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.

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

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

Safety of Home Discharge With a Chest Tube After Bronchoscopic Lung Volume Reduction Complicated by Persistent Airleak.

BACKGROUND: The incidence of pneumothorax after bronchoscopic lung volume reduction (BLVR) using Zephyr (Pulmonx Corporation) endobronchial valves is ~26%. Many patients who develop a postprocedural pneumothorax require chest tube placement. If a persistent airleak is present, patients tolerating waterseal can be discharged home with a mini-atrium with a low risk of empyema. METHODS: Data were collected on patients from the Epic (Epic System Corporation) electronic medical record between July 2019 and November 2022. Our retrospective study reviewed a total of 102 BLVR procedures. Twenty-six of these procedures were complicated by a pneumothorax post-BLVR (25%). After 24 procedures, patients were discharged home with a chest tube after a persistent airleak. The primary endpoint of the study was the incidence of intrapleural infection in this population. The secondary endpoint was the average length of time the chest tube was in place until outpatient removal. RESULTS: Out of the 24 discharge events, 2 events (8.3%) were complicated by an intrapleural infection before chest tube removal. The average number of days requiring a chest tube until outpatient removal was 16.9 days, which is similar to the duration observed in patients discharged home with a chest tube after lung volume reduction surgery. CONCLUSION: Discharging patients home with a chest tube after BLVR therapy is safe and may reduce hospital length of stay. Our study shows the incidence of intrapleural infection after home discharge with a chest tube after BLVR is low.

DNA methylation in lung cells is associated with asthma endotypes and genetic risk.

The epigenome provides a substrate through which environmental exposures can exert their effects on gene expression and disease risk, but the relative importance of epigenetic variation on human disease onset and progression is poorly characterized. Asthma is a heterogeneous disease of the airways, for which both onset and clinical course result from interactions between host genotype and environmental exposures, yet little is known about the molecular mechanisms for these interactions. We assessed genome-wide DNA methylation using the Infinium Human Methylation 450K Bead Chip and characterized the transcriptome by RNA sequencing in primary airway epithelial cells from 74 asthmatic and 41 nonasthmatic adults. Asthma status was based on doctor's diagnosis and current medication use. Genotyping was performed using various Illumina platforms. Our study revealed a regulatory locus on chromosome 17q12-21 associated with asthma risk and epigenetic signatures of specific asthma endotypes and molecular networks. Overall, these data support a central role for DNA methylation in lung cells, which promotes distinct molecular pathways of asthma pathogenesis and modulates the effects of genetic variation on disease risk and clinical heterogeneity.

Bronchial thermoplasty failure in severe persistent asthma: a case report.

INTRODUCTION: Bronchial thermoplasty (BT) is an emerging therapy for patients with severe persistent asthma who remain poorly controlled despite standard maximal medical therapy. Thermoplasty elicits asthma control over time by applying thermal radiofrequency energy to airways to ablate underlying smooth muscle. While this therapy is suggested to eliminate such smooth muscle permanently, no human studies have examined the possibility of treatment failure. CASE REPORT: We present a 62-year-old female with severe, refractory asthma symptoms who underwent BT without apparent complications. However, severe symptoms including multiple clinical exacerbations persisted despite BT treatment. Repeat endobronchial biopsy done six months after BT treatment demonstrated persistent smooth muscle hyperplasia in multiple airways that previously had been treated. The patient continued to have uncontrolled, refractory asthma despite multiple therapies. CONCLUSION: This case is the first to describe a failure of BT to reduce or eliminate airway smooth muscle in a patient with severe persistent asthma. It suggests the potential for treatment failure in the management of these patients after BT and highlights the need for further study of potential BT-refractory patients.

Isolation of persistent air leaks and placement of intrabronchial valves.

OBJECTIVES: Alveolar-pleural fistulas causing persistent air leaks are conditions associated with prolonged hospital courses, high morbidity, and possibly increased mortality. Intrabronchial valves serve as a noninvasive therapeutic option for the closure of alveolar-pleural fistulas. METHODS: The present review describes a brief history of, and indications for, the placement of intrabronchial valves in patients with persistent air leaks. The essential steps necessary for placement are air leak isolation, airway sizing, and valve deployment. Additionally, the indications and methods for intrabronchial valve removal, along with the potential complications from intrabronchial valve placement, are described. CONCLUSIONS: The increased use of intrabronchial valves in the treatment of persistent air leaks requires bronchoscopists and clinicians to understand the procedural steps and techniques necessary for intrabronchial valve placement.

Safety and feasibility of bronchial thermoplasty in asthma patients with very severe fixed airflow obstruction: a case series.

OBJECTIVE: Bronchial thermoplasty (BT) can provide relief for patients with severe, uncontrolled asthma despite maximal medical therapy. However, it is unclear whether BT is safe in patients with very severe airflow obstruction. METHODS: We performed BT in eight patients with severe asthma as defined by Expert Panel Report 3 (EPR-3) guidelines who were poorly controlled despite step 5 therapy. Data were available on each subject for 1 year prior to and 15-72 weeks following BT. RESULTS: The mean (±SEM) pre-bronchodilator forced expiratory volume in one second (FEV(1)) prior to BT was 51.8 ± 8.6% of predicted, and the mean (±SEM) number of hospitalizations for asthma in the year prior to BT was 2.9 ± 1.2. No subject had an unexpected severe adverse event due to BT. Among the eight patients with follow-up of at least 15 weeks, there was no significant decline in FEV(1) (p = .4). CONCLUSION: We suggest that BT may be safe for asthma patients with severe airflow obstruction and higher hospitalization rates than previously reported.