Therapeutic bronchoscopy for malignant central airway obstruction: Introduction to the EpiGETIF registry.

BACKGROUND AND OBJECTIVE: EpiGETIF is a web-based, multicentre clinical database created in 2019 aiming for prospective collection of data regarding therapeutic rigid bronchoscopy (TB) for malignant central airway obstruction (MCAO). METHODS: Patients were enrolled into the registry from January 2019 to November 2022. Data were prospectively entered through a web-interface, using standardized definitions for each item. The objective of this first extraction of data was to describe the population and the techniques used among the included centres to target, facilitate and encourage further studies in TB. RESULTS: Overall, 2118 patients from 36 centres were included. Patients were on average 63.7 years old, mostly male and smokers. Most patients had a WHO score ≤2 (70.2%) and 39.6% required preoperative oxygen support, including mechanical ventilation in 6.7%. 62.4% had an already known histologic diagnosis but only 46.3% had received any oncologic treatment. Most tumours were bronchogenic (60.6%), causing mainly intrinsic or mixed obstruction (43.3% and 41.5%, respectively). Mechanical debulking was the most frequent technique (67.3%), while laser (9.8%) and cryo-recanalization (2.7%) use depended on local expertise. Stenting was required in 54.7%, silicone being the main type of stent used (55.3%). 96.3% of procedure results were considered at least partially successful, resulting in a mean 4.1 points decrease on the Borg scale of dyspnoea. Complications were noted in 10.9%. CONCLUSION: This study exposes a high volume of TB that could represent a good source of future studies given the dismal amount of data about the effects of TB in certain populations and situations.

Endobronchial Coil System versus Standard-of-Care Medical Management in the Treatment of Subjects with Severe Emphysema.

BACKGROUND: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. OBJECTIVE: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. METHOD: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George's Respiratory Questionnaire (SGRQ) total score at 6 months. RESULTS: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by -10.6 [-15.9 to -5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. CONCLUSION: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.

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).

Cost-effectiveness of lung volume reduction coil treatment in patients with severe emphysema: results from the 2-year follow-up crossover REVOLENS study (REVOLENS-2 study).

BACKGROUND: The REVOLENS study compared lung volume reduction coil treatment to usual care in patients with severe emphysema at 1 year, resulting in improved quality-adjusted life-year (QALY) and higher costs. Durability of the coil treatment benefit and its cost-effectiveness at 2 years are now assessed. METHODS: After one year, the REVOLENS trial's usual care group patients received coil treatment (second-line coil treatment group). Costs and QALYs were assessed in both arms at 2 years and an incremental cost-effectiveness ratio in cost per QALY gained was calculated. The uncertainty of the results was estimated by probabilistic bootstrapping. RESULTS: The average cost of coil treatment in both groups was estimated at €24,356. The average total cost at 2 years was €9655 higher in the first-line coil treatment group (p = 0.07) and the difference in QALY between the two groups was 0.127 (p = 0.12) in favor of first-line coil treatment group. The 2-year incremental cost-effectiveness ratio (ICER) was €75,978 / QALY. The scatter plot of the probabilistic bootstrapping had 92% of the replications in the top right-hand quadrant. CONCLUSION: First-line coil treatment was more expensive but also more effective than second-line coil treatment at 2 years, with a 2-year ICER of €75,978 / QALY. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01822795 .

