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Gene expression profiling reveals novel TGFβ targets in adult lung fibroblasts
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Research Interests: Research Design, Medicine, Safety, Humans, COPD, and 13 moreInternal Medicine, Statistical Significance, Clinical Sciences, Public health systems and services research, Odds ratio, Chronic obstructive pulmonary disease, Cardiovascular Diseases, Case Control Study, Anticholinergic, Ipratropium Uk, Relative Risk, Cholinergic antagonists, and Pulmonary Disease Chronic Obstructive
Sexual pain is frequently seen in gynecological practice as a consequence of lower tract pathology. When organic causes are ruled out, we must think of a functional pain syndrome such as the genital pelvic pain/penetration disorder... more
Sexual pain is frequently seen in gynecological practice as a consequence of lower tract pathology. When organic causes are ruled out, we must think of a functional pain syndrome such as the genital pelvic pain/penetration disorder (GPPD). Vaginismus and vulvodynia require different treatments. Even if gynecologists do not usually manage functional sexual pain, they can easily reach the differential diagnosis through the sexual pain anamnesis, because some symptoms are specific of one or the other condition. To verify our hypothesis we retrospectively evaluated the clinical records of 44 women affected by functional sexual pain. The words patients, used to describe their pain, were categorized in the following symptoms: dyspareunia, burning pain, stabbing pain, dryness, itching, and obstacle to penetration, each coded as present or absent. The unsupervised cluster analysis of the reported symptoms identified two groups: 19 out of 20 women were clinically diagnosed as having vaginism...
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In order to better characterize the mechanisms which regulate the immune response at the pulmonary level, the effects of beta-interferon (IFN-beta) and lymphokines (LK) on prostaglandin E (PGE) release and the suppressive capacity of... more
In order to better characterize the mechanisms which regulate the immune response at the pulmonary level, the effects of beta-interferon (IFN-beta) and lymphokines (LK) on prostaglandin E (PGE) release and the suppressive capacity of mouse resident alveolar (AM phi) and pleural macrophages (PlM phi) were investigated in comparison with peritoneal macrophages (PM phi). After in vitro exposure to IFN-beta, PlM phi and PM phi showed a significant decrease of suppressive capacity and PGE release, whereas LK treatment did not affect such activities. In contrast, pre-treatment of AM phi with LK caused a strong impairment of their suppressive capacity. This effect was optimal after an incubation time of 20 h, was evident also at very low doses of LK and was not paralleled by any change of PGE release. Again in contrast with PlM phi and PM phi, suppressive capacity of AM phi was decreased only by very high doses of IFN-beta, whereas lower doses caused either an increase or no change of this...
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The results of the National Lung Screening Trial (NLST)(Aug. 4 issue) 1 showed a relative reduction in lung-cancer mortality of 20% in former and current heavy smokers who underwent screening with low-dose computed tomography (CT), as... more
The results of the National Lung Screening Trial (NLST)(Aug. 4 issue) 1 showed a relative reduction in lung-cancer mortality of 20% in former and current heavy smokers who underwent screening with low-dose computed tomography (CT), as compared with ...
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To investigate the role of lung lymphocytes (LL) in the local defense mechanisms, we studied the natural antibacterial (NA) activity of mouse LL with an in vitro assay using S. pneumoniae type 3 as target. In parallel, natural killer (NK)... more
To investigate the role of lung lymphocytes (LL) in the local defense mechanisms, we studied the natural antibacterial (NA) activity of mouse LL with an in vitro assay using S. pneumoniae type 3 as target. In parallel, natural killer (NK) activity against YAC-1 tumor cells was investigated. Lung cells obtained by enzymatic digestion were found to exert detectable NA and NK activities, which were further increased after purification of LL (greater than 90% lymphocytes) by carbonyl iron and magnet treatment. Depletion experiments with antibodies and complement indicated that the effector cell of NA activity was a Thy 1.2+, L3T4+, aGM1+ lymphocyte, whereas the effector of NK activity was found to have a Thy 1.2-, aGM1+ phenotype. Preincubation of LL with anti-IgA antibodies, but not with anti-IgG, completely inhibited NA activity, suggesting that it was mediated by preexisting IgA bound to the LL surface. Furthermore, purified IgA from S107 plasmacytoma with specificity for phosphorylcholine, a component of the outer wall of S. pneumoniae, was able to enhance the antibacterial activity of LL and to restore their activity after treatment with anti-IgA. In addition, S107 antibodies were found to specifically induce antibacterial activity against S. pneumoniae in resident alveolar macrophages (AM) and peritoneal exudate cells, which did not express NA activity. We conclude that mouse LL include a subset of IgA-bearing lymphocytes with the phenotype of helper-T cells, which are able to exert NA activity against pneumococcus through an IgA-driven mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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Research Interests: Microbiology, Immunology, Immune response, Biology, Medicine, and 15 moreBiological Sciences, HUMAN PAPILLOMAVIRUS, Mice, Female, Animals, Bacteria, Immunization, Recombinant DNA, Immune system, Antibody, Bacterial, Sexually Transmitted Diseases, Sexually Transmitted Disease, Mucosal Immunity, and Medical and Health Sciences
