Feasibility of Continuous Bronchoscopy During Exercise in the assessment of large airway movement in healthy subjects.

Excessive dynamic airway collapse (EDAC) is a recognized cause of exertional dyspnea arising due to invagination of the trachea and/ or main bronchi. EDAC is typically assessed by evaluating large airway movement with forced expiratory maneuvers. This differs from the respiratory response to exercise hyperpnea. We aimed to evaluate large airway movement during physical activity, with continuous bronchoscopy during exercise (CBE), in healthy subjects and compare findings with resting bronchoscopic maneuvers and imaging techniques. Twenty-eight individuals were recruited to complete two visits including treadmill-based CBE, to voluntary exhaustion and cine magnetic resonance imaging (MRI) with forced expiratory maneuvers at rest. 25 subjects (aged 29 (26 - 33) years, 52% female) completed the study (n=2 withdrew before bronchoscopy, and one was unable to tolerate insertion of bronchoscope). The majority (76%) achieved a peak heart rate of >90% predicted during CBE. The procedure was prematurely terminated in five subjects (n=3; elevated blood pressure and n=2; minor oxygen desaturation). The CBE assessment enabled adequate tracheal visualization in all cases. Excessive dynamic airway collapse (tracheal collapse ≥50%) was identified in 16 subjects (64%) on MRI, and in 6 (24%) individuals during resting bronchoscopy, but in no cases with CBE. No serious adverse events were reported, but minor adverse events were evident. The CBE procedure permits visualization of large airway movement during physical activity. In healthy subjects, there was no evidence of EDAC during strenuous exercise, despite evidence during forced maneuvers on imaging, thus challenging conventional approaches to diagnosis.

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Airway smooth muscle and long-term clinical efficacy following bronchial thermoplasty in severe asthma.

The mechanism of action of bronchial thermoplasty (BT) treatment for patients with severe asthma is incompletely understood. This study investigated the 2.5-year impact of BT on airway smooth muscle (ASM) mass and clinical parameters by paired data analysis in 22 patients. Our findings demonstrate the persistence of ASM mass reduction of >50% after 2.5 years. Furthermore, sustained improvement in asthma control, quality of life and exacerbation rates was found, which is in line with previous reports. An association was found between the remaining ASM and both the exacerbation rate (r=0.61, p=0.04 for desmin, r=0.85, p<0.01 for alpha smooth muscle actin (SMA)) and post-bronchodilator forced expiratory volume in 1 s predicted percentage (r=-0.69, p=0.03 for desmin, r=-0.58, p=0.08 for alpha SMA). This study provides new insight into the long-term impact of BT.

Low bleeding rates following transbronchial lung cryobiopsy in unclassifiable interstitial lung disease.

BACKGROUND AND OBJECTIVE: Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline-endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post-procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert-consensus airway bleeding scale, in addition to other complications and diagnostic yield. METHODS: A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon. RESULTS: One hundred twenty-six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1-59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1-14, p = 0.046) and the presence of medium-large vessels on histology (OR 37.3, CI 6.5-212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30-day mortality was 0%. Diagnostic yield was 80.6%. CONCLUSION: TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC.

Determining the impact of an artificial intelligence tool on the management of pulmonary nodules detected incidentally on CT (DOLCE) study protocol: a prospective, non-interventional multicentre UK study.

INTRODUCTION: In a small percentage of patients, pulmonary nodules found on CT scans are early lung cancers. Lung cancer detected at an early stage has a much better prognosis. The British Thoracic Society guideline on managing pulmonary nodules recommends using multivariable malignancy risk prediction models to assist in management. While these guidelines seem to be effective in clinical practice, recent data suggest that artificial intelligence (AI)-based malignant-nodule prediction solutions might outperform existing models. METHODS AND ANALYSIS: This study is a prospective, observational multicentre study to assess the clinical utility of an AI-assisted CT-based lung cancer prediction tool (LCP) for managing incidental solid and part solid pulmonary nodule patients vs standard care. Two thousand patients will be recruited from 12 different UK hospitals. The primary outcome is the difference between standard care and LCP-guided care in terms of the rate of benign nodules and patients with cancer discharged straight after the assessment of the baseline CT scan. Secondary outcomes investigate adherence to clinical guidelines, other measures of changes to clinical management, patient outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable opinion by the South Central-Oxford C Research Ethics Committee in UK (REC reference number: 22/SC/0142).Study results will be available publicly following peer-reviewed publication in open-access journals. A patient and public involvement group workshop is planned before the study results are available to discuss best methods to disseminate the results. Study results will also be fed back to participating organisations to inform training and procurement activities. TRIAL REGISTRATION NUMBER: NCT05389774.

