Adrenocortical suppression in children with nephrotic syndrome treated with corticosteroids.

BACKGROUND: Children with nephrotic syndrome are exposed to alternate day steroids for prolonged periods and this poses the need for evaluation of adrenocortical suppression using the adrenocorticotropic hormone (ACTH) stimulation test. METHODS: This cross-sectional study enrolled children (2-18 years) both with steroid sensitive nephrotic syndrome (SSNS) (n = 27) and steroid resistant (SRNS) (n = 25); those on daily prednisolone or having serious bacterial infections or hospitalized were excluded. The primary objective was to determine prevalence of adrenocortical suppression in those on low dose alternate day steroids for more than 8 weeks or having received > 2 mg/kg/d for > 2 weeks in the past 1 year and currently in remission. A baseline morning fasting sample of serum cortisol was taken and 25 IU of ACTH (Acton Prolongatum*) injected intramuscularly and repeat serum cortisol sample taken after 1 h. All patients with 1 h post ACTH cortisol < 18.0 µgm/dl were diagnosed with adrenal insufficiency. Receiver operating characteristic curve was drawn to predict the prednisolone dose for adrenal insufficiency. RESULTS: Fifty-two (33 males) children were enrolled (mean age 9.4 years); proportion of adrenal insufficiency was 50% and 64% using baseline and post stimulation cutoffs. The total cumulative annual dose of prednisolone 0.22 mg/kg/day predicted adrenocortical suppression with AUC 0.76 (95% CI 0.63-0.89), with sensitivity of 63.9% and specificity of 81.3%. CONCLUSIONS: A significant proportion of children with nephrotic syndrome were detected with adrenal insufficiency on ACTH stimulation test. A cumulative steroid intake of > 0.22 mg/kg/day on an alternate day basis emerged as a risk factor for predicting adrenocortical suppression.

Performance of Biopsy Tools in Procurement of Lung Tissue in Robot-Assisted Peripheral Navigation: A Comparison.

INTRODUCTION: Robot-assisted navigation bronchoscopy (RANB) has been gaining traction as a new technology for minimally invasive biopsies of peripheral pulmonary lesions (PPLs). Cryobiopsy is an established method of procuring satisfactory lung tissues and can be safely paired with RANB. While some studies have evaluated the diagnostic accuracy and yield of this procedure, there is limited data on the utility of various biopsy tools, the sequence of use and differences in tissue characteristics based on the sampling techniques. Therefore, this study aims to examine the real-life performance of needle, forceps and cryoprobe when utilized in succession with RANB in the biopsy of PPLs, and to evaluate the specific types of tissue samples obtained from each instrument. METHODS: In a single-center retrospective study, 50 patients presenting 52 PPLs underwent biopsies sequentially using fine-needle aspiration (FNA), forceps, and cryoprobe. All procedures were performed via cone-beam CT-assisted RANB. Performance metrics, such as diagnostic yield, sensitivity, and specificity, were determined by classifying malignancy as true positives and explicit benign findings as true negatives. Tissue sizes and subtypes were based on pathology description and compared with Student's t test and χ2, respectively. RESULTS: Cryobiopsy, when performed sequentially after FNA then forceps, was able to retrieve more alveolar tissue (p = 0.0098) among diagnosed lesions and showed higher diagnostic yield (p = 0.001) in PPL biopsy with RANB platform. Cryobiopsy was also able to obtain larger sample size (p = 0.0087). No difference was observed in the diagnosis of malignancy between forceps and cryobiopsy (p = 0.8877). CONCLUSION: The integration of RANB and sequential biopsies, utilizing FNA, forceps, and cryoprobe, can efficiently diagnose PPLs and procure alveolar tissues. Further research based on histopathological subtypes is required to assess its prognostic significance.

Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Intravenous Infusions of PF-07304814 (Lufotrelvir) in Participants Hospitalized With COVID-19.

