Nir Peled | Tel Aviv University (original) (raw)

Papers by Nir Peled

Research paper thumbnail of FGFR Fusions as an Acquired Resistance Mechanism Following Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) and a Suggested Novel Target in Advanced Non-Small Cell Lung Cancer (aNSCLC)

Journal of Clinical Medicine

Background. FGFR1/2/3 fusions have been reported infrequently in aNSCLC, including as a rare, acq... more Background. FGFR1/2/3 fusions have been reported infrequently in aNSCLC, including as a rare, acquired resistance mechanism following treatment with EGFR TKIs. Data regarding their prevalence and therapeutic implications are limited. Methods. The Guardant Health (GH) electronic database (ED) was evaluated for cases of aNSCLC and FGFR2/3 fusions; FGFR2/3 fusion prevalence with and without a co-existing EGFR mutation was assessed. The ED of Tel-Aviv Sourasky Medical Center (TASMC, June 2020–June 2021) was evaluated for cases of aNSCLC and de novo FGFR1/2/3 fusions. Patients with EGFR mutant aNSCLC progressing on EGFR TKIs and developing an FGFR1/2/3 fusion were selected from the ED of Davidoff Cancer Center (DCC) and Oncology Department, Bnei-Zion hospital (BZ) (April 2014–April 2021). Clinicopathological characteristics, systemic therapies, and outcomes were assessed. Results. In the GH ED (n = 57,445), the prevalence of FGFR2 and FGFR3 fusions were 0.02% and 0.26%, respectively. FGF...

Research paper thumbnail of Osimertinib in advanced EGFR-mutant lung adenocarcinoma with asymptomatic brain metastases: an open-label, 3-arm, phase II pilot study

Neuro-Oncology Advances, 2021

Background Osimertinib is selective for both epidermal growth factor receptor (EGFR)-tyrosine-kin... more Background Osimertinib is selective for both epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor (TKI) sensitizing and Thr790Met mutations. While intracranial activity of osimertinib is documented in larger trials, a prospective study focusing exclusively on patients with asymptomatic brain metastases has not been reported. Methods In this nonrandomized, phase II, open-label, 3-arm prospective proof-of-concept pilot study, 48 patients with metastatic EGFR-mutant lung adenocarcinoma (LUAD) received osimertinib 80 mg daily. Patients were either treatment naive (arm A = 20) or previously treated with an EGFR-TKI and Thr790Met positive (arm B = 18) or negative (arm C = 10). In cases of isolated intracranial progression, osimertinib dose was escalated (160 mg). The primary endpoints were intracranial objective response rate (iORR) and intracranial disease control rate (iDCR). The secondary endpoint was intracranial progression-free survival (iPFS). This study is registered ...

Research paper thumbnail of Dose escalation of osimertinib for intracranial progression in EGFR mutated non-small-cell lung cancer with brain metastases

Neuro-Oncology Advances, 2020

Background Osimertinib is a selective irreversible epidermal growth factor receptor tyrosine kina... more Background Osimertinib is a selective irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with increased penetration across the blood–brain barrier compared with previous EGFR-TKIs, and thus, a 52% reduction in the risk of intracranial disease progression is seen when it is used as a first line of therapy compared with gefitinib and erlotinib. It is also efficient as second-line therapy for patients who developed the T790M resistance mutation following treatment with previous generation TKIs. Here, we report 11 patients who were treated by an increasing dose of osimertinib from 80 mg to 160 mg QD orally following intracranial progression in either first- or second-line setting. Methods This is a subcohort analysis from a larger nonrandomized, phase 2, open-label trial, evaluating the efficacy of osimertinib dose escalation from 80 mg to 160 mg in EGFR-mutated advanced non-small-cell lung cancer (NSCLC) patients with intracranial progression in either f...

Research paper thumbnail of An Update on the Use of Exhaled Breath Analysis for the Early Detection of Lung Cancer

Lung Cancer: Targets and Therapy, 2021

Lung cancer has historically been the main responsible for cancer associated deaths. Owing to thi... more Lung cancer has historically been the main responsible for cancer associated deaths. Owing to this is our current inability to screen for and diagnose early pathological findings, preventing us from a timely intervention when cure is still achievable. Over the last decade, together with the extraordinary progress in therapeutical alternatives in the field, there has been an ongoing search for a biomarker that would allow for this. Numerous technologies have been developed but their clinical application is yet to come. In this review, we provide an update on volatile organic compounds, a non-invasive method that can hold the key for detecting early metabolic pathway changes in carcinogenesis. For its compilation, web-based search engines of scientific literature such as PubMed were explored and reviewed, using articles, research, and papers deemed meaningful by authors discretion. After a brief description, we depict how this technique can complement current methods and present the value of electronic noses in the identification of the "breathprint". Lastly, we bring some of the latest updates in the field together with the current limitations and final remarks.

Research paper thumbnail of Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe

Cancers, 2020

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the Nati... more Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and pr...

Research paper thumbnail of Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2018

EGFR exon 20 insertions (EGFRex20ins) comprise an uncommon subset of EGFR-activating alterations ... more EGFR exon 20 insertions (EGFRex20ins) comprise an uncommon subset of EGFR-activating alterations relatively insensitive to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). However, recent early clinical data suggests these patients may benefit from newer-generation EGFR-TKIs. Comprehensive genomic profiling (CGP) identifies a broad spectrum of EGFRex20ins and associated co-occurring genomic alterations (GAs) present in NSCLC. Hybrid capture-based CGP was performed prospectively on 14,483 clinically annotated consecutive NSCLC specimens to a mean coverage depth of greater than 650X for 236 or 315 cancer-related genes. Of 14,483 NSCLC cases, CGP identified 263 (1.8%) cases with EGFRex20ins, representing 12% (263 of 2251) of cases with EGFR mutations. Sixty-four unique EGFRex20ins were identified, most commonly D770_N771>ASVDN (21%) and N771_P772>SVDNP (20%). EGFR amplification occurred in 22% (57 of 263). The most common co-occurring GAs effected tumor protei...