Airway wall extracellular matrix changes induced by bronchial thermoplasty in severe asthma.

BACKGROUND: Airway remodeling is a prominent feature of asthma, which involves increased airway smooth muscle mass and altered extracellular matrix composition. Bronchial thermoplasty (BT), a bronchoscopic treatment for severe asthma, targets airway remodeling. OBJECTIVE: We sought to investigate the effect of BT on extracellular matrix composition and its association with clinical outcomes. METHODS: This is a substudy of the TASMA trial. Thirty patients with severe asthma were BT-treated, of whom 13 patients were treated for 6 months with standard therapy (control group) before BT. Demographic data, clinical data including pulmonary function, and bronchial biopsies were collected. Biopsies at BT-treated and nontreated locations were analyzed by histological and immunohistochemical staining. Associations between histology and clinical outcomes were explored. RESULTS: Six months after treatment, it was found that the reticular basement membrane thickness was reduced from 7.28 µm to 5.74 µm (21% relative reduction) and the percentage area of tissue positive for collagen increased from 26.3% to 29.8% (13% relative increase). Collagen structure analysis revealed a reduction in the curvature frequency of fibers. The percentage area positive for fibulin-1 and fibronectin increased by 2.5% and 5.9%, respectively (relative increase of 124% and 15%). No changes were found for elastin. The changes in collagen and fibulin-1 negatively associated with changes in FEV1 reversibility. CONCLUSIONS: Besides reduction of airway smooth muscle mass, BT has an impact on reticular basement membrane thickness and the extracellular matrix arrangement characterized by an increase in tissue area occupied by collagen with a less dense fiber organization. Both collagen and fibulin-1 are negatively associated with the change in FEV1 reversibility.

Bronchoscopic interventions for chronic bronchitis.

PURPOSE OF REVIEW: Chronic bronchitis is a phenotype of chronic obstructive pulmonary disease (COPD), characterized by chronic cough and sputum production, associated with an increased rate of COPD exacerbations and hospital admissions, a more rapid decline in lung function and reduced life expectancy. Despite optimal medical therapy, chronic bronchitis remains difficult to treat. Interventional bronchoscopic procedures offer novel therapeutic approaches to this highly symptomatic condition. RECENT FINDINGS: A characteristic feature of chronic bronchitis is the presence of an abnormal epithelium with excessive mucus producing cells, parasympathetic overactivity, and airway inflammation. Metered cryospray and bronchial rheoplasty are designed to target this abnormal epithelium to reduce mucus production and inflammation. Targeted lung denervation aims to reduce parasympathetic overactivity, which may drive mucus hypersecretion. Here, we review the available evidence to determine the safety and efficacy across the bronchoscopic interventions. SUMMARY: Interventional bronchoscopy is a rapidly expanding field and its application in the treatment of chronic bronchitis has been recognized by the Global initiative for chronic Obstructive Lung Disease (GOLD). The outcomes from the latest clinical trials will guide future treatment approaches in patients with difficult to treat chronic bronchitis.

Surgical and bronchoscopic pulmonary function-improving procedures in lung emphysema.

COPD is a highly prevalent, chronic and irreversible obstructive airway disease without curative treatment. Standard therapeutic strategies, both non-pharmacological and pharmacological, have only limited effects on lung function parameters of patients with severe disease. Despite optimal pharmacological treatment, many patients with severe COPD still have a high burden of dyspnoea and a poor quality of life. If these patients have severe lung emphysema, with hyperinflation as the driver of symptoms and exercise intolerance, lung volume reduction may be an effective treatment with a significant impact on lung function, exercise capacity and quality of life. Currently, different lung volume reduction approaches, both surgical and bronchoscopic, have shown encouraging results and have been implemented in COPD treatment recommendations. Nevertheless, choosing the optimal lung volume reduction strategy for an individual patient remains challenging. Moreover, there is still room for improving durability of effect and safety in all available procedures. Ongoing and innovative research is essential to push this field forwards. This review provides an overview of results and limitations of the current lung volume reduction options for patients with severe lung emphysema and hyperinflation.

