post-treatment at 16 centers: 137 treated with BT during a previous study, 18 control/sham treated with BT post-study, and 37 control/sham only. Rates for hospitalisations, emergency visits and SE for BT subjects from the year prior to BT to the year prior to the BT 10+ visit are shown in Figure 1. No increases in hospitalisations or ER visits were observed compared to baseline and SE were stable compared to Year 1. No deterioration in rates were shown for control/sham only and post-study BT patients. Quality of life and spirometry results were comparable between Years 1, 5, and 10+ for all groups. Conclusion: The BT10+ study suggests that efficacy of bronchial thermoplasty is sustained over 10 years. Funding: Boston Scientific

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 (

Stereotactic body radiotherapy (SBRT) has evolved as an improved treatment strategy for early-stage lung cancer in individuals who are unfit for surgery[1][1] and for oligometastatic disease.[2][2] Precision targeting of small lesions for high-dose radiation is key. This is frequently facilitated

Rationale: Targeted lung denervation (TLD) is a bronchoscopic radiofrequency ablation therapy for chronic obstructive pulmonary disease (COPD), which durably disrupts parasympathetic pulmonary nerves to decrease airway resistance and mucus hypersecretion.Objectives: To determine the safety and impact of TLD on respiratory adverse events.Methods: We conducted a multicenter, randomized, sham bronchoscopy-controlled, double-blind trial in patients with symptomatic (modified Medical Research Council dyspnea scale score, ≥2; or COPD Assessment Test score, ≥10) COPD (FEV1, 30-60% predicted). The primary endpoint was the rate of respiratory adverse events between 3 and 6.5 months after randomization (defined as COPD exacerbation, tachypnea, wheezing, worsening bronchitis, worsening dyspnea, influenza, pneumonia, other respiratory infections, respiratory failure, or airway effects requiring therapeutic intervention). Blinding was maintained through 12.5 months.Measurements and Main Results: Eighty-two patients (50% female; mean ± SD: age, 63.7 ± 6.8 yr; FEV1, 41.6 ± 7.3% predicted; modified Medical Research Council dyspnea scale score, 2.2 ± 0.7; COPD Assessment Test score, 18.4 ± 6.1) were randomized 1:1. During the predefined 3- to 6.5-month window, patients in the TLD group experienced significantly fewer respiratory adverse events than those in the sham group (32% vs. 71%, P = 0.008; odds ratio, 0.19; 95% confidence interval, 0.0750-0.4923, P = 0.0006). Between 0 and 12.5 months, these findings were not different (83% vs. 90%; P = 0.52). The risk of COPD exacerbation requiring hospitalization in the 0- to 12.5-month window was significantly lower in the TLD group than in the sham group (hazard ratio, 0.35; 95% confidence interval, 0.13-0.99; P = 0.039). There was no statistical difference in the time to first moderate or severe COPD exacerbation, patient-reported symptoms, or other physiologic measures over the 12.5 months of follow-up.Conclusions: Patients with symptomatic COPD treated with TLD combined with optimal pharmacotherapy had fewer study-defined respiratory adverse events, including hospitalizations for COPD exacerbation.Clinical trial registered with www.clinicaltrials.gov (NCT02058459).

Background Studies using public health records have reported an increased risk of developing lung cancer in patients with interstitial lung disease (ILD). However little information exists on the frequency of lung cancer in UK ILD practice. Method All cases discussed in the Royal Brompton Hospital Lung Cancer MDT meetings between May 2015 and April 2018 were interrogated for referring indication, patient attributes, staging and cancer confirmation. Results 74 ILD patients (45 male) and 223 COPD patients (132 male) were identified; median age at cancer diagnosis (70) was similar in both groups. ‘Ever’ smokers formed three-quarters (55/74) of the ILD group. 1 in 4 ILD patients had IPF. Cancer was pathologically proven in 25/74 (33.8%) of ILD patients, against 56/223 (25.1%) of those with COPD. Cancer that was suspected due to CT morphology or progression but were not amenable to sampling because of poor fitness, inaccessibility or metastatic disease occurred in 15/74 (20.3%) and 22/223 (9.9%) of ILD and COPD patients respectively (p Conclusion The risk of developing lung cancer is high amongst those with ILD especially in IPF and when there is evidence of suspicious ‘interval CT’ change. Stage IV NSCLC and aggressive (SCLC) are frequent in patients with IPF and scleroderma who develop lung malignancies. Delayed cancer diagnosis may result from decreased suspicion in patients who have progressive ILD or diffuse lung disease that complicates radiological interpretation.

Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up.TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life.Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEVTLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

Purpose of review The last decade has seen a real drive to develop novel bronchoscopic tools for diagnosis and therapy in a number of disease areas, in particular in cancer diagnosis and the treatment of airways disease. Nowhere has this been more evident than in the field of chronic obstructive pulmonary disease/emphysema. Recent findings The clinical trials with randomized endobronchial valves (EBVs) have demonstrated significant improvements in pulmonary function, quality of life and exercise capacity providing patients with heterogeneous disease with absence of collateral ventilation are selected. The responder rates are improved by valve adjustment or replacement where necessary. The results for endobronchial coils have been mixed with clinically meaningful results for pulmonary function and quality of life but at 1 year, the benefits in walk tests have been marginal. Vapour therapy appears promising and has the capacity for more targeted and staged therapy. Other therapies such as sealants which induce focal fibrosis, targeted vagal nerve ablation and cryoablation of bronchitis mucosa are also under development. Summary Patients with severe heterogenous emphysema, evidence of hyperinflation and intact lobar fissures confirmed to have absent collateral ventilation may be considered for EBVs. Those with collateral ventilation or homogenous distribution of emphysema may be considered for endobronchial coils.

Lung volume reduction of emphysematous lobes results in clinical improvement for patients with severe emphysema. However, some segments within a lobe are often substantially more diseased than others, thereby warranting a more targeted approach of the emphysematous parts of a lobe. We therefore did a study to assess whether or not selective sequential treatment of the more diseased upper lobe segments with bronchoscopic vapour ablation led to clinical improvement.For the multicentre, parallel-group, randomised, controlled, open-label Sequential Staged Treatment of Emphysema with Upper Lobe Predominance (STEP-UP) trial, adult patients aged 45-75 years with severe, upper lobe-predominant emphysema with a forced expiratory volume in 1 s (FEV1) between 20% and 45%, substantial hyperinflation, and post-rehabilitation 6-min walk test (6MWT) greater than 140 m were enrolled from 13 hospital sites in Europe (ten sites) and Australia (three sites). A computer-generated blocked randomisation scheme (block size three per site based on a random table from an independent biostatistician) stratified by site was used to randomly assign enrolled patients 2:1 to segmental vapour ablation (treatment group) or standard medical management (control group). Patients and investigators were not masked to group assignment. The primary efficacy endpoints were statistically significant changes in FEV1 and St George's Respiratory Questionnaire (SGRQ-C) scores between trial groups at 6 months, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01719263.Between June 30, 2013, and Oct 1, 2014, 134 patients were screened and 70 were enrolled and randomly assigned: 46 to the treatment group and 24 to the control group. One patient in the treatment group did not receive treatment because of physician decision post-randomisation; this patient is excluded from all analyses. The mean relative improvement in FEV1 between the treatment group versus the control group was 14·7% (95% CI 7·8-21·5%; p0·0001) and in SGRQ-C was -9·7 points (95% CI -15·7 to -3·7; p=0·0021). COPD exacerbation was the most common serious adverse event, occurring in 11 (24%) of 45 patients in the treatment group and one (4%) of 24 in the control group. One exacerbation resulted in a patient death 84 days after treatment; this was judged by the data and safety monitoring board to be possibly related to treatment. No pneumothorax occurred within 30 days of treatment.Compared with standard medical management, targeted thermal vapour ablation of more diseased segments and preservation of less diseased segments resulted in clinically meaningful and statistically significant improvements in lung function and quality of life at 6 months, with an acceptable safety profile.Uptake Medical.

