Exploring the Interaction between Fractional Exhaled Nitric Oxide and Biologic Treatment in Severe Asthma: A Systematic Review.

Background: Fractional exhaled nitric oxide (FeNO) is a biomarker of airway inflammation associated with airway hyper-responsiveness and type-2 inflammation. Its role in the management of severe asthmatic patients undergoing biologic treatment, as well as FeNO dynamics during biologic treatment, is largely unexplored.

Purpose: The aim was to evaluate published data contributing to the following areas: (1) FeNO as a predictive biomarker of response to biologic treatment; (2) the influence of biologic treatment in FeNO values; (3) FeNO as a biomarker for the prediction of exacerbations in patients treated with biologics.

Immune checkpoint analysis of T-cell responses to pp65 and IE-1 antigens in end-stage lung diseases.

Lung transplant (LTX) patients are at high risk of cytomegalovirus (CMV) infection, which is often associated with high mortality and morbidity. Reactivation of CMV causes cell injury due to the cytopathic effect of viral replication and triggering of T cell immunity. The aim of this study was to compare expression of immune checkpoints (ICs) (PD-1, CTLA-4, LAG-3 and TIGIT) in CD4, CD8 and CD56 and activation markers CD137, CD154 and CD69 of end-stage patients awaiting lung transplant.

The Effectiveness of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis, Familial Pulmonary Fibrosis and Progressive Fibrosing Interstitial Lung Diseases: A Real-World Study.

Background: Nintedanib is an oral multitarget tyrosine kinase inhibitor approved for the treatment of patients with idiopathic pulmonary fibrosis (IPF). Recent evidence demonstrated that nintedanib reduced functional disease progression also in subjects with non-IPF progressive fibrosing interstitial lung disease (PF-ILD). However, real-life data on the effectiveness of nintedanib in PF-ILD and familial pulmonary fibrosis (FPF) are lacking.

Cytomegalovirus Infection Is Associated with Development of Chronic Lung Allograft Dysfunction.

Background: Cytomegalovirus (CMV) is the major and most common opportunistic infection complicating lung transplant (LTX). The aim of this study was to analyse the epidemiological aspects of CMV infection in lung transplant patients subject to a pre-emptive anti-CMV approach and to study the impact of this infection on lung transplant outcome, in terms of onset of chronic lung allograft dysfunction (CLAD).

Methods: This single-centre retrospective study enrolled 87 LTX patients (median age 55.

Adaptive immune system in pulmonary sarcoidosis-Comparison of peripheral and alveolar biomarkers.

Sarcoidosis is a multi-systemic granulomatous disease of unknown origin. Recent research has focused upon the role of autoimmunity in its development and progression. This study aimed to determine and define the disturbance and distribution of T and B cell subsets in the alveolar and peripheral compartments.

Immunologic responses to antifibrotic treatment in IPF patients.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease limited to the lungs. Immunological dysregulation may significantly participate in the pathophysiology of IPF. The immunological responses to nintedanib therapy in IPF patients were investigated for the first time in this study.

Serum Concentrations of KL-6 in Patients with IPF and Lung Cancer and Serial Measurements of KL-6 in IPF Patients Treated with Antifibrotic Therapy.

Background: Krebs von den Lungen-6 (KL-6) was suggested as ILD biomarker including idiopathic pulmonary fibrosis (IPF). Lung cancer is one of the most severe comorbidity of IPF patients. This study aims to serially analyze KL-6 in IPF patients after 24 months of Nintedanib and to first investigate the biomarker behavior in IPF associated with adenocarcinoma.

Peripheral and alveolar biomarkers of fibrotic hypersensitivity pneumonitis.

Fibrotic hypersensitivity pneumonitis (fHP) is a frequently misdiagnosed fibrosing interstitial pneumonia, which often remains undiagnosed due to the lack of uniformity of diagnostic criteria. Its features are similar to those of other ILDs, especially idiopathic pulmonary fibrosis (IPF), and biomarkers with potential clinical value have been proposed. We reviewed the recent literature on serum and BAL biomarkers, focusing on their clinical role in the diagnosis and management of fHP.

Hypercalciuria in Sarcoidosis: A Specific Biomarker With Clinical Utility.

Changes in calcium metabolism are quite common in sarcoidosis: hypercalciuria is linked to a persistent clinical phenotype and more active disease. No data is yet available on the specificity of parameters of calcium metabolism as biomarkers for distinguishing different chronic interstitial lung diseases (ILD). Here we assessed calcium metabolism in an Italian population of sarcoidosis patients, which included a group with stage IV fibrotic disease, and compared the results with those of idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (cHP) patients.

The role of the combination of echo-HRCT score as a tool to evaluate the presence of pulmonary hypertension in idiopathic pulmonary fibrosis.

Pulmonary hypertension (PH) is defined as an elevated mean pulmonary artery pressure at rest (mPAP ≥ 25 mmHg), evaluated by right heart catheterization (RHC). The aim of the present study was to evaluate HRCT findings in relation to transthoracic echocardiographic data to better characterize PH in IPF patients and to identify a non-invasive composite index with high predictive value for PH in these patients. 37 IPF patients were enrolled in this retrospective study.

Long-Term Follow-Up of Patients With Idiopathic Pulmonary Fibrosis Treated With Pirfenidone or Nintedanib: A Real-Life Comparison Study.