Research paper thumbnail of IASLC Statement Paper: Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC)

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jan 6, 2018

The isolation of circulating cell-free tumoral DNA (ctDNA) in plasma and its subsequent molecular... more The isolation of circulating cell-free tumoral DNA (ctDNA) in plasma and its subsequent molecular analysis is a powerful tool that can help improve clinical outcomes across multiple cancer types, including non-small cell lung cancer (NSCLC). Assays of this nature that utilize blood as opposed to tumor samples are frequently referred to as liquid biopsies. An increasing number of new platforms have been recently developed that improve not only the fidelity of the molecular analysis of the liquid biopsy but also the number of tests performed on a single specimen. ctDNA assays for detection of both epidermal growth factor receptor (EGFR) sensitizing and resistance mutations have already entered clinical practice and many other molecular tests - such as resistance mutations for ALK rearrangements - are likely to do so in the near future. Due to an abundance of new evidence, an appraisal was warranted to review strengths and weaknesses, to describe what is already in clinical practice an...

Research paper thumbnail of Familial Mediterranean fever and incidence of cancer An analysis of 8534 patients with 258,803 person-years

Arthritis & rheumatology (Hoboken, N.J.), Jan 9, 2017

Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested with recurrent seros... more Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested with recurrent serosal inflammation. The association between FMF and malignancy has not been described. The aim of this study was to estimate cancer risk in a large single-institution cohort of FMF patients. The study cohort consisted of 8,534 FMF patients registered in the Israel National FMF Center at Tel Hashomer, Israel. We linked the study cohort to the database of the Israel National Cancer Registry using the national identity number. Cancer incidence in FMF patients was determined and stratified by age and gender. Standardized incidence ratios (SIR) for cancers were calculated. Among 8,534 FMF patients (4,400 men, 4,134 women), 350 developed cancer during the years 1970-2011. Overall cancer risk among patients with FMF was significantly lower than that expected in the following gender and ethnic groups of the Israeli population: males of Jewish ethnicity SIR 0.66, CI 95% [0.55-0.77], p<0.001; fema...

Research paper thumbnail of Pulmonary sarcomatoid carcinomas commonly harbor either potentially targetable genomic alterations or high tumor mutational burden as observed by comprehensive genomic profiling

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jun 15, 2017

Pulmonary sarcomatoid carcinoma (PSC) is a high-grade non-small cell lung carcinoma (NSCLC) chara... more Pulmonary sarcomatoid carcinoma (PSC) is a high-grade non-small cell lung carcinoma (NSCLC) characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered due to limited and inconsistent molecular characterization. Hybrid-capture based comprehensive genomic profiling (CGP) was performed on DNA from 15,867 FFPE NSCLCs including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1.11 Mb of sequenced DNA. The median age of PSC patients was 67 years (range 32-87), 58% were male, and 78% had stage IV disease. TP53 genomic alterations (GA) were identified in 74% of cases, which had distinct genomics from TP53-wild-type cases. 62% featured a GA in KRAS (34%) or one of 7 genes currently recommended for testing in the NSCLC NCCN guidelines including: MET (13.6%), EGFR (8.8%), BRAF (7.2%), HER2 (1.6%) or RET (0.8%). MET exon 14 alterations were enriched in PSC (12%) compared to non-PSC NSCLCs (∼3%) (P&lt...

Research paper thumbnail of Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules

ACS Nano, 2017

This is an open access article published under an ACS AuthorChoice License, which permits copying... more This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

Research paper thumbnail of Silicon Nanowire Sensors Enable Diagnosis of Patients via Exhaled Breath

ACS nano, Jul 6, 2016

Two of the biggest challenges in medicine today are the need to detect diseases in a non-invasive... more Two of the biggest challenges in medicine today are the need to detect diseases in a non-invasive manner, and to differentiate between patients using a single diagnostic tool. The current study targets these two challenges by developing a molecularly-modified Silicon Nanowire Field Effect Transistors (SiNW FETs) and showing its use in the detection and classification of many disease breathprints (lung cancer, gastric cancer, asthma and Chronic Obstructive Pulmonary Disease). The fabricated SiNW FETs are characterized and optimized based on a training set that correlated their sensitivity and selectivity towards volatile organic compounds (VOCs) linked with diseased states. The best sensors obtained in the training set are then examined under real-world clinical conditions, using breath samples from 374 subjects. Analysis of the clinical samples showed that the optimized SiNW FETs can detect and discriminate between almost all binary comparisons of the diseases under examination with...

Research paper thumbnail of Exhaled Breath Analysis for Monitoring Response to Treatment in Advanced Lung Cancer

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jan 8, 2016

RECIST criteria serve as the gold standard method to monitor treatment efficacy in lung cancer. H... more RECIST criteria serve as the gold standard method to monitor treatment efficacy in lung cancer. However, time-intervals between consecutive CT scans might be too long to allow early identification of treatment failure. This study examines the use of breath sampling to monitor responses to anti-cancer treatments in patients with advanced lung cancer. 143 breath samples were collected from 39 patients with advanced lung cancer. The exhaled breath signature, determined by GC-MS(1)fn1 and nanomaterial-based array of sensors, was correlated with the response to therapy assessed by RECIST: Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). GC-MS(1) analysis identified 3 volatile organic compounds (VOCs) as significantly indicating disease control (PR/SD), with one of them also significantly discriminating PR/SD from PD. The nano-array had the ability to monitor changes in tumor response across therapy, also indicating any lack of further respo...

Research paper thumbnail of Predictive and prognostic markers for epidermal growth factor receptor inhibitor therapy in non-small cell lung cancer

Therapeutic advances in medical oncology, 2009

Epidermal growth factor receptor (EGFR) related therapies - mainly tyrosine kinase inhibitors (TK... more Epidermal growth factor receptor (EGFR) related therapies - mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example, cetuximab - have been investigated in numerous settings in non-small cell lung cancer (NSCLC) and in different combinations. The overall clinical benefit of EGFR TKI therapy is roughly 10-30%, with higher benefit in nonsmoker Asiatic women with EGFR-mutated adenocarcinoma. Currently, there are several biomarkers that are able to direct and predict the yield of EGFR-related therapies in NSCLC. These include EGFR mutation status, EGFR protein expression, EGFR gene copy number and a serum proteomic marker (Veristrat®, Biodesix; CO). The usage of such biomarkers is important from many aspects. First, it helps clinicians to make the right treatment decisions and second, it leads to a wiser usage of financial resources. This review will focus on EGFR-related biomarkers for their prognostic power an...

