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Barak Pertzov,1,2 Maysaa Soliman,2 Yael Shostak,1,2 Moshe Heching,1,2 Dror Rosengarten,1,2 Gabriel Izbicki,3,4,* Mordechai Reuven Kramer1,2,* 1Pulmonary Division, Rabin Medical Center, Petach Tikva, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Pulmonary Institute, Shaare Zedek Medical Center, Jerusalem, Israel; 4Hebrew University-Hadassah Medical School, Jerusalem, Israel*These authors contributed equally to this workCorrespondence: Barak PertzovPulmonary Division, Rabin Medical Center, Petach Tikva, IsraelTel +972-3-9377221/3Fax +972-3-9242091Email pertzovb@gmail.comBackground: Lung volume reduction with endobronchial coils treatment (ECT), for patients with severe emphysema, has shown modest improvement in exercise capacity and lung functions in clinical trials, yet the benefit of this procedure is still unclear.Methods: We conducted a multicenter retrospective cohort study including all patients who underwent ECT in Israel and a propensity score matched control group of patients with chronic obstructive pulmonary disease (COPD) that were treated with usual care. The primary outcome was six-minute walk test distance (6MWTD), secondary outcomes were lung function tests and patient survival.Results: Overall, 46 patients were included in the ECT group. Their mean 6MWTD at baseline and at 6 and at 24 months post procedure was 331.0± 101.4, 372.9± 76.8 and 338.8± 104.8, respectively (overall P=0.04, pairwise comparison: baseline to 6 months (P=0.1), baseline to 24 months (P=1.0)). Mean FEV1 values at baseline and at 6 and at 24 months post procedure were 0.86± 0.38, 0.92± 0.37 and 0.82± 0.36 liters, respectively (overall P=0.003, pairwise comparison: baseline to 6 months (P=0.04), baseline to 24 months (P=0.75)). The median 6MWTD for the ECT and control groups at 24 months were 333.0 (262.5– 390) and 280 (210– 405), respectively (P=0.16). There was no difference in overall survival (P=0.84). Heterogenous emphysema was a significant predictor of treatment success in univariate analysis (p=0.004).Conclusion: Lung volume reduction with endobronchial coils may improve the exercise capacity and FEV1 of COPD patients. However, the majority of the effect was diminished after 24 months. The current state of evidence does not support regulatory approval of ECT and warrant its use only after consideration of the benefit-harm ratio in a highly selected patient population.Keywords: emphysema, endobronchial coils, lung volume reduction, six-minute walk, residual volume, FEV1, survival

To compare the effectiveness of a combined aerobic, strength, and flexibility training program with flexibility alone on disease-specific and health-related symptoms in ambulatory amyotrophic lateral sclerosis (ALS) patients. Thirty-two ambulatory patients with ALS were equally randomized into a combined aerobic-strength intervention group or a stretching control group. The intervention period for both groups was identical, 12 consecutive weeks, two sessions per week. The combined intervention program consisted of aerobic training by recumbent cycling, flexibility achieved by stretching and passive exercises, and strength training via functional exercises. Patients in the control group performed basic stretching exercises of the upper and lower limb at home. Outcome measures included the ALS Functional Rating Scale-Revised (ALSFRS-R), respiratory function, mobility, fatigue, and quality of life and were collected 1-week prior to the intervention, after 6-weeks of training, and at the completion of the intervention. Twenty-eight participants (17 males, 11 females); mean age (S.D.) = 58.5 (13.2) years; mean disease duration (S.D.) = 7.3 (12.0) years, completed the study. According to the group X time analysis, significant differences were found in respiratory function, mobility, and the ALSFRS-R in favor of the aerobic-strength group. These patients maintained their abilities, whereas, a significant decrease was observed in the flexibility training group. Scores of the SF-36 categories “physical functioning”, “energy fatigue” and “wellbeing” were higher following the intervention in the aerobic-strength group compared with the stretching control group. A 12-week combined aerobic and strength training program is far superior to flexibility alone in improving respiratory function, mobility, and wellbeing in ambulatory ALS patients.

