Bronchoscopy for management and identification of etiology of right middle lobe syndrome: Analysis of 66 cases.

BACKGROUND: Right middle lobe (RML) syndrome is a recurrent or chronic obstruction of the RML causing atelectasis of the right middle lobe due to mechanical and nonmechanical etiologies. The consequences of untreated RML syndrome range from chronic cough to post-obstructive pneumonia and bronchiectasis. We report here our bronchoscopy experience in patients with RML syndrome. METHODS: We conducted a retrospective study of adult patients who underwent bronchoscopy for RML syndrome at Rabin Medical Center from 2008 through 2022. Demographic data and medical history, bronchoscopy findings and procedures, and follow-up results were collected. RESULTS: A total of 66 patients (57.6% male, mean age 63 ± 13 years) underwent bronchoscopy for RML syndrome during the study period. Bronchoscopy revealed a mechanical etiology in 49 (74.2%) cases, including endobronchial mass (21, 31.8%) and external compression (7, 10.6%). Malignancy was identified in 20 (30.3%) cases. In 62 patients (93.9%), the bronchoscopy resulted in partial or complete reopening of the RML bronchus. The therapeutic bronchoscopic procedures were balloon dilatation (19), laser ablation (17), mechanical debridement (12), endobronchial stent insertion (11), and cryoablation (6). CONCLUSIONS: Malignancy was identified as the etiology of RML syndrome in approximately 25% of cases, suggesting bronchoscopy should be performed in every case of RML atelectasis. To our knowledge, this is the first reported series of endobronchial stenting of the RML bronchus in the context of RML syndrome.

Prognostic Significance of the N-Terminal Pro-B-Type Natriuretic Peptide in Lung Transplant Candidates on the Waiting List.

We investigated the prognostic significance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in lung transplant candidates, in a retrospective single-center study. Data regarding various baseline characteristics and all-cause mortality were collected for 205 lung transplant candidates placed on waitlist for transplantation from November 2017 to December 2019. Associations of NT-proBNP levels with baseline characteristics and mortality were analyzed. Results showed NT-proBNP values correlated positively with age, forced vital capacity, mean pulmonary artery pressure (MPAP), and pulmonary capillary wedge pressure; and negatively with diffusing lung capacity for carbon monoxide and cardiac index. The optimal cut-off of NT-proBNP for predicting MPAP levels > 35 mmHg was 251 pg/mL; with 58.1% sensitivity, 85.7% specificity, 45.0% positive predictive value, and 91.0% negative predictive value. During a median follow-up period of 2.2 years, 97 patients underwent lung transplantation, 42 died waiting for donation, and 66 were alive and still waiting for transplantations. On multivariate analysis, higher NT-proBNP levels were strongly associated with increased mortality among waitlisted lung transplant candidates (HR 1.49, 95% CI 1.10−2.03, p = 0.01). In conclusion NT-proBNP can predict mortality among waitlisted lung transplant candidates. Lower levels of NT-proBNP can preclude severe pulmonary artery hypertension. Assessment of NT-proBNP may improve risk stratification among lung transplant candidates.

Carboxyhemoglobin Does Not Predict the Need of Mechanical Ventilation and Prognosis during COPD Exacerbation.

Background: Carboxyhemoglobin (COHb) is a complex formed by the binding of carbon monoxide to hemoglobin in blood. Higher COHb levels have been associated with poor prognosis in a variety of pulmonary disorders. However, little is known regarding the prognostic significance of COHb among individuals with chronic obstructive pulmonary disease (COPD) exacerbation. Methods: In a retrospective study, we evaluated associations of venous COHb levels on hospital admission with the need for invasive mechanical ventilation, in-hospital mortality, and rehospitalization, among 300 patients hospitalized for COPD exacerbation in internal medical wards. Results: Rates of in-hospital death and 1-year recurrent hospitalizations were 11.0% and 59.6%, respectively. COHb levels were not significantly associated with in-hospital mortality (OR = 0.82, P=0.25, 95% CI 0.59-1.15) or with 1-year rehospitalizations (OR = 0.91, P=0.18, 95% CI 0.79-1.04). The mean COHb level did not differ significantly between patients who needed invasive mechanical ventilation and those who were not invasively mechanically ventilated during the current hospitalization (2.01 ± 1.42% vs. 2.19 ± 1.68%, P=0.49). Conclusions: Among patients hospitalized with COPD exacerbation in internal medicine wards, COHb levels on admission were not associated with invasive mechanical ventilation treatment, rehospitalizations, or mortality.

