Pulmonary hypertension associated with lung diseases.

Pulmonary hypertension (PH) associated with chronic lung disease (CLD) is both common and underrecognised. The presence of PH in the setting of lung disease has been consistently shown to be associated with worse outcomes. Recent epidemiological studies have advanced understanding of the heterogeneity of this patient population and shown that defining both the specific type of CLD as well as the severity of PH (i.e. deeper phenotyping) is necessary to inform natural history and prognosis. A systematic diagnostic approach to screening and confirmation of suspected PH in CLD is recommended. Numerous uncontrolled studies and one phase 3 randomised, controlled trial have suggested a benefit in treating PH in some patients with CLD, specifically those with fibrotic interstitial lung disease (ILD). However, other studies in diseases such as COPD-PH showed adverse outcomes with some therapies. Given the expanding list of approved pharmacological treatments for pulmonary arterial hypertension, developing a treatment algorithm for specific phenotypes of PH-CLD is required. This article will summarise existing data in COPD, ILD and other chronic lung diseases, and provide recommendations for classification of PH-CLD and approach to the diagnosis and management of these challenging patients.

Immediate Unilateral Subpectoral Implant-Based Breast Reconstruction does not Impair Pulmonary Functions: A Preliminary Prospective Study.

BACKGROUND: Implant-based breast reconstruction is one of the most common procedures among women with breast cancer undergoing mastectomy. Prosthetic devices may be positioned either beneath or above the pectoralis major muscle, which is considered an accessory muscle of ventilation. This preliminary prospective study aimed to investigate whether subpectoral unilateral implant-based breast reconstruction has any effect on patients' pulmonary functions. METHODS: A prospective study of fourteen women who underwent immediate unilateral implant-based subpectoral breast reconstruction by a single surgeon over 10 months was conducted. Spirometry and maximal voluntary ventilation tests were conducted 1 day prior to surgery, and 1- and 3 months following breast reconstruction. ANOVA or Friedman test were used to compare pulmonary function tests before and after surgery. RESULTS: Fourteen patients completed the study protocol. No statistically significant differences were found when comparing spirometry parameters in the three time points. CONCLUSIONS: Pectoralis muscle release does not impair pulmonary function among patients undergoing immediate unilateral implant-based breast reconstruction following mastectomy. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A novel, accurate, and non-invasive liquid biopsy test to measure cellular immune responses as a tool to diagnose early-stage lung cancer: a clinical trials study.

INTRODUCTION: Lung cancer remains the leading cause of death from cancer, worldwide. Developing early detection diagnostic methods, especially non-invasive methods, is a critical component to raising the overall survival rate and prognosis for lung cancer. The purpose of this study is to evaluate two protocols of a novel in vitro cellular immune response test to detect lung cancer. The test specifically quantifies the glycolysis metabolism pathway, which is a biomarker for the activation level of immune cells. It summarizes the results of two clinical trials, where each deploys a different protocol's version of this test for the detection of lung cancer. In the later clinical trial, an improved test protocol is applied. METHOD: The test platform is based on changes in the metabolic pathways of the immune cells following their activation by antigenic stimuli associated with Lung cancer. Peripheral Blood Mononuclear Cells are loaded on a multiwell plate together with various lung tumor associated antigens and a fluorescent probe that exhibits a pH-dependent absorption shift. The acidification process in the extracellular fluid is monitored by a commercial fluorescence plate reader device in continuous reading for 3 h at 37 °C to document the fluorescent signal received from each well. RESULTS: In the later clinical trial, an improved test protocol was applied and resulted in increased test accuracy. Specificity of the test increased to 94.0% and test sensitivity increased to 97.3% in lung cancer stage I, by using the improved protocol. CONCLUSION: The improved protocol of the novel cellular immune metabolic response based test detects stage I and stage II of lung cancer with high specificity and sensitivity, with low material costs and fast results.

Transbronchial Cryobiopsy Is Superior to Forceps Biopsy for Diagnosing both Fibrotic and Non-Fibrotic Interstitial Lung Diseases.