The movement of ions and water across the membranes of bronchial cells is part of the control of the bronchial obstructive response to physical stimuli. In a double-blind, randomized, crossover study, we compared the effect of an aerosol... more
The movement of ions and water across the membranes of bronchial cells is part of the control of the bronchial obstructive response to physical stimuli. In a double-blind, randomized, crossover study, we compared the effect of an aerosol of the loop diuretic furosemide with that of a placebo on the early (within 60 minutes) and late (4 to 12 hours) asthmatic responses to a specific inhaled allergen. We studied 11 subjects with mild allergic asthma, who had both early and late asthmatic responses to a specific inhaled allergen in a preliminary challenge. After placebo administration, the maximal changes (mean +/- SE) from base line in the forced expiratory volume in one second (FEV1) and specific airway resistance were, respectively, a decrease of 35 +/- 4 percent and an increase of 288 +/- 56 percent between 0 and 60 minutes after inhalation of the allergen (early response) and a decrease of 35 +/- 5 percent and an increase of 301 +/- 40 percent between 4 and 12 hours (late response). After furosemide administration (4 ml; 10 mg per milliliter), the early response to inhaled allergen was markedly attenuated in all the subjects, and the late response in all but one. The maximal changes in the FEV1 and specific airway resistance were, respectively, a decrease of 11 +/- 2 percent and an increase of 61 +/- 2 percent between 0 and 60 minutes and a decrease of 20 +/- 4 percent and an increase of 178 +/- 25 percent between 4 and 12 hours (P less than 0.05 for all comparisons). No significant differences were seen in the bronchoconstrictor response to inhaled methacholine after furosemide or placebo administration. We conclude that a furosemide-sensitive mechanism in the airways is involved in the pathogenesis of the reactions of patients with allergic asthma. Whether inhaled furosemide might be useful in the treatment of allergic asthma is uncertain and will require further study.
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Background A discipline which critically looks at the evidence for practice should itself be critically examined. Credible evidence for the effectiveness of training in evidence-based healthcare (EBHC) is essential. We attempted to... more
Background A discipline which critically looks at the evidence for practice should itself be critically examined. Credible evidence for the effectiveness of training in evidence-based healthcare (EBHC) is essential. We attempted to summarise the current knowledge on evaluating the effectiveness of training in EBHC while identifying the gaps. Methods A working group of EBHC teachers developed a conceptual framework of key areas of EBHC teaching and practice in need of evidence mapped to appropriate methods and outcomes. A literature search was conducted to review the current state of research in these key areas. Studies of training interventions that evaluated effectiveness by considering learner, patient or health system outcomes in terms of knowledge, skills, attitude, judgement, competence, decision-making, patient satisfaction, quality of life, clinical indicators or cost were included. There was no language restriction. Results Of 55 articles reviewed, 15 met the inclusion criteria: six systematic reviews, three randomised controlled trials and six before-after studies. We found weak indications that undergraduate training in EBHC improves knowledge but not skills, and that clinically integrated postgraduate teaching improves both knowledge and skills. Two randomised controlled trials reported no impact on attitudes or behaviour. One before-after study found a positive impact on decision-making, while another suggested change in learners' behaviour and improved patient outcome. We found no studies assessing the impact of EBHC training on patient satisfaction, health-related quality of life, cost or population-level indicators of health. Conclusions Literature evaluating the effectiveness of training in EBHC has focused on short-term acquisition of knowledge and skills. Evaluation designs were methodologically weak, controlled trials appeared inadequately powered and systematic reviews could not provide conclusive evidence owing to weakness of study designs.
