David A. Sonetti

Effects of respiratory muscle training versus placebo on endurance exercise performance

We evaluated the effects of a 5 week (25 sessions); (30-35 min/day, 5 days/week), respiratory muscle training (RMT) program in nine competitive male cyclists. The experimental design included inspiratory resistance strength training (3-5 min/session) and hyperpnea endurance training (30 min/session), a placebo group which used a sham hypoxic trainer (n=8), and three exercise performance tests, including a highly reproducible 8 km time trial test. RMT intensity, measured once a week in terms of accumulated inspiratory pressure and the level of sustainable hyperpnea increased significantly after 5 weeks (+64% and +19%, respectively). The RMT group showed a significant 8% increase in maximal inspiratory pressure (P<0.05) while the placebo group showed only a 3.7% increase (P>0.10). RMT and placebo groups both showed significant increases in the fixed work-rate endurance test performance time (+26% and +16%, respectively) and in the peak work-rate achieved during the incremental maximal oxygen consumption (V(O2)max) test (+9 and +6%). The 8 km time trial performance increased 1.8+/-1.2% (or 15+/-10 sec; P<0.01) in the RMT group with 8 of 9 subjects increasing; the placebo group showed a variable non-significant change in 5 of 8 subjects (-0.3+/-2.7%, P=0.07). The changes observed in these three performance tests were not, however, significantly different between the RMT and placebo groups. Heart rate, ventilation, or venous blood lactate, at equal work-rates during the incremental exercise test or at equal times during the fixed work-rate endurance test were not changed significantly across these exercise trials in either group. We propose that the effect of RMT on exercise performance in highly trained cyclists does not exceed that in a placebo group. Significant placebo and test familiarization effects must be accounted for in experimental designs utilizing performance tests which are critically dependent on volitional effort.

The presence or severity of pulmonary hypertension does not affect outcomes for single-lung transplantation

Advanced lung disease (ALD) that requires lung transplantation (LTX) is frequently associated with pulmonary hypertension (PH). Whether the presence of PH significantly affects the outcomes following single-lung transplantation (SLT) remains controversial. Therefore, we retrospectively examined the outcomes of 279 consecutive SLT recipients transplanted at our centre, and the patients were split into four groups based on their mean pulmonary artery pressure values. Outcomes, including long-term survival and primary graft dysfunction, did not differ significantly for patients with versus without PH, even when PH was severe. We suggest that SLT can be performed safely in patients with ALD-associated PH.