Radiomics-based decision support tool assists radiologists in small lung nodule classification and improves lung cancer early diagnosis.

BACKGROUND: Methods to improve stratification of small (≤15 mm) lung nodules are needed. We aimed to develop a radiomics model to assist lung cancer diagnosis. METHODS: Patients were retrospectively identified using health records from January 2007 to December 2018. The external test set was obtained from the national LIBRA study and a prospective Lung Cancer Screening programme. Radiomics features were extracted from multi-region CT segmentations using TexLab2.0. LASSO regression generated the 5-feature small nodule radiomics-predictive-vector (SN-RPV). K-means clustering was used to split patients into risk groups according to SN-RPV. Model performance was compared to 6 thoracic radiologists. SN-RPV and radiologist risk groups were combined to generate "Safety-Net" and "Early Diagnosis" decision-support tools. RESULTS: In total, 810 patients with 990 nodules were included. The AUC for malignancy prediction was 0.85 (95% CI: 0.82-0.87), 0.78 (95% CI: 0.70-0.85) and 0.78 (95% CI: 0.59-0.92) for the training, test and external test datasets, respectively. The test set accuracy was 73% (95% CI: 65-81%) and resulted in 66.67% improvements in potentially missed [8/12] or delayed [6/9] cancers, compared to the radiologist with performance closest to the mean of six readers. CONCLUSIONS: SN-RPV may provide net-benefit in terms of earlier cancer diagnosis.

Clinical outcomes by supplemental oxygen use in remdesivir-treated, hospitalised adults with COVID-19.

BACKGROUND: Clinical trials show different effects of remdesivir on clinical outcomes relative to COVID-19 severity at hospital admission; in Europe, there are few real-world data. METHODS: A multicentre, multinational retrospective cohort study in adult patients hospitalised with PCR-confirmed COVID-19 was conducted to understand remdesivir clinical use in different countries and to describe outcomes for patients receiving remdesivir stratified by oxygen use. Primary endpoints were all-cause mortality at day 28 and hospitalisation duration. Patients were categorised by baseline disease severity: no supplemental oxygen (NSO); low flow oxygen ≤ 6 litres (l)/minute (LFO); high flow oxygen > 6 l/minute (HFO). RESULTS: Four hundred and forty-eight (448) patients (72 [16.1%] HFO; 295 [65.8%] LFO; 81 (18.1%] NSO) were included; median age was 65 years and 64% were male. Mortality was higher in patients on HFO (rate 23.6%) compared to LFO (10.2%; p = 0.001) or NSO (6.2%; p = 0.002). Duration of hospitalisation was longer in patients on HFO (13 days) compared to LFO (9 days; p = 0.003) and NSO (9 days; p = 0.021). Patients who initiated remdesivir ≥ 2 days compared to within a day of hospitalisation had a 4.2 times higher risk of death, irrespective of age, sex, comorbidities, and oxygen support at baseline. Requirement for mechanical ventilation/ECMO and readmission within 28 days of discharge was similar across groups. Remdesivir use and outcomes differed by country. CONCLUSIONS: A higher mortality rate and duration of hospitalisation was seen in remdesivir-treated COVID-19 patients on HFO compared to LFO and NSO. Initiation of remdesivir upon admission as opposed to delayed initiation has a mortality benefit. CLINICAL TRIALS REGISTRATION: NCT04847622.

Mitigation of Respirable Aerosol Particles from Speech and Language Therapy Exercises.

