Bronchoscopy-related outbreaks and pseudo-outbreaks: A systematic review.

OBJECTIVE: To identify and report the pathogens and sources of contamination associated with bronchoscopy-related outbreaks and pseudo-outbreaks. DESIGN: Systematic review. SETTING: Inpatient and outpatient outbreaks and pseudo-outbreaks after bronchoscopy. METHODS: PubMed/Medline databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the search terms "bronchoscopy," "outbreak," and "pseudo-outbreak" from inception until December 31, 2022. From eligible publications, data were extracted regarding the type of event, pathogen involved, and source of contamination. Pearson correlation was used to identify correlations between variables. RESULTS: In total, 74 studies describing 23 outbreaks and 52 pseudo-outbreaks were included in this review. The major pathogens identified in these studies were Pseudomonas aeruginosa, Mycobacterium tuberculosis, nontuberculous mycobacteria (NTM), Klebsiella pneumoniae, Serratia marcescens, Stenotrophomonas maltophilia, Legionella pneumophila, and fungi. The primary sources of contamination were the use of contaminated water or contaminated topical anesthetics, dysfunction and contamination of bronchoscopes or automatic endoscope reprocessors, and inadequate disinfection of the bronchoscopes following procedures. Correlations were identified between primary bronchoscope defects and the identification of P. aeruginosa (r = 0.351; P = .002) and K. pneumoniae (r = 0.346; P = .002), and between the presence of a contaminated water source and NTM (r = 0.331; P = .004) or L. pneumophila (r = 0.280; P = .015). CONCLUSIONS: Continued vigilance in bronchoscopy disinfection practices remains essential because outbreaks and pseudo-outbreaks continue to pose a significant risk to patient care, emphasizing the importance of stringent disinfection and quality control measures.

Coexistence of Autoimmune Pulmonary Alveolar Proteinosis With Small Cell Lung Cancer in a Man Presenting With Acute Onset Respiratory Failure.

A 60-year-old man was referred to our Respiratory Department with progressive dyspnea on exertion and productive cough over the past two months. High-resolution computed tomography showed diffuse ground glass opacities with superimposed interlobular and intralobular septal thickening mainly in the middle and lower lobes, compatible with crazy paving pattern. Serology tests revealed positive antibody transcriptional intermediary factor-γ1 (TIF-1γ) in myositis panel and bronchoalveolar lavage revealed milky appearance and positive periodic acid-Schiff (PAS) stain. Pulmonary function tests showed moderate reduction in diffusing capacity for carbon monoxide. The working diagnosis of autoimmune pulmonary alveolar proteinosis was established by high detectable levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies. Despite clinical and radiological improvement following treatment with whole lung lavage and inhaled sargramostim, patient's follow-up chest computed tomography revealed an enlargement of lower left paratracheal lymph node 4L. Endobronchial ultrasound bronchoscopy (EBUS) biopsy was compatible with small cell lung cancer (SCLC). Chemotherapeutic agents were promptly administrated, with no adverse events up until now.

SRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis.

The activation and accumulation of lung fibroblasts resulting in aberrant deposition of extracellular matrix components, is a pathogenic hallmark of Idiopathic Pulmonary Fibrosis, a lethal and incurable disease. In this report, increased expression of TKS5, a scaffold protein essential for the formation of podosomes, was detected in the lung tissue of Idiopathic Pulmonary Fibrosis patients and bleomycin-treated mice. Τhe profibrotic milieu is found to induce TKS5 expression and the formation of prominent podosome rosettes in lung fibroblasts, that are retained ex vivo, culminating in increased extracellular matrix invasion. Tks5+/- mice are found resistant to bleomycin-induced pulmonary fibrosis, largely attributed to diminished podosome formation in fibroblasts and decreased extracellular matrix invasion. As computationally predicted, inhibition of src kinase is shown to potently attenuate podosome formation in lung fibroblasts and extracellular matrix invasion, and bleomycin-induced pulmonary fibrosis, suggesting pharmacological targeting of podosomes as a very promising therapeutic option in pulmonary fibrosis.

A comprehensive analysis of GATA3 expression in carcinomas of various origins with emphasis on lung carcinomas.