Surprised but Not Shaken: AQuIRE Sheds New Light on Innovations in Bronchoscopy

The development of the flexible bronchoscope in 1968 changed the practice of pulmonary medicine more than any other advance in technology. Previously limited to the trachea, mainstem, and lobar bronchi with rigid bronchoscopy, the reach of the flexible scope took chest physicians to places not previously seen without surgical exposure. The basic tools of bronchoscopy were developed rapidly over the subsequent years, along with algorithms on their best use. Each advancement opened doors to more peripheral abnormalities, smaller nodules, and more diverse diagnoses (1, 2). Coupled with the invention and refinement of computerized tomography and ultrasonography, chest physicians are now able to reach even further into the lung with tools such as radial probe ultrasound, computer-aided navigational planning, and electromagnetic navigational bronchoscopy (3–5). Referred to as guided bronchoscopy, or navigational bronchoscopy, these tools have become commonplace for the diagnosis of peripheral lung lesions after published results that demonstrated diagnostic yields as high as 86% in selected populations (6, 7). These data, however, have several limitations, such as small sample sizes, selection bias, and retrospective designs. In a comprehensive meta-analysis, it appears that overall, the diagnostic yields are closer to 70% (8). In this issue of the Journal, Ost and colleagues (pp. 68–77) present results from the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) Registry regarding the use of navigational bronchoscopy for the diagnosis of peripheral lung abnormalities (9). The results are surprising. Or are they? In this study, conventional bronchoscopy (CB) performed better than guided bronchoscopy, with diagnostic yields of 63.7% and 38.5–57%, respectively. Tobacco use, larger size, non–upper lobe location, and the use of transbronchial needle aspiration were associated with significantly increased diagnostic yields. The strengths of their study are the numbers of subjects and procedures collected, as well as the longitudinal method of collecting the data via a registry, which provides a good representation of the use of this technology in practice from multiple institutions. In addition, the centers participating in this part of the AQuIRE Registry are leading institutions involved in the advancement of bronchoscopy and have a great deal of collective experience. However, a few drawbacks are necessary to mention: This is not a randomized controlled trial of CB versus guided bronchoscopy, which would be a necessary trial to determine the added value of guided bronchoscopy to CB, a point the authors clearly state. In addition, institutions were not all uniform in how they perform bronchoscopy, nor did they use the same technologies, and each bronchoscopist chose what procedure and techniques to perform, leading to the potential for selection bias. Despite these limitations, it seems counterintuitive that CB would perform better than guided bronchoscopy. Beyond publication bias and differences in disease prevalence and type, the authors propose some unique reasons that can be further developed. First, in the practice of bronchoscopy, physicians choose the procedure type based on a number of tangible and intangible factors. When all the technologies are available, the procedures used are often those that are most familiar to the bronchoscopist for a clinical scenario. As an example, if a lesion is felt to be approachable by CB, the bronchoscopist is not likely to use guided bronchoscopy. This shifts the easiest patients to diagnose into the CB group. Further, the patients undergoing guided bronchoscopy, when compared with those undergoing CB, are typically very different. In other words, lesions that were previously felt to be inaccessible by CB now appear within reach when guided bronchoscopic techniques are available (6). This shifts the most difficult patients to diagnose into the guided bronchoscopy group. Furthermore, many chest physicians performing guided bronchoscopy are doing so on the most diagnostically complex patients, some of which have had multiple attempts at making a diagnosis before bronchoscopy is performed. This complexity remains difficult to quantify and may partially underpin the unexpectedly low diagnostic yields found in this study. Differences in the application of navigational bronchoscopy are another reason proposed to explain the low diagnostic yields in this study. In this hypothesis set out by the authors, navigational bronchoscopy may be less diagnostic because of errors introduced by taking multiple biopsies from the exact same location because of the use of the extended working channel (or guidance itself), whereas in CB, multiple biopsies taken would all be from slightly different locations in the target, increasing the chances of having at least one pass retrieve diagnostic tissue. In other words, if guidance is inaccurate, even to a small degree, the guidance does not allow for enough pass-to-pass variation to adequately sample the lesion of interest. Although these are very reasonable hypotheses, knowing exactly why there is a difference is likely impossible at this time. Another aspect of this study worth discussing is its relatively low prevalence of cancer compared with in other studies (10). In the sensitivity analysis, the sensitivity for lung cancer was slightly higher than the diagnostic yield in the overall study. This implies that as the prevalence of cancer in the study population rises, so too will the diagnostic yield rise, as more patients will receive a diagnosis. The relatively low diagnostic yield overall also indicates that the sensitivity of bronchoscopy for benign disease is less than ideal. Indeed, an examination of Ost and colleagues’ Table E4 illustrates the limitations of bronchoscopy in making a benign diagnosis. Here there were 336 subjects with 219 malignant diagnoses made by bronchoscopy, subsequent procedures, or radiographic follow-up. Of the remaining 117 subjects, 84 (72%) had an inconclusive bronchoscopy at the first evaluation, typically necessitating follow-up or additional invasive testing. Because many patients who undergo bronchoscopy for a suspicion of lung cancer fall into an intermediate risk category (11), many will have benign disease and may be challenging to diagnose with certainty. When we take prevalence of disease, poor sensitivity for benign disease, patient selection in actual practice rather than research, and possible error introduced by the method of application of the navigation into account, the data really are not as surprising as we initially thought. The question for pulmonary medicine now is, How do we use these data so that we can best help those patients with undiagnosed pulmonary lesions? First, we have to be honest: we are not as good as we think we are. We do not believe, however, that these data suggest we abandon guided bronchoscopy. Certainly, prudence and humility should be exercised in the future application of guided bronchoscopy, and