Research paper thumbnail of Diagnostic value of complement components in pleural fluid: Report of 135 cases

Respiratory Medicine, 2008

We prospectively assessed the diagnostic value of pleural fluid complement levels (total, C3, C4)... more We prospectively assessed the diagnostic value of pleural fluid complement levels (total, C3, C4) in 135 patients with pleural effusion of five main etiologies, using novel markers. Complement levels correlated with pleural levels of protein, amylase, and transuded fluids. On univariate analysis, CHF-related pleural effusions were associated with significantly lower C4 levels than postsurgery or parapneumonic effusions. On multivariate analysis, pleural fluid C4 level was a significant predictor of CHF. Although the specificity, positive predictive value, and accuracy of the parameters were low in all diagnostic groups, their negative predictive value as well as the AUC ROC was high for CHF and post-LTX. We conclude that pleural fluid C4 levels can differentiate CHF-related pleural effusion from other etiologies and that normal level of C3 or C4 rule out CHF or LTX as causes of pleural effusion. Complement should be included in the assessment of pleural effusion when traditional diagnostic methods fail.

Research paper thumbnail of Clinical and radiological features of Mycobacterium kansasii infection and Mycobacterium simiae infection

Respiratory Medicine, 2008

Background: Mycobacterium kansasii infection is one of the most common causes of nontuberculous m... more Background: Mycobacterium kansasii infection is one of the most common causes of nontuberculous mycobacterial lung disease in the world. However, it is not possible to differentiate completely between M. kansasii and other nontuberculous mycobacteria (NTM) because of a lack of direct comparative studies. This retrospective study sought to identify their clinical and radiological features systematically. Methods: The sample included 98 consecutive patients with a culture-positive diagnosis of NTM infection, derived from the databases of the Laboratory of Microbiology of a tertiary medical center and two outpatient tuberculosis centers. Sixty-four patients had M. kansasii infection. All patients fulfilled disease criteria for treatment. Data on patient background and clinical features were collected, and chest radiographs were evaluated. Results: In the M. kansasii group, n Z 27 (42%) were native-born Israelis compared to 9.4% (n Z 3) of all other NTM groups (p Z 0.0001). Similar rates of co-morbid diseases, including diabetes mellitus, heart disease, lung diseases, and malignancy were noted in both groups. Old TB was less common in the M. kansasii group compared to the other NTM (3.1% vs. 23.5%, p Z 0.003). Clinical symptoms were significantly more common in patients with M. kansasii infection. On radiological study, M. kansasii infection was associated with more cavitations and unilaterality. Patients with M. kansasii infection had a higher likelihood of right upper lobe disease (p Z 0.001). Pleural effusions and lymphadenopathy were found only in a few patients in each group. Conclusion: Major differences in the epidemiologic and clinical features of M. kansasii infection and other NTM have important diagnostic and clinical implications.

Research paper thumbnail of Use of the 15-steps climbing exercise oximetry test in patients with idiopathic pulmonary fibrosis

Respiratory Medicine, 2008

Idiopathic pulmonary fibrosis (IPF) is often associated with exercise-induced hypoxemia. Although... more Idiopathic pulmonary fibrosis (IPF) is often associated with exercise-induced hypoxemia. Although maximal oxygen consumption (VO 2(max)) is considered the gold-standard index of functional capacity in IPF, its measurement requires sophisticated equipment and trained personnel. The aim of the present study was to investigate the value of the simple 15-steps climbing exercise oximetry test in patients with IPF. The 15-steps climbing test was administered to 51 patients with IPF. Pulmonary function tests (PFTs), cardiopulmonary exercise test (CPET), and the 6-min walk distance (6MWD) test were performed in the same session. Oxygen saturation in the 15-steps climbing test was measured by continuous oximetry, and quantified oxygen desaturation was determined by calculating the area under the curve of oxygen saturation from the beginning of exercise through the lowest desaturation point until recovery to baseline (''desaturation area''). There was a statistically significant correlation between all parameters of the 15-steps climbing test and both VO 2(max) on the CPET (lowest saturation, p ¼ 0.002, r ¼ 0.43; saturation difference, p ¼ 0.02, r ¼ À0.33; recovery time, p ¼ 0.02, r ¼ À0.32; and desaturation area, p ¼ 0.005, r ¼ À0.39), and carbon dioxide diffusion in the lungs (DLCO) on the PFTs (lowest saturation, p ¼ 0.0001, r ¼ 0.52; saturation difference, p ¼ 0.0002, r ¼ À0.50; recovery time, p ¼ 0.0001, r ¼ À0.53; and desaturation area, p ¼ 0.0001, r ¼ À0.53). On stepwise linear regression analysis, independent significant predictors of VO 2(max) were lowest saturation on the 15-steps test and the 6MWD.

