scholarly journals Extracellular Vesicle Surface Signatures in IPF Patients: A Multiplex Bead-Based Flow Cytometry Approach

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1045
Author(s):  
Miriana d’Alessandro ◽  
Piera Soccio ◽  
Laura Bergantini ◽  
Paolo Cameli ◽  
Giulia Scioscia ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Extracellular Vesicle ◽  
Interstitial Lung Diseases ◽  
Hazard Ratio ◽  
Term Survival ◽  
Antifibrotic Therapy ◽  
Kaplan Meier ◽  
Significant Difference ◽  
First Time ◽  
Multiplex Bead

Background: Extracellular vesicles (EVs) are secreted by cells from their membrane within circulation and body fluids. Knowledge of the involvement of EVs in pathogenesis of lung diseases is increasing. The present study aimed to evaluate the expression of exosomal surface epitopes in a cohort of idiopathic pulmonary fibrosis (IPF) patients followed in two Italian Referral Centres for Interstitial Lung Diseases, comparing them with a group of healthy volunteers. Materials and Methods: Ninety IPF patients (median age and interquartile range (IQR) 71 (66–75) years; 69 males) were selected retrospectively. Blood samples were obtained from patients before starting antifibrotic therapy. A MACSPlex Exosome Kit, human, (Miltenyi Biotec, Bergisch-Gladbach, Germany), to detect 37 exosomal surface epitopes, was used. Results: CD19, CD69, CD8, and CD86 were significantly higher in IPF patients than in controls (p = 0.0023, p = 0.0471, p = 0.0082, and p = 0.0143, respectively). CD42a was lower in IPF subjects than in controls (p = 0.0153), while CD209, Cd133/1, MCSP, and ROR1 were higher in IPF patients than in controls (p = 0.0007, p = 0.0050, p = 0.0139, and p = 0.0335, respectively). Kaplan-Meier survival analysis for IPF patients: for median values and a cut-off of 0.48 for CD25, the two subgroups showed a significant difference in survival rate (p = 0.0243, hazard ratio: 0.52 (95%CI 0.29–0.92); the same was true for CD8 (cut-off 1.53, p = 0.0309, hazard ratio: 1.39 (95%CI 0.75–2.53). Conclusion: Our multicenter study showed for the first time the expression of surface epitopes on EVs from IPF patients, providing interesting data on the communication signatures/exosomal profile in serum from IPF patients and new insights into the pathogenesis of the disease and a promising reliability in predicting mid-term survival of IPF patients.

scholarly journals Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD

2021 ◽  
Vol 10 (11) ◽  
pp. 2285
Author(s):  
John N. Shumar ◽  
Abhimanyu Chandel ◽  
Christopher S. King
Keyword(s):  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Treatment Pathway ◽  
Antifibrotic Therapy ◽  
New Treatment ◽  
Fibrotic Lung Diseases

Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways.

scholarly journals The Role of Transthoracic Ultrasound in the Study of Interstitial Lung Diseases: High-Resolution Computed Tomography Versus Ultrasound Patterns: Our Preliminary Experience

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 439
Author(s):  
Donato Lacedonia ◽  
Giulia Scioscia ◽  
Angelamaria Giardinelli ◽  
Carla Maria Irene Quarato ◽  
Ennio Vincenzo Sassani ◽  
...  
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
High Resolution Computed Tomography ◽  
Pleural Line ◽  
Complementary Role ◽  
Number Of Patients ◽  
Significant Difference ◽  
Transthoracic Ultrasound

Transthoracic ultrasound (TUS) is a readily available imaging tool that can provide a quick real-time evaluation. The aim of this preliminary study was to establish a complementary role for this imaging method in the approach of interstitial lung diseases (ILDs). TUS examination was performed in 43 consecutive patients with pulmonary fibrosis and TUS findings were compared with the corresponding high-resolution computed tomography (HRCT) scans. All patients showed a thickened hyperechoic pleural line, despite no difference between dominant HRCT patterns (ground glass, honeycombing, mixed pattern) being recorded (p > 0.05). However, pleural lines’ thickening showed a significant difference between different HRCT degree of fibrosis (p < 0.001) and a negative correlation with functional parameters. The presence of >3 B-lines and subpleural nodules was also assessed in a large number of patients, although they did not demonstrate any particular association with a specific HRCT finding or fibrotic degree. Results allow us to suggest a complementary role for TUS in facilitating an early diagnosis of ILD or helping to detect a possible disease progression or eventual complications during routine clinical practice (with pleural line measurements and subpleural nodules), although HRCT remains the gold standard in the definition of ILD pattern, disease extent and follow-up.