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The observation that changes in bronchial osmolarity can induce bronchoconstriction in asthma inspired the experimental studies which, unexpectedly, revealed that frusemide is an effective bronchoprotective agent against a variety of... more
The observation that changes in bronchial osmolarity can induce bronchoconstriction in asthma inspired the experimental studies which, unexpectedly, revealed that frusemide is an effective bronchoprotective agent against a variety of osmotic and non osmotic stimuli. Although the mechanism of this protective effect is not fully understood, studies in vivo and in vitro suggest that frusemide may inhibit the activation of different cell types induced by bronchoconstrictor stimuli. Other loop diuretics also exert bronchoprotective activity, but frusemide appears to be the more effective bronchoprotective agent of this family, regardless of their diuretic potency and lipid solubility. Despite the relatively large amount of experimental evidence, there is currently little information on the clinical effectiveness of frusemide in asthma and a long-term controlled study is currently in progress. The observations that treatment with a combination of inhaled acetylsalicylate and frusemide res...
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New educational technologies might help to compensate for the decrease in time and emphasis dedicated to physical examination in medical training. This may, in particular, be applicable for improving the skills in auscultation of the... more
New educational technologies might help to compensate for the decrease in time and emphasis dedicated to physical examination in medical training. This may, in particular, be applicable for improving the skills in auscultation of the chest. We investigated whether a multimedia presentation of acoustic and graphic characteristics of lung sounds could improve the learning of pulmonary auscultation by medical students, in comparison with conventional teaching methods. We studied 48 medical students without clinical experience, who had received conventional formal teaching on chest examination. Chest auscultation skills were evaluated using an inaccuracy score for the student's auscultation report on three patients, selected according to a standardized procedure. After a baseline evaluation, 27 students in groups of 5-10, participated in a multimedia seminar on lung sounds during which digitized lung sounds were played and the corresponding time-expanded waveform and frequency spect...
Research Interests: Educational Technology, Medicine, Methods, Medical Students, Humans, and 15 moreComputer Assisted Instruction, Computer Aided Learning, Audio Visual, Questionnaires, Physical examination, Clinical Competence, Respiratory Sounds, Control Group, Psychology Teaching, Medical, audiovisual aids, Frequency spectrum, auscultation, multimedia presentation, and Medical and Health Sciences
BACKGROUND Broncho-alveolar lavage (BAL) is a safe diagnostic procedure, useful for differentiating fibrotic lung disorders and for excluding malignancy and infection. A recent multicenter study demonstrated a new, relatively sensitive,... more
BACKGROUND Broncho-alveolar lavage (BAL) is a safe diagnostic procedure, useful for differentiating fibrotic lung disorders and for excluding malignancy and infection. A recent multicenter study demonstrated a new, relatively sensitive, and specific index called Bronchoalveolar Cytology Threshold (BCT), useful for distinguishing healthy individuals from patients with lung diseases. OBJECTIVES In our study, BCT was applied for the first time to the analysis of interstitial lung diseases (ILDs), investigating its potential for differential diagnosis. Combinations of BAL cells that improve diagnostic accuracy for ILDs were studied and are proposed. METHODS A retrospective analysis of BAL samples was performed. We considered more than 1000 BAL samples from patients investigated for ILD, performed at Siena University Hospital. The samples enrolled for the study included 468 patients: 413 with and 55 without ILD. BAL was performed for diagnostic purposes in line with international guidelines. BCT were calculated according to available literature. RESULTS Among ILDs, patients with fibrotic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis showed significantly lower BCTs than unclassified ILD. Asbestosis patients showed significantly lower BCTs than nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), connective tissue disease related ILD (CTD-ILD), sarcoidosis and unclassified ILD patients. COP patients showed significantly higher BCT than IPF, f-HP and sarcoidosis. Moreover, COP patients were best distinguished by BCT. CONCLUSION The analysis of BAL features is currently included in the diagnostic algorithm of ILDs. BAL cell patterns and BCT index can provide useful information for distinguishing ILDs, reducing the need for invasive procedures. Integrated approaches to BAL analysis can improve the interpretation of results without further cost or loss of time.
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Introduction: Cytomegalovirus (CMV) is the leading opportunistic infection in lung transplant (LTx) recipients. CMV is associated with graft failure and decreased survival. Recently, new antiviral therapies have been proposed. The present... more
Introduction: Cytomegalovirus (CMV) is the leading opportunistic infection in lung transplant (LTx) recipients. CMV is associated with graft failure and decreased survival. Recently, new antiviral therapies have been proposed. The present study aimed to investigate NK and T cell subsets of patients awaiting LTx. We analyzed the cellular populations between reactive and non-reactive QuantiFERON (QF) CMV patients for the prediction of immunological response to infection. Methods: Seventeen pre-LTx patients and 15 healthy controls (HC) have been enrolled. QF and IFN-γ ELISA assay detections were applied. NK cell subsets and T cell and proliferation assay were detected before and after stimulation with pp-65 and IE-1 CMV antigens after stratification as QF+ and QF−. Furthermore, we quantified the serum concentrations of NK− and T-related cytokines by bead-based multiplex analysis. Results: CD56brCD16lowNKG2A+KIR+ resulted in the best discriminatory cellular subsets between pre-LTx and H...