BACKGROUND: Interstitial lung disease (ILD) evaluation often requires lung biopsy for definite diagnosis. In recent years, transbronchial cryobiopsy (TBCB) emerged as a procedure with higher diagnostic yield than transbronchial forceps biopsy (TBFB), especially for fibrotic ILDs. Nonetheless, studies comparing these modalities in non-fibrotic ILDs and for specific ILD diagnoses are scarce. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield and safety of TBCB and TBFB in patients with fibrotic and non-fibrotic ILDs. METHOD: An observational retrospective multicenter study including patients with ILD diagnosis by multidisciplinary discussion that underwent TBCB or TBFB between 2017 and 2021. Chest CT scans were reviewed by a chest radiologist. Biopsy specimens were categorized as diagnostic (with specific histological pattern), nondiagnostic, or without lung parenchyma. Nondiagnostic samples were reassessed by a second lung pathologist. TBCB and TBFB diagnostic yields were analyzed by multivariate regression. Procedural complications were evaluated as well. RESULTS: 276 patients were included, 116 (42%) underwent TBCB and 160 (58%) TBFB. Fibrotic ILDs were present in 148 patients (54%). TBCB diagnostic yield was 78% and TBFB 48% (adjusted odds ratio [AOR] 4.2, 95% CI: 2.4-7.6, p < 0.01). The diagnostic yield of TBCB was higher than TBFB among patients with fibrotic ILD (AOR 3.8, p < 0.01), non-fibrotic ILD (AOR 5.8, p < 0.01), and across most ILD diagnoses. TBCB was associated with higher risk for significant bleeding (10% vs. 3%, p < 0.01), but similar risk for pneumothorax. CONCLUSIONS: Diagnostic yield of TBCB was superior to that of TBFB for both fibrotic and non-fibrotic ILDs, and across most diagnoses.

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

Cognitive dysfunction following COVID-19 infection.

The coronavirus (COVID-19) pandemic is still evolving, causing hundreds of millions of infections around the world. The long-term sequelae of COVID-19 and neurologic syndromes post COVID remain poorly understood. The present study aims to characterize cognitive performance in patients experiencing cognitive symptoms post-COVID infection. Patients evaluated at a post COVID clinic in Northern Israel who endorsed cognitive symptoms were referred for neurologic consultation. The neurologic work-up included detailed medical history, symptom inventory, neurological examination, the Montreal Cognitive Assessment (MoCA), laboratory tests and brain CT or MRI. Between December 2020 and June 2021, 46 patients were referred for neurological consultation (65% female), mean age 49.5 (19-72 years). On the MoCA test, executive functions, particularly phonemic fluency, and attention, were impaired. In contrast, the total MoCA score, and memory and orientation subscores did not differ from expected ranges. Disease severity, premorbid condition, pulmonary function tests and hypoxia did not contribute to cognitive performance. Cognitive decline may affect otherwise healthy patients post-COVID, independent of disease severity. Our examination identified abnormalities in executive function, attention, and phonemic fluency. These findings occurred despite normal laboratory tests and imaging findings.

COVID-19 risk and outcomes in adult asthmatic patients treated with biologics or systemic corticosteroids: Nationwide real-world evidence.

BACKGROUND: Managing severe asthma during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging, particularly due to safety concerns regarding the use of systemic corticosteroids and biologics. OBJECTIVES: We sought to determine the association between biologics or systemic corticosteroids use and PCR positivity for SARS-CoV-2 and coronavirus disease 2019 (COVID-19) outcomes among asthmatic patients. METHODS: We used the computerized database of Clalit Health Services, the largest health care provider in Israel, to identify all asthmatic adult patients who underwent PCR testing for SARS-CoV-2, between March 1, 2020, and December 7, 2020. A cohort approach was used to assess the association between biologics use and steroids treatment and COVID-19 severity and 90-day mortality. RESULTS: Overall, 8,242 of 80,602 tested asthmatic patients had positive PCR testing result for SARS-CoV-2. Both biologics and systemic corticosteroids were not associated with increased risk of SARS-CoV-2 infection. Multivariate analyses revealed that biologics were not associated with a significantly increased risk of moderate to severe COVID-19, nor with the composite end point of moderate to severe COVID-19 or all-cause mortality within 90 days. Chronic systemic corticosteroid use was associated with significantly increased risk of all tested outcome. Recent (within the previous 120 days) systemic corticosteroid use, but not former use, was significantly associated with increased risk of both moderate to severe COVID-19 and the composite of moderate to severe COVID-19 or all-cause mortality. CONCLUSIONS: Biologics approved for asthma and systemic corticosteroids are not associated with increased risk of SARS-CoV-2 infection. In contrast, systemic corticosteroids are an independent risk factor for worst COVID-19 severity and all-cause mortality. Our findings underscore the risk of recent or current exposure to systemic corticosteroids in asthmatic patients infected with SARS-CoV-2.