Mediastinal "deep freeze"-transcarinal lymph node cryobiopsy.

BACKGROUND: The diagnostic yield of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) from mediastinal lymph nodes ranges from 66%-89%. However, in many cases cytologic material is not sufficient for full molecular evaluation. A novel method of transcarinal cryobiopsy aims to provide bronchoscopically obtained, larger specimen samples from mediastinal lymph nodes. We aimed to assess the efficacy and safety of transcarinal EBUS-guided lymph node cryobiopsy. METHODS: Patients referred for EBUS-TBNA, based on abnormal mediastinal clinical and radiographic findings, were enrolled into this prospective interventional study between July 2020 and August 2021. All EBUS-TBNA procedures were performed using ProCore 22G needle (Cook Medical) to create, both a transcarinal tract for the cryoprobe and to obtain TBNA samples. For EBUS guided transcarinal cryobiopsy, we used flexible 1.1 mm or 1.7 mm cryoprobe inserted into the working channel of the EBUS scope and into the target subcarinal lymph node. RESULTS: Twenty-four patients with male predominance 2:1 and mean age of 60.12 ± 10.16 years were enrolled. All target lymph nodes had hypoechoic, homogenic consistency with demarcated borders, without central structures. Cryobiopsy provided pathological diagnosis in 20 cases (83.33%), with 1.1 mm cryoprobe in 14 and with 1.7 mm cryoprobe in 6 cases. In one case each, pathology was provided by TBNA or by cryoprobe alone. No immediate or late complications were encountered during the procedures. CONCLUSION: Transcarinal EBUS guided lymph node cryobiopsy following EBUS-TBNA proved to be efficient with a high diagnostic yield and can be considered safe, because no immediate or late complications occurred.

Marked safety and high diagnostic yield of freehand ultrasound-guided core-needle biopsies performed by pulmonologists.

BACKGROUND: Adequate tissue sampling is fundamental for establishing a definitive diagnosis, assessing prognosis and tailoring therapy. Each of the methods for obtaining tissue (e.g., endoscopic, image guidance and surgical biopsies) results in a different diagnostic yield and complication rate profile. OBJECTIVES: Present feasibility, and assess safety and efficacy of freehand transthoracic ultrasound-guided core-needle biopsies (USGNB) of thoracic lesions performed by pulmonologist. METHODS: A retrospective analysis study of ultrasound-guided core-needle biopsies of thoracic lesions performed at the Pulmonary Institute of Rabin Medical Center was conducted from September 2020 to October 2021. All core-needle biopsies were performed under local anesthesia with guidance of Mindray TE7 2019 US system. Procedural variables including complications and pathological diagnostic yield were the primary end point. IRB 0671-21-RMC. RESULTS: In total 91 biopsy procedures were analyzed in38 females and 53 males, average age 71.1 years. Twenty-three (25.3%) cases were lung lesions, 7 (7.7%) - mediastinal, 13 (14.3%) - chest wall, 27 (29.7%) - pleural, and 21 (23.1%) supraclavicular lesions. Average lesion size was 51.6 mm, the largest in the mediastinum and the smallest in supraclavicular locations (97.7mm and 28.0 mm, respectively). Overall pathological diagnostic yield was 90%, highest success in chest wall (100%) and lowest in mediastinal biopsies (71.4%). We had only one complication -hemothorax resolved by chest tube drainage- accounting for only 1.1% complication rate. CONCLUSION: Safety and efficacy were demonstrated in freehand US-guided core-needle biopsy of thoracic lesions performed by pulmonologists. We suggest thoracic ultrasound and USG-CNB be part of training and clinical practice in interventional pulmonology.