IMPROVING TIMELINESS OF NSCLC TREATMENT

PURPOSE: There are no widely accepted guidelines on timeliness of the treatment of NSCLC. The National Lung Screening Trial made it clear that early diagnosis results in improved outcomes. The GAIN summit began as an educational curriculum designed to improve the knowledge, competence, and performance of a team of interdisciplinary specialists responsible for assessing and managing patients with non-small cell lung cancer. GAIN summits have been carried out nationally and internationally. We propose that by increasing awareness of the process and teaching appropriate staging techniques, the GAIN Summit can improve the timeliness of NSCLC treatment.

Effectiveness of Reprocessing for Flexible Bronchoscopes and Endobronchial Ultrasound Bronchoscopes

BACKGROUND: Infections have been linked to inadequately reprocessed flexible bronchoscopes, and recent investigations determined that pathogen transmission occurred even when bronchoscope cleaning and disinfection practices aligned with current guidelines. This multisite, prospective study evaluated the effectiveness of real‐world bronchoscope reprocessing methods, using a systematic approach. METHODS: This study involved direct observation of reprocessing methods for flexible bronchoscopes, multifaceted evaluations performed after manual cleaning and after high‐level disinfection, and assessments of storage conditions. Visual inspections of ports and channels were performed using lighted magnification and borescopes. Contamination was detected using microbial cultures and tests for protein, hemoglobin, and adenosine triphosphate (ATP). Researchers assessed reprocessing practices, and storage cabinet cleanliness was evaluated by visual inspection and ATP tests. RESULTS: Researchers examined 24 clinically used bronchoscopes. After manual cleaning, 100% of bronchoscopes had residual contamination. Microbial growth was found in 14 fully reprocessed bronchoscopes (58%), including mold, Stenotrophomonas maltophilia, and Escherichia coli/Shigella species. Visible irregularities were observed in 100% of bronchoscopes, including retained fluid; brown, red, or oily residue; scratches; damaged insertion tubes and distal ends; and filamentous debris in channels. Reprocessing practices were substandard at two of three sites. CONCLUSIONS: Damaged and contaminated bronchoscopes were in use at all sites. Inadequate reprocessing practices may have contributed to bioburden found on bronchoscopes. However, even when guidelines were followed, high‐level disinfection was not effective. A shift toward the use of sterilized bronchoscopes is recommended. In the meantime, quality management programs and updated reprocessing guidelines are needed.

Single lung transplantation has equivalent long term outcomes to bilateral lung transplantation in patients with pulmonary hypertension associated with advanced lung disease

Whether bilateral lung transplantation (BLT) rather than single lung transplantation (SLT) should be preferentially performed for patients with World Health Association (WHO) Group 3 pulmonary hypertension (PH) associated with advanced lung disease has been controversial. We retrospectively examined the outcomes of 474 consecutive patients who underwent BLT or SLT at our center between 1999 and 2013. After exclusion of patients with cystic fibrosis or those undergoing retransplantation, 179 patients with PH were split into four groups based on their pulmonary artery pressure values (mild versus severe) and transplant type (BLT versus SLT). The incidence of grade 2-3 primary graft dysfunction and mechanical ventilation >48 hours was significantly higher for the BLT versus the SLT recipients. However, long-term survival via the Kaplan-Meier method and appropriate log rank tests did not differ significantly among the four cohorts. Because long-term outcomes for patients who undergo SLT for advanced lung disease associated with WHO Group 3 PH did not differ significantly from those for BLT recipients, even if PH was severe, we suggest that SLT can be performed safely in patients with Group 3 PH associated with ALD and potentially allows improved donor organ utilization. Correspondence to: Keith C. Meyer, Professor of Medicine, University of Wisconsin Lung Transplant and Advanced Lung Disease Program, Section of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, USA, Tel: 608 263-6363/608 263-3035, Fax: 608 263-3104; E-mail: kcm@medicine.wisc.edu