Chronic obstructive pulmonary disease (COPD) is a progressive condition comprising a constellation of disorders from chronic bronchitis, airflow obstruction through to emphysema. The global burden of COPD is estimated at more than 6% of the population. The standard of care is based on a combination of smoking cessation, immunization, pharmacological treatments and pulmonary rehabilitation. However, the more advanced stages of COPD are challenging to manage. In this situation, our current standards of care do not adequately control patient symptoms nor halt the progressive decline. For the emphysema phenotype, lung volume reduction surgery has shown a beneficial effect in selected patients but is counterbalanced by the morbidity experienced by some patients. Bronchoscopic volume reduction technologies have been developed to improve the clinical situation of emphysema patients. This expert statement provides broad guidance regarding patient selection and the current position of the available techniques for patients with advanced emphysema. (C) 2016 S. Karger AG, Basel

Endobronchial ultrasound has been one of the success stories of the last decade, and the utility of the procedure continues to expand. Originally, it was developed for the staging and diagnosis of lung cancer, but its use rapidly expanded to other malignancies and even benign disease. We present the case of a patient originally referred with suspected endocarditis who was found to have a mass involving the right ventricle and the pulmonary outflow tract. Endobronchial ultrasound-guided biopsy was used to obtain a tissue diagnosis from the cardiac mass.

AS: A 74-year-old male was transferred to the Royal Brompton hospital from a local hospital with respiratory failure and expectoration of bronchial casts (see figure 1A). The patient recalls recurrent chest infections with occasional haemoptysis in his teens with no prior history of asthma, TB or pertussis. Despite investigation and antibiotic treatment, his symptoms of intermittent, chronic recurrent bronchial cast expectoration continued. A fibreoptic bronchoscopy on the patient, aged 41, revealed erythematous bronchial mucosa in the right middle lobe, with a ventilation/perfusion scan revealing concomitant decreased ventilation. Bronchial washings were unremarkable, and given concern of a pathology originating from the right middle lobe, a right middle lobectomy was performed. Histology showed non-specific inflammatory fibrosis around the lobar bronchus. Figure 1 (A) Representative image of an expectorated bronchial cast by the patient. (B and C) CT image demonstrating marked diffuse bronchial wall thickening with mild bilateral patchy ground glass opacities with extensive consolidation in the right upper lobe. Minimal interlobular septal thickening in the lower lobes is also noted. (D) Image following centrifugation of a liquefied bronchial cast expectorated by the patient revealing a turbid fatty layer confirming its chylous nature. (E) Images of lymphangioscintogram (anterior thorax with and without right shoulder and costal margin markers) showing abnormal tracer activity in the right lung (indicated by red arrow) confirming chylous leak. Tracer activity is also seen in the abdominal lymphatic channels and in the liver (indicated by red star) due to systemic circulation of radiotracer on delayed images. His symptoms, however, did not resolve. Microbiological examination of his casts revealed no growth, and histological examination showed fibrin and mucus with some lymphocytes. Further trials of corticosteroids, nebulised N-acetylcysteine, hypertonic saline, prophylactic azithromycin, systemic antifungals and oral cyclophosphamide were unsuccessful. Extensive immunological and allergic tests were normal. His symptoms remained stable till age …

IntroductionLung cancer is accountable for 35 000 deaths annually, and prognosis is improved when the cancer is diagnosed early. CT-guided biopsy (transthoracic needle aspiration, TTNA) and electromagnetic navigation bronchoscopy (ENB) can be used to investigate indeterminate pulmonary nodules if the patient is unfit for surgery. However, there is a paucity of clinical and health economic evidence that directly compares ENB with TTNA in this population group. This cost-effectiveness study aimed to explore potential scenarios whereby ENB may be considered cost-effective when compared with TTNA.MethodsA cohort decision analytic model was developed using a UK National Health Service perspective. ENB was assumed to have equal sensitivity to TTNA at 82%. Lifetime costs and quality-adjusted life-year (QALY) gain were calculated to estimate the net monetary benefit at a £20 000 per QALY threshold. Sensitivity analyses were used to explore scenarios where ENB could be considered a cost-effective intervention.ResultsUnder the assumption that ENB has equal efficacy to TTNA, ENB was found to be dominant (less costly and more effective) when compared with TTNA, due to having a reduced risk and cost of adverse events. This conclusion was most sensitive to changes in the cost of intervention, estimates of effectiveness and adverse event rates.DiscussionENB is expected to be cost-effective when the likelihood of an accurate diagnosis is equal to (or better than) TTNA, which may occur in certain subgroups of patients in whom TTNA is unlikely to accurately diagnose malignancy or when an experienced practitioner achieves a high accuracy with ENB.