Effect of Endobronchial Coils on Exercise Tolerance and Lung Functions in Patients with Severe Emphysema - A Retrospective Cohort Study of 48 Patients.

BACKGROUND: 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.

Quantitation of Silica Contents in Lung Explants of Transplanted Patients: Artificial Stone-Induced Silicosis vs. Idiopathic Pulmonary Fibrosis.

Spectrophotometric techniques provide qualitative but not quantitative data on lung particles. We aimed to quantitate silica content in biopsies of lung-transplanted silicosis patients by applying X-ray fluorescence (XRF) spectrometry. Lung biopsies of 17 lung-transplanted artificial patients were quantitated for silica and other minerals particles by Niton XL3 XRF spectrometry. Occupational and clinical history data were assessed. Lung biopsies of artificial stone-induced silicosis (ASIS) patients contained significantly higher levels of silica compared to those of idiopathic pulmonary fibrosis (IPF) patients (7284.29 ± 4693.75 ppm vs. 898.88 ± 365.66 ppm, p < 0.0001). Silica content correlated negatively with age, body mass index, and pulmonary function test results. A 1128 ppm silica cut-off value yielded 100% sensitivity and 94% specificity for predicting ASIS (AUC = 0.94, p < 0.0001). In conclusion, XRF measurements in lung biopsies can differentiate between silica and mineral particles in ASIS and IPF.

The LungVision navigational platform for peripheral lung nodule biopsy and the added value of cryobiopsy.

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.

Hypoxia Inducible Factor 1A Supports a Pro-Fibrotic Phenotype Loop in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. The IPF-conditioned matrix (IPF-CM) system enables the study of matrix-fibroblast interplay. While effective at slowing fibrosis, nintedanib has limitations and the mechanism is not fully elucidated. In the current work, we explored the underlying signaling pathways and characterized nintedanib involvement in the IPF-CM fibrotic process. Results were validated using IPF patient samples and bleomycin-treated animals with/without oral and inhaled nintedanib. IPF-derived primary human lung fibroblasts (HLFs) were cultured on Matrigel and then cleared using NH4OH, creating the IPF-CM. Normal HLF-CM served as control. RNA-sequencing, PCR and western-blots were performed. HIF1α targets were evaluated by immunohistochemistry in bleomycin-treated rats with/without nintedanib and in patient samples with IPF. HLFs cultured on IPF-CM showed over-expression of 'HIF1α signaling pathway' (KEGG, p < 0.0001), with emphasis on SERPINE1 (PAI-1), VEGFA and TIMP1. IPF patient samples showed high HIF1α staining, especially in established fibrous tissue. PAI-1 was overexpressed, mainly in alveolar macrophages. Nintedanib completely reduced HIF1α upregulation in the IPF-CM and rat-bleomycin models. IPF-HLFs alter the extracellular matrix, thus creating a matrix that further propagates an IPF-like phenotype in normal HLFs. This pro-fibrotic loop includes the HIF1α pathway, which can be blocked by nintedanib.

Effects of a 12-week combined aerobic and strength training program in ambulatory patients with amyotrophic lateral sclerosis: a randomized controlled trial.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Efficacy and safety of mepolizumab in a real-world cohort of patients with severe eosinophilic asthma.