Background: An urgent need remains for antiviral therapies to treat patients hospitalized with COVID-19. PF-07304814-the prodrug (lufotrelvir) and its active moiety (PF-00835231)-is a potent inhibitor of the SARS-CoV-2 3CL protease. Method: Eligible participants were 18 to 79 years old and hospitalized with confirmed COVID-19. This first-in-human phase 1b study was designed with 2 groups: single ascending dose (SAD) and multiple ascending dose (MAD). Participants could receive local standard-of-care therapy. In SAD, participants were randomized to receive a 24-hour infusion of lufotrelvir/placebo. In MAD, participants were randomized to receive a 120-hour infusion of lufotrelvir/placebo. The primary endpoint was to assess the safety and tolerability of lufotrelvir. The secondary endpoint was to evaluate the pharmacokinetics of lufotrelvir and PF-00835231. Results: In SAD, participants were randomized to receive 250 mg lufotrelvir (n = 2), 500 mg lufotrelvir (n = 2), or placebo (n = 4) by continuous 24-hour infusion. In MAD, participants were randomized to receive 250 mg lufotrelvir (n = 7), 500 mg lufotrelvir (n = 6), or placebo (n = 4) by continuous 120-hour infusion. No adverse events or serious adverse events were considered related to lufotrelvir. At doses of 250 and 500 mg, concentrations for the prodrug lufotrelvir and active moiety PF-00835231 increased in a dose-related manner. Unbound concentrations of the lufotrelvir active metabolite reached steady state approximately 2- and 4-fold that of in vitro EC90 following 250- and 500-mg doses, respectively. Conclusions: These safety and pharmacokinetic findings support the continued evaluation of lufotrelvir in clinical studies. Clinical Trials Registration. ClinicalTrials.gov NCT04535167.

Cone Beam CT Guidance Improves Transbronchial Lung Cryobiopsy Safety.

INTRODUCTION: Determining the cause of diffuse parenchymal lung disease (DPLD) is challenging. While surgical lung biopsy has been the standard approach, transbronchial lung cryobiopsy (TBLC) represents a minimally invasive alternative with an acceptable safety profile and reasonable accuracy. In this study, we prospectively assessed whether the use of cone beam CT (CBCT) coupled with a novel bronchoscope holder and prophylactic administration of vasoconstricting medications decreases potential complications and improves diagnostic accuracy when performing TBLC. METHODS: 33 patients presenting for evaluation of newly diagnosed DPLD were enrolled. Demographic data, pulmonary function values, chest imaging pattern, procedural information, and diagnosis were recorded. RESULTS: Mean patient age was 67, with the majority Caucasian (n = 26, 79%) and male (n = 20, 61%). Mean pulmonary function values revealed restrictive lung disease (76 ± 14% predicted) and diffusing capacity impairment (52 ± 16%). A non-usual interstitial pneumonia imaging pattern was commonly seen (n = 20, 61%). CBCT guided TBLC was performed in one lobe (n = 29, 88%) or two lobes (n = 4, 12%) with mean probe-to-pleura distance of 4.2 ± 1.3 mm. No peri or post procedural complications occurred. 32 patients (97%) received a histological diagnosis with a final multidisciplinary conference diagnosis possible for 32 (97%). CONCLUSION: CBCT guided TBLC coupled with a novel articulating scope holder and prophylactic phenylephrine administration has the potential to increase safety and diagnostic yield for patients with newly identified DPLD. Future studies comparing different aspects of this approach in isolation and with other modalities have the potential to refine this procedure to improve patient care.

Endobronchial Leiomyoma: A case report with cryoprobe extraction and review of literature.

Large airway tumors are uncommon, accounting for about 0.6% of all pulmonary tumors [[1], [2], [3]]. The majority of these tumors (80-90%) are malignant, represented primarily by squamous cell carcinoma and adenoid cystic carcinoma [2,4]. Benign central airway tumors are less common and are generally comprised of hamartomas and papillomas. Tracheobronchial leiomyomas are exceedingly rare, representing only about 0.6% of all benign lung neoplasms [3]. We report here on a case of primary endobronchial leiomyoma without uterine involvement treated successfully with cryoresection with excellent outcome.

Robotic-Assisted Navigation Bronchoscopy as a Paradigm Shift in Peripheral Lung Access.

INTRODUCTION: The sensitivity of suspicious lung nodules biopsied by currently available techniques is suboptimal. Robotic-assisted navigation bronchoscopy (RANB) is a novel method for biopsying lung nodules. Our study objective was to determine the sensitivity for malignancy and overall diagnostic accuracy for RANB when combined with cone beam CT (CBCT) for secondary confirmation. METHODS: 52 consecutive patients were prospectively enrolled. Demographic data, nodule characteristics, procedural information, and follow-up results were obtained. RESULTS: Mean patient age was 66, with the majority Caucasian (73%) females (65%) with a similar number of never (46%) and former (46%) smokers. 15 patients had a history of cancer and 3 had a prior thoracic surgery. 59 total nodules were included as 7 patients had two nodules biopsied. Mean nodule diameter was < 2 cm in all dimension with the majority solid (41, 70%) and located in the upper lobes (left: 22, 37%; right: 17, 29%). Bronchus sign was absent (32, 54%) or present (27, 46%) in a similar number. All nodules were successfully reached with nine (15%) requiring minor directional changes after initial cone beam CT. A tissue diagnosis was obtained in 83% (49/59) of biopsied nodules, with malignancy (31, 65%) most common. Including all biopsy results and follow-up imaging, we obtained an 84% (31/37) procedural sensitivity for malignancy and an overall 86% (51/59) diagnostic yield. CONCLUSION: RANB with CBCT increases sensitivity for malignancy and diagnostic accuracy of lung nodule biopsies. Combining these modalities has the potential to shift the diagnostic approach to pulmonary nodules.

