Impact and timing of pulmonary rehabilitation in patients undergoing bronchoscopic lung volume reduction with endobronchial valves: A multicentre randomized controlled trial in patients with severe emphysema.

BACKGROUND AND OBJECTIVE: Both bronchoscopic lung volume reduction with endobronchial valves (BLVR-EBV) and pulmonary rehabilitation (PR) are effective treatments for improving exercise capacity and patient-reported outcomes in patients with severe Chronic Obstructive Pulmonary Disease (COPD). According to current recommendations, all BLVR-EBV patients should have undergone PR first. Our aim was to study the effects of PR both before and after BLVR-EBV compared to BLVR-EBV alone. METHODS: We included patients with severe COPD who were eligible for BLVR-EBV and PR. Participants were randomized into three groups: PR before BLVR-EBV, PR after BLVR-EBV or BLVR-EBV without PR. The primary outcome was change in constant work rate cycle test (CWRT) endurance time at 6-month follow-up of the PR groups compared to BLVR-EBV alone. Secondary endpoints included changes in 6-minute walking test, daily step count, dyspnoea and health-related quality of life. RESULTS: Ninety-seven participants were included. At 6-month follow-up, there was no difference in change in CWRT endurance time between the PR before BLVR-EBV and BLVR-EBV alone groups (median: 421 [IQR: 44; 1304] vs. 787 [123; 1024] seconds, p = 0.82) or in any of the secondary endpoints, but the PR after BLVR-EBV group exhibited a smaller improvement in CWRT endurance time (median: 107 [IQR: 2; 573], p = 0.04) and health-related quality of life compared to BLVR-EBV alone. CONCLUSION: The addition of PR to BLVR-EBV did not result in increased exercise capacity, daily step count or improved patient-reported outcomes compared to BLVR-EBV alone, neither when PR was administered before BLVR-EBV nor when PR was administered after BLVR-EBV.

Prevalence and Impact of COVID-19 among Severe COPD Patients post Bronchoscopic Lung Volume Reduction Treatment with Endobronchial Valves.

BACKGROUND: The COVID-19 pandemic has a great impact on numberless aspects of our society. In our bronchoscopic lung volume reduction interventional program, we work with severe COPD patients on a daily basis. OBJECTIVES: We were interested in the prevalence and outcome of COVID-19, impact of the pandemic on daily life, and the vaccination coverage in our severe COPD patients who have been treated with one-way endobronchial valves. METHOD: A questionnaire, which consisted of questions related to the infection rate, treatment, and outcome of COVID-19 infections; feelings of anxiety related to the pandemic; adherence to preventive measures; and willingness to be vaccinated; was sent to our patients in June 2021. RESULTS: The questionnaire was sent to 215 patients, and the response rate was 100%. The vaccination rate was 97% in our surveyed population. The majority of patients (63%) indicated that they were quite or very anxious to get infected with COVID-19. Twenty-five (11.5%) patients were diagnosed with COVID-19, with none of these patients having been vaccinated at the time of infection. The infection rate reported in this study is comparable to that of the general Dutch population. However, the hospital admission rate and mortality rates are higher. CONCLUSIONS: Our results show that the SARS-CoV-2 infection rate in severe COPD patients treated with endobronchial valves was comparable with the general population; however, the hospital admission and mortality rates were worse.

Bronchoscopic Lung Volume Reduction in Patients with Emphysema due to Alpha-1 Antitrypsin Deficiency.

BACKGROUND: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) is a valid therapy for severe emphysema patients. However, alpha-1 antitrypsin (AAT)-deficient patients were excluded from the majority of clinical trials investigating this intervention. OBJECTIVES: The aim of this study was to investigate the feasibility, efficacy, and safety of EBV treatment in patients with AAT deficiency (AATD) or a reduced AAT level. METHOD: A retrospective analysis was performed of all patients treated with EBV with confirmed AATD or with a reduced AAT serum level at the University Medical Center Groningen between 2013 and 2021. Baseline and 6-month follow-up assessment included chest CT, pulmonary function measurement, 6-min walking distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ). RESULTS: In total, 53 patients were included, 30 patients in the AATD group (AAT <0.6 g/L or confirmed ZZ phenotype) and 23 patients in the reduced AAT group (AAT 0.6-1 g/L). In both groups, all response variables improved significantly after treatment. There was a median increase in forced expiratory volume in 1 s of 105 mL (12% relative) and 280 mL (31% relative) in the AATD and reduced AAT groups, respectively. 6MWD increased by 62 min and 52 min, and SGRQ decreased by 12.5 patients and 18.7 patients, respectively. A pneumothorax occurred in 10% and 13% of patients, and no patients died. CONCLUSIONS: EBV treatment in patients with emphysema and AATD or a reduced AAT level is feasible and results in significant improvements in pulmonary function, exercise capacity, and quality of life and has an acceptable safety profile.