BACKGROUND: The interleukin 5 (IL-5) pathway is an important component in the pathophysiology of severe eosinophilic asthma. Mepolizumab is a monoclonal antibody that targets the IL-5 pathway. Clinical trials showed efficacy of Mepolizumab in patients with severe eosinophilic asthma. However, reports on experience with treatment in a real-world cohort are limited. OBJECTIVES: Evaluation of the efficacy and safety of Mepolizumab for treatment of severe eosinophilic asthma in a real-world cohort of patients. METHODS: A clinical prospective observational trial included all patients >18 years treated with Mepolizumab between March 2016 to March 2019 at Rabin Medical Center. The composite primary outcome measures evaluated: increase in FEV1 by≥ 200 ml and/or decrease in exacerbation rate of ≥50% and/or cessation of oral corticosteroids (OCS) treatment or ≥50% decrease in dosage. Also evaluated: blood eosinophil count, adverse events and quality of life. RESULTS: Of 61 patients, 50 (82.0%) achieved the primary outcome. The number of patients who suffered from frequent exacerbations decreased from 52 (85.2%) to 8 (13.1%) (p < 0.001). Twenty-two patients (68%) stopped OCS treatment or received >50% reduced dosage (p < 0.001). Mean FEV1 increased from 1.72 ± 0.78 liters to 1.87 ± 0.85 liters (p = 0.043). Response to therapy was seen within six months. Forty-nine patients (80%) reported an improvement in quality of life (p < 0.001). Only minor adverse events were reported. CONCLUSION: Treatment with mepolizumab was well tolerated and significantly lowered the exacerbation rate and OCS dependence in a real-world cohort of severe eosinophilic asthma patients. Response to therapy was within six months and treatment effect was sustained over time.

Lung Transplantation in Idiopathic Pulmonary Fibrosis: Risk Factors and Outcome.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50. OBJECTIVES: To evaluate which IPF patients have better prognosis following LTx. METHODS: A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis. RESULTS: Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates. CONCLUSIONS: IPF patients with higher mean PHT, older age (> 65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.

Post-transplant diabetes mellitus: incidence, predicting factors and outcomes.

PURPOSE: To identify predictors and evaluate outcomes of posttransplant diabetes mellitus (PTDM) and to investigate the effect of treatment modalities on outcomes. METHODS: The database of a tertiary medical center was searched for all adult patients without prior diabetes who underwent lung, liver, or heart transplantation between January 1, 2012 and June 30, 2018. Patients in whom PTDM (defined as HbA1C ≥ 6.5% at least 3 months post transplantation) developed during follow-up (mean 3.32 years) were identified. Risk factors for PTDM, determined by regression analysis and clinical outcomes [all-cause mortality, severe infections, graft loss, and major adverse cardiovascular events (MACE)], were compared between those who developed PTDM and those who did not; in the former, insulin-based therapy was compared with non-insulin regimen. RESULTS: The cohort included 281 transplant recipients: 158 lung, 109 liver, and 14 heart. PTDM was diagnosed in 60 (21.35%) patients at a mean of 11.3 ± 12.89 months post transplantation. The only significant independent risk factor for PTDM was age (HR 1.028, 95% CI = 1.002-1.054, P = 0.0314). PTDM was associated with higher rates of severe infections (HR 2.565, 95% CI = 1.626-4.050, P < 0.0001), MACE (HR 1.856, 95% CI = 1.013-3.401, P = 0.0454) and death (HR 1.840, 95% CI = 1.024-3.304, P = 0.0413). Recipients treated with insulin-based regimens had a higher risk of severe infections (HR 2.579, 95% CI = 1.640-4.055, P < 0.0001), MACE (1.925, 95% CI = 1.074-3.451, P = 0.0278) and death (HR 1.960, 95% CI = 1.071-3.586, P = 0.0291). CONCLUSIONS: PTDM is associated with increased mortality and poor outcomes in lung, liver, and heart transplant recipients. Early identification and aggressive treatment of PTDM and its associated cardiometabolic risk factors may improve outcomes.

Prospective Long-Term Follow-Up of Pulmonary Diffusion Capacity Reduction Caused by Dose-Dense Chemotherapy in Patients with Breast Cancer.