Sleep-related breathing disorders and pulmonary hypertension.

Sleep-related breathing disorders (SBDs) include obstructive apnoea, central apnoea and sleep-related hypoventilation. These nocturnal events have the potential to increase pulmonary arterial pressure (PAP) during sleep but also in the waking state. "Pure" obstructive sleep apnoea syndrome (OSAS) is responsible for a small increase in PAP whose clinical impact has not been demonstrated. By contrast, in obesity hypoventilation syndrome (OHS) or overlap syndrome (the association of chronic obstructive pulmonary disease (COPD) with obstructive sleep apnoea (OSA)), nocturnal respiratory events contribute to the development of pulmonary hypertension (PH), which is often severe. In the latter circumstances, treatment of SBDs is essential in order to improve pulmonary haemodynamics.Patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are at risk of developing SBDs. Obstructive and central apnoea, as well as a worsening of ventilation-perfusion mismatch, can be observed during sleep. There should be a strong suspicion of SBDs in such a patient population; however, the precise indications for sleep studies and the type of recording remain to be specified. The diagnosis of OSAS in patients with PAH or CTEPH should encourage treatment with continuous positive airway pressure (CPAP). The presence of isolated nocturnal hypoxaemia should also prompt the initiation of long-term oxygen therapy. These treatments are likely to avoid worsening of PH; however, it is prudent not to treat central apnoea and Cheyne-Stokes respiration (CSR) with adaptive servo-ventilation in patients with chronic right-heart failure because of a potential risk of serious adverse effects from such treatment.In this review we will consider the current knowledge of the consequences of SBDs on pulmonary haemodynamics in patients with and without chronic respiratory disease (group 3 of the clinical classification of PH) and the effect of treatments of respiratory events during sleep on PH. The prevalence and consequences of SBDs in PAH and CTEPH (groups 1 and 4 of the clinical classification of PH, respectively), as well as therapeutic options, will also be discussed.

Radiologic Characteristics of Non-tuberculous Mycobacteria Infection in Patients with Bronchiectasis.

INTRODUCTION: Non-tuberculous mycobacteria pulmonary disease (NTM-pd) commonly complicates bronchiectasis. However, clinical and radiological features of NTM-pd and bronchiectasis are very similar. We aimed to develop a radiologic prediction tool for bronchiectasis to identify NTM-pd. METHODS: We reviewed clinical, laboratory and radiological data in patients with bronchiectasis. Radiologic features on CT scans and the individual components of the Bhalla scoring system were compared between people with and without NTM-pd. Logistic regression and receiver-operating curve (ROC) analysis were performed to predict NTM-pd. RESULTS: People with NTM-pd had more pulmonary segments with bronchiectasis (13 ± 5 vs. 11 ± 5, p = 0.03), presence of mucus plugging (47% vs. 19%, p < 0.0001) and tree in bud infiltrates (53% vs. 28%, p = 0.004). The total modified- Bhalla score was worse among people with NTM-pd (median [IQR] 11[9,13] vs. 9[8,12], p = 0.03). Logistic regression identified the number of pulmonary segments involved, presence of bullae, consolidations, and a total score of 10 or more to be independently associated with presence of NTM-pd. ROC analysis with radiographic variables only identified an AUC of 0.706 (95% CI 0.644-0.762). When people with chronic Pseudomonas infection were excluded from the ROC analysis, prediction for NTM was improved: AUC = 0.87 (95% CI 0.796-0.945). DISCUSSION AND CONCLUSIONS: Radiological features together with advanced age and female gender may predict NTM-pd among people with bronchiectasis. Infection with Pseudomonas aeruginosa may resemble NTM radiographically, and this prediction rule may better differentiate people with and without NTM-pd when Pseudomonas infection is not present.

Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Diseases in a Community Medical Center.

BACKGROUND: Transbronchial cryobiopsy (TBC) has recently emerged for the assessment of diffuse parenchymal lung disease (DPLD) as a less invasive procedure than surgical lung biopsy. The diagnostic usefulness and safety of TBC is still controversial. OBJECTIVES: To evaluate the safety and diagnostic yield of TBC in a peripheral community medical center. METHODS: We retrospectively reviewed the charts of all patients with DPLD who underwent TBC from January 2015 to January 2020. RESULTS: The study comprised 97 patients. Three samples were taken from each patient with an average diameter of 0.59 cm. The histologic diagnostic yield was 54% (52 of 97 procedures). The most frequent histopathologic diagnoses were usual interstitial pneumonia in 13 patients (13%). Bleeding was observed in 19 cases (19%) and only one patient (1%) had severe bleeding. Pneumothorax developed in seven patients (7%) and one patient (1%) suffered from Interstitial lung disease exacerbation. CONCLUSIONS: TBC was found to be safe; however, the diagnostic yield was rather low compared to other studies, which emphasizes the need for interstitial lung disease centers with expert in this field.

Prognostic Value of Follow-Up Hemodynamic Variables After Initial Management in Pulmonary Arterial Hypertension.

BACKGROUND: Hemodynamic variables such as cardiac index and right atrial pressure have consistently been associated with survival in pulmonary arterial hypertension (PAH) at the time of diagnosis. Recent studies have suggested that pulmonary arterial compliance may also predict prognosis in PAH. The prognostic importance of hemodynamic values achieved after treatment initiation is less well established. METHODS: Our objective was to evaluate the prognostic importance of clinical and hemodynamic variables during follow-up, including pulmonary arterial compliance, after initial management in PAH. We evaluated incident patients with idiopathic, drug- and toxin-induced, or heritable PAH enrolled in the French pulmonary hypertension registry between 2006 and 2016 who had a follow-up right-sided heart catheterization (RHC). The primary outcome was death or lung transplantation. We used stepwise Cox regression and the Kaplan-Meier method to assess variables obtained at baseline and at first follow-up RHC. RESULTS: Of 981 patients, a primary outcome occurred in 331 patients (33.7%) over a median follow-up duration of 2.8 years (interquartile range, 1.1-4.6 years). In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis. Median time to first follow-up RHC was 4.6 months (interquartile range, 3.7-7.8 months). At first follow-up RHC (n=763), New York Heart Association functional class, 6-minute walk distance, stroke volume index (SVI), and right atrial pressure were independently associated with death or lung transplantation, adjusted for age, sex, and type of PAH. Pulmonary arterial compliance did not independently predict outcomes at baseline or during follow-up. The adjusted hazard ratio for SVI was 1.28 (95% confidence interval, 1.11-1.49; P<0.01) per 10-mL/m2 decrease and for right atrial pressure was 1.05 (95% confidence interval, 1.02-1.09; P<0.01) per 1-mm Hg increase. Among patients who had 2 (n=355) or 3 (n=193) low-risk prognostic features at follow-up, including a cardiac index ≥2.5 L·min-1·m-2, 6-minute walk distance >440 m, and New York Heart Association class I or II functional class, lower SVI was still associated with higher rates of death or lung transplantation (P<0.01). CONCLUSIONS: SVI and right atrial pressure were the hemodynamic variables that were independently associated with death or lung transplantation at first follow-up RHC after initial PAH treatment. These findings suggest that the SVI could be a more appropriate treatment target than cardiac index in PAH.

Importance of the relationship between symptoms and self-reported physical activity level in stable COPD based on the results from the SPACE study.