Impact of Endobronchial Valve Treatment on Lung Function Decline.

INTRODUCTION: Endobronchial valve (EBV) treatment has been shown to be beneficial for patients with severe emphysema. The forced expiratory volume in 1 s (FEV1) was found to be significantly higher compared to baseline for up to 3 years after treatment although the magnitude of improvement gradually decreases over time. So far, it has not been investigated whether this treatment decelerates the decline in lung function. Therefore, our aim was to investigate the lung function decline before and after EBV treatment. METHODS: We included patients who were treated with EBVs in our hospital, of whom pre-treatment spirometry results were available (at least 4 measurements within at least 2 years before treatment) and who had an annual FEV1 measurement up to 3 years after treatment. RESULTS: In total, 45 patients were included (73% female, FEV1: 28 ± 7% of predicted, residual volume: 232 ± 32% of predicted) who had a mean pre-treatment FEV1 decline of -64 mL/year. Mean FEV1 "decline" after treatment was +13 mL/year, since FEV1 was still above the baseline level at 3-year follow-up. However, the FEV1 decline between 1 and 3 years of follow-up was not significantly different compared to the pre-treatment decline (-73 mL/year, p = 0.179). CONCLUSIONS: Our results show that the EBV treatment does not influence the progression of disease in terms of lung function decline. However, the treatment does improve the FEV1 up to a level that is still comparable 3 years after treatment with the baseline level.

Reduction of Lung Hyperinflation Improves Cardiac Preload, Contractility, and Output in Emphysema: A Clinical Trial in Patients Who Received Endobronchial Valves.

Rationale: Pulmonary hyperinflation in patients with chronic obstructive pulmonary disease has been related to smaller cardiac chamber sizes and impaired cardiac function. Currently, bronchoscopic lung volume reduction (BLVR) with endobronchial valves is a treatment option to reduce pulmonary hyperinflation in patients with severe emphysema. Objectives: We hypothesized that reduction of hyperinflation would improve cardiac preload in this patient group. In addition, we investigated whether the treatment would result in elevated pulmonary artery pressures because of pulmonary vascular bed reduction. Methods: We included patients with emphysema and severe hyperinflation (defined by a baseline residual volume >175% of predicted) who were eligible for BLVR with endobronchial valves. Cardiac magnetic resonance imaging was obtained one day before treatment and at 8-week follow-up. Primary endpoint was cardiac preload, as measured by the right ventricle end-diastolic volume index. As secondary endpoints, we measured indexed end-diastolic and end-systolic volumes of the right ventricle, left atrium, and left ventricle; pulmonary artery pressures; cardiac output; ejection fraction; and strain. Measurements and Main Results: Twenty-four patients were included. At 8-week follow-up, right ventricle end-diastolic volume index was significantly improved (+7.9 ml/m2; SD, 10.0; P = 0.001). In addition to increased stroke volumes, we found significantly higher ejection fractions and strain measurements. Although cardiac output was significantly increased (+0.9 L/min; SD, 1.5; P = 0.007), there were no changes in pulmonary artery pressures. Conclusions: We found that reduction of hyperinflation using BLVR with endobronchial valves significantly improved cardiac preload, myocardial contractility, and cardiac output, without changes in pulmonary artery pressures. Clinical trial registered with www.clinicaltrials.gov (NCT03474471).

Bronchoscopic Targeted Lung Denervation in Patients with Severe Asthma: Preliminary Findings.