Introduction: Zephyr® Endobronchial Valve (EBV®) treatment in severe emphysema patients, improves lung function, exercise capacity and quality of life. Objective: Evaluate effectiveness and safety of EBV treatment in severe emphysema. Methods: 190 severe heterogeneous emphysema subjects (M47%/F53%) with hyperinflation (FEV1 27.4 %pred; RV 224.5 %pred) and absent collateral ventilation (Chartis®) were randomized 2:1 (EBV:Standard-of-Care (SoC). Responders were classified according to established Minimal Clinically Important Differences for outcome measures. Results: At 12-months 84.2% EBV subjects had a target lobe volume reduction ≥350mL. Between group differences (ΔEBV–SoC) for mean changes from baseline were significant (p

Patients with severe emphysema typically have segments that are more diseased and hyperinflated than others. These segments have low density, poor ventilation, and minimal gas exchange, contributing to hyperinflation, reduced pulmonary function and quality of life (QOL). Reducing hyperinflated air volume of emphysematous segments with BTVA leads to an increase in healthier non-treated segments. The authors hypothesize that in addition to reduced hyperinflation, reduction in tissue mass may contribute to patient improvement, particularly QOL. Objective: Does BTVA remove mass in the ablated most diseased segments, thus increasing the mass of untreated heathier segments? Results: All treated patients from STEP-UP RCT with available baseline and 6-month follow-up scans (n=41) were quantitatively (QCT) analyzed with VIDA Apollo software. Changes in lobar and segmental tissue mass were measured. Treated segments had an average tissue mass removal of 14.1 grams (SD=13.4 g) a 22% reduction in mass. 98% of segments ablated had mass reduction. Preserved segments within those lobes had an average tissue mass increase of 7.8 g (SD=16.5 g) after each procedure. Net result of treated diseased segment mass reduction and untreated healthier segment mass was an average tissue mass reduction of 7.2 g (SD=16.8 g) in the lobe after each procedure. Conclusion: BTVA typically removes mass of ablated diseased segments and increases mass in healthier segments. Additionally, data from these measurements may result in ways to better identify BTVA responders and continue to improve on good patient outcomes.

Background: Microvesicles (MV) play an important role in mediating intra-alveolar inflammation during acute lung injury (Soni et al. Thorax 2016). We investigated the profile of MVs present within bronchoalveolar lavage fluid (BALF) and plasma in patients with another inflammatory disease, COPD, and assessed relationship to disease severity. Methods: Moderate to severe COPD patients (n=30) underwent clinical evaluation (symptom scores, lung function, exercise testing) and bronchoscopy. Paired plasma/BALF samples were analysed by flow cytometry for MVs derived from leucocytes (CD45+), neutrophils (CD66b+/CD11b+), monocytes (CD45+/CD14+), alveolar macrophages (CD206+/CD71+), platelets (CD31+/42b+), epithelial (EpCAM+/T1α+) and endothelial cells (CD146+/CD62E+/CD144+). Results: We identified MV subpopulations within BALF (leukocyte, neutrophil, monocyte, alveolar macrophage, epithelial, platelet) and plasma (leukocyte, neutrophil, monocyte, endothelial) samples. Only BALF neutrophil MV numbers correlated with modified MRC dyspnoea scale (p Conclusions: We have undertaken for the first time a comprehensive evaluation of MVs within BALF/plasma of COPD patients, and demonstrated BALF neutrophil-derived MV numbers correlate with functional and clinically relevant disease severity indices. Our data strongly suggest BALF neutrophil MVs are a novel, clinically relevant biomarker for COPD disease severity, and may have a pathogenic role in COPD progression and be a potential target to modulate the inflammation in COPD.