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Time-limited protective effect of inhaled frusemide against aspirin-induced bronchocon- striction in aspirin-sensitive asthmatics. P. Sestini, M.G. Pieroni, R.M. Refini, M. Robuschi, G. Gambaro, S. Spagnotto, A. Vaghi, S. Bianco. ERS... more
Time-limited protective effect of inhaled frusemide against aspirin-induced bronchocon- striction in aspirin-sensitive asthmatics. P. Sestini, M.G. Pieroni, R.M. Refini, M. Robuschi, G. Gambaro, S. Spagnotto, A. Vaghi, S. Bianco. ERS Journals Ltd 1994. ABSTRACT: Inhaled frusemide effectively prevents the bronchial obstructive response to allergens and to a number of nonallergic stimuli. In most of the ex- perimental models in which it has been tested, the protective effect of frusemide has been evaluated for only a short time after administration. In aspirin-sensitive patients, acetylsalicylic acid causes an asthmatic reaction which typically lasts for 2 h or more after exposure. We investigated the presence and duration of the protective effect of inhaled frusemide against the bronchial response to aspirin in sensitive patients, using a specific inhalation challenge with lysine acetylsalicylate (LASA). In the first study, eight subjects with aspirin-asthma underwent two bronchial ...
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Sarcoidosis is a heterogeneous granulomatous disease. Biological markers and clinical features could allow specific phenotypes to be associated with different prognosis, severity and treatment responses. This retrospective multicentre... more
Sarcoidosis is a heterogeneous granulomatous disease. Biological markers and clinical features could allow specific phenotypes to be associated with different prognosis, severity and treatment responses. This retrospective multicentre study aims to analyse the clinical and immunological features of sarcoidosis and to identify a routine non-invasive biomarker useful in clinical practice. Materials and methods: 129 Caucasian patients with sarcoidosis (median age IQR, 56 (47-62)) were enrolled retrospectively in the study. Medical history, routine laboratory findings, lung function results and radiological features from the last examination of October 2019 – February 2020 were gathered from the patients’ clinical records. Results: Regardless their clinical status at disease onset, at the last clinical examination we didn’t observe any differences in terms of therapeutic management between symptomatic and asymptomatic patients. Stratifying sarcoidosis population according to therapeutic...
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Background: Serum Amyloid A (SAA) is an acute phase protein and we analyzed its concentrations in lung transplantated patients (LTX). Methods: 26 LTX patients (58.6 ± 11 years) and 11 healthy controls (55 ± 11.3 years). Three groups of... more
Background: Serum Amyloid A (SAA) is an acute phase protein and we analyzed its concentrations in lung transplantated patients (LTX). Methods: 26 LTX patients (58.6 ± 11 years) and 11 healthy controls (55 ± 11.3 years). Three groups of LTX patients: acute rejection (AR, 7) bronchiolitis obliterans syndrome (BOS, 3), acute infection (INF, 9) and stable patients (NEG, 7). Results: In LTX patients SAA concentrations were significantly increased, particularly in AR and INF. In LTX-AR patients were observed a correlation between SAA levels and peripheral CD4+ lymphocyte percentage (r=0.9, p<0.01) and a reverse correlation with FVC percentages (r -0.94, p=0.01). Conclusions: SAA may represent a potential biomarker of LTX acute complications, with a prognostic value in AR. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 2-7)
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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... more
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. Thirteen patients were selected for the study [median age, interquartile range (IQR) = 57 years (48–59); 23% were male]. Twelve healthy controls [median age, IQR = 53 years (52–65); 16% male] were also enrolled into the study. Cellular and cytokine patterns were measured using the cytofluorimetric approach. Peripheral CD8 percentages were higher in sarcoidosis patients (SP) than healthy controls (HC) (p = 0.0293), while CD4 percentages were lower (p = 0.0305). SP showed low bronchoalveolar lavage (BAL) percentages of CD19 (p = 0.0004) and CD8 (p = 0.0035), while CD19+CD5+CD27− percentages were higher (p = 0.0213); the same was found for CD4 (p = 0.0396), follicular regulatory T ...