INTRODUCTION: Phonation and speech are known sources of respirable aerosol in humans. Voice assessment and treatment manipulate all the subsystems of voice production, and previous work (Saccente-Kennedy et al., 2022) has demonstrated such activities can generate >10 times more aerosol than conversational speech and 30 times more aerosol than breathing. Aspects of voice therapy may therefore be considered aerosol generating procedures and pose a greater risk of potential airborne pathogen (eg, SARS-CoV-2) transmission than typical speech. Effective mitigation measures may be required to ensure safe service delivery for therapist and patient. OBJECTIVE: To assess the effectiveness of mitigation measures in reducing detectable respirable aerosol produced by voice assessment/therapy. METHODS: We recruited 15 healthy participants (8 cis-males, 7 cis-females), 9 of whom were voice-specialist speech-language pathologists. Optical Particle Sizers (OPS) (Model 3330, TSI) were used to measure the number concentration of respirable aerosol particles (0.3 µm-10 µm) generated during a selection of voice assessment/therapy tasks, both with and without mitigation measures in place. Measurements were performed in a laminar flow operating theatre, with near-zero background aerosol concentration, allowing us to quantify the number concentration of respiratory aerosol particles produced. Mitigation measures included the wearing of Type IIR fluid resistant surgical masks, wrapping the same masks around the end of straws, and the use of heat and moisture exchange microbiological filters (HMEFs) for a water resistance therapy (WRT) task. RESULTS: All unmitigated therapy tasks produced more aerosol than unmasked breathing or speaking. Mitigation strategies reduced detectable aerosol from all tasks to a level significantly below, or no different to, that of unmasked breathing. Pooled filtration efficiencies determined that Type IIR surgical masks reduced detectable aerosol by 90%. Surgical masks wrapped around straws reduced detectable aerosol by 96%. HMEF filters were 100% effective in mitigating the aerosol from WRT, the exercise that generated more aerosol than any other task in the unmitigated condition. CONCLUSIONS: Voice therapy and assessment causes the release of significant quantities of respirable aerosol. However, simple mitigation strategies can reduce emitted aerosol concentrations to levels comparable to unmasked breathing.

Lung volume reduction surgery versus endobronchial valves: a randomised controlled trial.

BACKGROUND: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. METHODS: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. RESULTS: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm. CONCLUSION: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

Computed tomographic airway morphology after targeted lung denervation treatment in COPD.

This post-hoc analysis of the AIRFLOW-2 trial investigated the changes in airway CT-parameters after targeted lung denervation (TLD) and whether these changes are associated with treatment response. In the treatment group (n = 32), an improvement in air trapping was significantly associated with an improvement in residual volume (RV). Furthermore, improvements in Pi10 and airway lumen were significantly associated with an improvement in both RV and FEV1. Our results could suggest that when improving airway characteristics like decreasing airway wall thickness and increasing the airway lumen, this leads to less air trapping and an improvement in clinical outcomes.

Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care.

BACKGROUND: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. METHODS: We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733. FINDINGS: Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87). INTERPRETATION: Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19. FUNDING: LifeArc and CW+.

Dual-energy Computed Tomographic Pulmonary Angiography Accurately Estimates Lobar Perfusion Before Lung Volume Reduction for Severe Emphysema.

PURPOSE: To assess if dual-energy computed tomographic pulmonary angiography (DECTPA) derived lobar iodine quantification can provide an accurate estimate of lobar perfusion in patients with severe emphysema, and offer an adjunct to single-photon emission CT perfusion scintigraphy (SPECT-PS) in assessing suitability for lung volume reduction (LVR). MATERIALS AND METHODS: Patients with severe emphysema (forced expiratory volume in 1 s <49% predicted) undergoing evaluation for LVR between May 2018 and April 2020 imaged with both SPECT-PS and DECTPA were included in this retrospective study. DECTPA perfused blood volume maps were automatically segmented and lobar iodine mass was estimated and compared with lobar technetium (Tc99m) distribution acquired with SPECT-PS. Pearson correlation and Bland-Altman analysis were used for intermodality comparison between DECTPA and SPECT-PS. Univariate and adjusted multivariate linear regression were modelled to ascertain the effect sizes of possible confounders of disease severity, sex, age, and body mass index on the relationship between lobar iodine and Tc99m values. Effective radiation dose and adverse reactions were recorded. RESULTS: In all, 123 patients (64.5±8.8 y, 71 men; mean predicted forced expiratory volume in 1 s 32.1 ±12.7%,) were eligible for inclusion. There was a linear relationship between lobar perfusion values acquired using DECTPA and SPECT-PS with statistical significance ( P <0.001). Lobar relative perfusion values acquired using DECTPA and SPECT-PS had a consistent relationship both by linear regression and Bland-Altman analysis (mean bias, -0.01, mean r2 0.64; P <0.0001). Individual lobar comparisons demonstrated moderate correlation ( r =0.79, 0.78, 0.84, 0.78, 0.8 for the right upper, middle, lower, left upper, and lower lobes, respectively, P <0.0001). The relationship between lobar iodine and Tc99m values was not significantly altered after controlling for confounders including symptom and disease severity, age, sex, and body mass index. CONCLUSIONS: DECTPA provides an accurate estimation of lobar perfusion, showing good agreement with SPECT-PS and could potentially streamline preoperative assessment for LVR.

