Regulatory T cell monitoring in severe eosinophilic asthma patients treated with mepolizumab.

Severe eosinophilic asthma (SEA) has been associated with T-helper type 2 (Th2) inflammatory response. A good understanding of T cell functions in asthma is important for therapy, especially in the choice of biological treatments for severe cases. Mepolizumab, an IL-5 antagonist, is indicated for the treatment of severe asthma. Regulatory T cells (Tregs) suppress inflammation by secreting cytokines that inhibit Th2 cell proliferation. We investigated peripheral Treg, CD4, CD8, CD19 and NK cell percentages and their relationship to clinical and functional parameters, including peripheral eosinophils, before and after anti-IL5 treatment. Subjects were 14 adult SEA patients (9 male, 54.1 ± 11.6 years), treated with mepolizumab, and 10 controls. T cells (CD4 and CD8), CD19, NK and Tregs were evaluated by flow cytometry. Comparison of lung function parameters before and after treatment with mepolizumab (T0 and T1) showed an increase in FEV1, FEV1/FVC ratio and a reduction in blood eosinophil percentages. CD8 and CD16/56+ CD3+ were significantly higher in SEA patients than controls (P = .04 and P = .03, respectively). A decrease in CD45+, CD8 + and CD16/56+ CD3+ cell percentages was observed between T0 and T1 (P = .02, P = .04, P = .03, respectively). A significant increase in Treg percentages (P = .0001) was recorded between T0 and T1. Mepolizumab therapy was found to modulate immune response, restoring immune balance in patients with SEA.

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting.

INTRODUCTION: Interleukin-5 (IL-5) is the principal cytokine regulating eosinophil growth, differentiation, activation, and expression. It is a specific target of mepolizumab, an anti-IL-5 monoclonal antibody used in the treatment of severe eosinophilic asthma. This new drug can improve symptoms, reduce asthma exacerbations and steroid use. Few data are available on its efficacy for nasal symptoms. OBJECTIVE: To describe the all-round clinical impact of mepolizumab in a real-life setting, evaluating the efficacy and safety of the drug in severe eosinophilic asthma patients. POPULATION AND METHODS: We retrospectively collected the clinical and functional data on 27 patients (16 males) affected with severe eosinophilic asthma, diagnosed at the Siena Regional Referral Centre and monitored for 6 months. Clinical, immunological, and functional data at baseline and follow-up were entered in a database together with comorbidities, number of exacerbations, steroid treatment, multiple-flow exhaled nitric oxide, and validated questionnaires. RESULTS: A significant reduction in asthma exacerbations was observed in all patients after 6 months of the biological therapy (p = 0.0009), and 4/6 patients discontinued chronic oral steroids. A significant improvement in ACT, FEV1, SNOT22, and alveolar nitric oxide was observed after 1 month of mepolizumab (p = 0.003, p = 0.007, p = 0.047, and p = 0.019, respectively) and maintained after 6 months of treatment. After 6 months, FeNO 50 was reduced as well (p = 0.030). Mepolizumab was very well tolerated, and no major side effects were observed. CONCLUSIONS: Our study suggests that mepolizumab is effective in improving control of asthma, lung function parameters, exhaled biomarkers, and nasal symptoms in patients with severe eosinophilic asthma.

Mepolizumab and Benralizumab in Severe Eosinophilic Asthma: Preliminary Results of a Proteomic Study.

Benralizumab and mepolizumab are new therapies for severe eosinophilic asthma. They are both humanized IgG antibodies, targeting the IL-5 receptor and IL-5, respectively, suppressing the corresponding pathways. No specific biomarkers have been proposed to evaluate treatment response to benralizumab or mepolizumab. The aim of this proteomic study was to compare serum protein profiles of patients with severe eosinophilic asthma before and after anti-IL5 or anti-IL5R therapies. Proteomic analysis highlighted 22 differently abundant spots. Among the proteins identified, CAYP1, A1AT and A2M expression was significantly modified in both groups of patients after therapies while ceruloplasmin showed a significant modification in the group of benralizumab treatment. These differentially expressed proteins could be potential biomarkers of response to mepolizumab and benralizumab treatments and need further evaluation.

Ceruloplasmin and oxidative stress in severe eosinophilic asthma patients treated with Mepolizumab and Benralizumab.