In vitro studies have demonstrated rescue of CFTR function with Elexacaftor/Tezacaftor/Ivacaftor (ETI) in several mutations other than F508del. However, clinical efficacy was not tested in vivo in people with CF (pwCF) carrying mutations other than F508del. We report effects of treatment with ETI in pwCF with non-F508del mutations.We retrospectively analyzed pwCF with non-F508del mutations who received treatment with ETI. We evaluated sweat chloride, nutritional status, spirometry, antibiotic treatment, and pulmonary exacerbations (PEx), at baseline and 3-6 months after commencing treatment with ETI.We included 16 pwCF, including eight without previous use of CFTR modulators. Median time on treatment was 5.3 (range, 1.8-7.7) months. Compared to baseline, in the "naïve" group sweat chloride concentration was reduced from 113.0 (98-129) to 64.0 (32-97) mEq/L (n=7; median (IQR), p=0.018), and rate of pulmonary exacerbations declined from a median of 1.5 (IQR 1, 2.75) in the previous year to 0 (0,0) (p= 0.019) with a significant decline in annualized days with antibiotics (oral + parenteral) per year: 36 (17.5; 42) in the year before to 0 (0,0) (median (IQR), p= 0.027). Mean FEVWe demonstrate the clinical efficacy of ETI in pwCF carrying CFTR processing non-F508del mutations which are predicted to respond by in vitro studies. Our results support routine clinical use of ETI in this patient group.

Summary Rationale While various nutritional assessment tools have been proposed, consensus is lacking with respect to the most effective tool to identify severe malnutrition in critically ill patients. Methods We conducted a retrospective study in an adult general intensive care unit (ICU) comparing four nutritional assessment tools: Nutrition Risk Screening (NRS), Nutrition Risk in Critically Ill (NUTRIC), and malnutrition criteria proposed by European Society of Clinical Nutrition and Metabolism (ESPEN) and American Society for Parenteral and Enteral Nutrition (ASPEN). These criteria were tested for their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in diagnosis of severe malnutrition, defined as Subjective Global Assessment (SGA) C. Results Hospitalization records for 120 critically ill patients were analyzed. 60 (50%), 17 (14.2%) and 43 (35.8%) patients were classified as SGA A, B, and C, respectively. The sensitivity in diagnosis of severe malnutrition was 79.1%, 58.1%, 65.1%, and 65.1%, and specificity was 94.8%, 74.0%, 94.8%, and 98.7% for NRS, NUTRIC, ESPEN, and ASPEN, respectively. NRS, ESPEN, and ASPEN had higher PPV (89.5%, 87.5%, and 87.5%, respectively) and NPV (89%, 83%, and 83.5%, respectively) than NUTRIC (PPV 55.6% and NPV 76%). NUTRIC showed the highest correlation with mortality, but none of the tools retained their correlation with mortality after adjustment for potential confounding factors. Conclusions NRS showed the highest sensitivity and high specificity, PPV, and NPV. NUTRIC had least effective overall performance in diagnosis of severe malnutrition in an ICU setting. A larger population may be required to explore the association between mortality and these nutritional assessment tools.

Objectives Data are limited regarding the clinical significance of nontuberculous mycobacteria pulmonary infections among lung transplant recipients. We investigated the incidence and characteristics of pulmonary nontuberculous mycobacteria infection in ourlung transplant patient population. Materials and methods We obtaineddata of the patients who underwent lung transplant in our center from January 1997 to March 2019. Results Of 690 patients, nontuberculous mycobacteria were identified in 58 patients (8.4%) over a median follow-up of 3 years. Types of species were as follows: Mycobacterium simiae (n = 24), avium complex (n = 12), abscessus (n = 9), fortuitum (n = 6), chelonae (n = 2), szulgai (n = 1), kansasii (n = 1), lentiflavum (n = 1), and undefined mycobacteria (n = 2). When we compared infections in the early versus late period posttransplant (before and after 6 months), infections with Mycobacterium simiae (16 vs 8 incidents) and Mycobacterium fortuitum (5 vs 1 incident) were more often observed within the early period, whereas most Mycobacterium abscessus (7 vs 1 incident) and Mycobacterium avium complex (9 vs 3 incidents) were observed in the later period. The median forced expiratory volume in 1 second overtime did not differ significantly between patients with and without nontuberculous mycobacteria infection (P = .29). Nontuberculous mycobacteria acquisition was significantly associated with decreased survival (relative risk of 2.41, 95% CI, 1.70-3.43; P ⟨ .001). Conclusions The nontuberculous mycobacteria species isolated varied according to the time elapsed since transplant. Among lung transplant recipients, nontuberculous mycobacteria infection was associated with increased mortality but not with lung dysfunction.