Sleeve lobectomy an affidable lung sparing procedure

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17159-17159
Author(s):  
G. Cavallesco ◽  
P. Maniscalco ◽  
F. Quarantotto ◽  
F. Acerbis ◽  
M. Santini ◽  
...  
Keyword(s):  
Main Bronchus ◽  
Rank Test ◽  
Sleeve Lobectomy ◽  
Term Survival ◽  
Average Hospital ◽  
Long Term Survival ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Similar Survival

17159 Background: Sleeve Lobectomy (Sl) is generally considered a surgical alternative of choice to Pneumonectomy (Pn) for the treatment of central NSCLC. The aim of this study is to value if the Sl could be really a Lung saving procedure that warrants right survivals, according to stage of disease, with acceptable perioperative risks. Methods: In 165 patients (67 Sl and 98 Pn) operated from 1995 to 2003 for NSCLC of main bronchus we have analyzed the hospital stay, morbidity and mortality within 30 days, long term survival. In 39 Sl and 46 Pn we compared spyrometric volume’s changes at a distance of 6–24 months from operation. Sl was performed where it was technically possible. Long term survivals had been separated and comparated according to pathologic stadium (TNM 1997) and lymphonodal involvement: all these data were estimated by Kaplan-Meier method and log rank test. All statistical data underwent SPSS elaboration and significant assumption for p < 0.05. Results: In our population of study we didn’t check any statistically significant’s differences comparing age, sex or preoperative Fev1. Complications occurred in 28% of cases where Sl was performed and in 36.7% after Pn with a mortality rate of 2.9% vs 5.1%. Average hospital staying was longer in patients underwent to Pneumonectomy. Long term survival (5 years) in Sl group is 36% and 24% in Pn group with a statistically significant difference P = 0.016, but this difference is not evident from the comparison between the two group’s survivals based on pathological stadium or lymphonodal involvement. Spyrometric values showed a global Fev1 reduction of 245 ml (−10%) after Sl procedure and 884ml (36.3%) after Pn with a significant difference of p = 0.0042. Conclusions: In this study Sl got similar survival results if not better, with those obtained after Pn. Moreover, Sl showed to be a lung sparing procedure with an acceptable operative risk. These data confirmed that SL is the gold standard surgical procedure in the treatment of central tumors where if technically possible. [Table: see text] No significant financial relationships to disclose.

Invasive penile carcinoma: Are p16, p53 and HPV ISH prognostically significant?

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 394-394
Author(s):  
Jasreman Dhillon ◽  
Anders E. Berglund ◽  
Julio Pow-Sang ◽  
Philippe E. Spiess ◽  
Anthony M. Magliocco
Keyword(s):  
Tumor Cells ◽  
Staining Intensity ◽  
Hpv Infection ◽  
Clinicopathological Characteristics ◽  
Hazard Ratio ◽  
Penile Carcinoma ◽  
P53 Expression ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Low Incidence