Research paper thumbnail of Non-invasive Breath Analysis of Pulmonary Nodules

Journal of Thoracic Oncology, 2012

Introduction: The search for non-invasive diagnostic methods of lung cancer (LC) has led to new a... more Introduction: The search for non-invasive diagnostic methods of lung cancer (LC) has led to new avenues of research, including the exploration of the exhaled breath. Previous studies have shown that LC can, in principle, be detected through exhaled-breath analysis. This study evaluated the potential of exhaled-breath analysis for the distinction of benign and malignant pulmonary nodules (PNs). Methods: Breath samples were taken from 72 patients with PNs in a prospective trial. Profiles of volatile organic compounds were determined by (1) gas chromatography/mass spectrometry (GC-MS) combined with solid-phase microextraction and (2) a chemical nanoarray. Results: Fifty-three PNs were malignant and 19 were benign with similar smoking histories and comorbidities. Nodule size (mean ± SD) was 2.7 ± 1.7 versus 1.6 ± 1.3 cm (p = 0.004), respectively. Within the malignant group, 47 were non-small-cell lung cancer and six were small-cell lung cancer. Thirty patients had early-stage disease and 23 had advanced disease. Gas chromatography/mass spectrometry analysis identified a significantly higher concentration of 1-octene in the breath of LC, and the nanoarray distinguished significantly between benign versus malignant PNs (p < 0.0001; accuracy 88 ± 3%), between adeno-and squamous-cell carcinomas (p < 0.0001; 88 ± 3%) and between early stage and advanced disease (p < 0.0001; 88 ± 2%). Conclusions: In this pilot study, breath analysis discriminated benign from malignant PNs in a high-risk cohort based on LC-related volatile organic compound profiles. Furthermore, it discriminated adenoand squamous-cell carcinoma and between early versus advanced disease. Further studies are required to validate this noninvasive approach, using a larger cohort of patients with PNs detected by computed tomography.

Research paper thumbnail of Peripheral Arterial Stiffness and Endothelial Dysfunction in Idiopathic and Scleroderma Associated Pulmonary Arterial Hypertension

The Journal of Rheumatology, 2009

Objective.Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves ... more Objective.Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves have been reported in pulmonary arterial hypertension (PAH). However, the systemic vascular involvement is not fully understood. Our study focused on the systemic arterial stiffness and endothelial involvement in idiopathic and scleroderma associated PAH.Methods.Peripheral arterial stiffness and endothelial function were evaluated in 38 patients with idiopathic (n = 28) and scleroderma associated (n = 10) PAH, and 21 control subjects (13 healthy; 8 with scleroderma and normal pulmonary pressure). All participants underwent clinical and cardiopulmonary evaluation. Arterial stiffness was measured through the fingertip tonometry derived augmentation index (AI), which is the boost increase in the late systolic pressure wave after the initial systolic shoulder. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion by a noninvasive plethysmogr...

Research paper thumbnail of Ambulatory Rehabilitation Improves Exercise Capacity in Patients With Pulmonary Hypertension

Journal of Cardiac Failure, 2011

Background: Rehabilitation is a central treatment modality for patients with chronic cardiopulmon... more Background: Rehabilitation is a central treatment modality for patients with chronic cardiopulmonary disease. Physical exertion for patients with pulmonary arterial hypertension (PAH) has typically been discouraged. Inpatient pulmonary rehabilitation has been shown to improve exercise capacity in patients with PAH. The present study aimed to evaluate outpatient pulmonary rehabilitation for patients with PAH. Methods and Results: Twenty-two patients with PAH or chronic pulmonary thromboembolic disease were allocated to ambulatory rehabilitation (n 5 11) or to the control group (n 5 11). All patients were stable on PAH-specific medication. The rehabilitation group underwent 24 1-hour sessions of exercise training/rehabilitation over 12 weeks. Primary end points were change in 6-minute walking distance (6MWD) and peak oxygen uptake (VO 2) on cardiopulmonary exercise testing. All of the patients assigned to rehabilitation and 9 control subjects completed the study. In the rehabilitation group, 6MWD increased by 32 m, and in the control group 6MWD decreased by 26 meters (P 5 .003). Peak VO 2 increased in the rehabilitation group by 1.1 mL kg À1 min À1 and decreased by 0.5 mL kg À1 min À1 in the control group (P ! .05). Peak work rate during cardiopulmonary exercise test also increased in the rehabilitation group, with borderline significance (P 5 .051). Echocardiography and blood N-terminal proebrain natriuretic peptide levels were unchanged. No adverse events occurred due to the rehabilitation program. Conclusions: Ambulatory rehabilitation is a safe and efficacious treatment for patients with pulmonary hypertension already on medical therapy.

Research paper thumbnail of Diagnosis of Pulmonary Pathology in Hemodialysis Patients Using a Combination of Imaging and Lung Function Tests

CHEST Journal, 2007

According to the medical literature, prolonged renal failure or hemodialysis treatment might have... more According to the medical literature, prolonged renal failure or hemodialysis treatment might have thoracic and pulmonary effects, such as caused decreased diffusion capacity and metastatic calcifications. Prompted by the successful transplantation at our center of two lungs from a donor who had been on long-term hemodialysis, we sought to determine if hemodialysis does indeed affect pulmonary function. METHODS: The study group included 18 patients aged 27 to 93 years (mean 67.4 years, standard deviation 16 years) treated with hemodialysis from 33 to 257 months (average 77.6 months, standard deviation 4.7 months). Immediately following a dialysis session, the patients underwent lung function tests, cardiopulmonary exercise test, and 6-minute walk test, non-contrast high-resolution computed tomography scanning of the chest and echocardiography. Findings were compared to predicted values. RESULTS: Fourteen patients (77.8%) had normal values on lung function tests. Of the remainder, 1 patient had a nearly normal restrictive pattern, 2 patients had a mild restrictive dysfunction, and 1 patient had a moderate restrictive dysfunction. Decreased diffusion capacity was noted in 11 patients (68.8%)-mild in 10 and moderate in 1 (48% of normal values). The distance on the 6-minute walk test measured less than 350 meters in 7 patients (38.9%), with no decrease in oxygen saturation. Echocardiograms demonstrated moderate to severe left ventricular dysfunction in 3 patients (16.7%); only 1 patient had right ventricular dysfunction. Mild pulmonary hypertension was measured in 4 patients (22.2%), and severe pulmonary hypertension in 1. Computed tomography findings possibly compatible with metastatic calcifications (bronchial calcifications, ground glass opacifications and/or pulmonary nodules) were noted in 15 patients (66.7%). CONCLUSION: Prolonged hemodialysis is apparently not associated with pulmonary dysfunction. Although most of the patients in our series had poor physical fitness, consistent with reports in the literature, the possible calcification noted on computed tomography was mild and apparently not clinically significant. CLINICAL IMPLICATIONS: On the basis of these findings, we suggest that patients on hemodialysis may be considered as potential lung donors.