Treatment options for severe asthma are limited, particularly in those patients who do not meet criteria for biologicals. Targeted lung denervation (TLD) is the bronchoscopic ablation of the peribronchial vagal nerve trunks to reduce cholinergic stimulation of airway smooth muscle and submucosal glands. This report describes the experience of the first 2 asthma patients treated with TLD worldwide. The participants were 54 and 51 years of age, and both had severe asthma (GINA 5) (FEV1: 53% and 113% of predicted; AQLQ scores: 5.3 and 4.4). Both participants were treated with TLD in a single day-case procedure under general anaesthesia. Lung function, health status, and adverse event data were collected at baseline and 12 months after TLD. No treatment-related serious adverse events were reported up to 12 months. Cough symptoms improved in both participants, and 1 participant reported a marked reduction in rescue medication use at 6 months. There were no significant changes in spirometry, lung volumes, or health status. In conclusion, TLD was performed safely in both participants, but more evidence is needed to clarify safety and efficacy of TLD in severe asthma. Therefore, further investigation of the treatment in severe asthma patients would be useful.

Bronchoscopic Lung Volume Reduction Coil Treatment for Severe Emphysema: A Systematic Review and Meta-Analysis of Individual Participant Data.

BACKGROUND: Lung volume reduction coil (LVR-coil) treatment provides a minimally invasive treatment option for severe emphysema patients which has been studied in multiple clinical trials. OBJECTIVES: The aim of the study was to assess the effect of LVR-coil treatment on pulmonary function, quality of life, and exercise capacity using individual participant data. METHOD: PubMed, Web of Science, and EMBASE were searched until May 17, 2021. Prospective single-arm and randomized controlled trials that evaluated the effect of LVR-coil treatment on forced expiratory volume in 1 s (FEV1), residual volume (RV), St. George Respiratory Questionnaire (SGRQ) total score, and/or 6-min walk distance (6MWD) and were registered in an official clinical trial database were eligible for inclusion. Individual patient data were requested, and a linear mixed effects model was used to calculate overall treatment effects. RESULTS: Eight trials were included in the final analysis, representing 680 individual patients. LVR-coil treatment resulted in a significant improvement in FEV1 at 3- (0.09 L [95% confidence interval (95% CI): 0.06-0.12]) and 6-month follow-up (0.07 L [95% CI: 0.03-0.10]), a significant reduction in RV at 3- (-0.45L [95% CI: -0.62 to -0.28]), 6- (-0.33L [95% CI: -0.52 to -0.14]), and 12-month follow-up (-0.36L [95% CI: -0.64 to -0.08]), a significant reduction in SGRQ total score at 3- (-12.3 points [95% CI: -15.8 to -8.8]), 6- (-10.1 points [95% CI: -12.8 to -7.3]), and 12-month follow-up (-9.8 points [95% CI: -15.0 to -4.7]) and a significant increase in 6MWD at 3-month follow-up (38 m [95% CI: 18-58]). CONCLUSIONS: LVR-coil treatment in emphysema patients results in sustained improvements in pulmonary function and quality of life and shorter lived improvements in exercise capacity. Since the owner of this LVR-coil has decided to stop the production and newer generations LVR-coils are currently being developed, these results can act as a reference for future studies and clinical guidance.

Determinants of Lung Fissure Completeness.

Rationale: New advanced bronchoscopic treatment options for patients with severe chronic obstructive pulmonary disease (COPD) have led to increased interest for COPD phenotyping, including fissure completeness. Objectives: We investigated clinical, environmental, and genetic factors contributing to fissure completeness in patients with and without COPD. Methods: We used data from 9,926 participants of the COPDGene study who underwent chest computed tomographic (CT) scans. Fissure completeness was calculated from CT scans after quantitative CT analysis at baseline and 5-year follow-up. Clinical and environmental factors, including sex, race, smoking, COPD, emphysema, maternal smoking during pregnancy and maternal COPD, were tested for impact on fissure completeness. Genome-wide association analyses were performed separately in non-Hispanic White subjects and African American subjects. Measurements and Main Results: African American subjects had significantly higher fissure completeness than non-Hispanic White subjects for all three fissures (P < 0.001). There was no change in fissure completeness between baseline and 5-year follow-up. For all fissures, no clinically relevant differences in fissure completeness were found for other clinical or environmental factors, including COPD severity. Rs2173623, rs264866, rs2407284, rs7310342, rs4904145, rs6504172, and rs7209556 showed genome-wide significant associations with fissure completeness in non-Hispanic White subjects. In African American subjects, rs264866, rs4904145 and rs6504172 were identified as significant associations. Rs2173623, rs6504172, and rs7209556 lead to WNT5A and HOXB antisense RNA expression, which play an important role during embryogenesis. Conclusions: Fissure completeness is genetically determined and not dependent on age, sex, smoking status, the presence and severity of COPD (including exacerbation frequency), maternal smoking during pregnancy, or maternal COPD.

Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. CONCLUSION: TLD 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.

Identifying Responders and Exploring Mechanisms of Action of the Endobronchial Coil Treatment for Emphysema.

BACKGROUND: So far, 3 randomized controlled trials have shown that the endobronchial treatment using coils is safe and effective. However, the more exact underlying mechanism of the treatment and best predictors of response are unknown. OBJECTIVES: The aim of the study was to gain more knowledge about the underlying physiological mechanism of the lung volume reduction coil treatment and to identify potential predictors of response to this treatment. METHODS: This was a prospective nonrandomized single-center study which included patients who were bilaterally treated with coils. Patients underwent an extensive number of physical tests at baseline and 3 months after treatment. RESULTS: Twenty-four patients (29% male, mean age 62 years, forced expiratory volume in 1 s [FEV1] 26% pred, residual volume (RV) 231% pred) were included. Three months after treatment, significant improvements were found in spirometry, static hyperinflation, air trapping, airway resistance, treated lobe RV and treated lobes air trapping measured on CT scan, exercise capacity, and quality of life. The change in RV and airway resistance was significantly associated with a change in FEV1, forced vital capacity, air trapping, maximal expiratory pressure, dynamic compliance, and dynamic hyperinflation. Predictors of treatment response at baseline were a higher RV, larger air trapping, higher emphysema score in the treated lobes, and a lower physical activity level. CONCLUSIONS: Our results confirm that emphysema patients benefit from endobronchial coil treatment. The primary mechanism of action is decreasing static hyperinflation with improvement of airway resistance which consequently changes dynamic lung mechanics. However, the right patient population needs to be selected for the treatment to be beneficial which should include patients with severe lung hyperinflation, severe air trapping, and significant emphysema in target lobes.

Comparison of Multiple Diagnostic Tests to Measure Dynamic Hyperinflation in Patients with Severe Emphysema Treated with Endobronchial Coils.

PURPOSE: For this study, we aimed to compare dynamic hyperinflation measured by cardiopulmonary exercise testing (CPET), a six-minute walking test (6-MWT), and a manually paced tachypnea test (MPT) in patients with severe emphysema who were treated with endobronchial coils. Additionally, we investigated whether dynamic hyperinflation changed after treatment with endobronchial coils. METHODS: Dynamic hyperinflation was measured with CPET, 6-MWT, and an MPT in 29 patients before and after coil treatment. RESULTS: There was no significant change in dynamic hyperinflation after treatment with coils. Comparison of CPET and MPT showed a strong association (rho 0.660, p < 0.001) and a moderate agreement (BA-plot, 202 ml difference in favor of MPT). There was only a moderate association of the 6-MWT with CPET (rho 0.361, p 0.024). CONCLUSION: MPT can be a suitable alternative to CPET to measure dynamic hyperinflation in severe emphysema but may overestimate dynamic hyperinflation possibly due to a higher breathing frequency.

A prospective safety and feasibility study of metered cryospray for patients with chronic bronchitis in COPD.