GATA3 is a transcription factor involved in embryogenesis of multiple human tissues and in maintaining cell differentiation and tissue homeostasis in the adult organism. GATA3 is also involved in carcinogenesis and regarded as a sensitive marker for urothelial and breast carcinomas, albeit expression in carcinomas of non-breast/urothelial origin has been frequently reported. We sought to examine the extent and intensity of GATA3 expression in various carcinomas, mainly lung, urothelial, and breast and various other primary sites. Patients with breast carcinoma (N=40), carcinoma of the urinary bladder/renal pelvis (N=40), lung carcinoma (N=110) and various other origins (N=45) were included in the study. One hundred and sixty-five patients had a primary tumor diagnosis, and 70 cases had a metastatic tumor diagnosis. Our results showed that GATA3 expression was significantly more common in carcinomas of the breast, urinary bladder and renal pelvis compared to all other origins. All primary and 93% of metastatic urinary bladder carcinomas and 94% of the primary and 80% of metastatic breast carcinomas expressed GATA3. Expression was lower in non-urothelial histology of urinary primaries and in triple negative breast carcinomas. Focal staining, mostly faint, was seen in 5.6% of the primary lung adenocarcinomas and 35% of the primary lung squamous cell carcinomas. More extensive and intense staining was seen in 3.7% of the primary lung adenocarcinomas and 12% of the primary lung squamous cell carcinomas. Expression, mostly focal was also seen in 30% of the metastatic lung carcinomas. Finally, high expression was seen in 12.5% of the other tumors (one metastatic pancreatic carcinoma, one metastatic salivary gland adenocarcinoma NOS, one metastatic squamous cell carcinoma of the skin, one primary uterine cervix serous carcinoma, and one squamous cell carcinoma of the head and neck) and focal expression was present in another 22% of them. No ideal cut-off for positivity for GATA3 staining could be identified. In conclusion our study shows that GATA3 staining has two caveats in its use: the first is that non classical histologies of urothelial carcinomas and TNBC may be negative for the marker and secondly carcinomas of various origins may show (although rarely) intense positivity.

Statins' still controversial role in pulmonary fibrosis: What does the evidence show?

Pulmonary fibrosis (PF) represents the end stage of a broad range of interstitial lung diseases (ILDs). Statins are among the compounds which have been implicated in drug-induced ILD development. However, recent studies (both in vitro and in vivo) have provided evidence that statins may exert anti-inflammatory and anti-fibrotic effects potentially offering benefits to patients with PF. Several protective molecular mechanisms including the suppression of mevalonic acid pathway, the inhibition of NADPH oxidase activation in macrophages and the inhibition of several profibrotic mediators have been proposed to explain the observed in vivo decrease of the oxidative stress in the lung and the preservation of lung function in patients. Earlier clinical studies relating statins with drug-induced ILD development are contradicted by increasing new data showing the beneficial effects of statins in clinical outcomes in ILD patients who receive statins for concomitant cardiovascular indications. Future research may further elucidate the wide spectrum of pathways of IPF pathogenesis, and genetic heterogeneity, identifying clinically applicable biomarkers and specific endotypes thus recognizing in which patients statins could confer benefit and in which they might cause detrimental effects.

Fanconi syndrome-associated interstitial lung disease.

A middle-aged man was referred to our respiratory department with dyspnoea progressively deteriorating and non-productive cough over the past 8 months. High-resolution CT revealed multiple bilateral consolidations, traction bronchiectasis, reticular pattern and honeycombing with basal and peripheral predominance. Serology tests were negative. Pulmonary function tests showed moderate restrictive functional impairment and severe reduction in diffusing capacity for carbon monoxide. Meticulous evaluation of patient's medical history revealed recent administration of oral corticosteroid due to pulmonary fibrosis potentially in the context of Fanconi syndrome diagnosed at childhood. The working diagnosis of interstitial lung disease (ILD) as a rare complication of Fanconi syndrome was proposed following multidisciplinary discussion. Despite combination treatment with low doses of corticosteroids and antifibrotic compound, the patient exhibited clinical, radiological and functional deterioration, was admitted to intensive care unit due to respiratory failure following infection-driven progression of fibrotic ILD and finally died.

Pulmonary adverse events following immune checkpoint inhibitors.