Bronchoscopic Treatment of Airway Obstructions With a Novel Electrosurgical Device.

OBJECTIVES: Airway obstructions (AOs) in the central airway or lobar bronchi develop due to malignant or benign disease. Because of the morbidity and mortality associated with AO, it is important to develop additional therapeutic ablative techniques. CoreCath2.7S is a novel monopolar radiofrequency electrosurgical device approved to treat obstructions of the upper airway and tracheobronchial tree by both cutting soft tissue and providing electrosurgical hemostasis. We present a large case series describing its use. METHODS: Retrospective chart review was performed of all patients with AO undergoing airway recanalization with CoreCath2.7S at 2 interventional pulmonology practices from October 2017 to May 2019. Demographic information, AO etiology, location, and degree, and therapeutic modalities used were recorded. RESULTS: Fifty-three patients underwent 64 procedures for AO due to malignant (n=30, 57%) or benign (n=23, 43%) disease. AOs were treated in the trachea (n=28), mainstem bronchi (n=23), and lobar bronchi (n=17). All AO occluded the airway at least 50%. Adjunctive therapeutic modalities were commonly used (n=60, 94%), including flexible cryoprobe (n=33), balloon dilation (n=23), rigid bronchoscopy (n=19), spray cryotherapy (n=19), argon plasma coagulation (n=14), and stenting (n=5). Restoration of airway patency was achieved in all cases without any periprocedural or immediate postprocedural complications. CONCLUSION: CoreCath2.7S was successfully used to treat patients with AO due to malignant or benign disease. Airway patency was restored with no periprocedural or immediate postprocedural complications. It should be considered as another therapeutic modality in the growing field of ablative techniques for the treatment of AO.

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.

The Impact of Bronchial Thermoplasty on Asthma-Related Quality of Life and Controller Medication Use.

BACKGROUND: Despite an improved understanding of the pathophysiology of asthma, severe asthma sufferers continue to experience a poor quality of life (QOL). Bronchial thermoplasty (BT) utilizes thermal energy to reduce airway smooth muscle. In industry-sponsored trials, BT improves QOL and reduces severe exacerbations; however, the impact of BT on asthma-related QOL and medication use in non-industry-sponsored trials is less clear. OBJECTIVE: The aim of this study was to determine the impact of BT on asthma QOL measures (mini-AQLQ) and asthma controller medication use during the year following treatment with BT. METHODS: We performed a prospective study of the impact of BT in 25 patients with severe persistent asthma. Our primary outcome was change in asthma-related QOL score (mini-AQLQ) 1 year after BT treatment. Our secondary outcome was change in asthma medication use 1 year after BT. RESULTS: BT led to an improvement in mini-AQLQ score from a baseline of 3.6 ± 0.3 before therapy to 5.6 ± 0.3 1 year after the final BT procedure. Overall, 88% percent of patients showed a clinically significant improvement in mini-AQLQ at 1 year. Patients treated with BT showed a reduction in the use of montelukast and omalizumab 1 year after BT. CONCLUSION: In patients with severe persistent asthma and low asthma-related QOL scores, BT leads to an improvement in asthma-related QOL and a decrease in asthma medication use when measured 1 year after the final BT treatment.

Using a Dedicated Interventional Pulmonology Practice Decreases Wait Time Before Treatment Initiation for New Lung Cancer Diagnoses.