Patients with COVID-19 report severe respiratory symptoms consistent with ARDS. The clinical presentation of ARDS in COVID-19 is often atypical, as patients with COVID-19 exhibit a disproportionate hypoxemia compared with relatively preserved lung mechanics. This pattern is more similar to neonatal respiratory distress syndrome secondary to surfactant deficiency, which has been shown to benefit from exogenous surfactant. We present our experience with exogenous surfactant treatment in a patient with COVID-19 experiencing COVID-19-related ARDS. The patient responded with improved oxygenation, and we believe surfactant was the catalyst for the successful extubation and clinical improvement of the patient.

Background Capnography waveform contains essential information regarding physiological characteristics of the airway and thus indicative of the level of airway obstruction. Our aim was to develop a capnography-based, point-of-care tool that can estimate the level of obstruction in patients with asthma and COPD. Methods Two prospective observational studies conducted between September 2016 and May 2018 at Rabin Medical Center, Israel, included healthy, asthma and COPD patient groups. Each patient underwent spirometry test and continuous capnography, as part of, either methacholine challenge test for asthma diagnosis or bronchodilator reversibility test for asthma and COPD routine evaluation. Continuous capnography signal, divided into single breaths waveforms, were analyzed to identify waveform features, to create a predictive model for FEV1 using an artificial neural network. The gold standard for comparison was FEV1 measured with spirometry. Measurements and main results Overall 160 patients analyzed. Model prediction included 32/88 waveform features and three demographic features (age, gender and height). The model showed excellent correlation with FEV1 (R = 0.84), R2 achieved was 0.7 with mean square error of 0.13. Conclusion In this study we have developed a model to evaluate FEV1 in asthma and COPD patients. Using this model, as a point-of-care tool, we can evaluate the airway obstruction level without reliance on patient cooperation. Moreover, continuous FEV1 monitoring can identify disease fluctuations, response to treatment and guide therapy. Trial registration clinical trials.gov, NCT02805114. Registered 17 June 2016, https://clinicaltrials.gov/ct2/show/NCT02805114

Background The LungVision system is a novel augmented‐fluoroscopy‐based real‐time navigation and guidance technology for bronchoscopy that can be integrated with any standard biopsy tool, including the cryoprobe, to enable real‐time visualization and localization of pulmonary nodules. Objectives To evaluate the diagnostic yield and safety among patients undergoing peripheral pulmonary nodule biopsy with the LungVision system. Methods This prospective, single‐center study was conducted at Rabin Medical Center in Israel. All patients that underwent peripheral pulmonary nodule biopsy with the LungVision system from January 2016 to August 2020 were included. All procedures were performed under moderate sedation. The primary outcome was tissue diagnosis by either identification of malignant cells or benign diagnosis. Secondary outcomes were safety and the added value of cryobiopsy. Results Sixty‐three procedures were performed during the study period. Median lesion size (interquartile range) was 25.0 mm (18–28 mm). The diagnostic yield overall was 27/33 (81.8%) and for lesions smaller than 20 mm was 13/18 (72.2%). In nine cases the transbronchial cryobiopsy showed tissue with malignant cells that were not found in any other biopsy material taken with other sampling tools. One patient was treated with a chest tube for a pneumothorax. No other major complications were reported. Conclusions The LungVision system showed good feasibility and safety for peripheral pulmonary nodule biopsy. The system is compatible with all biopsy tools, including the cryoprobe. Randomized controlled trials are needed to accurately ascertain its diagnostic yield., The LungVision fluoroscopy‐based navigation and guidance technology for bronchoscopic biopsy of peripheral pulmonary nodules is safe and effective.