BACKGROUND: The burden of symptoms and risk of exacerbations are the main drivers of the overall assessment of the Chronic Obstructive Pulmonary Disease (COPD) and the adequate treatment approaches per current Global Initiative for Chronic Obstructive Lung Disease (GOLD). Physical activity has emerged as both functional outcome and non-pharmacological intervention in COPD patients, despite the lack of standardized measures or guidelines in clinical practice. This study aimed to explore in more depth the 24-h respiratory symptoms, the physical activity level (PAL) and the relationship between these two determinants in stable COPD patients. METHODS: This was a multinational, multicenter, observational, cross-sectional study conducted in ten European countries and Israel. Dedicated questionnaires for each part of the day (morning, daytime, night) were used to assess respiratory symptoms. PAL was evaluated with self- and interview-reported tools [EVS (exercise as vital sign) and YPAS (Yale Physical Activity Survey)], and physician's judgement. Patients were stratified in ABCD groups by 2013 and 2017 GOLD editions using the questionnaires currently recommended: modified Medical Research Council dyspnea scale and COPD Assessment Test. RESULTS: The study enrolled 2190 patients (mean age: 66.9 years; male: 70.0%; mean % predicted FEV1: 52.6; GOLD groups II-III: 84.5%; any COPD treatment: 98.9%). Most patients (> 90%) reported symptoms in any part of the 24-h day, irrespective of COPD severity. PAL evaluations showed discordant results between patients and physicians: 32.9% of patients considered themselves completely inactive, while physicians judged 11.9% patients as inactive. By YPAS, the overall study population spent an average of 21.0 h/week performing physical activity, and 68.4% of patients were identified as sedentary. In any GOLD ABCD group, the percentage of inactive patients was high. Our study found negative, weak correlations between respiratory symptoms and self-reported PAL (p < 0.001). CONCLUSIONS: Despite regular treatment, the majority of stable COPD patients with moderate to severe disease experienced daily variable symptoms. Physical activity level was low in this COPD cohort, and yet overestimated by physicians. With evidence indicating the negative consequences of inactivity, its adequate screening, a more active promotion and regular assessment of physical activity are urgently needed in COPD patients for better outcomes. TRIAL REGISTRATION: NCT03031769 , retrospectively registered, 23 Jan 2017.

Per-Esophageal Needle Aspiration of Parenchymal Lung Lesions and Mediastinal Lymph Nodes Using an Endobronchial Ultrasound Bronchoscope.

BACKGROUND: Transesophageal endoscopic ultrasound-guided fine-needle aspiration using a bronchoscope (EUS-B-FNA) allows clinicians to determine mediastinal staging and lung mass evaluation of lesions not accessible by endobronchial ultrasound (EBUS) or where endobronchial ultrasound-guided transbronchial needle aspiration might not be safe. OBJECTIVES: To evaluate the safety, diagnostic accuracy, and feasibility of EUS-B-FNA. METHODS: The study comprised patients who underwent a pulmonologist-performed EUS-B-FNA of mediastinal lymph nodes and parenchymal lung lesions between June 2015 and September 2017 at the Carmel Medical Center, Haifa, Israel. RESULTS: EUS-B-FNA was performed in 81 patients. The transesophageal procedure was performed for easier accessibility (49.4%) and in high-risk patients (43.3%). The most frequently sampled mediastinal stations were left paratracheal and sub-carinal lymph nodes or masses (38.3% and 56.7%, respectively). There were no complications (e.g., acute respiratory distress, esophageal perforation, or bleeding). An accurate diagnosis was determined in 91.3% of cases. CONCLUSIONS: Pulmonologist-performed EUS-B-FNA is safe and accurate for evaluating mediastinal and parenchymal lung lesions and lymphadenopathy. Diagnostic accuracy is high. EUS-B-FNA may allow access to sites not amenable to other forms of bronchoscopic sampling, or may increase diagnostic accuracy in patients where anatomic position predicts a low diagnostic yield.

COPD Exacerbator Phenotype is Inversely Associated with Current Smoking But Not with Haptoglobin Phenotype.