BACKGROUND: Our previous study of pulmonary function in 34 patients with early breast cancer without preexisting lung disease showed that anthracycline- and taxane-based adjuvant dose-dense chemotherapy (DDC) caused a significant 16.4% mean reduction in carbon monoxide diffusing capacity (DLCO). The present study reports the pulmonary and oncological outcomes of these patients on long-term follow-up. PATIENTS AND METHODS: The primary endpoint was DLCO measured by the pulmonary function test (PFT) performed at a median of 27 months after DDC (range, 8-97) in 25 patients without disease recurrence. DLCO values were recorded as a percentage of predicted values according to age, height, and hemoglobin level and analyzed relative to baseline pre-DDC DLCO values. The secondary endpoints were symptoms, additional therapies, and cancer outcomes during a median of 11 years' follow-up (range, 4.4-11.4). RESULTS: A longitudinal general linear model showed significant effects of time on DLCO and its trend (F(1, 87) = 14.68, p < 0.001 and F(1, 87) = 10.26, p=0.002, respectively). Complementary descriptive analysis showed a significant recovery on the follow-up PFT (75.6% vs. 81.9%, p=0.002), but it was still significantly lower than the baseline DLCO (81.9% vs. 92.0%, p=0.003). Five patients (20%) still showed a >20% relative DLCO reduction from baseline. Patients with dyspnea or fatigue at later clinical follow-up had a significantly lower DLCO value on the follow-up PFT than nonsymptomatic patients (80.5% vs. 92.1%, p=0.02). DLCO recovery was inversely correlated with age (R = -0.39, p=0.05), but no significant correlation was found with the length of time until the follow-up PFT or additional therapies. There was no association of DDC-related DLCO reduction with cancer outcomes. CONCLUSIONS: The significant reduction in DLCO seen after DDC in patients with potentially curable breast cancer is evident years afterwards, especially in older patients. While most patients partly recover, some will have a lasting symptomatic DLCO impairment.

Physiological Responses and Prognostic Value of Common Exercise Testing Modalities in Idiopathic Pulmonary Fibrosis.

PURPOSE: This pilot study aimed to compare physiological responses between cycle cardiopulmonary exercise tests (CPETs) and 6-min walk tests (6MWTs) and to assess their prognostic value among patients with idiopathic pulmonary fibrosis (IPF). METHODS: Thirty-four patients with IPF (68 ± 8 yr) underwent CPETs and 6MWTs and were followed up for 40 mo. Differences, levels of agreement, and relative risks for mortality were analyzed between measured and estimated peak responses for the 2 tests. RESULTS: Compared with the CPET, oxygen uptake ((Equation is included in full-text article.)O2), heart rate (HR), and the nadir of SpO2 were lower during the 6MWT, whereas work rate (WR) was higher. Mean differences were as follows: (Equation is included in full-text article.)O2 =-1.9 mL/kg/min, 95% CI, -1.1 to -2.7, P < .001; HR =-9 beats/min, 95% CI, -4 to -14, P = .002; SpO2 =-6%, 95% CI, -4 to -7, P < .001; and WR = 9 W/min, 95% CI, 3 to 16, P = .008. Interclass correlations ranged from 0.84 to 0.90 and both tests demonstrated prognostic value for mortality. CONCLUSIONS: Significant differences and variation in peak physiological responses were observed between cycle CPETs and 6MWTs in patients with IPF. However, good agreement was evident, suggesting that both tests provide value for clinical and research settings. Future studies should compare the physiological responses between treadmill CPETs and 6MWTs for prognostic utility in IPF.

8-Foot-Up-and-Go Test is Associated with Hospitalizations and Mortality in Idiopathic Pulmonary Fibrosis: A Prospective Pilot Study.