To compare the effectiveness of a combined aerobic, strength, and flexibility training program with flexibility alone on disease-specific and health-related symptoms in ambulatory amyotrophic lateral sclerosis (ALS) patients.Thirty-two ambulatory patients with ALS were equally randomized into a combined aerobic-strength intervention group or a stretching control group. The intervention period for both groups was identical, 12 consecutive weeks, two sessions per week. The combined intervention program consisted of aerobic training by recumbent cycling, flexibility achieved by stretching and passive exercises, and strength training via functional exercises. Patients in the control group performed basic stretching exercises of the upper and lower limb at home. Outcome measures included the ALS Functional Rating Scale-Revised (ALSFRS-R), respiratory function, mobility, fatigue, and quality of life and were collected 1-week prior to the intervention, after 6-weeks of training, and at the completion of the intervention.Twenty-eight participants (17 males, 11 females); mean age (S.D.) = 58.5 (13.2) years; mean disease duration (S.D.) = 7.3 (12.0) years, completed the study. According to the group X time analysis, significant differences were found in respiratory function, mobility, and the ALSFRS-R in favor of the aerobic-strength group. These patients maintained their abilities, whereas, a significant decrease was observed in the flexibility training group. Scores of the SF-36 categories "physical functioning", "energy fatigue" and "wellbeing" were higher following the intervention in the aerobic-strength group compared with the stretching control group.A 12-week combined aerobic and strength training program is far superior to flexibility alone in improving respiratory function, mobility, and wellbeing in ambulatory ALS patients.

Background: Leukocytosis (white blood cell count >12 000/µL) in the delayed postoperative period (4-7 days) after lung transplantation is due to diverse etiologies. We aimed to describe the etiologies of delayed postoperative leukocytosis in lung transplant recipients and to evaluate the association of leukocytosis causes with short-term survival. Methods: A retrospective chart review of 274 lung transplantations performed in our institution during 2006 to 2013. Results: Delayed postoperative leukocytosis was seen in 159 (58.0%) of lung transplant recipients. In 57 (35.8%) of them, the etiology of the leukocytosis was not identified. The etiologies of leukocytosis that were identified were infection (n = 39), second surgery, acute rejection (n = 12), primary graft dysfunction (n = 3), multiple etiologies (n = 17), and other causes (n = 10). On multivariate analysis, delayed postoperative leukocytosis was one of the variables that most significantly associated with decreased survival in the entire sample (hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.01-2.29, P = .040). On additional analysis for mortality assessing each leukocytosis subgroup, the data were acute graft rejection (HR = 8.21, 95% CI: 4.09-16.49, P < .001), second surgery (HR = 2.05, 95% CI: 1.08-3.90, P = .020), primary graft dysfunction (HR = 2.72, 95% CI: 0.65-11.33, P = .169), other causes (HR = 1.30, 95% CI: 0.47-3.62, P = .620), and unknown etiology (HR = 0.94, 95% CI: 0.54-1.62, P = .800). Conclusions: Delayed post-lung transplant leukocytosis is a poor prognostic sign, especially when attributed to acute graft rejection, infection, and multiple etiologies. In the absence of an identifiable etiology, it can be attributed to postoperative reactive stress, is not associated with increased mortality, and likely does not warrant further diagnostic investigation.