BACKGROUND: Frequent chronic obstructive pulmonary disease (COPD) exacerbators are at a higher risk of adverse health outcomes when compared to infrequent exacerbators. A COPD frequent exacerbator phenotype and its definition has been reported. Haptoglobin (Hp) polymorphism has been associated with differing clinical outcomes in cardiovascular and renal disease. The Hp 2-2 phenotype has been found to have bacteriostatic properties, while the Hp 1-1 phenotype was found to be associated with infections. OBJECTIVES: To determine the correlation in haptoglobin phenotypes and the frequent exacerbator status compared to COPD non-exacerbators. METHODS: Inclusion criteria included previous diagnosis of COPD and presence of at least two documented exacerbations of COPD in the previous 12 months (frequent exacerbator group) or absence of such exacerbations in the previous 24 months (non-exacerbator group). Descriptive data was analyzed using Fisher's exact test and the nonparametric Kruskal-Wallis test. Multivariate logistic regression analysis was performed. RESULTS: The multivariate logistic regression yielded a model in which haptoglobin phenotype did not have a statistically significant association with frequent exacerbator status. Smoking status was found to be negatively related with the frequent exacerbator status (odds ratio [OR] 0.240, 95% confidence interval (95%CI) 0.068-0.843, P = 0.03). Number of pack-years was negatively related to being a frequent exacerbator (OR 0.979, 95%CI 0.962-0.996, P = 0.02). CONCLUSIONS: We found no relationship between haptoglobin polymorphism and frequent exacerbator status. However, frequent exacerbator status had a statistically significant association with COPD Assessment Test scores and pack-years and a negative correlation with current smoking status.

Novel non-invasive early detection of lung cancer using liquid immunobiopsy metabolic activity profiles.

Lung cancer is the leading cause of cancer death worldwide. Survival is largely dependent on the stage of diagnosis: the localized disease has a 5-year survival greater than 55%, whereas, for spread tumors, this rate is only 4%. Therefore, the early detection of lung cancer is key for improving prognosis. In this study, we present an innovative, non-invasive, cancer detection approach based on measurements of the metabolic activity profiles of immune system cells. For each Liquid ImmunoBiopsy test, a 384 multi-well plate is loaded with freshly separated PBMCs, and each well contains 1 of the 16 selected stimulants in several increasing concentrations. The extracellular acidity is measured in both air-open and hermetically-sealed states, using a commercial fluorescence plate reader, for approximately 1.5 h. Both states enable the measurement of real-time accumulation of 'soluble' versus 'volatile' metabolic products, thereby differentiating between oxidative phosphorylation and aerobic glycolysis. The metabolic activity profiles are analyzed for cancer diagnosis by machine-learning tools. We present a diagnostic accuracy study, using a multivariable prediction model to differentiate between lung cancer and control blood samples. The model was developed and tested using a cohort of 200 subjects (100 lung cancer and 100 control subjects), yielding 91% sensitivity and 80% specificity in a 20-fold cross-validation. Our results clearly indicate that the proposed clinical model is suitable for non-invasive early lung cancer diagnosis, and is indifferent to lung cancer stage and histological type.

EBUS-TBNA is Sufficient for Successful Diagnosis of Silicosis with Mediastinal Lymphadenopathy.

BACKGROUND: Silicosis is an occupational lung disease resulting from inhalation of respirable crystalline silica. Recently, an international silicosis epidemic has been noted among artificial stone workers. OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is currently used for patients with unexplained lymphadenopathy. Since silicosis may present with prominent lymphadenopathy, the diagnostic yield of EBUS-TBNA in diagnosing silicosis was evaluated. METHODS: Twenty-eight patients with suspected silicosis referred for outpatient evaluation in three large tertiary hospitals were evaluated. Patients with mediastinal lymphadenopathy underwent EBUS-TBNA, while others underwent TBB and/or video-assisted thoracoscopic surgery (VATS). RESULTS: Eleven patients with mediastinal lymphadenopathy (39%) were evaluated using EBUS-TBNA. The diagnosis was accurate in all cases, demonstrating silica particles under polarized light, with no complications. Among the remaining patients, TBB was only 76% diagnostic, therefore requiring VATS. CONCLUSIONS: EBUS-TBNA is a useful and sufficient tool to diagnose silicosis in patients with mediastinal lymphadenopathy along compatible exposure histories.