Research paper thumbnail of FGFR Fusions as an Acquired Resistance Mechanism Following Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) and a Suggested Novel Target in Advanced Non-Small Cell Lung Cancer (aNSCLC)

Journal of Clinical Medicine

Background. FGFR1/2/3 fusions have been reported infrequently in aNSCLC, including as a rare, acq... more Background. FGFR1/2/3 fusions have been reported infrequently in aNSCLC, including as a rare, acquired resistance mechanism following treatment with EGFR TKIs. Data regarding their prevalence and therapeutic implications are limited. Methods. The Guardant Health (GH) electronic database (ED) was evaluated for cases of aNSCLC and FGFR2/3 fusions; FGFR2/3 fusion prevalence with and without a co-existing EGFR mutation was assessed. The ED of Tel-Aviv Sourasky Medical Center (TASMC, June 2020–June 2021) was evaluated for cases of aNSCLC and de novo FGFR1/2/3 fusions. Patients with EGFR mutant aNSCLC progressing on EGFR TKIs and developing an FGFR1/2/3 fusion were selected from the ED of Davidoff Cancer Center (DCC) and Oncology Department, Bnei-Zion hospital (BZ) (April 2014–April 2021). Clinicopathological characteristics, systemic therapies, and outcomes were assessed. Results. In the GH ED (n = 57,445), the prevalence of FGFR2 and FGFR3 fusions were 0.02% and 0.26%, respectively. FGF...

Research paper thumbnail of Osimertinib in advanced EGFR-mutant lung adenocarcinoma with asymptomatic brain metastases: an open-label, 3-arm, phase II pilot study

Neuro-Oncology Advances, 2021

Background Osimertinib is selective for both epidermal growth factor receptor (EGFR)-tyrosine-kin... more Background Osimertinib is selective for both epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor (TKI) sensitizing and Thr790Met mutations. While intracranial activity of osimertinib is documented in larger trials, a prospective study focusing exclusively on patients with asymptomatic brain metastases has not been reported. Methods In this nonrandomized, phase II, open-label, 3-arm prospective proof-of-concept pilot study, 48 patients with metastatic EGFR-mutant lung adenocarcinoma (LUAD) received osimertinib 80 mg daily. Patients were either treatment naive (arm A = 20) or previously treated with an EGFR-TKI and Thr790Met positive (arm B = 18) or negative (arm C = 10). In cases of isolated intracranial progression, osimertinib dose was escalated (160 mg). The primary endpoints were intracranial objective response rate (iORR) and intracranial disease control rate (iDCR). The secondary endpoint was intracranial progression-free survival (iPFS). This study is registered ...

Research paper thumbnail of Dose escalation of osimertinib for intracranial progression in EGFR mutated non-small-cell lung cancer with brain metastases

Neuro-Oncology Advances, 2020

Background Osimertinib is a selective irreversible epidermal growth factor receptor tyrosine kina... more Background Osimertinib is a selective irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with increased penetration across the blood–brain barrier compared with previous EGFR-TKIs, and thus, a 52% reduction in the risk of intracranial disease progression is seen when it is used as a first line of therapy compared with gefitinib and erlotinib. It is also efficient as second-line therapy for patients who developed the T790M resistance mutation following treatment with previous generation TKIs. Here, we report 11 patients who were treated by an increasing dose of osimertinib from 80 mg to 160 mg QD orally following intracranial progression in either first- or second-line setting. Methods This is a subcohort analysis from a larger nonrandomized, phase 2, open-label trial, evaluating the efficacy of osimertinib dose escalation from 80 mg to 160 mg in EGFR-mutated advanced non-small-cell lung cancer (NSCLC) patients with intracranial progression in either f...

Research paper thumbnail of An Update on the Use of Exhaled Breath Analysis for the Early Detection of Lung Cancer

Lung Cancer: Targets and Therapy, 2021

Lung cancer has historically been the main responsible for cancer associated deaths. Owing to thi... more Lung cancer has historically been the main responsible for cancer associated deaths. Owing to this is our current inability to screen for and diagnose early pathological findings, preventing us from a timely intervention when cure is still achievable. Over the last decade, together with the extraordinary progress in therapeutical alternatives in the field, there has been an ongoing search for a biomarker that would allow for this. Numerous technologies have been developed but their clinical application is yet to come. In this review, we provide an update on volatile organic compounds, a non-invasive method that can hold the key for detecting early metabolic pathway changes in carcinogenesis. For its compilation, web-based search engines of scientific literature such as PubMed were explored and reviewed, using articles, research, and papers deemed meaningful by authors discretion. After a brief description, we depict how this technique can complement current methods and present the value of electronic noses in the identification of the "breathprint". Lastly, we bring some of the latest updates in the field together with the current limitations and final remarks.

Research paper thumbnail of Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe

Cancers, 2020

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the Nati... more Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and pr...

Research paper thumbnail of Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2018

EGFR exon 20 insertions (EGFRex20ins) comprise an uncommon subset of EGFR-activating alterations ... more EGFR exon 20 insertions (EGFRex20ins) comprise an uncommon subset of EGFR-activating alterations relatively insensitive to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). However, recent early clinical data suggests these patients may benefit from newer-generation EGFR-TKIs. Comprehensive genomic profiling (CGP) identifies a broad spectrum of EGFRex20ins and associated co-occurring genomic alterations (GAs) present in NSCLC. Hybrid capture-based CGP was performed prospectively on 14,483 clinically annotated consecutive NSCLC specimens to a mean coverage depth of greater than 650X for 236 or 315 cancer-related genes. Of 14,483 NSCLC cases, CGP identified 263 (1.8%) cases with EGFRex20ins, representing 12% (263 of 2251) of cases with EGFR mutations. Sixty-four unique EGFRex20ins were identified, most commonly D770_N771>ASVDN (21%) and N771_P772>SVDNP (20%). EGFR amplification occurred in 22% (57 of 263). The most common co-occurring GAs effected tumor protei...