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) have significantly higher incidence of lung cancer (LC) relative to the general population. There is a further increase in LC incidence in patients with IPF subsequent to lung transplant, specifically in patients with IPF undergoing single lung transplant.ObjectivesTo examine the incidence and characteristics of LC in patients with IPF during follow-up and after lung transplantation (LTX).MethodsWe conducted a retrospective analysis of all patients with IPF diagnosed with LC in Rabin Medical Center, Israel, over an 11-year period. We compared the characteristics of transplanted patients with IPF diagnosed with LC to patients with IPF who did not undergo lung transplant. Data were accessed from database registries using the words ‘fibrosis’, ‘lung-cancer’ and ‘lung-transplantation’. Demographic parameters included age, gender and smoking history (pack years). Clinical-pathological parameters included lapse in time from IPF diagnosis to LC, type of malignancy, affected pulmonary lobe, and stage at diagnosis, oncological treatment and survival.ResultsBetween 2008 and 2018, 205 patients with IPF underwent lung transplantation at our medical centre. Double LTX was performed in 83 and single LTX in 122 cases. Subsequently, 15 (12.3%) single LTX patients were diagnosed with LC during the study period. During the same period, of 497 non-transplanted patients with IPF followed in our centre, 45 (9.1%) were diagnosed with LC. In all 15 transplanted patients with IPF, LC was diagnosed exclusively in the native fibrotic lung. LC incidence was higher in the transplanted as compared with the non-transplanted group, but this difference did not reach statistical significance (OR=0.7, 95% CI 0.38 to 1.32, p=0.28). At LC diagnosis, the non-transplanted group was older than the transplanted group with average age of 67.7 versus 60.8 years, respectively (p=0.006). Both groups showed male predominance. In both groups, LC was primarily peripheral, lower lobe predominant and most frequently squamous cell carcinoma. The median survival time after LC diagnosis was 4 months in the transplanted group and 11 months in the non-transplanted group (p=0.19). Multivariate analysis showed improved survival in the non-transplanted group among those patients who received oncological treatment.ConclusionChest CT should be performed regularly in order to evaluate IPF patients for potential LC. Single lung transplant IPF patients face an increased risk of post-transplant LC in the native fibrotic lung. Where practicable, IPF patients should be prioritised for double lung transplant.

Prior studies assessing the diagnostic utility of bronchoscopy for chronic unexplained cough have focused primarily on identifying endobronchial anomalies to determine chronic cough etiology. On the basis of our institutional experience, expanding bronchoscopy to include cultures and biopsies can considerably increase its diagnostic yield for identifying the etiology of chronic unexplained cough.This retrospective review analyzed bronchoscopies conducted in our institution between 2013 and 2017. Eligibility criteria were bronchoscopies conducted for chronic unexplained cough for which no etiology had been identified before the bronchoscopy. Microbiology, pathology, and cytology results from bronchoscopy were reviewed to identify the etiology of the cough.Over the study period, 169 bronchoscopies met the eligibility criteria. The average patient age at bronchoscopy was 59.7±14.8 years; 61% were female individuals. Direct visualization identified anatomic etiologies in 48 (28%) patients, most commonly tracheobronchomalacia, and less common conditions, such as tracheobronchopathia osteochondroplastica. Microbiology cultures were positive in 33 (20%) patients, principally Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and nontuberculosis mycobacterium. Pathology results from endobronchial biopsies identified respiratory conditions associated with cough, primarily eosinophilic bronchitis (n=15), as well as neurofibromatosis (n=1) and amyloidosis (n=1). Cytology results did not reveal alternate diagnoses not previously identified.Inclusion of bronchial washings and endobronchial biopsies during bronchoscopy for chronic unexplained cough increased diagnostic yield from 28%, attributable to directly visualized anatomic etiologies, to 41%. The addition of microbiology cultures and pathology analysis significantly increased the diagnostic yield of bronchoscopy in identifying the potential etiology of chronic heretofore unexplained cough.

Contrast echocardiography demonstrating microbubbles in the pericardial space has often been cited as evidence of ventricular rupture requiring emergent surgical intervention. We report a case where no myocardial perforation was found during post-myocardial infarction surgery despite prior echocardiographic evidence of contrast extravasation into the pericardial effusion. Clinical decision making requires balancing imaging evidence with clinical circumstances to determine the optimal timing for surgical intervention.