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

IMPORTANCE: Therapeutic options for severe emphysema are limited. Lung volume reduction using nitinol coils is a bronchoscopic intervention inducing regional parenchymal volume reduction and restoring lung recoil. OBJECTIVE: To evaluate the efficacy, safety, cost, and cost-effectiveness of nitinol coils in treatment of severe emphysema. DESIGN, SETTING, AND PARTICIPANTS: Multicenter 1:1 randomized superiority trial comparing coils with usual care at 10 university hospitals in France. Enrollment of patients with emphysema occurred from March to October 2013, with 12-month follow-up (last follow-up, December 2014). INTERVENTIONS: Patients randomized to usual care (n = 50) received rehabilitation and bronchodilators with or without inhaled corticosteroids and oxygen; those randomized to bilateral coil treatment (n = 50) received usual care plus additional therapy in which approximately 10 coils per lobe were placed in 2 bilateral lobes in 2 procedures. MAIN OUTCOMES AND MEASURES: The primary outcome was improvement of at least 54 m in the 6-minute walk test at 6 months (1-sided hypothesis test). Secondary outcomes included changes at 6 and 12 months in the 6-minute walk test, lung function, quality of life as assessed by St George's Respiratory Questionnaire (range, 0-100; 0 being the best and 100 being the worst quality of life; minimal clinically important difference, ≥4), morbidity, mortality, total cost, and cost-effectiveness. RESULTS: Among 100 patients, 71 men and 29 women (mean age, 62 years) were included. At 6 months, improvement of at least 54 m was observed in 18 patients (36%) in the coil group and 9 patients (18%) in the usual care group, for a between-group difference of 18% (1-sided 95% CI, 4% to ∞; P = .03). Mean between-group differences at 6 and 12 months in the coil and usual care groups were +0.09 L (95% CI, 0.05 L to ∞) (P = .001) and +0.08 L (95% CI, 0.03 L to ∞) (P = .002) for forced expiratory volume in the first second, +21 m (95% CI, -4 m to ∞) (P = .06) and +21 m (95% CI, -5 m to ∞) (P = .12) for 6-minute walk distance, and -13.4 points (95% CI, -8 points to ∞) and -10.6 points (95% CI, -5.8 points to ∞) for St George's Respiratory Questionnaire (1-sided P < .001 for both). Within 12 months, 4 deaths occurred in the coil group and 3 in the usual care group. The mean total 1-year per-patient cost difference between groups was $47,908 (95% CI, $47,879-$48,073) (P < .001); the incremental cost-effectiveness ratio was $782,598 per additional quality-adjusted life-year. CONCLUSIONS AND RELEVANCE: In this preliminary study of patients with severe emphysema followed up for 6 months, bronchoscopic treatment with nitinol coils compared with usual care resulted in improved exercise capacity with high short-term costs. Further investigation is needed to assess durability of benefit and long-term cost implications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01822795.

Coping strategies, anxiety and depression related to the COVID-19 pandemic in lung transplant candidates and recipients. Results from a monocenter series.

BACKGROUND: The COVID-19 pandemic has been associated with an increase in anxiety and depression symptoms in people. We investigated the impact of the pandemic on coping strategies and anxiety and depression in lung transplantation (LT) recipients and patients with end-stage chronic lung disease awaiting LT. METHODS: We retrospectively investigated coping strategies by using the Coping Inventory for Stressful Situations questionnaire and anxiety and depression symptoms by the Hospital Anxiety and Depression scale in 115 LT candidates and recipients. RESULTS: Overall, 63 participants (20 women; median age 59 years [interquartile range 52•65]) answered one or both questionnaires (49 LT recipients and 14 LT candidates). The preferred coping strategy was task-focused for 51 (86.4%) participants, with no difference between LT recipients and candidates nor according to the main anamnestic and clinical data. Eleven patients had suspected or proven depression symptoms, and 18 had suspected or proven anxiety symptoms. Coping strategies related to COVID-19 did not differ by presence of anxiety or depression symptoms. CONCLUSION: In the current pandemic, healthcare professionals should consider these results to provide relevant psychological help to these fragile populations and promote a systematic and wide multidisciplinary assessment of LT recipients and candidates.

Two-Year Outcomes for the Double-Blind, Randomized, Sham-Controlled Study of Targeted Lung Denervation in Patients with Moderate to Severe COPD: AIRFLOW-2.

Purpose: COPD exacerbations are associated with worsening clinical outcomes and increased healthcare costs, despite use of optimal medical therapy. A novel bronchoscopic therapy, targeted lung denervation (TLD), which disrupts parasympathetic pulmonary innervation of the lung, has been developed to reduce clinical consequences of cholinergic hyperactivity and its impact on COPD exacerbations. The AIRFLOW-2 study assessed the durability of safety and efficacy of TLD additive to optimal drug therapy compared to sham bronchoscopy and optimal drug therapy alone in subjects with moderate-to-severe, symptomatic COPD two years post randomization. Patients and Methods: TLD was performed in COPD patients (FEV1 30-60% predicted, CAT≥10 or mMRC≥2) in a 1:1 randomized, sham-controlled, double-blinded multicenter study (AIRFLOW-2) using a novel lung denervation system (Nuvaira, Inc., USA). Subjects remained blinded until their 12.5-month follow-up visit when control subjects were offered the opportunity to undergo TLD. A time-to-first-event analysis on moderate and severe and severe exacerbations of COPD was performed. Results: Eighty-two subjects (FEV1 41.6±7.4% predicted, 50.0% male, age 63.7±6.8 yrs, 24% with prior year respiratory hospitalization) were randomized. Time-to-first severe COPD exacerbation was significantly lengthened in the TLD arm (p=0.04, HR=0.38) at 2 years post-TLD therapy and trended towards similar attenuation for moderate and severe COPD exacerbations (p=0.18, HR=0.71). No significant changes in lung function or SGRQ-C were found 2 years post randomization between groups. Conclusion: In a randomized trial, TLD demonstrated a durable effect of significantly lower risk of severe AECOPD over 2 years. Further, lung function and quality of life remained stable following TLD. Clinical Trial Registration: NCT02058459.