PURPOSE: To assess the prognostic value of the 8-foot-up-and-go test (8-FUGT) in pilot cohort of patients with idiopathic pulmonary fibrosis (IPF). METHODS: Thirty-four patients with IPF (68 ± 8 years) underwent 8-FUGT at baseline and were followed for up to 40 months. Receiver operating characteristics and age-adjusted Cox hazard ratios (HR) were analyzed for 8-FUGT, hospitalizations, and mortality. Correlation coefficients were determined between 8-FUGT and other exercise tests. RESULTS: 8-FUGT ≥ 6.9 s was found to be associated with hospitalization (sensitivity = 77%, specificity = 76%, p = 0.03) and mortality (sensitivity = 91%, specificity = 70% p = 0.008) in patients with IPF. Categorical models demonstrated that 8-FUGT ≥ 6.9 s was associated with 14.1- (p < 0.001) and 55.4-fold (p = 0.001) increased risks for hospitalization and mortality, respectively. In continuous models, for every 1-s slower performance in the 8-FUGT there were 54% [HR = 1.54, 95% CI (1.11-2.15) p = 0.01] increased risk for hospitalization and 94% [HR = 1.94, 95% CI (1.26-2.99) p = 0.003] increased risk for mortality. 8-FUGT was inversely related to 6-min walk distance (r = - 0.61), peak oxygen consumption (r = - 0.58), and peak work rate (r = - 0.72), all p < 0.001. CONCLUSIONS: The 8-FUGT was strongly associated with hospitalizations and mortality in patients with IPF, as well as correlated with established prognostic markers. These novel findings suggest a prognostic value of the 8-FUGT for risk stratification, referral to pulmonary rehabilitation, and considering listing for lung transplantation. 8-FUGT is an inexpensive and practical tool that has prospective for implementation in clinical and research settings in IPF. Future prospective studies should evaluate the effect of changes in 8-FUGT on clinical outcomes. TRIAL REGISTRATION: NCT01499745, Clinicaltrials.gov.

Significant Delay in the Detection of Desaturation between Finger Transmittance and Earlobe Reflectance Oximetry Probes during Fiberoptic Bronchoscopy: Analysis of 104 Cases.

PURPOSE: There is clinical significance to a delay in response time for detecting desaturation by pulse oximetry. Our aim in this study was to compare the response time of the reflectance and transmittance saturation probes during fiberoptic bronchoscopy (FOB) under monitored anesthesia care. METHODS: A prospective study included 104 patients scheduled for FOB. Patients were monitored with transmittance (finger) and reflectance (ear) oximetry probes. The response time was evaluated during desaturation and resaturation. We also acquired blood tests for arterial oxygen saturation to assess the agreement with the oximetry probes. RESULTS: Ninety patients had a desaturation episode during FOB and were included in the final analysis. Mean time difference between the reflectance ear probe (reference probe) and transmittance finger probe for the detection of desaturation (SpO2 = 90%) was + 36 s (CI 27.0-45.0, P < 0.001). The time difference between probes at end of desaturation episode (SpO2 = 95%) was + 31 s (CI 19.0-43.0; P < 0.001). A significant difference in response time was evident throughout the episode in all saturation values. The reflectance ear probe showed better agreement with arterial blood gases. The bias (and precision) for the earlobe and finger oximeters were of 0.24 (1.04) and 2.31 (3.37), respectively. CONCLUSION: The data displayed by a centrally located reflectance probe are more accurate and allows for earlier identification, treatment, and resolution of desaturation events. In light of these data and the added value of the reflectance probe ability to measure transcutaneous PCO2, we recommend monitoring bronchoscopy by a reflectance oximetry probe.