394 Background: Penile carcinoma accounts for 0.4% to 0.6% of all malignancies in men. Due to its low incidence the prognostic role of clinicopathological characteristics, p16, p53 and HPV infection remains unclear. We report our experience with p16, p53 and HPV ISH (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 66) in determining the aggressive nature of this carcinoma. Methods: A tissue microarray (TMA) of 57 cases of invasive penile squamous cell carcinomas was immunohistochemically stained with immunohistochemical stains p16 and p53. HPV ISH was performed as well. The TMA slides were scored semi quantitatively by a specialized genitourinary surgical pathologist. The H score was calculated for p53 using a combination of staining intensity and extent according to the following formula: H score = 1 x % of tumor cells with weak staining + 2 x % of tumor cells with moderate staining + 3 x % of tumor cells with strong staining, resulting in a total score of 0 – 300. Calculations for p53 were done considering values above 0 as positive. For p16 and HPV ISH, the results were recorded as negative or positive. The overall survival curves for up to 60 months were estimated by Kaplan-Meier (KM) method. Results: HPV ISH was positive in 23 cases and p16 was positive in 23 cases as well. However, there were 9 discordant cases between the two (p16+/HPV ISH- = 5; p16-/HPV ISH+ = 4). p53 was positive in 39 cases. Tumors positive for HPV ISH had a better survival as compared to HPV ISH negative tumors (p = 0.0040; Hazard ratio 4.991). Whereas p16 (p = 0.206; Hazard ratio 1.838) and p53 (p = 0.1582; Hazard ratio 0.5198) were not significantly associated with survival at 60 months. Conclusions: Overall HPV positive penile carcinomas appear to have a distinct biology with better prognosis. There is no significant difference in survival for tumors with different p16 and p53 expression.

Clinical outcome of local treatment in synchronous oligometastatic non-small cell lung cancer (NSCLC): A preliminary analysis of prospective data.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21698-e21698
Author(s):  
Shangbiao Li ◽  
Xiaoxia Zhu ◽  
Zhihao Zheng
Keyword(s):  
Clinical Trial ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Untreated Group ◽  
First Line ◽  
Term Survival ◽  
Nccn Guidelines ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Nsclc Patients

e21698 Background: Advanced NSCLC is a heterogeneous disease, a large number of retrospective studies suggested that patients with oligometastases may achieve long-term survival from aggressive local treatment. However, relevant prospective studies were limited. Therefore, we prospectively evaluated the role of local treatment in synchronous oligometastatic NSCLC. Methods: We prospectively identified 50 NSCLC patients newly diagnosed with synchronous oligometastases (≤5)in two centers between 11/2017 and 12/2019, among whom there were 24 patients from a randomized clinical trial NCT03119519. Patients were given first-line systemic therapy according to the latest NCCN guidelines with either local radiotherapy or surgery to thoracic primary tumor and/or radiotherapy to metastases. They were divided into combined therapies (Tx), systemic Tx and untreated groups. Kaplan Meier Survival analysis was used to compare progression free survival (PFS) and overall survival (OS) among the groups. Results: Median age of all patients was 61 years old (range: 27-80 years) and median follow up was 5.7 months (range: 0.5-23.3 months). A total of 10 deaths were observed. In the combined Tx group, 23 patients received radiotherapy, and 2 patients received primary surgical resection. The median OS of the combined Tx group (n = 25), the systemic Tx group (n = 19) and the untreated group (n = 6) was 18.47 months, not reached, 3.27 months, respectively. Compared with the untreated group, the combined group and the systemic Tx group had better OS (hazard ratio [HR] = 0.1047, p = 0.0001; HR = 0.1125, p= 0.0006). However, the patients in the combined group did not show significant OS advantage compared with those in the systemic Tx group (HR = 1.376, p= 0.667). In addition, we conducted an ITT analysis in clinical trial NCT03119519, in which 8 progression events were observed. There was no significant difference in PFS between the combined group (n = 13) and the systemic Tx group (n = 11) (13.2 months vs. not reached, HR = 1.317, p= 0.7015; 1-year PFS: 74% vs. 54%, p = 0.7015, respectively). Conclusions: Current analysis shows that the addition of local treatment to first-line systemic Tx does not improve PFS and OS. More samples, further updated data and selection of potential beneficer are necessary. Funding: 81972853, 81572279, 2016J004, LC2019ZD009, 2018CR033. Clinical trial information: NCT03119519.

scholarly journals Differential diagnosis of idiopathic pulmonary fibrosis

2020 ◽  
Vol 92 (3) ◽  
pp. 102-108
Author(s):  
E. I. Shmelev ◽  
A. E. Ergeshov ◽  
V. Ya. Gergert
Keyword(s):  
Differential Diagnosis ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Diseases ◽  
Respiratory Diseases ◽  
Clinical Signs ◽  
Interstitial Lung Diseases ◽  
Antifibrotic Therapy ◽  
Inflammatory Drugs ◽  
Diffuse Lung