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICIs) have rapidly become a mainstay of cancer treatment. However, immune modulation resulting from checkpoint inhibition can cause inflammation in any organ system, with pneumonitis being one of the most severe immune-related adverse events (irAEs). Here, we review the most recent literature on pulmonary adverse events following ICIs. RECENT FINDINGS: Several systematic reviews and meta-analyses of data from trials of antiprogrammed death-1 (PD-1; nivolumab, pembrolizumab), anti-PD-ligand-1 (PD-L1; atezolizumab, avelumab, durvalumab) and anticytotoxic T lymphocyte antigen-4 (CTLA-4; ipilimumab or tremelimumab) in patients with advanced cancer have explored the relative risk and incidence of lung toxicity among different tumor types and therapeutic regimens. They have showed that the incidence of all-grade (1-4) and high-grade (3-4) pneumonitis is significantly higher in nonsmall cell lung cancer (NSCLC) compared with other tumor types. In addition, they have demonstrated that immunotherapy, especially monoimmunotherapy, has a significantly lower risk of irAEs compared to immune-chemotherapy. Treatment for lung cancer, preexisting interstitial lung disease, smoking history and male sex appear to increase the risk for ICI-related pneumonitis. SUMMARY: Lung toxicity is an uncommon but potentially severe and even fatal complication of ICIs. Timely recognition is critically important but challenging, particularly in patients with lung cancer wherein drug toxicity can mimic disease progression or recurrence.

High-flow versus conventional nasal cannula oxygen supplementation therapy and risk of hypoxia in gastrointestinal endoscopies: a systematic review and meta-analysis.

BACKGROUND: Gastrointestinal endoscopy (GIE) represents a mainstay diagnostic and therapeutic procedure in clinical practice. Hypoxemia constitutes a major complication for endoscopists. Emerging evidence supports the utilization of high-flow nasal cannula (HFNC) over conventional nasal cannula (CNC) for avoidance of hypoxemia. Our aim was to compare the hypoxemia risk in patients undergoing GIE with HFNC versus CNC oxygen supplementation recruited by randomized controlled trials (RCTs). METHODS: We searched in medical databases PubMed, EMBASE and Cochrane to identify RCTs investigating the abovementioned association. Enrolled studies were evaluated for risk of bias and inserted into a random effects model for meta-analysis; subgroup analyses and publication bias were also assessed. RESULTS: Out of 271 articles, five RCTs were eligible (patients n=2656, HFNC 1299 and CNC 1357). A statistically significant reduced relative risk (RR) of hypoxemia among HFNC patients was revealed (RR=0.18, CI95%: 0.05-0.61), whilst with high heterogeneity (I2:79.94%, p<0.01). Patients undergoing upper GIE with HFNC displayed a significantly lower hypoxemia risk (96%, p<0.001, I2:15.59%), even after exclusion of endoscopic retrograde cholangiopancreatography cases (RR:0.03, CI95%:0.01-0.21), albeit with higher heterogeneity (I2:41.82%).    . CONCLUSION: Patients undergoing upper GIE with HFNC experience significantly less hypoxemia burden than CNC counterparts. Further research is warranted to target optimal safety during endoscopy.Abbreviations: ASA, American Society of Anesthesiologists; ASGE, American Society for Gastrointestinal Endoscopy; BMI, Body Mass Index; CI, confidence interval; CNC, conventional nasal cannula; ERCP, endoscopic retrograde cholangiopancreatography; FiO2, fraction of inspired O2; GI, gastrointestinal; GIE, gastrointestinal endoscopies; HFNC, High-Flow nasal cannula; ICU, intensive care unit; PEEP, positive end-expiratory pressure; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analysis; RCTs, randomized control trials; RR, relative risk (or risk ratio).

Genotype-Phenotype Relationships in Inheritable Idiopathic Pulmonary Fibrosis: A Greek National Cohort Study.

BACKGROUND: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability. PATIENTS AND METHODS: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed. RESULTS: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis. CONCLUSION: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease's genetic "richesse," complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating "personalized" medical care driven by genotypes in the near future.

Safety and Effectiveness of Mycophenolate Mofetil in Interstitial Lung Diseases: Insights from a Machine Learning Radiographic Model.