Bronchiectasis Complicating Lung Volume Reduction Coil Treatment.

Endoscopic lung volume reduction has emerged over the past several years as a promising technique to improve the respiratory functional status of patients with advanced emphysema. Nevertheless, the procedure may be associated with various complications; among them, the development of bronchiectasis related to the coils has not yet been described. We report the case of a patient with emphysema who developed localized bronchiectasis at the site of coil insertion several months after lung volume reduction coil treatment.

Lung retransplantation for bronchiolitis obliterans syndrome: long-term follow-up in a series of 15 recipients.

BACKGROUND: Although lung retransplantation is the only definitive therapeutic option in lung recipients with bronchiolitis obliterans syndrome (BOS), its value remains a considerable source of controversy. We report our experience of retransplantation for BOS performed in our center since 1988. METHODS: Between 1988 and 2002, 15 lung retransplantations for BOS were performed. Patient survival, causes of death, long-term functional status, and BOS recurrence rate were reviewed. RESULTS: The retransplantation procedure was single-lung transplantation (SLT) in all cases (ipsilateral SLT, n = 4; contralateral SLT, n = 9; SLT after previous double-lung transplantation, n = 2). The median time between primary lung transplantation and retransplantation was 31 months (range, 12 to 39 months). The median follow-up duration of the 10 patients surviving beyond 6 months was 49.5 months (range, 16.5 to 105 months), and 5 patients were followed up for > 5 years. Actuarial survival rates at 1 year, 2 years, and 5 years after retransplantation were 60%, 53%, and 45%, respectively. Ten patients died during long-term follow-up, 6 of them from infection (60%). The retained graft was the initial site of the fatal infection in four of these six patients (66%). Two other patients with a retained graft experienced disabling chronic purulent expectoration arising from the old graft. In the 10 patients surviving beyond 6 months, mean best FEV(1) was 58 +/- 13% of predicted (+/- SD), and actuarial freedom from BOS (stage 1, 2, or 3) at 1 year, 3 years, and 5 years was 90%, 72%, and 66%, respectively. CONCLUSION: Lung retransplantation offered a viable therapeutic option for selected lung recipients with BOS. Given the morbidity and mortality related to the retained graft, we now favor replacement of the primary graft when retransplantation is considered.

Functional results of unilateral lung volume reduction surgery in alpha1-antitrypsin deficient patients.

Lung volume reduction surgery (LVRS) has been shown to improve lung function and exercise tolerance in patients with severe emphysema. Some predictors of poor outcome have been described but the role of alpha1-antitrypsin (alpha1-AT) deficiency is still not well known. The aim of this study was to analyze the results of unilateral LVRS in our center according to the alpha1-AT status. The results of LVRS in 17 deficient patients and 35 nondeficient patients were analyzed at 3-6 months and 1 year after surgery. Compared with baseline, a significant improvement of FEV1, partial pressure in arterial blood (PaO2), dyspnea score and walking distance was observed in the two groups at 3-6 months after surgery and the studied parameters remained significantly improved at 1 year in the nondeficient group. By contrast, PaO2 and walking distance returned towards baseline in the deficient group at 1 year whereas improvement of FEV1 and dyspnea score was persistent. Mean values of FEV, at baseline, 3-6 months, and 1 year were 22 +/- 6%, 29 +/- 11%, and 26 +/- 9% and 28 +/- 12%, 38 +/- 17%, and 40 +/- 17% predicted in the deficient group and in the non-deficient group, respectively. In conclusion, the functional benefit is short-lasting in alpha1-AT deficient patients after unilateral LVRS.

Acute respiratory failure due to diaphragmatic weakness revealing a polymyositis.

Of the different respiratory disorders that complicate the course of polymyositis, diaphragmatic weakness is one that is seldom described and most often suspected rather than confirmed. We report a case of severe diaphragmatic weakness as a cause of acute respiratory failure revealing a polymyositis. The diaphragmatic involvement was proven by a very low esophageal pressure in response to cervical magnetic stimulation of the phrenic nerve. Corticosteroids and intravenous gammaglobulin, combined with mechanical ventilation, achieved a progressive recovery of diaphragmatic weakness.