Research paper thumbnail of IASLC Statement Paper: Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC)

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jan 6, 2018

The isolation of circulating cell-free tumoral DNA (ctDNA) in plasma and its subsequent molecular... more The isolation of circulating cell-free tumoral DNA (ctDNA) in plasma and its subsequent molecular analysis is a powerful tool that can help improve clinical outcomes across multiple cancer types, including non-small cell lung cancer (NSCLC). Assays of this nature that utilize blood as opposed to tumor samples are frequently referred to as liquid biopsies. An increasing number of new platforms have been recently developed that improve not only the fidelity of the molecular analysis of the liquid biopsy but also the number of tests performed on a single specimen. ctDNA assays for detection of both epidermal growth factor receptor (EGFR) sensitizing and resistance mutations have already entered clinical practice and many other molecular tests - such as resistance mutations for ALK rearrangements - are likely to do so in the near future. Due to an abundance of new evidence, an appraisal was warranted to review strengths and weaknesses, to describe what is already in clinical practice an...

Research paper thumbnail of Familial Mediterranean fever and incidence of cancer An analysis of 8534 patients with 258,803 person-years

Arthritis & rheumatology (Hoboken, N.J.), Jan 9, 2017

Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested with recurrent seros... more Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested with recurrent serosal inflammation. The association between FMF and malignancy has not been described. The aim of this study was to estimate cancer risk in a large single-institution cohort of FMF patients. The study cohort consisted of 8,534 FMF patients registered in the Israel National FMF Center at Tel Hashomer, Israel. We linked the study cohort to the database of the Israel National Cancer Registry using the national identity number. Cancer incidence in FMF patients was determined and stratified by age and gender. Standardized incidence ratios (SIR) for cancers were calculated. Among 8,534 FMF patients (4,400 men, 4,134 women), 350 developed cancer during the years 1970-2011. Overall cancer risk among patients with FMF was significantly lower than that expected in the following gender and ethnic groups of the Israeli population: males of Jewish ethnicity SIR 0.66, CI 95% [0.55-0.77], p<0.001; fema...

Research paper thumbnail of Pulmonary sarcomatoid carcinomas commonly harbor either potentially targetable genomic alterations or high tumor mutational burden as observed by comprehensive genomic profiling

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jun 15, 2017

Pulmonary sarcomatoid carcinoma (PSC) is a high-grade non-small cell lung carcinoma (NSCLC) chara... more Pulmonary sarcomatoid carcinoma (PSC) is a high-grade non-small cell lung carcinoma (NSCLC) characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered due to limited and inconsistent molecular characterization. Hybrid-capture based comprehensive genomic profiling (CGP) was performed on DNA from 15,867 FFPE NSCLCs including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1.11 Mb of sequenced DNA. The median age of PSC patients was 67 years (range 32-87), 58% were male, and 78% had stage IV disease. TP53 genomic alterations (GA) were identified in 74% of cases, which had distinct genomics from TP53-wild-type cases. 62% featured a GA in KRAS (34%) or one of 7 genes currently recommended for testing in the NSCLC NCCN guidelines including: MET (13.6%), EGFR (8.8%), BRAF (7.2%), HER2 (1.6%) or RET (0.8%). MET exon 14 alterations were enriched in PSC (12%) compared to non-PSC NSCLCs (∼3%) (P&lt...

Research paper thumbnail of Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules

ACS Nano, 2017

This is an open access article published under an ACS AuthorChoice License, which permits copying... more This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

Research paper thumbnail of Silicon Nanowire Sensors Enable Diagnosis of Patients via Exhaled Breath

ACS nano, Jul 6, 2016

Two of the biggest challenges in medicine today are the need to detect diseases in a non-invasive... more Two of the biggest challenges in medicine today are the need to detect diseases in a non-invasive manner, and to differentiate between patients using a single diagnostic tool. The current study targets these two challenges by developing a molecularly-modified Silicon Nanowire Field Effect Transistors (SiNW FETs) and showing its use in the detection and classification of many disease breathprints (lung cancer, gastric cancer, asthma and Chronic Obstructive Pulmonary Disease). The fabricated SiNW FETs are characterized and optimized based on a training set that correlated their sensitivity and selectivity towards volatile organic compounds (VOCs) linked with diseased states. The best sensors obtained in the training set are then examined under real-world clinical conditions, using breath samples from 374 subjects. Analysis of the clinical samples showed that the optimized SiNW FETs can detect and discriminate between almost all binary comparisons of the diseases under examination with...

Research paper thumbnail of Exhaled Breath Analysis for Monitoring Response to Treatment in Advanced Lung Cancer

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jan 8, 2016

RECIST criteria serve as the gold standard method to monitor treatment efficacy in lung cancer. H... more RECIST criteria serve as the gold standard method to monitor treatment efficacy in lung cancer. However, time-intervals between consecutive CT scans might be too long to allow early identification of treatment failure. This study examines the use of breath sampling to monitor responses to anti-cancer treatments in patients with advanced lung cancer. 143 breath samples were collected from 39 patients with advanced lung cancer. The exhaled breath signature, determined by GC-MS(1)fn1 and nanomaterial-based array of sensors, was correlated with the response to therapy assessed by RECIST: Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). GC-MS(1) analysis identified 3 volatile organic compounds (VOCs) as significantly indicating disease control (PR/SD), with one of them also significantly discriminating PR/SD from PD. The nano-array had the ability to monitor changes in tumor response across therapy, also indicating any lack of further respo...

Research paper thumbnail of Predictive and prognostic markers for epidermal growth factor receptor inhibitor therapy in non-small cell lung cancer

Therapeutic advances in medical oncology, 2009

Epidermal growth factor receptor (EGFR) related therapies - mainly tyrosine kinase inhibitors (TK... more Epidermal growth factor receptor (EGFR) related therapies - mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example, cetuximab - have been investigated in numerous settings in non-small cell lung cancer (NSCLC) and in different combinations. The overall clinical benefit of EGFR TKI therapy is roughly 10-30%, with higher benefit in nonsmoker Asiatic women with EGFR-mutated adenocarcinoma. Currently, there are several biomarkers that are able to direct and predict the yield of EGFR-related therapies in NSCLC. These include EGFR mutation status, EGFR protein expression, EGFR gene copy number and a serum proteomic marker (Veristrat®, Biodesix; CO). The usage of such biomarkers is important from many aspects. First, it helps clinicians to make the right treatment decisions and second, it leads to a wiser usage of financial resources. This review will focus on EGFR-related biomarkers for their prognostic power an...