INTRODUCTION: Severe eosinophilic asthma has been associated with Th2 airway inflammation and elevated proinflammatory cytokines and chemokines, such as IL-5. Precision therapies have recently been shown to improve asthma symptoms with a steroid-sparing effect. Two such therapies, Benralizumab and Mepolizumab, humanized IgG antibodies directed against the IL-5 receptor and IL-5, have been approved for severe eosinophilic asthma. METHODS: Here we used a differential proteomic approach to analyse serum from patients with severe eosinophilic asthma treated with Benralizumab and Mepolizumab in a search for differential molecular modifications responsible of their effects. Enrichment analysis of differential proteins was performed for the two treatments. RESULTS AND DISCUSSION: After one month of Benralizumab treatment we detected up-regulation of certain protein species of the antioxidant ceruloplasmin. To investigate oxidative stress, we performed redox proteomics which detected lower oxidative burst after one month of Benralizumab treatment than in the pre-treatment phase or after one month of Mepolizumab therapy.

Spontaneous abdominal bleeding associated with SARS-CoV-2 infection: causality or coincidence?

Authors present 6 cases of abdominal bleeding associated with COVID-19, representing 1.35% of all hospitalized COVID-19 patients and hypothesize that there could be, although not very frequently, a relationship between SARS-CoV2 and bleeding. They excluded a side effect of the low molecular weight heparin therapy that all patients underwent during the course of the disease or other possible causes. Alterations of the coagulation state or a weakness of the vascular wall due toa presumed endotheliitis SARS-CoV-2 infection induced, are hypothesized by the authors. Investigation and follow-up for possible hemorrhagic problems in patients with COVID-19 is recommended. In particular, clinicians should be vigilant about retroperitoneal hemorrhage in COVID-19 patients. In addition to the fact that these patients are being treated with anticoagulants, anemia and abdominal pain are the signs that should lead us to suspect this type of haemorrhage. More studies are needed to understand if COVID-19 can be directly associated with bleeding. (www.actabiomedica.it)

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. METHODS: We enrolled 91 patients with IPF (71 males) treated with pirfenidone. Clinical, survival and functional details were collected retrospectively at start of therapy and after 12, 24, 36 and 48 months of treatment. Lung function tests at least 12 months before starting therapy were available for 40 patients and were entered in the database, as well as side effects. RESULTS: During the observation period (922 ± 529 days), 27 patients died, 5 patients underwent lung transplant and 10 patients interrupted therapy due to adverse events or IPF progression. The median survival was 1606 days. There was a significant reduction in disease progression rate, as measured by trend of forced vital capacity, after 1 year of therapy with respect to before treatment (p = 0.0085). Forced vital capacity reduction rate was progressively higher in the subsequent years of treatment. Treatment-related side effects were reported in 25 patients and were predominantly mild. Overall, four patients discontinued therapy due to severe photosensitivity. CONCLUSIONS: Our findings confirm the efficacy of pirfenidone in reducing functional progression of IPF and its excellent safety profile in a real-life setting. This study, designed on a long-term follow up, contributes to the growing evidence on safety, tolerability and efficacy of pirfenidone in IPF. The reviews of this paper are available via the supplemental material section.

The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a peripheral subpleural interstitial lung disorder limited to the lung not involving the airways. It has a poor prognosis (survival less than 5 years) and commonly an interstitial pneumonia radiological pattern. Patients complain of a chronic dry cough in 80% of cases. A cough is often the first symptom of this rare disease, preceding dyspnea by years, and is associated with a poor prognosis, high dyspnea scores and low FVC percentages. The pathogenetic mechanisms leading to coughing in IPF are unclear. This review focuses on recent evidence of cough pathophysiology in this disease. Gastroesophageal reflux may promote coughing in IPF patients; bile salts and pepsin may be abundant in BAL of these patients, inducing overproduction of TGF-ß by airway epithelial cells and mesenchymal transition with fibroblast recruitment/activation and extracellular matrix deposition. Patients have an enhanced cough reflex to capsaicin and substance P with respect to control subjects. Moreover, patients with the MUC5B polymorphism show more severe coughing as MUC5B encodes for the dominant mucin in the honeycomb cysts of IPF patients. Comorbidities, including asthma, gastroesophageal reflux, hypersensitivity pneumonitis, bronchiectasis, chronic obstructive pulmonary disease and emphysema, can induce coughing in IPF patients. There is no clear explanation of the causes of coughing in IPF. Further research into the pathophysiology of IPF and the pathogenetic mechanisms of coughing is necessary to improve survival and quality of life.