The review is devoted to the urgent problem of modern pulmonology: the differential diagnosis of idiopathic pulmonary fibrosis (ILF). ILF occupies a special place among many interstitial lung diseases for a number of reasons: 1) it is a deadly disease; 2) early diagnosis and adequate antifibrotic therapy significantly extend the life expectancy of patients; 3) anti-inflammatory drugs (corticosteroids) and cytostatics with ILF that are widely used in other forms of interstitial lung diseases are ineffective and accelerate the progression of the process; 4) the commonality of the main clinical signs (increasing respiratory failure) of various interstitial lung diseases. The list of respiratory diseases with which ILF should be differentiated is huge, and if with diffuse lung lesions of a known nature (disseminated pulmonary tuberculosis, pneumoconiosis, etc.) with a certain experience/qualification, the diagnosis is relatively simple, then the isolation of ILF from the group of idiopathic interstitial pneumonias always represents certain difficulties. The main methods used in the diagnosis of ILF are summarized taking into account current international and national recommendations.

scholarly journals Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sebastiano Emanuele Torrisi ◽  
Nicolas Kahn ◽  
Julia Wälscher ◽  
Nilab Sarmand ◽  
Markus Polke ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Randomized Clinical Trials ◽  
Pulmonary Function Tests ◽  
Interstitial Lung Diseases ◽  
Insurance Company ◽  
Meaningful Improvement ◽  
Tertiary Referral Center ◽  
Antifibrotic Therapy ◽  
Antifibrotic Drugs

Abstract Background Fibrosing, non-idiopathic pulmonary fibrosis (non-IPF) interstitial lung diseases (fILDs) are a heterogeneous group of diseases characterized by a different amount of inflammation and fibrosis. Therapy is currently based on corticosteroids and/or immunomodulators. However, response to these therapies is highly variable, sometimes without meaningful improvement, especially in more fibrosing forms. Pirfenidone and nintedanib have recently demonstrated to reduce functional decline in patients with IPF. However, their antifibrotic mechanism makes these two drugs an interesting approach for treatment of fibrosing ILDs other than IPF. Objectives We here report our experience with antifibrotic drugs in fibrosing non-IPF ILDs patients having a progressive phenotype during immunosuppressive therapy. Methods Patients with a multidisciplinary team diagnosis of fibrosing non-IPF ILDs experiencing a progressive phenotype during treatment with corticosteroids and/or immunomodulators between October-2014 and January-2018 at our tertiary referral Center for ILDs were retrospectively analyzed. Antifibrotic therapy was administered after application with the respective health insurance company and after consent by the patient. Pulmonary-function-tests and follow-up visits were performed every 6 ± 1 months. Results Eleven patients were treated with antifibrotic drugs (8 males, mean age 62 ± 12.8 years, mean FVC% 62.8 ± 22.3, mean DLCO% 35.5 ± 10.7, median follow-up under antifibrotic treatment 11.1 months). Patients had a diagnosis of unclassifiable ILD in 6 cases, pleuroparenchymal fibroelastosis in 2 cases, idiopathic-NSIP in 1 case, asbestos-related ILD in 1 case and Hermansky-Pudlak syndrome in 1 case. Treatment before antifibrotics consisted of corticosteroids in all patients: 5 combined with Azathioprin, 1 with either methotrexate or cyclophosphamide (i.v.). Ten patients were treated with pirfenidone (2403 mg/die) and 1 with nintedanib (300 mg/die). Median FVC was 56, 56, 50%, at time points − 24, − 12, − 6 before initiation, 44% at time of initiation and 46.5% at 6 months after initiation of antifibrotic treatment. Antifibrotic treatment was generally well tolerated with a need of dose reduction in 2 cases (rash and nausea) and early termination in 3 cases. Conclusions Antifibrotic treatment may be a valuable treatment option in patients with progressive fibrosing non-IPF ILD if currently no other treatment options exist. However, prospective, randomized clinical trials are urgently needed to assess the real impact of antifibrotic therapy in these patients.

