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.

Sustained Clinical Benefits of Spiration Valve System in Patients with Severe Emphysema: 24-Month Follow-Up of EMPROVE.

Rationale: Follow-up of patients with emphysema treated with endobronchial valves is limited to 3-12 months after treatment in prior reports. To date, no comparative data exist between treatment and control subjects with a longer follow-up. Objectives: To assess the durability of the Spiration Valve System (SVS) in patients with severe heterogeneous emphysema over a 24-month period. Methods: EMPROVE, a multicenter randomized controlled trial, presents a rigorous comparison between treatment and control groups for up to 24 months. Lung function, respiratory symptoms, and quality-of-life (QOL) measures were assessed. Results: A significant improvement in forced expiratory volume in 1 second was maintained at 24 months in the SVS treatment group versus the control group. Similarly, significant improvements were maintained in several QOL measures, including the St. George's Respiratory Questionnaire and the COPD Assessment Test. Patients in the SVS treatment group experienced significantly less dyspnea than those in the control group, as indicated by the modified Medical Research Council dyspnea scale score. Adverse events at 24 months did not significantly differ between the SVS treatment and control groups. Acute chronic obstructive pulmonary disease exacerbation rates in the SVS treatment and control groups were 13.7% (14 of 102) and 15.6% (7 of 45), respectively. Pneumothorax rates in the SVS treatment and control groups were 1.0% (1 of 102) and 0.0% (0 of 45), respectively. Conclusions: SVS treatment resulted in statistically significant and clinically meaningful durable improvements in lung function, respiratory symptoms, and QOL, as well as a statistically significant reduction in dyspnea, for at least 24 months while maintaining an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Case series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC).

Post-acute sequelae of COVID (PASC), or long COVID, is a multisystem complication of SARS-CoV-2 infection that continues to debilitate millions worldwide thus highlighting the public health importance of identifying effective therapeutics to alleviate this illness. One explanation behind PASC may be attributed to the recent discovery of persistent S1 protein subunit of SARS-CoV-2 in CD16+ monocytes up to 15 months after infection. CD16+ monocytes, which express both CCR5 and fractalkine receptors (CX3CR1), play a role in vascular homeostasis and endothelial immune surveillance. We propose targeting these receptors using the CCR5 antagonist, maraviroc, along with pravastatin, a fractalkine inhibitor, could disrupt the monocytic-endothelial-platelet axis that may be central to the etiology of PASC. Using five validated clinical scales (NYHA, MRC Dyspnea, COMPASS-31, modified Rankin, and Fatigue Severity Score) to measure 18 participants' response to treatment, we observed significant clinical improvement in 6 to 12 weeks on a combination of maraviroc 300 mg per oral twice a day and pravastatin 10 mg per oral daily. Subjective neurological, autonomic, respiratory, cardiac and fatigue symptoms scores all decreased which correlated with statistically significant decreases in vascular markers sCD40L and VEGF. These findings suggest that by interrupting the monocytic-endothelial-platelet axis, maraviroc and pravastatin may restore the immune dysregulation observed in PASC and could be potential therapeutic options. This sets the framework for a future double-blinded, placebo-controlled randomized trial to further investigate the drug efficacy of maraviroc and pravastatin in treating PASC.

Standardized Definitions of Bleeding After Transbronchial Lung Biopsy: A Delphi Consensus Statement From the Nashville Working Group.

BACKGROUND: Transbronchial lung biopsies are commonly performed for a variety of indications. Although generally well tolerated, complications such as bleeding do occur. Description of bleeding severity is crucial both clinically and in research trials; to date, there is no validated scale that is widely accepted for this purpose. Can a simple, reproducible tool for categorizing the severity of bleeding after transbronchial biopsy be created? METHODS: Using the modified Delphi method, an international group of bronchoscopists sought to create a new scale tailored to assess bleeding severity among patients undergoing flexible bronchoscopy with transbronchial lung biopsies. Cessation criteria were specified a priori and included reaching > 80% consensus among the experts or three rounds, whichever occurred first. RESULTS: Thirty-six expert bronchoscopists from eight countries, both in academic and community practice settings, participated in the creation of the scale. After the live meeting, two iterations were made. The second and final scale was vetted by all 36 participants, with a weighted average of 4.47/5; 53% were satisfied, and 47% were very satisfied. The panel reached a consensus and proposes the Nashville Bleeding Scale. CONCLUSIONS: The use of a simplified airway bleeding scale that can be applied at bedside is an important, necessary tool for categorizing the severity of bleeding. Uniformity in reporting clinically significant airway bleeding during bronchoscopic procedures will improve the quality of the information derived and could lead to standardization of management. In addition to transbronchial biopsies, this scale could also be applied to other bronchoscopic procedures, such as endobronchial biopsy or endobronchial ultrasound-guided needle aspiration.

Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System (EMPROVE). A Multicenter, Open-Label Randomized Controlled Clinical Trial.

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Balloon-facilitated percutaneous dilational tracheostomy tube placement: preliminary report of a novel technique.

OBJECTIVE: To describe a novel technique for percutaneous tracheotomy (PT) that could be an alternative to current dilational techniques. DESIGN: An observational animal study of PT was performed using the Seldinger guide wire technique with a tracheostomy tube preloaded onto a dilational balloon catheter. A small skin incision was done with an 11-blade scalpel, but no blunt subcutaneous tissue dissection was performed. SETTING: Animal laboratory in a university hospital. SUBJECTS: Seven adult pigs (approximate weight, 16 to 21 kg). MEASUREMENTS AND RESULTS: Successful tracheostomy was accomplished in all seven pigs without apparent complication. Vital signs and oximetry results remained unchanged throughout the procedure. The mean duration of the procedure was 5.5 min from tracheal puncture to ventilation. CONCLUSION: This novel procedure is a simple and effective means of PT tube placement without subcutaneous tissue dissection and could potentially have decreased complications when compared to the standard methods of PT currently employed in humans. Human studies are pending.