Expression of human Interferon Regulatory Factor 3 (IRF-3) in alveolar macrophages relates to clinical and functional traits in COPD.

Introduction: Chronic obstructive pulmonary disease (COPD) is a frequent cause of morbidity and mortality. Dysregulated and enhanced immune-inflammatory responses have been described in COPD. Recent data showed impaired immune responses and, in particular, of interferon (IFNs) signaling pathway in these patients.

Thymic Stromal Lymphopoietin and Tezepelumab in Airway Diseases: From Physiological Role to Target Therapy.

Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα.

Moderate asthma: burden, mechanisms and therapeutic perspectives.

Purpose Of Review: Global Initiative for Asthma (GINA) document provides a classification of asthma severity according with the current level of treatment required to achieve diseases control and underlines the limitations of this approach. In this review, we will provide an overview of recent investigations that have analyzed clinical and molecular features of moderate asthma.

Recent Findings: Moderate asthma is heterogeneous in terms of response to inhaled treatment and pathogenetic mechanisms underlying the clinical features.

Nasal cytology as a reliable non-invasive procedure to phenotype patients with type 2 chronic rhinosinusitis with nasal polyps.

Background: The identification of type-2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) acquires a crucial role in the endotypization needed for selecting patients for biological drugs targeting type-2 inflammation: to date, the parameters used include systemic and histological biomarkers. The aim of this study was to investigate whether nasal cytology could identify type-2 inflammation in patients with CRSwNP.

Methodology: Thirty-three consecutive patients with CRSwNP underwent nasal cytology sampling at the level of the lower nasal turbinate, and of the polypoid tissue, and surgical polyp tissue sample was collected.

Severe asthma: One disease and multiple definitions.

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used.

In Vitro Reduction of Interleukin-8 Response to by Strains Isolated from the Same Polymicrobial Urines.

Urinary tract infections are often polymicrobial and are mainly due to uropathogenic (UPEC). We previously demonstrated a link among clinical fluoroquinolone susceptible reducing in vitro urothelial interleukin-8 (CXCL8) induced by K-12, polymicrobial cystitis, and pyuria absence. Here, we evaluated whether fifteen clinical fluoroquinolone susceptible UPEC were able to reduce CXCL8 induced by that had been isolated from the same mixed urines, other than CXCL8 induced by K-12.

Quick Olfactory Sniffin' Sticks Test (Q-Sticks) for the detection of smell disorders in COVID-19 patients.

Background: Coronavirus disease (COVID-19) infection represents a worldwide critical health burden from the sanitary perspective. This disease's symptoms range from a mild flu-like form to a severe life-threatening respiratory disease and respiratory failure. Several patients, however, remain paucisymptomatic.

Efficacy of Benralizumab in severe asthma in real life and focus on nasal polyposis.

Introduction: Severe asthma occurs in 5-10% of asthmatic patients, with nasal polyposis as one of the most frequent comorbidity. Benralizumab was recently marketed, thus we could analyse its effects in real-life in severe asthma, and compare the effects of the drug in patients with and without polyposis.

Methods: Patients with severe asthma, receiving Benralizumab were enrolled in Italian asthma centres.

Plasma Galectin-3 and urine proteomics predict FEV improvement in omalizumab-treated patients with severe allergic asthma: Results from the PROXIMA sub-study.

Background: Patients with severe allergic asthma (SAA) when treated with omalizumab may exhibit different extent of response. Identifying biomarkers that can predict the extent of treatment effectiveness in patients can be useful in personalizing omalizumab treatment.

Methods: Patients from the longitudinal phase of the PROXIMA study were selected for this ancillary study.

Evolving phenotypes to endotypes: is precision medicine achievable in asthma?

: The development of biologic molecules led to a drastic change in the therapeutic approach to asthma. With the prospect of acting on different pathophysiological mechanisms of the disease, the idea of precision medicine was developed, in which a single molecule is able to modify a specific triggering mechanism. Thus, it seemed limiting to stop at the distinction of patients phenotypes and the concept of endotypes became more relevant in the therapeutic approach.

Immune induction of airway remodeling.

Airway remodeling is accepted to be a determining component within the natural history of asthma. It is a phenomenon characterized by changes in the airways structures that marches in parallel with and can be influenced by airway inflammation, floating at the interface between both natural and adaptive immunity and physical and mechanical cells behavior. In this review we aimed to highlight the comprehensive, yet not exhaustive, evidences of how immune cells induce, regulate and adapt to the recognized markers of airway remodeling.

One year of mepolizumab. Efficacy and safety in real-life in Italy.

Background: Severe asthma is a disease with a heavy socio-economic burden and a relevant impact on the life of patients. Mepolizumab (MEP) was recently introduced in practice. The previous data were favourable as efficacy and safety are concerned.

Galectin-3: an early predictive biomarker of modulation of airway remodeling in patients with severe asthma treated with omalizumab for 36 months.

Background: Bronchial asthma is a heterogeneous disease characterized by three cardinal features: chronic inflammation, variable airflow obstruction, and airway hyperresponsiveness. Asthma has traditionally been defined using nonspecific clinical and physiologic variables that encompass multiple phenotypes and are treated with nonspecific anti-inflammatory therapies. Based on the modulation of airway remodeling after 12 months of anti-immunoglobulin E (IgE) treatment, we identified two phenotypes (omalizumab responder, OR; and non-omalizumab responder, NOR) and performed morphometric analysis of bronchial biopsy specimens.