[DIAGNOSIS AND TREATMENT OF BRONCHIECTASIS: POSITION PAPER OF THE ISRAELI PULMONOLOGY SOCIETY AND THE ISRAELI PEDIATRIC PULMONOLOGY SOCIETY].

INTRODUCTION: Bronchiectasis is anatomically defined by irreversible distortion of the bronchi. Clinically, its manifestations are cough with sputum production and a predisposition to pulmonary infections. Unlike asthma and COPD, where ample clinical data are present regarding the course and effective treatment, knowledge of bronchiectasis has yet to evolve. Lately, bronchiectasis is gaining renewed attention among the medical community, with growing basic and clinical research-based data. In Israel, no registered treatments exist for bronchiectasis, which makes it difficult to treat these patients. This paper is a summary of the position of the Israeli Pulmonology Association and the Israeli Pediatric Pulmonology Association for diagnosis and treatment of bronchiectasis.

Pulmonary hemodynamics in heart failure patients with reduced or preserved ejection fraction and pulmonary hypertension: Similarities and disparities.

OBJECTIVE: The current understanding of pulmonary hypertension (PH) due to left ventricular diseases does not distinguish heart failure (HF) with reduced ejection fraction (HFrEF) from HF and preserved ejection fraction (HFpEF), in terms of pulmonary hemodynamics. The value of pulmonary vascular compliance (PCa) and diastolic pulmonary gradient (DPG) as predictors of survival in either HF syndrome is controversial. The aims of our study were to compare the pulmonary hemodynamics in the two HF phenotypes, given similar values of pulmonary artery wedge pressure (PAWP), and to evaluate the impact of PCa and DPG on survival. METHODS: We retrospectively reviewed the charts of 168 PH-HFrEF and 86 PH-HFpEF patients. The independent association of PCa and DPG with prognosis was assessed by means of a Cox proportional hazard model. All cause survival was analyzed over an average follow-up period of 50 months. RESULTS: PH-HFpEF patients had a significantly higher DPG than PH-HFrEF patients (6.1±7.1 vs 1.8±4.5 mmHg, adjusted P=.025). PCa was similar in PH-HFpEF and PH-HFrEF. PCa was a significant predictor of survival, according to previously described preset cutoffs (2.15 mL/mmHg in HFrEF and 1.1 mL/mmHg in HFpEF) and based on a continuous scale; whereas DPG had no impact on survival in both patients groups. CONCLUSION: Our findings suggest that for similar levels of PAWP, pulmonary circulation may be stiffer in patients with HFpEF-PH than patients with HFrEF-PH, leading to higher DPGs. Nonetheless, PCa rather than DPG emerged as the stronger predictor of survival in both left-sided PH phenotypes.

[LONG TERM TREATMENT WITH MACROLIDES IN CHRONIC LUNG DISEASES].

INTRODUCTION: Macrolide agents have both antibacterial properties as well as various effects on the inflammatory system. In recent years there is growing evidence regarding the favourable effects of macrolides in a range of chronic respiratory conditions. Historically, erythromycin and clarithromycin were found to stabilize pulmonary deterioration in diffuse panbronchiolitis. In cystic fibrosis patients colonized with pseudomonas aeruginosa, long term treatment with azithromycin reduces exacerbations and presents improved lung function. A similar effect on prevention of exacerbations has been demonstrated in noncystic fibrosis bronchiectasis. In patients undergoing lung transplantation, long term azithromycin prevents bronchiolitis obliterans syndrome. In patients with chronic obstructive pulmonary disease (COPD), azithromycin prevents acute exacerbations. Chronic treatment with macrolides is associated with adverse effects including gastrointestinal symptoms, interactions with other drugs and cardiovascular complications. Of the macrolides, azithromycin is associated with the lowest interactions and adverse effects and is also the most investigated.