PURPOSE: While there is significant mortality and morbidity with lung cancer, early stage diagnoses carry a better prognosis. As lung cancer screening programs increase with more pulmonary nodules detected, expediting definitive treatment initiation for newly diagnosed patients is imperative. The objective of our analysis was to determine if the use of a dedicated interventional pulmonology practice decreases time delay from new diagnosis of lung cancer or metastatic disease to the chest to treatment initiation. METHODS: Retrospective chart analysis was done of 87 consecutive patients with a new diagnosis of primary lung cancer or metastatic cancer to the chest from our interventional pulmonology procedures. Demographic information and time intervals from abnormal imaging to procedure and to treatment initiation were recorded. RESULTS: Patients were older (mean age 69) and former or current smokers (72%). A median of 27 days (1-127 days) passed from our diagnostic biopsy to treatment initiation. A median of 53 total days (2-449 days) passed from abnormal imaging to definitive treatment. Endobronchial ultrasound-guided transbronchial needle aspiration was the most commonly used diagnostic procedure (59%), with non-small cell lung cancer the majority diagnosis (64%). For surgical patients, all biopsy-negative lymph nodes from our procedures were cancer-free at surgical excision. CONCLUSIONS: Compared to prior reports from international and United States cohorts, obtaining a tissue biopsy diagnosis through a gatekeeper interventional pulmonology practice decreases median delay from abnormal imaging to treatment initiation. This finding has the potential to positively impact patient outcomes and requires further evaluation.

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).

RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

Transbronchial Cryobiopsies for the Diagnosis of Diffuse Parenchymal Lung Diseases: Expert Statement from the Cryobiopsy Working Group on Safety and Utility and a Call for Standardization of the Procedure.

Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on "Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease" (Ravenna, October 27-28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.

Endobronchial Ultrasound-guided Transbronchial Needle Injection of Liposomal Amphotericin B for the Treatment of Symptomatic Aspergilloma.

Surgical treatment with lung resection has traditionally been the treatment of choice for pulmonary cavities containing aspergillomas that cause hemoptysis. Endobronchial ultrasound (EBUS) is a minimally invasive bronchoscopic technique that is commonly used for transbronchial needle aspiration of hilar and mediastinal lymph nodes as well as centrally located parenchymal lesions. Here, we describe a case of a 71-year-old woman who was found to have a cavitary lesion in the lung containing aspergillomas. Under direct ultrasound visualization with EBUS, liposomal amphotericin B was injected into the aspergillomas. These aspergillomas regressed after treatment. To our knowledge, this is the first reported treatment of aspergilloma with EBUS-guided transbronchial needle injection of liposomal amphotericin B.

Electromagnetic Navigational Bronchoscopy Spares a Drunken Crab From the Surgeon's Knife.

Surgical resection is traditionally the preferred treatment for fluorodeoxyglucose-avid peripheral pulmonary nodules that grow over time. However, new technologies, including electromagnetic navigational bronchoscopy (ENB), provide an opportunity to confirm or possibly exclude a cytologic cancer diagnosis, before resection. We present a case of a 56-year-old North American man who presented with a fluorodeoxyglucose-avid pulmonary nodule and sought a second opinion after being recommended thoracotomy with lobectomy. The peripheral nodule was biopsied using ENB and pathologic evaluation of the lesion demonstrated parasitic eggs with features of Paragonimus westermani. No evidence of malignancy was found. The radiographic abnormalities resolved after treatment with praziquantel. Using a minimally invasive procedure with ENB, we successfully diagnosed pulmonary infection with P. westermani, a rare infectious cause of peripheral pulmonary lesions in a patient without travel to an endemic area. Furthermore, an alternative diagnosis to cancer was established, sparing this patient an unnecessary thoracotomy with right middle lobectomy.

Improved targeting accuracy of lung tumor biopsies with scanning-beam digital x-ray tomosynthesis image guidance.