Targeted lung denervation modulates the mucosal epithelial transcriptome in COPD.

This study shows that TLD reduces airway epithelial expression of genes related to acetylcholine processing and airway inflammation, which may help to elucidate the mechanism for its effect of reducing severe exacerbations in COPD https://bit.ly/3dWcqZk.

Airway Inflammation Before and After Bronchial Thermoplasty in Severe Asthma.

Background: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma, of which the working mechanism and responder profile are partly unknown. The aim of this study is to analyse whether BT alters airway inflammation by epithelial gene expression, inflammatory cell counts and cytokines, and whether this relates to treatment response. Methods: In this clinical trial, 28 severe asthma patients underwent bronchoscopy before and after treatment to obtain bronchial brushes and bronchoalveolar lavage fluid (BALF) from treated and untreated airways. RNA was extracted from bronchial brushes for transcriptome analysis, and BALF cells and cytokines were analysed. Asthma quality of life questionnaires were used to distinguish responders from non-responders. We compared results before and after treatment, between treated and untreated airways, and between responders and non-responders. Results: Gene expression of airway epithelium related to airway inflammation gene set was significantly downregulated in treated airways compared to untreated airways, although this did not differ for patients before and after treatment. No differences were observed in cell counts and cytokines, neither from the untreated compared to treated airways, nor before and after treatment. At baseline, compared to non-responders, the expression of genes related to glycolysis in bronchial epithelium was downregulated and both BALF and blood eosinophil counts were higher in responders. Conclusion: Local differences in gene sets pertaining to epithelial inflammatory status were identified between treated and untreated airways after treatment, not resulting in changes in differential cell counts and cytokine analyses in BALF. Secondly, baseline epithelial glycolysis genes and eosinophil counts in BALF and blood were different between responders and non-responders. The observations from this study demonstrate the potential impact of BT on epithelial gene expression related to airway inflammation while also identifying a possible responder profile.

Crossover Patient Outcomes for Targeted Lung Denervation in Moderate to Severe Chronic Obstructive Pulmonary Disease: AIRFLOW-2.

BACKGROUND: Targeted Lung Denervation (TLD) is a potential new therapy for COPD. Radiofrequency energy is bronchoscopically delivered to the airways to disrupt pulmonary parasympathetic nerves, to reduce bronchoconstriction, mucus hypersecretion, and bronchial hyperreactivity. OBJECTIVES: This work assesses the effect of TLD on COPD exacerbations (AECOPD) in crossover subjects in the AIRFLOW-2 trial. METHOD: The AIRFLOW-2 trial is a multicentre, randomized, double-blind, sham-controlled crossover trial of TLD in COPD. Patients with symptomatic COPD on optimal medical therapy with an FEV1 of 30-60% predicted received either TLD or sham bronchoscopy in a 1:1 randomization. Those in the sham arm had the opportunity to cross into the treatment arm after 12 months. The primary end point was rate of respiratory adverse events. Secondary end points included adverse events, changes in lung function and health-related quality of life and symptom scores. RESULTS: Twenty patients were treated with TLD in the crossover phase and were subsequently followed up for 12 months (50% female, mean age 64.1 ± 6.9 years). After TLD, there was a trend towards a reduction in time to first AECOPD (hazard ratio 0.65, p = 0.28, not statistically significant) in comparison to sham follow-up period. There was also a reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, p = 0.227, not statistically significant). Symptom scores and lung function showed stability. CONCLUSIONS: AIRFLOW-2 crossover data support that of the randomization phase, showing trends towards reduction in COPD exacerbations with TLD.