BACKGROUND: No currently approved intervention counteracts airway metaplasia and mucus hypersecretion of chronic bronchitis in COPD. However, metered cryospray (MCS) delivering liquid nitrogen to the tracheobronchial airways ablates abnormal epithelium and facilitates healthy mucosal regeneration. The objective of this study was to evaluate the feasibility, efficacy and safety of MCS in chronic bronchitis. METHODS: Patients with a forced expiratory volume in 1 s of 30-80% predicted who were taking optimal medication were recruited. Primary outcomes were feasibility (completion of treatments), efficacy (3-month change in St George's Respiratory Questionnaire (SGRQ)) and safety (incidence of adverse events). Secondary outcomes were lung function, exercise capacity and additional patient-reported outcomes. RESULTS: 35 patients, 19 male/16 female, aged 47-76 years, Global Initiative for Chronic Obstructive Lung Disease grade I (n=3), II (n=10) and III (n=22), underwent staggered liquid nitrogen treatments to the tracheobronchial tree. 34 patients completed three treatments, each lasting 34.3±12.1 min, separated by 4-6 weeks; one withdrew after the first treatment. ∼1800 doses of MCS were delivered. Clinically meaningful improvements in patient-reported outcomes were observed at 3 months: change in SGRQ -6.4 (95% CI -11.4 to -1.3; p=0.01), COPD Assessment Test (CAT) -3.8 (95% CI -6.4 to -1.3; p<0.01) and Leicester Cough Questionnaire (LCQ) 21.6 (95% CI 7.3 to 35.9; p<0.01). Changes in CAT were durable to 6 months (-3.4, 95% CI -5.9 to -0.9; p=0.01); changes in SGRQ and LCQ were durable to 9 months (-6.9, 95% CI -13.0 to -0.9; p=0.03 and 13.4, 95% CI 2.1 to 24.6; p=0.02, respectively. At 12 months, 14 serious adverse events were recorded in 11 (31.4%) subjects; six (43%) moderate and eight (57%) severe. Nine were respiratory-related: six exacerbations of COPD, two pneumonias and one case of increased coughing; all recovered without sequelae. None were serious device- or procedure-related adverse events. CONCLUSION: MCS is safe, feasible and associated with clinically meaningful improvements in multidimensional patient-reported outcomes.

Endobronchial coils for emphysema: Dual mechanism of action on lobar residual volume reduction.

BACKGROUND AND OBJECTIVE: The RENEW trial demonstrated that bronchoscopic lung volume reduction using endobronchial coils improves quality of life, pulmonary function and exercise performance. In this post hoc analysis of RENEW, we examine the mechanism of action of endobronchial coils that drives improvement in clinical outcomes. METHODS: A total of 78 patients from the RENEW coil-treated group who were treated in one or both lobes that were deemed as the most destroyed were included in this retrospective analysis. Expiratory and inspiratory HRCT scans were used to assess lobar volume change from baseline to 12 months post coil treatment in treated and untreated lobes. RESULTS: Reduction in lobar RV in treated lobes was significantly associated with favourable clinical improvement. Independent predictor of the change in RV and FEV1 was the change in lobar RV reduction in the treated lobes and for change in 6MWD the absence of cardiac disease and the change in SGRQ, while the independent predictor of change in SGRQ was the change in 6MWD. CONCLUSION: Our results suggest that residual lobar volume reduction in treated lobes measured by QCT is the driving mechanism of action of endobronchial coils leading to positive clinical outcomes. However, the improvement in exercise capacity and quality of life seems to be affected by the presence of cardiac disease.

Endobronchial Valve Treatment in Emphysema Patients with a Very Low DLCO.

BACKGROUND: For selected patients with severe emphysema, bronchoscopic lung volume reduction with endobronchial valves (EBV) is recognized as an additional treatment option. In most trials investigating EBV treatment, patients with a very low diffusing capacity (DLCO) were excluded from participation. OBJECTIVES: Our goal was to investigate whether EBV treatment in patients with emphysema with a very low DLCO is safe and effective. METHODS: This was a single-center retrospective analysis including patients with emphysema and a DLCO ≤20%pred who underwent EBV treatment. Follow-up was performed 6 months post-treatment. Outcome parameters were compared to a historical matched control group (DLCO >20%pred, matched for sex, age, forced expiratory volume in 1 s [FEV1], and residual volume [RV]). RESULTS: Twenty patients (80% female, 64 ± 6 years, FEV1 26 ± 6%pred, RV 233 ± 45%pred, DLCO 18 ± 1.6%pred) underwent EBV treatment. At 6 months follow-up, we found a statistically significant improvement in FEV1 (0.08 ± 0.12 L), RV (-0.45 ± 0.95 L), 6-min walking distance (38 ± 65 m), and St. George's Respiratory Questionnaire (-12 ± 13 points). With the exception of FEV1, all exceeded the minimal clinically important difference. The most common serious adverse event was a pneumothorax requiring intervention (15%). There were no significant differences in outcome compared to the DLCO >20%pred control group. CONCLUSIONS: In this single-center retrospective analysis, we showed statistically significant and clinically relevant improvements in lung function, exercise capacity, and quality of life up to 6 months after EBV treatment in emphysema patients with a DLCO ≤20% (14-20%) of predicted with no increased risk of serious adverse events.