Background: Targeted Lung Denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung. Aim: Evaluate safety and efficacy of TLD + tiotropium compared to sham bronchoscopy + tiotropium at 6 months. Methods: TLD was performed in stable COPD patients (FEV1/FVC

Background: The mechanism of action of Bronchial Thermoplasty (BT) and its related responder profile is unclear. Objective: Investigate if BT-induced airway smooth muscle mass (ASM) change correlates with FEV1. Methods: 16 severe asthma patients were analyzed. Before and after BT, pre- and post-bronchodilator FEV1 was measured and bronchial biopsies were taken and stained with ASM-specific desmin and ASM/myofibroblast/myoepithelial α-smooth muscle actin (α-SMA). Results: BT treatment reduced ASM mass significantly as assessed by both desmin (55%) and α-SMA analysis (40%)(Fig1A). Baseline pre-and post-bronchodilator FEV1 correlated negatively with desmin-determined baseline ASM mass (resp. R=-0.61;p=0.01 and R=-0.62;p=0.01). Furthermore desmin-determined ASM mass decrease correlated negatively with baseline pre- and post-bronchodilator FEV1 (resp. R=-0.61;p=0.01 and R=-0.54;p=0.03 Fig1B). Patients with FEV1 80%(n=10): 2.4%(0.4;6.3 IQR (p=0.01)Fig1C). This correlation was not found with α-SMA staining. Conclusions: The correlation between ASM and FEV1 seems to depend on the fully differentiated contractile ASM only. Patients with a FEV1< 80% show the most reduction of ASM mass after BT treatment. Whether this “obstructive” asthma phenotype qualifies as a responder criteria needs to be determined.

This paper presents a new flexible RF cut and microwave ablation device for dissection and assisted “tunneling” into the hard surface of a tumour, prior to ablation. The distal applicator structure consists of twin bipolar RF electrodes and a helical “leaky” coaxial microwave antenna. Several antenna embodiments are discussed with associated design challenges presented. Finite element analysis (FEA) simulation, the prototype device and initial ex-vivo evaluation are presented. It is shown that the FEA simulation data corresponded well to the ex-vivo ablation profile. The results successfully validate this concept and its capability of supporting both RF cut and microwave ablation using a single antenna structure.

Background: Recent advances in bronchoscopic lung volume reduction offer new therapies for patients with emphysema and hyperinflation. Pulmonary lobe segmentation with quantification of lobar volumes and emphysema severity plays a pivotal role in treatment planning and post-interventional assessment. Computed tomography (CT)-derived lobar volumes could reflect more accurate regional changes in pulmonary function. Objectives: The aim of our study is to validate the reliability of an in-house CT Lung Segmentation software (LungSeg; the Hamlyn Centre, Imperial College London, UK) for lung lobar volume and emphysema quantification for chronic obstructive pulmonary disease (COPD) patients. Methods: A total of 108 CT scans from subjects who participated in an endobronchial coil treatment trial were included. Lobar volume and emphysema quantification were performed using the LungSeg and Syngo CT Pulmo 3D package (Siemens Healthcare GmbH, Germany). The inter-user reliability of the LungSeg program was investigated. Correlation coefficients and Bland-Altman analyses were used to quantify the inter-software variability. The agreement between CT volume analysis and plethysmography analysis was also examined. Results: The high intraclass correlation coefficients (mean ICC = 0.98) of the lobar volumes and emphysema indices measured by LungSeg suggest its excellent reproducibility. The LungSeg and Syngo program have good correlation (rho ≥0.94) and agreement for both lobar volume (median difference = 94 mL and LOAnp = 214.6 mL) and emphysema index (median difference ≤1.5% and LOAnp ≤2.03%) calculations. CT analysis provides a higher estimation of total lung capacity (TLCCT) than body plethysmography (TLCpleth), while there is a fair agreement on residual volume (RVCT) by LungSeg as compared with body plethysmography (RVpleth). Conclusions: CT-derived lobar volume and emphysema quantification using the LungSeg program is efficient and reliable in allowing lobar volume assessment. LungSeg has low inter-user variability and agrees better with plethysmography for COPD assessment in our study.

