Airway Bypass Stents for Emphysema, Algorithm to Exclude Precapillary Pulmonary Hypertension, and Sildenafil for Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction

Matthew R. Lammi, Nicholas Panetta, Maria Elena Vega
2012 American Journal of Respiratory and Critical Care Medicine  
Shah PL, et al. Bronchoscopic Lung-Volume Reduction with Exhale Airway Stents for Emphysema (EASE Trial): Randomized, Sham-controlled, Multicentre Trial. Lancet (1) Reviewed by Matthew R. Lammi In selected patients with emphysema, lung volume reduction surgery has been shown to improve exercise capacity, quality of life, and survival (2). Because of restrictive inclusion criteria and risk of surgery, there has been interest in bronchoscopic lung volume reduction as an alternative to lung volume
more » ... tive to lung volume reduction surgery. Creating airway bypass tracts (ABTs) attempts to bypass collapsed small airways, allowing air to escape on expiration. The Exhale Airway Stents for Emphysema (EASE) trial was the first randomized, double-blind, sham-controlled study of ABTs (1). Patients were included if they had homogeneous emphysema with an FEV 1 less than 50% predicted and an RV/TLC greater than 0.65. Of the 1,522 patients assessed for eligibility, 208 were randomized to ABT and 107 to sham bronchoscopy. All patients had bronchoscopy under general anesthesia; the intervention group had passages created in the airway and paclitaxel stents placed to maintain patency. Bayesian analysis did not show any superiority of ABT for the coprimary efficacy end point, which was met if the FVC increased by at least 12% and modified Medical Research Council (mMRC) score fell by 1 point from baseline at 6 months of follow-up. Mean FVC increased on Day 1 in the ABT group, but this returned to baseline by 3 months. Mean mMRC scores were significantly lower only at the 6-month time point in the intervention group. This trial used a robust randomized, sham-controlled study design that included patients most likely to benefit from the treatment. There was no benefit in the coprimary end point, likely due to stent expectoration and low rates of stent patency (66% on Day 1 and 21% at 6 mo). Although there were no differences in composite safety end points or 6-month mortality between the groups, the risk of chronic obstructive pulmonary disease exacerbation or infection was almost twofold higher in the treatment group. This highlights the importance of noting individual safety end points that may be masked by reporting a composite end point alone. The EASE trial demonstrates that airway bypass tract formation with paclitaxel stents does not improve outcomes in patients with severe homogeneous emphysema. This is an interesting example of how theoretical benefit was attained through an intervention but was not sustained because of technical aspects of the procedure. References 1. Shah PL, Slebos D-J, Cardoso PFG, Cetti E, Voelker K, Levine B, Russell ME, Goldin J, Brown M, Cooper JD, Sybrecht GW; EASE Study Group. Bronchoscopic lung-volume reduction with Exhale Airway Stents for Emphysema (EASE trial): randomised, sham-controlled, multicentre trial. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003;348:2059-2073. Bonderman D, et al. A Noninvasive Algorithm to Exclude Pre-capillary Pulmonary Hypertension. Eur Respir J (3) Reviewed by Nicholas Panetta Current international guidelines recommend right-heart catheterization (RHC) in symptomatic patients at risk for pulmonary hypertension (PH) with systolic pulmonary artery pressures greater than 36 mm Hg by transthoracic echocardiography (TTE) (4). TTE is frequently inaccurate in estimating pulmonary artery pressures and cannot distinguish precapillary PH from postcapillary PH (5). This study, through retrospective analysis, sought to identify a noninvasive diagnostic algorithm to identify or exclude precapillary PH, which was then validated prospectively. Data, including TTE, 12-lead electrocardiography, serum N-terminal pro-brain natriuretic peptide (NT-proBNP), lung function tests, and RHC from 251 patients referred for suspicion of precapillary PH, were used to develop a noninvasive diagnostic decision tree algorithm. A prospective study of 121 patients then served as temporal validation of this diagnostic algorithm, which dichotomized patients as "precapillary PH excluded" and "precapillary PH likely." A bootstrap approach was also used to provide internal validation. All patients subsequently underwent RHC. Precapillary PH was defined as a mean pulmonary artery pressure greater than 25 mm Hg at rest with a pulmonary capillary wedge pressure less than 15 mm Hg.
doi:10.1164/rccm.201202-0235rr pmid:22707735 fatcat:hlyryug6rncxpkwsh4rr3tqm2q