CT-Derived Pulmonary Artery Diameters to Preselect for Echocardiography in COPD Patients Eligible for Bronchoscopic Treatments.

BACKGROUND: Currently, patients with COPD who are evaluated for bronchoscopic treatments are routinely screened for pulmonary hypertension (PH) and systolic left ventricle dysfunction by echocardiography. OBJECTIVES: We evaluated the prevalence of PH and systolic left ventricle dysfunction in this patient group and investigated if the previously proposed CT-derived pulmonary artery to aorta (PA:A) ratio >1 and PA diameter measurements can be used as alternative screening tools for PH. METHODS: Two hundred fifty-five patients were included in this retrospective analysis (FEV1 25%pred, RV 237%pred). All patients received transthoracic echocardiography and chest CT scans on which diameters of the aorta and pulmonary artery were measured at the bifurcation and proximal to the bifurcation. RESULTS: Following echocardiography, 3 patients (1.2%) had PH and 1 (0.4%) had systolic left ventricle dysfunction. Using a PA:A ratio >1, only 10.3% of the patients with a right ventricular systolic pressure (RVSP) ≥35 mm Hg were detected and none of the patients with an RVSP >50 mm Hg were detected. Patients with an RVSP ≥35 mm Hg had significantly higher PA diameters (29.5 vs. 27.5 mm; p = 0.02) but no significantly different PA:A ratios. All patients with an RVSP >50 mm Hg had PA diameters >30 mm. CONCLUSIONS: The prevalence of PH and systolic left ventricle dysfunction is low in this preselected cohort of patients with severe COPD. In this population, a PA:A ratio >1 is not a useful cardiac screening tool for PH. A PA diameter >30 mm could substitute for routinely performed echocardiography in the screening for PH in this patient group.

Temporary Right Middle Lobe Occlusion with a Blocking Device to Enable Collateral Ventilation Measurement of the Right Major Fissure.

BACKGROUND: Absence of interlobar collateral ventilation is essential to achieve lobar volume reduction after endobronchial valve (EBV) treatment and can be assessed using the Chartis measurement. However, especially in lower lobe measurements, Chartis can be complicated by the "no-flow phenomenon", during which a sudden cessation of flow is observed, leading to an unreliable measurement. If this phenomenon occurs in the right lower lobe, when measuring collateral flow over the right major fissure, the entrance to the right middle lobe should be occluded, and the Chartis balloon should be placed in the right upper lobe. Both Watanabe spigots and balloon catheters can be used to achieve occlusion. OBJECTIVE: Our aim was to demonstrate that right middle lobe occlusion with a blocking device is helpful in obtaining a reliable Chartis outcome in case of the no-flow phenomenon in the right lower lobe. METHODS: We performed a retrospective analysis of patients scheduled for EBV treatment in an EBV registry between September 2016 and September 2019. RESULTS: We included 15 patients with severe emphysema (median age 63 years [range 47-73], 73% female, and FEV1 24% [range 19-36] of predicted), who required temporary middle lobe occlusion (12 Watanabe spigot, 3 balloon catheter). After occlusion, a reliable Chartis outcome was obtained in all patients. CONCLUSION: Temporary middle lobe occlusion using a blocking device is helpful in obtaining a reliable Chartis outcome in case of a right lower lobe no-flow phenomenon.

Change in Dynamic Hyperinflation After Bronchoscopic Lung Volume Reduction in Patients with Emphysema.

BACKGROUND AND PURPOSE: In patients with severe emphysema, dynamic hyperinflation is superimposed on top of already existing static hyperinflation. Static hyperinflation reduces significantly after bronchoscopic lung volume reduction (BLVR). In this study, we investigated the effect of BLVR compared to standard of care (SoC) on dynamic hyperinflation. METHODS: Dynamic hyperinflation was induced by a manually paced tachypnea test (MPT) and was defined by change in inspiratory capacity (IC) measured before and after MPT. Static and dynamic hyperinflation measurements were performed both at baseline and 6 months after BLVR with endobronchial valves or coils (treatment group) or SoC (control group). RESULTS: Eighteen patients underwent BLVR (78% female, 57 (43-67) years, FEV1 25(18-37) %predicted, residual volume 231 (182-376) %predicted). Thirteen patients received SoC (100% female, 59 (44-74) years, FEV1 25 (19-37) %predicted, residual volume 225 (152-279) %predicted. The 6 months median change in dynamic hyperinflation in the treatment group was: + 225 ml (range - 113 to + 803) (p < 0.01) vs 0 ml (- 1067 to + 500) in the control group (p = 0.422). An increase in dynamic hyperinflation was significantly associated with a decrease in residual volume (r = - 0.439, p < 0.01). CONCLUSION: Bronchoscopic lung volume reduction increases the ability for dynamic hyperinflation in patients with severe emphysema. We propose this is a consequence of improved static hyperinflation.