Molecular diagnosis and precision medicine in allergy management.

Precision medicine (PM) can be defined as a structural model aimed at customizing healthcare, with medical decisions/products tailored on an individual patient at a highly detailed level. In this sense, allergy diagnostics based on molecular allergen components allows to accurately define the patient's IgE repertoire. The availability of highly specialized singleplexed and multiplexed platforms support allergists with an advanced diagnostic armamentarium.

CD4(+)CD25(high)CD127(-) regulatory T-cells in COPD: smoke and drugs effect.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by poorly reversible airway obstruction and its pathogenesis remains largely misunderstood. Local changes of regulatory T-cell populations in the lungs of COPD patients have been demonstrated although data concerning their pathologic role are contrasting. The aim of our study was to evaluate the relative percentage of regulatory T-cells in the peripheral blood of current and former smoker subjects, affected or not by COPD.

Molecular phenotyping and biomarker development: are we on our way towards targeted therapy for severe asthma?

Although different phenotypes of severe asthma can be identified, all are characterized by common symptoms. Due to their heterogeneity, they exhibit differences in pathogenesis, etiology and clinical responses to therapeutic approaches. The identification of distinct molecular phenotypes to define severe asthmatic patients will allow us to better understand the pathophysiology of the disease and thus to more precisely target the treatment for each patient.

Biomarkers and severe asthma: a critical appraisal.

Severe asthma (SA) is a clinically and etiologically heterogeneous respiratory disease which affects among 5-10 % of asthmatic patients. Despite high-dose therapy, a large patients percentage is not fully controlled and has a poor quality of life. In this review, we describe the biomarkers actually known in scientific literature and used in clinical practice for SA assessment and management: neutrophils, eosinophils, periostin, fractional exhaled nitric oxide, exhaled breath condensate and galectins.

Proteomics of bronchial biopsies: galectin-3 as a predictive biomarker of airway remodelling modulation in omalizumab-treated severe asthma patients.

Asthma is a chronic inflammatory disease. Reticular basement membrane (RBM) thickening is considered feature of airway remodelling (AR) particularly in severe asthma (SA). Omalizumab, mAb to IgE is effective in SA and can modulate AR.

Biomarker discovery in asthma and COPD by proteomic approaches.

Asthma and chronic obstructive pulmonary disease (COPD) are multifactorial respiratory diseases, characterized by reversible and irreversible airway obstruction, respectively. Even if the primary causes of these diseases remain unknown, inflammation is a central feature that leads to progressive and permanent pulmonary tissue damage (airway remodeling) up to the total loss of lung function. Therefore, the elucidation of the inflammation mechanisms and the characterization of the biological pathways, involved in asthma and COPD pathogenesis, are relevant in finding new possible diagnostic/prognostic biomarkers and for the validation of new drug targets.

Allergenius, an expert system for the interpretation of allergen microarray results.

Background: An in vitro procedure based on a microarray containing many different allergen components has recently been introduced for use in allergy diagnosis. Recombinant and highly purified allergens belonging to different allergenic sources (inhalants, food, latex and hymenoptera) are present in the array. These components can either be genuine or cross-reactive, resistant or susceptible to heat and low pH, and innocuous or potentially dangerous.

The administration of a polyvalent mechanical bacterial lysate in elderly patients with COPD results in serological signs of an efficient immune response associated with a reduced number of acute episodes.

The administration of a polyvalent mechanical bacterial lysate (PMBL) in elderly patients with COPD has been shown to reduce the number of exacerbation. This is largely related to the involvement of cells belonging to the innate and the adaptive immune system (including dendritic cells, granulocytes, T and B lymphocytes and NK cells) that actively cooperate inducing the production of specific opsonizing antibodies directed to the antigens of PMBL. We have evaluated the production of antibodies directed to respiratory and systemic pathogens in a group of elderly COPD patients, recruited in a clinical trial, ancillary to a larger multicenter double blind, placebo-controlled, parallel-designed clinical trial in which patients were randomized to daily receive either PMBL or placebo.

Assessment of extravascular lung water by quantitative ultrasound and CT in isolated bovine lung.

Lung ultrasonography (LUS) and computed tomography (CT) were compared for quantitative assessment of extravascular lung water (EVLW) in 10 isolated bovine lung lobes. LUS and CT were obtained at different inflation pressures before and after instillation with known amounts of hypotonic saline. A video-based quantitative LUS analysis was superior to both single-frame quantitative analysis and visual scoring in the assessment of EVLW.

Administration of a polyvalent mechanical bacterial lysate to elderly patients with COPD: Effects on circulating T, B and NK cells.

The modifications of the subsets of circulating lymphocytes were evaluated in a group of patients with COPD undergoing treatment with a polyvalent mechanical bacterial lysate (PMBL), a drug that is able to significantly modify the natural history of these patients. Using multicolor immune-florescence and flow cytometry, T, B subsets and NK cells were extensively studied both in the group of treated patients and in a disease and age matched controls. Despite the age, in treated patients, T and NK cells were significantly increased in numbers of circulating cells, but not in percentages, while B cells remained unmodified.