Lifestyle Behaviors and Clinical Outcomes in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Lifestyle behaviors are not well-characterized in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To assess the association between lifestyle behaviors and clinical outcomes in patients with IPF. METHODS: A total of 34 IPF patients (median age 68 years) were assessed for daily sitting and weekly walking times using the International Physical Activity Questionnaire by in-person interview at baseline, and they were followed up for up to 40 months. Cox proportional hazard analysis was conducted for cardiorespiratory-related hospitalizations and mortality as outcomes. RESULTS: Fifty percent of all patients were hospitalized, and 32% died during the follow-up period. Sitting and walking times were associated with hospitalizations and mortality in IPF. Compared to patients who reported a sitting time of <5 h/day, patients who sat 5 to <10 and ≥10 h/day experienced an increased risk of 2.4 and 5.8 (p trend = 0.036) for hospitalization and of 4.6 and 21.2 (p trend = 0.018) for mortality, respectively. Compared to patients walking <100 min/week, patients with a walking time of 100 to <150 and ≥150 min/week were associated with a 49 and 74% reduced risk for hospitalizations (p trend = 0.022) and a 62 and 86% reduced risk for mortality (p trend = 0.018), respectively. The risk for mortality was further reduced with a combination of shorter sitting and extended walking times. CONCLUSIONS: Shorter daily sitting and longer weekly walking times were associated with reduced hospitalization and mortality risks in patients with IPF. These findings suggest a clinical importance of assessing lifestyle behaviors in a comprehensive evaluation and prognostication of IPF patients. The results underscore potential clinical benefits of reducing sedentary behaviors among IPF patients; however, this warrants further investigation.

Tacrolimus Levels Are Not Associated with Risk of Malignancy in Lung Transplant Recipients.

BACKGROUND Lung transplant (LTx) recipients suffer from high rates of malignancy. Exposure to immunosuppressive medication such as tacrolimus has been proposed as a risk factor for tumorigenesis. We hypothesized that chronically high levels of tacrolimus would be associated with risk of malignancy. MATERIAL AND METHODS The study was performed in a transplant center in Israel, with a nested case-control design. Cases were LTx recipients who were diagnosed with any solid or hematological malignancy except non-melanoma skin cancer. Controls were tumor-free during their entire follow-up after LTx and had at least the same follow-up time as their matched case. Controls were matched to cases by age and type of transplant received (single/double). Tacrolimus levels were extracted and analyzed for median drug level and also integrated over time (area under the curve - AUC-tacrolimus). RESULTS We reviewed 412 LTx recipients in our registry. Thirty-nine cases of malignancy were diagnosed and 160 controls were matched, giving a crude tumor incidence rate of 26/100 000/year. Lung cancers were the commonest diagnosis. Cases and controls were well matched by age, smoking status, and LTx type. Median tacrolimus levels were 11.0 ng/ml and 11.3 ng/ml in cases and controls, respectively (p=0.88). The median log (AUC-tacrolimus) was 9.4 in the cases and 9.5 in the controls (p=0.59). CONCLUSIONS In this nested case-control study, exposure to tacrolimus was similar in tumor cases and non-tumor controls. These data, based on a cohort with modest size, suggest either that tumorigenesis in LTx recipients is unrelated to tacrolimus exposure or that levels in these patients are above an unknown threshold at which the dose-response effect is saturated.

Physical Activity and Exertional Desaturation Are Associated with Mortality in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that manifests in hypoxemia, inactivity, and poor prognosis. This study aimed to assess the prognostic role of physical activity (PA) and exertional desaturation (ED) with mortality in IPF. At baseline, 34 IPF patients (68 (50-81) years) were interviewed using the International Physical Activity Questionnaire (IPAQ), and SpO2 was assessed pre to post 6-min walking test (∆SpO2). Patients were prospectively followed up for 40 months. Receiver operating characteristics curve analysis determined cut-off points associated with mortality, and Cox proportional hazard ratio (HR) were conducted. Thresholds for increased mortality risk in IPF patients were determined as IPAQ ≤ 417 metabolic equivalent task (METS)-min/week, p = 0.004 (HR; 9.7, CI 95% (1.3-71.9), p = 0.027), and ∆SpO2 ≥ 10%, p = 0.002, (HR; 23.3, CI 95% (1.5-365), p = 0.025). This study demonstrated a significant association of PA and ED with mortality in IPF patients. The findings emphasize the clinical importance of PA and ED assessments to aid in IPF risk stratification, prognosis prediction, and in providing early appropriate treatments, such as pulmonary rehabilitation, PA consultation, oxygen supplementation, and lung transplantation referral. These results underscore that even low levels of PA corresponding to 100-105 min/week were associated with a reduced mortality risk and better survival in IPF.