Research paper thumbnail of Diagnostic value of complement components in pleural fluid: Report of 135 cases

Respiratory Medicine, 2008

We prospectively assessed the diagnostic value of pleural fluid complement levels (total, C3, C4)... more We prospectively assessed the diagnostic value of pleural fluid complement levels (total, C3, C4) in 135 patients with pleural effusion of five main etiologies, using novel markers. Complement levels correlated with pleural levels of protein, amylase, and transuded fluids. On univariate analysis, CHF-related pleural effusions were associated with significantly lower C4 levels than postsurgery or parapneumonic effusions. On multivariate analysis, pleural fluid C4 level was a significant predictor of CHF. Although the specificity, positive predictive value, and accuracy of the parameters were low in all diagnostic groups, their negative predictive value as well as the AUC ROC was high for CHF and post-LTX. We conclude that pleural fluid C4 levels can differentiate CHF-related pleural effusion from other etiologies and that normal level of C3 or C4 rule out CHF or LTX as causes of pleural effusion. Complement should be included in the assessment of pleural effusion when traditional diagnostic methods fail.

Research paper thumbnail of Clinical and radiological features of Mycobacterium kansasii infection and Mycobacterium simiae infection

Respiratory Medicine, 2008

Background: Mycobacterium kansasii infection is one of the most common causes of nontuberculous m... more Background: Mycobacterium kansasii infection is one of the most common causes of nontuberculous mycobacterial lung disease in the world. However, it is not possible to differentiate completely between M. kansasii and other nontuberculous mycobacteria (NTM) because of a lack of direct comparative studies. This retrospective study sought to identify their clinical and radiological features systematically. Methods: The sample included 98 consecutive patients with a culture-positive diagnosis of NTM infection, derived from the databases of the Laboratory of Microbiology of a tertiary medical center and two outpatient tuberculosis centers. Sixty-four patients had M. kansasii infection. All patients fulfilled disease criteria for treatment. Data on patient background and clinical features were collected, and chest radiographs were evaluated. Results: In the M. kansasii group, n Z 27 (42%) were native-born Israelis compared to 9.4% (n Z 3) of all other NTM groups (p Z 0.0001). Similar rates of co-morbid diseases, including diabetes mellitus, heart disease, lung diseases, and malignancy were noted in both groups. Old TB was less common in the M. kansasii group compared to the other NTM (3.1% vs. 23.5%, p Z 0.003). Clinical symptoms were significantly more common in patients with M. kansasii infection. On radiological study, M. kansasii infection was associated with more cavitations and unilaterality. Patients with M. kansasii infection had a higher likelihood of right upper lobe disease (p Z 0.001). Pleural effusions and lymphadenopathy were found only in a few patients in each group. Conclusion: Major differences in the epidemiologic and clinical features of M. kansasii infection and other NTM have important diagnostic and clinical implications.

Research paper thumbnail of Use of the 15-steps climbing exercise oximetry test in patients with idiopathic pulmonary fibrosis

Respiratory Medicine, 2008

Idiopathic pulmonary fibrosis (IPF) is often associated with exercise-induced hypoxemia. Although... more Idiopathic pulmonary fibrosis (IPF) is often associated with exercise-induced hypoxemia. Although maximal oxygen consumption (VO 2(max)) is considered the gold-standard index of functional capacity in IPF, its measurement requires sophisticated equipment and trained personnel. The aim of the present study was to investigate the value of the simple 15-steps climbing exercise oximetry test in patients with IPF. The 15-steps climbing test was administered to 51 patients with IPF. Pulmonary function tests (PFTs), cardiopulmonary exercise test (CPET), and the 6-min walk distance (6MWD) test were performed in the same session. Oxygen saturation in the 15-steps climbing test was measured by continuous oximetry, and quantified oxygen desaturation was determined by calculating the area under the curve of oxygen saturation from the beginning of exercise through the lowest desaturation point until recovery to baseline (''desaturation area''). There was a statistically significant correlation between all parameters of the 15-steps climbing test and both VO 2(max) on the CPET (lowest saturation, p ¼ 0.002, r ¼ 0.43; saturation difference, p ¼ 0.02, r ¼ À0.33; recovery time, p ¼ 0.02, r ¼ À0.32; and desaturation area, p ¼ 0.005, r ¼ À0.39), and carbon dioxide diffusion in the lungs (DLCO) on the PFTs (lowest saturation, p ¼ 0.0001, r ¼ 0.52; saturation difference, p ¼ 0.0002, r ¼ À0.50; recovery time, p ¼ 0.0001, r ¼ À0.53; and desaturation area, p ¼ 0.0001, r ¼ À0.53). On stepwise linear regression analysis, independent significant predictors of VO 2(max) were lowest saturation on the 15-steps test and the 6MWD.