scholarly journals Exhalative Breath Markers Do Not Offer for Diagnosis of Interstitial Lung Diseases: Data from the European IPF Registry (eurIPFreg) and Biobank

2019 ◽  
Vol 8 (5) ◽  
pp. 643 ◽  
Author(s):  
Ekaterina Krauss ◽  
Maike Froehler ◽  
Maria Degen ◽  
Poornima Mahavadi ◽  
Ruth C. Dartsch ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Obstructive ◽  
Exhaled Breath ◽  
Obstructive Pulmonary Disease ◽  
Significant Difference ◽  
New Biomarkers ◽  
Diagnostic Benefit

Background: New biomarkers are urgently needed to facilitate diagnosis in Interstitial Lung Diseases (ILD), thus reducing the need for invasive procedures, and to enable tailoring and monitoring of medical treatment. Methods: In this study we investigated if patients with idiopathic pulmonary fibrosis (IPF; n = 21), non-IPF ILDs (n = 57) and other lung diseases (chronic obstructive pulmonary disease (COPD) n = 24, lung cancer (LC) n = 16) as well as healthy subjects (n = 20) show relevant differences in exhaled NO (FeNO; Niox MINO), or in eicosanoid (PGE2, 8-isoprostane; enzyme-linked immunosorbent assay (ELISA)) levels as measured in exhaled breath condensates (EBC) and bronchoalveolar lavage fluids (BALF). Results: There was no significant difference in FeNO values between IPF, non-IPF ILDs and healthy subjects, although some individual patients showed highly elevated FeNO. On the basis of the FeNO signal, it was neither possible to differentiate between the kind of disease nor to detect exacerbations. In addition, there was no correlation between FeNO values and lung function. The investigation of the eicosanoids in EBCs was challenging (PGE2) or unreliable (8-isoprostane), but worked out well in BALF. A significant increase of free 8-isoprostane was observed in BALF, but not in EBCs, of patients with IPF, hypersensitivity pneumonitis (HP) and sarcoidosis, possibly indicating severity of oxidative stress. Conclusions: FeNO-measurements are not of diagnostic benefit in different ILDs including IPF. The same holds true for PGE2 and 8-isoprostane in EBC by ELISA.

Interstitial lung diseases, progressive phenotype: urgent problems of early diagnosis and early initiation of antifibrotic therapy

Therapy ◽  
2021 ◽  
Vol 7_2021 ◽  
pp. 126-131
Author(s):  
Kostina N.E. Kostina ◽  
Starodubtseva I.A. Starodubtseva ◽  
Sharapova Yu.A. Sharapova ◽  
Malyavin A.G. Malyavin ◽  
◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Early Initiation ◽  
Antifibrotic Therapy

Chronic fibrosing progressing interstitial lung disease: a decision of Multidisciplinary Expert Board

2021 ◽  
Vol 31 (4) ◽  
pp. 505-510
Author(s):  
S. N. Avdeev ◽  
S. Yu. Chikina ◽  
I. E. Tyurin ◽  
A. S. Belevskiy ◽  
S. A. Terpigorev ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Russian Federation ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Diagnosis And Treatment ◽  
Antifibrotic Therapy

Introduction. The natural course of some interstitial lung diseases (ILD) is characterized by progressive fibrosing phenotype resembling idiopathic pulmonary fibrosis (IPF). Until recently, the antifibrotic drug nintedanib was approved for treatment of the only fibrosing ILD which was IPF. A new indication for this drug which has been registered in Russian Federation in 2021 includes other fibrosing ILDs with progressive phenotype (PF-ILDs) and ILD associated with systemic scleroderma (SS-ILD).The aim of this publication is to describe general considerations of the decision of Multidisciplinary Expert Board on diagnosis and treatment of PF-ILDs including SS-ILD.Results. According to the extension in nintedanib use mentioned above, the Expert Board created an algorithm for diagnosis and treatment of patients with PF-ILDs and criteria for nuntedanib administration in PF-ILDs.Conclusion. Antifibrotic therapy is needed for patients with PF-ILDs with the failure of the stanrard therapy. In those patients antifibrotic treatment should be initiated as early as possible to better preserve the lung function.

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