The lung biopsy in interstitial lung disease (ILD) represents an important diagnostic step when the clinical and radiological data are insufficient for a firm diagnosis. A growing body of evidence suggests the utility of transbronchial lung cryobiopsy (TBLC) in the diagnostic algorithm of ILD as it allows, compared to transbronchial lung biopsy with conventional forceps, a better identification of complex histological patterns – such as usual interstitial pneumonia – and can provide information which has a clinical impact on the multidisciplinary discussion similar to that provided by surgical lung biopsy. Performed correctly, it appears to have a better safety profile than surgery. The decision to perform a lung biopsy should be a multidisciplinary decision process where it is felt that there is sufficient diagnostic doubt after a careful clinical evaluation including review of the computed tomograms of the thorax. The presence of severe pulmonary hypertension (> 50 mm Hg), poor lung function (FVC < 50%), or dismissed gas transfer (DLCO of < 35%) are considered relative contraindications for TBLC. Anticoagulants and antiplatelet drugs should be discontinued for the minimum period required for the specific drugs. The greatest consideration should be given to ensure the biopsy is performed safely and we recommend the use of either an endotracheal tube or rigid bronchoscopy. Deep sedation or general anesthesia allow better control of the procedure and a better patient experience. Prophylactic balloon blockers should be used to tamponade any bleeding and also to prevent overspill of blood from the segment that is being sampled. The procedure should be performed under fluoroscopy to ensure that samples are ideally obtained about 10 mm from the pleural edge. The cryoprobe is activated for about 5 s for the first biopsy and then adjusted according to the sample size obtained. With a careful standardized approach it is possible to obtain good-quality lung specimens for diagnosis in a safe manner.

Objective: To determine the impact of endobronchial coils on health-related quality-of-life (HRQoL). This paper utilizes trial data to identify the predictors of HRQoL in patients with severe emphysema, and subsequently estimates the impact of a new treatment on HRQoL (measured by utilities). These utility estimates are used to generate indicative long-term QALY estimates for a range of clinically plausible scenarios as a precursor to cost-effectiveness analyses.Methods: Patient level HRQoL data from RENEW and the National Emphysema Treatment Trial (NETT) were combined and mapped to generic EuroQol 5-dimension health utility questionnaire (EQ-5D) values using a published algorithm. Multilevel statistical models were developed using treatment, time, response, and baseline characteristics (EQ-5D, age, gender, FEV1, lung RV) to predict EQ-5D over time. Lifetime QALY estimates were generated using published survival data from NETT (assuming no impact of treatment on mortality) and four clinically plausible response profiles. Each response profile was combined with assumptions around treatment impact (constant or time varying).Results: After controlling for baseline characteristics, both treatment and response had a statistically significant impact (p Conclusions: Coils and SoC resulted in statistically significant improvements in HRQoL compared to SoC alone in patients with severe emphysema.

This paper describes a novel flexible prototype device capable of both RF and microwave delivery for coagulation and ablation. The concept offers additional freedom to tailor the ablation profile in addition to key multimodality benefits (adjustable profile, thermal management, local current path, larger ablation). Finite element analysis, the prototype device and ex-vivo testing is presented. Good agreement was achieved between simulated and ex-vivo ablation profiles along with successful validation of the antenna design capable of delivering both RF and microwave energy. To the best of the authors knowledge, this is the first ablation antenna structure reported that combines the delivery of RF and microwave energy to produce optimal ablation volumes.

Background Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration is a well-established first-line minimally invasive modality for mediastinal lymph node sampling. Although results are excellent overall, the technique underperforms in certain situations. We aimed to describe our results using a new 19-G EBUS-guided transbronchial needle aspiration device to determine safety and feasibility of this approach. Methods We completed a retrospective chart review of all cases performed to the time of data analysis at each of 3 study sites. Results A total of 165 procedures were performed with a total of 297 individual lymph nodes or lesions sampled with the 19-G device by 10 bronchoscopists. Relatively large targets were selected for sampling with the device (mean lymph node size: 20.4 mm; lung lesions: 33.5 mm). A specific diagnosis was obtained in 77.3% of cases with an additional 13.6% of cases with benign lymphocytes, for a procedural adequacy rate of 90.9%. Procedure sample adequacy was 88.6% in suspected malignant cases, 91.0% in suspected sarcoidosis/lymphadenopathy cases, and 85.7% of cases with suspected lymphoma. On a per-node basis, a specific diagnosis was noted in 191/280 (68.2%) of samples, with an additional 61 showing benign lymphocytes for a per-node sample adequacy rate of 90%. One case (0.6%) of intraprocedure bleeding was noted. Conclusions A new flexible 19-G EBUS needle was successfully and safely applied in a large patient cohort for sampling of lung and enlarged mediastinal lesions with high diagnostic rates across clinical indications.