INTRODUCTION: Treatment of interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) often includes systemic corticosteroids. Use of steroid-sparing agents is amenable to avoid potential side effects. METHODS: Functional indices and high-resolution computed tomography (HRCT) patterns of patients with non-IPF ILDs receiving mycophenolate mofetil (MMF) with a minimum follow-up of 1 year were analyzed. Two independent radiologists and a machine learning software system (Imbio 1.4.2.) evaluated HRCT patterns. RESULTS: Fifty-five (n = 55) patients were included in the analysis (male: 30 [55%], median age: 65.0 [95% CI: 59.7-70.0], mean forced vital capacity %predicted [FVC %pred.] ± standard deviation [SD]: 69.4 ± 18.3, mean diffusing capacity of lung for carbon monoxide %pred. ± SD: 40.8 ± 14.3, hypersensitivity pneumonitis: 26, connective tissue disease-ILDs [CTD-ILDs]: 22, other ILDs: 7). There was no significant difference in mean FVC %pred. post-6 months (1.59 ± 2.04) and 1 year (-0.39 ± 2.49) of treatment compared to baseline. Radiographic evaluation showed no significant difference between baseline and post-1 year %ground glass opacities (20.0 [95% CI: 14.4-30.0] vs. 20.0 [95% CI: 14.4-25.6]) and %reticulation (5.0 [95% CI: 2.0-15.6] vs. 7.5 [95% CI: 2.0-17.5]). A similar performance between expert radiologists and Imbio software analysis was observed in assessing ground glass opacities (intraclass correlation coefficient [ICC] = 0.73) and reticulation (ICC = 0.88). Fourteen patients (25.5%) reported at least one side effect and 8 patients (14.5%) switched to antifibrotics due to disease progression. CONCLUSION: Our data suggest that MMF is a safe and effective steroid-sparing agent leading to disease stabilization in a proportion of patients with non-IPF ILDs. Machine learning software systems may exhibit similar performance to specialist radiologists and represent fruitful diagnostic and prognostic tools.

Increased Autotaxin Levels in Severe COVID-19, Correlating with IL-6 Levels, Endothelial Dysfunction Biomarkers, and Impaired Functions of Dendritic Cells.

Autotaxin (ATX; ENPP2) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling phospholipid. Genetic and pharmacologic studies have previously established a pathologic role for ATX and LPA signaling in pulmonary injury, inflammation, and fibrosis. Here, increased ENPP2 mRNA levels were detected in immune cells from nasopharyngeal swab samples of COVID-19 patients, and increased ATX serum levels were found in severe COVID-19 patients. ATX serum levels correlated with the corresponding increased serum levels of IL-6 and endothelial damage biomarkers, suggesting an interplay of the ATX/LPA axis with hyperinflammation and the associated vascular dysfunction in COVID-19. Accordingly, dexamethasone (Dex) treatment of mechanically ventilated patients reduced ATX levels, as shown in two independent cohorts, indicating that the therapeutic benefits of Dex include the suppression of ATX. Moreover, large scale analysis of multiple single cell RNA sequencing datasets revealed the expression landscape of ENPP2 in COVID-19 and further suggested a role for ATX in the homeostasis of dendritic cells, which exhibit both numerical and functional deficits in COVID-19. Therefore, ATX has likely a multifunctional role in COVID-19 pathogenesis, suggesting that its pharmacological targeting might represent an additional therapeutic option, both during and after hospitalization.

Increased monocyte count and red cell distribution width as prognostic biomarkers in patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. METHODS: We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). RESULTS: Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/µL had significantly lower median FVC%pred [75.0, (95% CI 71.3-76.7) vs. 80.9, (95% CI 77.5-83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3-52.3) vs. 53.0, (95% CI 48.0-56.7), (P = 0.02)] than patients with monocyte count < 0.60 K/µL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred [75.5, (95% CI 71.2-79.2) vs. 78.3, (95% CI 76.0-81.0), (P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3-50.5) vs. 53.0, (95% CI 50.8-56.8), (P = 0.008)] than patients with RDW < 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count [37.8, (95% CI 35.5-41.1) vs. 45.5, (95% CI 41.9-49.4), (P < 0.001)] and RDW [37.9, (95% CI 33.4-40.7) vs. 44.4, (95% CI 41.5-48.9), (P < 0.001)]. Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan-Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/µL) vs. low monocyte count (< 0.60 K/µL) [HR 2.05, (95% CI 1.19-3.53), (P = 0.01)]. CONCLUSIONS: Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.

Bronchoscopy during the COVID-19 pandemic: effect on current practices and strategies to reduce procedure-associated transmission.

Introduction: Bronchoscopy and related procedures have unambiguously been affected during the Corona Virus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS COV-2). Ordinary bronchoscopy practices and lung cancer services might have changed over this pandemic and for the years to come.Areas covered: This manuscript summarizes the utility of bronchoscopy in COVID-19 patients, and the impact of the pandemic in lung cancer diagnostic services, in view of possible viral spread during these We conducted a literature review of articles published in PubMed/Medline from inception to November 5th, 2020 using relevant terms.Expert opinion: Without doubt this pandemic has changed the way bronchoscopy and related procedures are being performed. Mandatory universal personal protective equipment, pre-bronchoscopy PCR tests, dedicated protective barriers and disposable bronchoscopes might be the safest and simpler way to perform even the most complicated procedures.