PURPOSE: Electromagnetic navigation bronchoscopy (ENB) provides improved targeting accuracy during transbronchial biopsies of suspicious nodules. The greatest weakness of ENB-based guidance is the registration divergence that exists between the planning CT, acquired days or weeks before the intervention, and the patient on the table on the day of the intervention. Augmenting ENB guidance with real-time tomosynthesis imaging during the intervention could mitigate the divergence and further improve the yield of ENB-guided transbronchial biopsies. The real-time tomosynthesis prototype, the scanning-beam digital x-ray (SBDX) system, does not currently display images reconstructed by the iterative algorithm that was developed for this lung imaging application. A protocol using fiducial markers was therefore implemented to permit evaluation of potential improvements that would be provided by the SBDX system in a clinical setting. METHODS: Ten 7 mm lesions (5 per side) were injected into the periphery of each of four preserved pig lungs. The lungs were then placed in a vacuum chamber that permitted simulation of realistic motion and deformation due to breathing. Standard clinical CT scans of the pig lung phantoms were acquired and reconstructed with isotropic resolution of 0.625 mm. Standard ENB-guided biopsy procedures including target identification, path planning, CT-to-lung registration and navigation to the lesion were carried out, and a fiducial marker was placed at the location at which a biopsy would have been acquired. The channel-to-target distance provided by the ENB system prior to fiducial placement was noted. The lung phantoms were then imaged using the SBDX system, and using high-resolution conebeam CT. The distance between the fiducial marker tip and the lesion was measured in SBDX images and in the gold-standard conebeam-CT images. The channel-to-target divergence predicted by the ENB system and measured in the SBDX images was compared to the gold standard to determine if improved targeting accuracy could be achieved using SBDX image guidance. RESULTS: As expected, the ENB system showed poorer targeting accuracy for small peripheral nodules. Only 20 nodules of the 40 injected could be adequately reached using ENB guidance alone. The SBDX system was capable of visualizing these small lesions, and measured fiducial-to-target distances on SBDX agreed well with measurements in gold-standard conebeam-CT images (p = 0.0001). The correlation between gold-standard conebeam-CT distances and predicted fiducial-to-target distances provided by the ENB system was poor (p = 0.72), primarily due to inaccurate ENB CT-to-body registration and movement due to breathing. CONCLUSIONS: The SBDX system permits visualization of small lung nodules, as well as accurate measurement of channel-to-target distances. Combined use of ENB with SBDX real-time image guidance could improve accuracy and yield of biopsies, particularly of those lesions located in the periphery of the lung.

Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial.

IMPORTANCE: Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. OBJECTIVE: To determine the effectiveness and safety of endobronchial coil treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. INTERVENTIONS: Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. MAIN OUTCOMES AND MEASURES: The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St George's Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. RESULTS: Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs -7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St George's Respiratory Questionnaire score improved -8.9 points (97.5% CI, -∞ to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. CONCLUSIONS AND RELEVANCE: Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01608490.

Patient dose simulations for scanning-beam digital x-ray tomosynthesis of the lungs.

PURPOSE: An improved method of image guidance for lung tumor biopsies could help reduce the high rate of false negatives. The aim of this work is to optimize the geometry of the scanning-beam digital tomography system (SBDX) for providing real-time 3D tomographic reconstructions for target verification. The unique geometry of the system requires trade-offs between patient dose, imaging field of view (FOV), and tomographic angle. METHODS: Tomosynthetic angle as a function of tumor-to-detector distance was calculated. Monte Carlo Software (PCXMC) was used to calculate organ doses and effective dose for source-to-detector distances (SDDs) from 90 to 150 cm, patient locations with the tumor at 20 cm from the source to 20 cm from the detector, and FOVs centered on left lung and right lung as well as medial and distal peripheries of the lungs. These calculations were done for two systems, a SBDX system and a GE OEC-9800 C-arm fluoroscopic unit. To evaluate the dose effect of the system geometry, results from PCXMC were calculated using a scan of 300 mAs for both SBDX and fluoroscopy. The Rose Criterion was used to find the fluence required for a tumor SNR of 5, factoring in scatter, air-gap, system geometry, and patient position for all models generated with PCXMC. Using the calculated fluence for constant tumor SNR, the results from PCXMC were used to compare the patient dose for a given SNR between SBDX and fluoroscopy. RESULTS: Tomographic angle changes with SDD only in the region near the detector. Due to their geometry, the source array and detector have a peak tomographic angle for any given SDD at a source to tumor distance that is 69.7% of the SDD assuming constant source and detector size. Changing the patient location in order to increase tomographic angle has a significant effect on organ dose distribution due to geometrical considerations. With SBDX and fluoroscopy geometries, the dose to organs typically changes in an opposing manner with changing patient location. When tumor SNR is held constant (i.e., x-ray fluence is scaled appropriately), SBDX gives 2-10 times less dose than fluoroscopy for the same conditions within the typical range of patient locations. The relative position of the patient (as a percent of SDD) has a much more significant impact on dose than either SDD or patient position. The patient position providing the minimum dose for a given tumor SNR and SDD is approximately the same as the position of maximum tomographic angle. CONCLUSIONS: SBDX offers a significant dose advantage over currently used C-arm fluoroscopy. The patient location with lowest dose coincides with the location of maximum tomographic angle. In order to provide adequate space for the patient and for the pulmonologists' equipment, a SDD of 100 cm is recommended.