Research paper thumbnail of Non-invasive Breath Analysis of Pulmonary Nodules

Journal of Thoracic Oncology, 2012

Introduction: The search for non-invasive diagnostic methods of lung cancer (LC) has led to new a... more Introduction: The search for non-invasive diagnostic methods of lung cancer (LC) has led to new avenues of research, including the exploration of the exhaled breath. Previous studies have shown that LC can, in principle, be detected through exhaled-breath analysis. This study evaluated the potential of exhaled-breath analysis for the distinction of benign and malignant pulmonary nodules (PNs). Methods: Breath samples were taken from 72 patients with PNs in a prospective trial. Profiles of volatile organic compounds were determined by (1) gas chromatography/mass spectrometry (GC-MS) combined with solid-phase microextraction and (2) a chemical nanoarray. Results: Fifty-three PNs were malignant and 19 were benign with similar smoking histories and comorbidities. Nodule size (mean ± SD) was 2.7 ± 1.7 versus 1.6 ± 1.3 cm (p = 0.004), respectively. Within the malignant group, 47 were non-small-cell lung cancer and six were small-cell lung cancer. Thirty patients had early-stage disease and 23 had advanced disease. Gas chromatography/mass spectrometry analysis identified a significantly higher concentration of 1-octene in the breath of LC, and the nanoarray distinguished significantly between benign versus malignant PNs (p < 0.0001; accuracy 88 ± 3%), between adeno-and squamous-cell carcinomas (p < 0.0001; 88 ± 3%) and between early stage and advanced disease (p < 0.0001; 88 ± 2%). Conclusions: In this pilot study, breath analysis discriminated benign from malignant PNs in a high-risk cohort based on LC-related volatile organic compound profiles. Furthermore, it discriminated adenoand squamous-cell carcinoma and between early versus advanced disease. Further studies are required to validate this noninvasive approach, using a larger cohort of patients with PNs detected by computed tomography.

Research paper thumbnail of Peripheral Arterial Stiffness and Endothelial Dysfunction in Idiopathic and Scleroderma Associated Pulmonary Arterial Hypertension

The Journal of Rheumatology, 2009

Objective.Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves ... more Objective.Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves have been reported in pulmonary arterial hypertension (PAH). However, the systemic vascular involvement is not fully understood. Our study focused on the systemic arterial stiffness and endothelial involvement in idiopathic and scleroderma associated PAH.Methods.Peripheral arterial stiffness and endothelial function were evaluated in 38 patients with idiopathic (n = 28) and scleroderma associated (n = 10) PAH, and 21 control subjects (13 healthy; 8 with scleroderma and normal pulmonary pressure). All participants underwent clinical and cardiopulmonary evaluation. Arterial stiffness was measured through the fingertip tonometry derived augmentation index (AI), which is the boost increase in the late systolic pressure wave after the initial systolic shoulder. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion by a noninvasive plethysmogr...

Research paper thumbnail of Ambulatory Rehabilitation Improves Exercise Capacity in Patients With Pulmonary Hypertension

Journal of Cardiac Failure, 2011

Background: Rehabilitation is a central treatment modality for patients with chronic cardiopulmon... more Background: Rehabilitation is a central treatment modality for patients with chronic cardiopulmonary disease. Physical exertion for patients with pulmonary arterial hypertension (PAH) has typically been discouraged. Inpatient pulmonary rehabilitation has been shown to improve exercise capacity in patients with PAH. The present study aimed to evaluate outpatient pulmonary rehabilitation for patients with PAH. Methods and Results: Twenty-two patients with PAH or chronic pulmonary thromboembolic disease were allocated to ambulatory rehabilitation (n 5 11) or to the control group (n 5 11). All patients were stable on PAH-specific medication. The rehabilitation group underwent 24 1-hour sessions of exercise training/rehabilitation over 12 weeks. Primary end points were change in 6-minute walking distance (6MWD) and peak oxygen uptake (VO 2) on cardiopulmonary exercise testing. All of the patients assigned to rehabilitation and 9 control subjects completed the study. In the rehabilitation group, 6MWD increased by 32 m, and in the control group 6MWD decreased by 26 meters (P 5 .003). Peak VO 2 increased in the rehabilitation group by 1.1 mL kg À1 min À1 and decreased by 0.5 mL kg À1 min À1 in the control group (P ! .05). Peak work rate during cardiopulmonary exercise test also increased in the rehabilitation group, with borderline significance (P 5 .051). Echocardiography and blood N-terminal proebrain natriuretic peptide levels were unchanged. No adverse events occurred due to the rehabilitation program. Conclusions: Ambulatory rehabilitation is a safe and efficacious treatment for patients with pulmonary hypertension already on medical therapy.

Research paper thumbnail of Diagnosis of Pulmonary Pathology in Hemodialysis Patients Using a Combination of Imaging and Lung Function Tests

CHEST Journal, 2007

According to the medical literature, prolonged renal failure or hemodialysis treatment might have... more According to the medical literature, prolonged renal failure or hemodialysis treatment might have thoracic and pulmonary effects, such as caused decreased diffusion capacity and metastatic calcifications. Prompted by the successful transplantation at our center of two lungs from a donor who had been on long-term hemodialysis, we sought to determine if hemodialysis does indeed affect pulmonary function. METHODS: The study group included 18 patients aged 27 to 93 years (mean 67.4 years, standard deviation 16 years) treated with hemodialysis from 33 to 257 months (average 77.6 months, standard deviation 4.7 months). Immediately following a dialysis session, the patients underwent lung function tests, cardiopulmonary exercise test, and 6-minute walk test, non-contrast high-resolution computed tomography scanning of the chest and echocardiography. Findings were compared to predicted values. RESULTS: Fourteen patients (77.8%) had normal values on lung function tests. Of the remainder, 1 patient had a nearly normal restrictive pattern, 2 patients had a mild restrictive dysfunction, and 1 patient had a moderate restrictive dysfunction. Decreased diffusion capacity was noted in 11 patients (68.8%)-mild in 10 and moderate in 1 (48% of normal values). The distance on the 6-minute walk test measured less than 350 meters in 7 patients (38.9%), with no decrease in oxygen saturation. Echocardiograms demonstrated moderate to severe left ventricular dysfunction in 3 patients (16.7%); only 1 patient had right ventricular dysfunction. Mild pulmonary hypertension was measured in 4 patients (22.2%), and severe pulmonary hypertension in 1. Computed tomography findings possibly compatible with metastatic calcifications (bronchial calcifications, ground glass opacifications and/or pulmonary nodules) were noted in 15 patients (66.7%). CONCLUSION: Prolonged hemodialysis is apparently not associated with pulmonary dysfunction. Although most of the patients in our series had poor physical fitness, consistent with reports in the literature, the possible calcification noted on computed tomography was mild and apparently not clinically significant. CLINICAL IMPLICATIONS: On the basis of these findings, we suggest that patients on hemodialysis may be considered as potential lung donors.