This paper presents an exercise in applying the bacterial foraging algorithm (BFA) optimisation method on a proportional—integral-derivative controller (PID) of a DC motor circuit. The paper presents the system description of the DC motor transfer function and the simulation of the close loop system using MATLAB. The BFA algorithm is described and discussed with the simulation results presented to illustrate the enhancement of the system response that in result enhances the operation of the DC motor system.

Background: Airway stenting (AS) commenced in Europe circa 1987 with the first placement of a dedicated silicone airway stent. Subsequently, over the last 3 decades, AS was spread throughout Europe, using different insertion techniques and different types of stents. Objectives: This study is an international survey conducted by the European Association of Bronchology and Interventional Pulmonology (EABIP) focusing on AS practice within 26 European countries. Methods: A questionnaire was sent to all EABIP National Delegates in February 2015. National delegates were responsible for obtaining precise and objective data regarding the current AS practice in their country. The deadline for data collection was February 2016. Results: France, Germany, and the UK are the 3 leading countries in terms of number of centres performing AS. These 3 nations represent the highest ranked nations within Europe in terms of gross national income. Overall, pulmonologists perform AS exclusively in 5 countries and predominately in 12. AS is performed almost exclusively in public hospitals. AS performed under general anaesthesia is the rule for the majority of institutions, and local anaesthesia is an alternative in 9 countries. Rigid bronchoscopy techniques are predominant in 20 countries. Amongst commercially available stents, both Dumon and Ultraflex are by far the most commonly deployed. Finally, 11 countries reported that AS is an economically viable activity, while 10 claimed that it is not. Conclusion: This EABIP survey demonstrates that there is significant heterogeneity in AS practice within Europe. Therapeutic bronchoscopy training and economic issues/reimbursement for procedures are likely to be the primary reasons explaining these findings.

Bronchial thermoplasty (BT) is a bronchoscopic treatment for patients with severe asthma who remain symptomatic despite optimal medical therapy. In this “expert best practice” paper, the background and practical aspects of BT are highlighted. Randomized, controlled clinical trials have shown BT to be safe and effective in reducing severe exacerbations, improving quality of life, and decreasing emergency department visits. Five-year follow-up studies have provided evidence of the functional stability of BT-treated patients with persistence of a clinical benefit. The Global Initiative for Asthma (GINA) guidelines state that BT can be considered as a treatment option for adult asthma patients at step 5. Patient selection for BT requires close collaboration between interventional pulmonologists and severe asthma specialists. Key patient selection criteria for BT will be reviewed. BT therapy is delivered in 3 separate bronchoscopy sessions at least 3 weeks apart, covering different regions of the lung separately. Patients are treated with 50 mg/day of prednisolone or equivalent for 5 days, starting treatment 3 days prior to the procedure. The procedure is performed under moderate-to-deep sedation or general anesthesia. At bronchos­copy a single-use catheter with a basket design is inserted through the instrument channel and the energy is delivered by a radiofrequency (RF) generator (AlairTM Bronchial Thermoplasty System). BT uses temperature-controlled RF energy to impact airway remodeling, including a reduction of excessive airway smooth muscle within the airway wall, which has been recognized as a predominant feature of asthma. The treatment should be performed in a systemic manner, starting at the most distal part of the (sub)segmental airway, then moving proximally to the main bronchi, ensuring that the majority of the airways are treated. In general, 40–70 RF activations are provided in the lower lobes, and between 50 and 100 activations in the upper lobes combined. The main periprocedural adverse events are exacerbation of asthma symptoms and increased cough and sputum production. Occasionally, atelectasis has been observed following the procedure. The long-term safety of BT is excellent. An optimized BT responder profile – i.e., which specific asthma phenotype benefits most – is a topic of current research.