Monocyte Count as a Prognostic Biomarker in Patients with Idiopathic Pulmonary Fibrosis.

Rationale: There is an urgent need for simple, cost-effective prognostic biomarkers for idiopathic pulmonary fibrosis (IPF); biomarkers that show potential include monocyte count. Objectives: We used pooled data from pirfenidone and IFNγ-1b trials to explore the association between monocyte count and prognosis in patients with IPF. Methods: This retrospective pooled analysis included patients (active and placebo arms) from the following four phase III, randomized, placebo-controlled trials: ASCEND (NCT01366209), CAPACITY (NCT00287729 and NCT00287716), and INSPIRE (NCT00075998). Outcomes included IPF progression (≥10% absolute decline in FVC% predicted, ≥50 m decline in 6-minute-walk distance, or death), all-cause hospitalization, and all-cause mortality over 1 year. The relationship between monocyte count (defined as time-dependent) and outcomes was assessed using bivariate and multivariable models. Measurements and Main Results: This analysis included 2,067 patients stratified by monocyte count (at baseline: <0.60 × 109 cells/L [n = 1,609], 0.60 to <0.95 × 109 cells/L [n = 408], and ≥0.95 × 109 cells/L [n = 50]). In adjusted analyses, a higher proportion of patients with monocyte counts of 0.60 to <0.95 × 109 cells/L or ≥0.95 × 109 cells/L versus <0.60 × 109 cells/L experienced IPF progression (P = 0.016 and P = 0.002, respectively), all-cause hospitalization (P = 0.030 and P = 0.003, respectively), and all-cause mortality (P = 0.005 and P < 0.001, respectively) over 1 year. Change in monocyte count from baseline was not associated with any of the outcomes over 1 year and did not appear to be affected by study treatment. Conclusions: In patients with IPF, elevated monocyte count was associated with increased risks of IPF progression, hospitalization, and mortality. Monocyte count may provide a simple and inexpensive prognostic biomarker in IPF.

Thoracic endosonography (EBUS/EUS-b) in the diagnosis of different intrathoracic diseases: A 4-year experience at a single-centre in Greece.

BACKGROUND: In the last decade, the advent of thoracic endosonography has revolutionised the field of diagnostic bronchoscopy. METHODS: We conducted a single-centre prospective study in "Sotiria" Chest diseases hospital between January 2016 and December 2019. The study aimed to evaluate the efficacy and diagnostic value of combined EBUS/EUS-b in comparison with EBUS-TBNA and EUS-b FNA in different intrathoracic diseases. RESULTS: A total of 266 patients were enrolled (70.7% males, 85.7% smokers, mean age ± SD: 62.8 ± 11.8). Diagnosis and staging of suspected lung cancer (LC) were the main indications for EBUS/EUS-b in 56.7% of patients, followed by lymphadenopathy of unknown origin in 27%, lymphadenopathy in previous malignancy in 10.9%, and staging of proven LC in 5.3%. EUS-b FNA alone or combined with EBUS-TBNA was performed in 14.7% of patients. A total of 512 lymph nodes was sampled (481 through EBUS-TBNA and 31 through EUS-b FNA). EBUS/EUS-b led to a definitive diagnosis in 68.4% of the patients. Most cases (50.4%) were malignancies, while 18% represented benign diseases (83.3% sarcoidosis). Sensitivity of combined EBUS/EUS-b was higher in comparison with sensitivity of both procedures alone (100% vs 89.4% vs 88.9%). Accordingly, the overall sensitivity of EBUS/EUS-b for the detection of malignancy and sarcoidosis was 93% and 95.2%, respectively. No severe complications were observed. CONCLUSION: Thoracic endosonography is an efficient, safe, minimally invasive tool yielding high sensitivity and diagnostic accuracy in patients with suspected malignancy and mediastinal lymphadenopathy. Experienced pulmonologists in EBUS-TBNA should more routinely perform EUS-b FNA to avoid unnecessary surgical interventions.