Background: Pirfenidone and nintedanib are the sole pharmacological therapies currently approved for idiopathic pulmonary fibrosis (IPF). Limited comparison data is available in literature, despite they are both prescribed for mild-to-moderate disease. Here, we describe our almost 10 years real-life experience with antifibrotic treatment to investigate potential differences in terms of efficacy.

Adiponectin and leptin levels in idiopathic pulmonary fibrosis: A new method for BAL and serum assessment.

Adipokines (APN) are mainly secreted by adipocytes, macrophages and various other cells, along with their role in the regulation and mediation of inflammatory responses. APN is almost exclusively synthesized by adipocytes and regulated by peroxisome proliferator-activated receptor γ (PPARγ) that is involved in the epithelial-mesenchymal transition, linked lung fibrosis. Leptin is involved in acute lung injury with a role in lung fibrogenesis.

Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review.

Fractional exhaled nitric oxide (FeNO) is a well-known and widely accepted biomarker of airways inflammation that can be useful in the therapeutic management, and adherence to inhalation therapy control, in asthmatic patients. However, the multiple-flows assessment of FeNO can provide a reliable measurement of bronchial and alveolar production of NO, supporting its potential value as biomarker also in peripheral lung diseases, such as interstitial lung diseases (ILD). In this review, we first discuss the role of NO in the pathobiology of lung fibrosis and the technique currently approved for the measurement of maximum bronchial flux of NO (J'awNO) and alveolar concentration of NO (CaNO).

Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disorder limited to the lung. New findings, starting from our proteomics studies on IPF, suggest that systemic involvement with altered molecular mechanisms and metabolic disorder is an underlying cause of fibrosis. The role of metabolic dysregulation in the pathogenesis of IPF has not been extensively studied, despite a recent surge of interest.

Personalized Approach of Severe Eosinophilic Asthma Patients Treated with Mepolizumab and Benralizumab.

Background: New anti-IL-5 antibodies, mepolizumab and benralizumab, have recently been approved for severe asthma, sharing the same inclusion criteria.

Objective: To contribute on biomarkers research leading to the personalized choice, we investigated L-selectin, Krebs von den Lungen (KL-6), and lymphocyte subsets as bioindicators of airway hyper-responsiveness and remodeling.

Materials And Methods: A cohort of 28 patients affected by severe eosinophilic asthma were treated with anti-IL-5 drugs.

Efficacy of baricitinib in treating rheumatoid arthritis: Modulatory effects on fibrotic and inflammatory biomarkers in a real-life setting.

Background: Baricitinib is a JAK inhibitor that blocks intracellular signalling pathways of inflammatory cytokines recommended for Rheumatoid arthritis (RA) patients not responding to initial treatment. Among RA extrareticular features, interstitial lung involvement is primarly characterized by fibrotic evolution. The aim of the present study was to analyse the effects of baricitinib in a population of RA and RA-ILD patients in a real-life setting, describing any changes in lung function parameters, serum inflammatory biomarkers and fibrotic biomarkers after 6 months of treatment.

Serum KL-6 concentrations as a novel biomarker of severe COVID-19.

Severe acute respiratory syndrome coronavirus 2-induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen-6 (KL-6) is mainly produced by damaged or regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL-6 in patients with coronavirus disease (COVID-19) to verify its potential as a prognostic biomarker of severity.

Coronavirus HKU 1 infection with bronchiolitis, pericardial effusion and acute respiratory failure in obese adult female.

Seven species of coronavirus cause acute respiratory illness in humans. Coronavirus HKU 1 (CoV HKU 1) was first described in 2005 in an adult patient with pneumonia in Hong Kong. Although it is a well-known respiratory tract pathogen, there is not much information about its role in hospitalized adults, especially in southern Europe.

The Role of Urinary Calcium and Chitotriosidase in a Cohort of Chronic Sarcoidosis Patients.

Background: Calcium metabolism alterations are quite common in sarcoidosis and have been correlated with disease activity.

Objectives: The aim of the study was to investigate the clinical significance of calcium metabolism alterations in patients with chronic sarcoidosis. We paid particular attention to associations with specific disease phenotypes and chitotriosidase (CTO) expression.

Bronchoalveolar lavage and serum KL-6 concentrations in chronic hypersensitivity pneumonitis: correlations with radiological and immunological features.

Chronic hypersensitivity pneumonitis (cHP) is a fibrotic interstitial lung disease (ILD) resulting from inhalation of different organic substances and chemical compounds determining an inflammatory and immunological response in sensitized individuals. KL-6, a human mucin protein expressed by type 2 pneumocytes, has been proposed as a prognostic biomarker of cHP. Assessment of usefulness KL-6 in ILD has been investigated primarily in Asiatic population.

Pirfenidone in idiopathic pulmonary fibrosis: real-life experience in the referral centre of Siena.

Background: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia and has a median survival after diagnosis of 2-5 years. Pirfenidone is the first approved antifibrotic drug for the treatment of IPF. Here we report the functional progress, side effects and survival data of a population of patients with IPF, diagnosed at our centre and treated with pirfenidone.

Correction to: Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis.

After publication of our article [1] the authors have notified us that one of the names has been incorrectly tagged.

Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis.

Background: Serum chitotriosidase is a promising biomarker that has shown high specificity and sensitivity in patients with sarcoidosis. The aim of this study was to investigate correlations between serum chitotriosidase, clinical phenotypes, disease localizations and different radiological lung involvement and to identify clinical features associated with over-expression of chitotriosidase in a large cohort of sarcoidosis patients.

Methods: Chitotriosidase activity was evaluated in a population of 694 consecutive patients (males 39%, age 55.