Determining Static Hyperinflation in Patients with Severe Emphysema: Relation Between Lung Function Parameters and Patient-Related Outcomes.

BACKGROUND: Bronchoscopic lung volume reduction techniques are minor invasive treatment modalities for severely hyperinflated emphysema patients. The severity of static lung hyperinflation determines eligibility and success rate for these treatments. However, it is not exactly known what parameter should be used to optimally reflect hyperinflation. Commonly used parameters are residual volume (RV) and the RV/Total lung capacity (TLC) ratio. Other parameters reflecting hyperinflation are Inspiratory Capacity/TLC and forced vital capacity. OBJECTIVES: To define which of these function parameters is the most optimal reflection of hyperinflationin in relation to patient-related outcomes. METHODS: In a retrospective cohort study, data from measurements during baseline visits of eight studies were pooled. Primary outcomes were RV/TLC ratio and RV as percentage of predicted (RV%pred), both measured by bodyplethysmography, compared to the patient-related outcome variables: 6-min walk distance (6MWD), the St. George's Respiratory Questionnaire (SGRQ), and the modified Medical Research Council (mMRC). RESULTS: Two hundred seventy-four COPD patients (mean age 59 years; 66% female), FEV1 0.74 ± 0.28 L, RV 4.94 ± 1.06 L, 6MWD of 339 ± 95 m, were included in the analysis. Significant correlations (all p < 0.01) were found between RV%pred and 6MWD (r = - 0.358), SGRQ (r = 0.184), and mMRC (r = 0.228). Also, there was a significant correlation between RV/TLC ratio and 6MWD (r = - 0.563), SGRQ (r = 0.289) and mMRC (r = 0.354). Linear regression analyses showed that RV/TLC ratio was a better predictor of patient outcomes than RV%pred. CONCLUSION: This study demonstrates that both RV/TLC ratio and RV%pred are relevant indicators of hyperinflation in patients with severe emphysema in relation to patient-related outcomes. RV/TLC ratio is more strongly related to the patient-related outcomes than RV%pred.

Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial.

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).

Safety and Dose Study of Targeted Lung Denervation in Moderate/Severe COPD Patients.

RATIONALE: Targeted lung denervation (TLD) is a novel bronchoscopic treatment for the disruption of parasympathetic innervation of the lungs. OBJECTIVES: To assess safety, feasibility, and dosing of TLD in patients with moderate to severe COPD using a novel device design. METHODS: Thirty patients with COPD (forced expiratory volume in 1 s 30-60%) were 1:1 randomized in a double-blinded fashion to receive TLD with either 29 or 32 W. Primary endpoint was the rate of TLD-associated adverse airway effects that required treatment through 3 months. Assessments of lung function, quality of life, dyspnea, and exercise capacity were performed at baseline and 1-year follow-up. An additional 16 patients were enrolled in an open-label confirmation phase study to confirm safety improvements after procedural enhancements following gastrointestinal adverse events during the randomized part of the trial. RESULTS: Procedural success, defined as device success without an in-hospital serious adverse event, was 96.7% (29/30). The rate of TLD-associated adverse airway effects requiring intervention was 3/15 in the 32 W versus 1/15 in the 29 W group, p = 0.6. Five patients early in the randomized phase experienced serious gastric events. The study was stopped and procedural changes made that reduced both gastrointestinal and airway events in the subsequent phase of the randomized trial and follow-up confirmation study. Improvements in lung function and quality of life were observed compared to baseline values for both doses but were not statistically different. CONCLUSIONS: The results demonstrate acceptable safety and feasibility of TLD in patients with COPD, with improvements in adverse event rates after procedural enhancements.