Idiopathic pulmonary fibrosis: Disease mechanisms and drug development.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of unknown cause characterized by relentless scarring of the lung parenchyma leading to reduced quality of life and earlier mortality. IPF is an age-related disorder, and with the population aging worldwide, the economic burden of IPF is expected to steadily increase in the future. The mechanisms of fibrosis in IPF remain elusive, with favored concepts of disease pathogenesis involving recurrent microinjuries to a genetically predisposed alveolar epithelium, followed by an aberrant reparative response characterized by excessive collagen deposition. Pirfenidone and nintedanib are approved for treatment of IPF based on their ability to slow functional decline and disease progression; however, they do not offer a cure and are associated with tolerability issues. In this review, we critically discuss how cutting-edge research in disease pathogenesis may translate into identification of new therapeutic targets, thus facilitate drug discovery. There is a growing portfolio of treatment options for IPF. However, targeting the multitude of profibrotic cytokines and growth factors involved in disease pathogenesis may require a combination of therapeutic strategies with different mechanisms of action.

Clinical utility of thoracic endosonography (EBUS/EUS-b) in mediastinal staging of patients with non-small cell lung cancer: comparison with integrated PET/CT-a real-life prospective study in Greece.

BACKGROUND: Accurate mediastinal staging in patients with non-small cell lung cancer (NSCLC) is crucial for the determination of optimal treatment management. METHODS: This was a real-life prospective study enrolling 140 patients between December 2016 and August 2018. We aimed to determine the clinical utility of EBUS/EUS-b in mediastinal staging of patients with NSCLC in comparison with integrated PET/CT. Furthermore, SUVmax cut-off value with the highest specificity/accuracy was evaluated. Subgroup analysis according to histological type was performed. RESULTS: One hundred and thirty patients were eligible for analysis (mean age ± SD: 67.6±7.6, males 97). Three hundred different lymph node stations were sampled (272 through EBUS-TBNA and 28 through EUS-b FNA). Mean SUVmax of all malignant lymph nodes was 7.46 (SD =5.54). Sensitivity, specificity, PPV and NPV of EBUS/EUS-b for the identification of mediastinal malignant lymph nodes was 93.8%, 100%, 100%, and 93.4%, respectively. Accordingly, PET/CT yielded 92.2% sensitivity, 43.9% specificity, 64.8% PPV and 83.3% NPV. For adenocarcinoma (n=76) NPV were 86.2% with EBUS/EUS-b and 75% with PET/CT. NPV for squamous cell (n=46) was 100% with EBUS/EUS-b and 90.9% with PET/CT. EBUS/EUS-b staging yielded excellent agreement with final staging (97.5%, Tau 0.94, P<0.001). ROC curve analysis identified the value 4.95 as the optimal SUVmax cut-off value with the best specificity (87.4%) and accuracy (79%) (AUC 0.69; 95% CI: 0.73-0.84, P<0.001). CONCLUSIONS: Thoracic endosonography is an excellent, minimally invasive tool yielding high sensitivity and diagnostic accuracy in mediastinal staging of patients with NSCLC. Implementation of both EBUS/EUS-b and PET/CT is necessary before any surgical intervention.

Chemotherapy-induced changes in bronchoalveolar lavage fluid CD4 + and CD8 + cells of the opposite lung to the cancer.

Published articles support the effect of chemotherapy in the immune environment of tumors, including lung carcinomas. The role of CD4 + T-cells is crucial for expansion and accumulation of other antigen-specific immune cells, and the participation of CD8 + cells in tumor killing activity has been confirmed by many studies. However, little is known about the effect of chemotherapy on the healthy lung parenchyma from lung cancer patients, and whether there are differences between the different chemotherapy compounds used to treat this patient population. The aim of our study was to explore the effect of chemotherapy on CD4 + and CD8 + cells in the bronchoalveolar lavage fluid (BALF) of the healthy lung in patients treated with standard chemotherapy regimens. Fifteen patients underwent BAL, in the healthy lung before and after six chemotherapy courses. Platinum-based regimens included vinolerbine (VN) in 6 patients, gemcitabine (GEM) in 4 patients and etoposide (EP) in 5 patients. All patients but one were males and smokers (93%). The median age of patients was 56 years (42-75). No significant difference was noted in the patients' age between the three treated groups. Furthermore, between the three groups, no significant changes in the means of CD4 + and CD8 + cells were noted. However, when we compared the mean CD4 + cells before and after chemotherapy within each group, changes were noted when comparing VN before versus after (p = 0.05), GEM before versus after (p = 0.03), and EP before versus after (p = 0.036). In our pilot study, changes were noted in BALF CD4 + cells for the three most applied regimens at the normal lung parenchyma.