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Severe acute respiratory syndrome caused by coronavirus 2 emerged in Wuhan (China) in December 2019 and has severely challenged the human population. NK and T cells are involved in the progression of COVID-19 infection through the ability... more
Severe acute respiratory syndrome caused by coronavirus 2 emerged in Wuhan (China) in December 2019 and has severely challenged the human population. NK and T cells are involved in the progression of COVID-19 infection through the ability of NK cells to modulate T-cell responses, and by the stimulation of cytokine release. No detailed investigation of the NK cell landscape in clinical SARS-CoV-2 infection has yet been reported. A total of 35 COVID-19 hospitalised patients were stratified for clinical severity and 17 healthy subjects were enrolled. NK cell subsets and T cell subsets were analysed with flow cytometry. Serum cytokines were detected with a bead-based multiplex assay. Fewer CD56dimCD16brightNKG2A+NK cells and a parallel increase in the CD56+CD69+NK, CD56+PD-1+NK, CD56+NKp44+NK subset were reported in COVID-19 than HC. A significantly higher adaptive/memory-like NK cell frequency in patients with severe disease than in those with mild and moderate phenotypes were reported...
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Background and aim. Community Acquired Pneumonia (CAP) remains a major cause of disease and death. We evaluated the levels of care, the outcome and the characteristics of hospitalised patients with CAP in a primary hospital in Italy. We... more
Background and aim. Community Acquired Pneumonia (CAP) remains a major cause of disease and death. We evaluated the levels of care, the outcome and the characteristics of hospitalised patients with CAP in a primary hospital in Italy. We also investigated the value of both the Pneumonia Severity Index (PSI) and the modified Appropriateness Evaluation Protocol (AEP) for recognising both the outcome and the unnecessary admissions and stay of hospitalised patients with CAP. Methods. A retrospective review of all the charts of adult patients with CAP at Manerbio, Brescia, Italy between January 2001 and December 2002 was performed. Results. We evaluated 148 patients; their mean age (±SD) was 70 (±17) years; 34% were female. Most patients (87%) had at least a concomitant co-morbid disease. The overall survival rate at 30 days was 88%. All but one death occurred in the high-risk group of patients according to the PSI. On the contrary, the death rate of patients with inappropriate hospital...
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Background: The immune mechanisms occurring during acute rejection (AR) and chronic lung allograft dysfunction are a challenge for research and the balance between effector and regulatory cells has not been defined completely. In this... more
Background: The immune mechanisms occurring during acute rejection (AR) and chronic lung allograft dysfunction are a challenge for research and the balance between effector and regulatory cells has not been defined completely. In this study, we aimed to elucidate the interaction of effector cells, mainly Th17, Th1 and Th2, and regulatory cells including (CD4+CD25+CD127low/−) T reg cells and phenotypes of B regs, CD19+CD24hiCD38hi, CD19+CD24hiCD27hi and CD19+CD5+CD1d+. Methods: Bronchoalveolar lavage cells (BAL) and peripheral blood mononuclear cells (PBMCs) from stable lung transplanted (LTx )subjects (n = 4), AR patients (n = 6) and bronchiolitis obliterans syndrome (BOS) (n = 6) were collected at the same time. Cellular subsets were detected through flow cytometry. Results: A predominance of Th17 cells subtypes in the PBMCs and BAL and a depletion of Tregs, that resulted in decrease Treg/Th17 ratio, was observed in the AR group. CD19+CD24hiCD38hi Bregs resulted increased in BAL of...
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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... more
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. All patients underwent a complete assessment for PH, including transthoracic Doppler echocardiography, HRCT scan and right heart catheterization. Right heart catheterization was done in 19 patients (51.3%) as pre-lung transplant assessment and in 18 patients (48.6%) to confirm PH, suspected on the basis of echocardiography. Twenty out of 37 patients (54%) were confirmed to have PH by RHC. Multivariate regression showed that the combination of sPAP, PA area measured by HRCT and the ratio of the diameter of the segmental a...
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INTRODUCTION 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... more
INTRODUCTION 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. EVIDENCE ACQUISITION We reviewed the recent literature on serum and BAL biomarkers, focusing on their clinical role in the diagnosis and management of fHP. We systematically searched Medline/Pubmed results from 2005 until April 2020. EVIDENCE SYNTHESIS The manuscripts of interest selected by our search were limited in number and proposed different clinical biomarkers in serum (IgG antibodies, macrophage inflammatory proteins-1, epithelial cell proteins) and BAL (lymphocytes, T cell mediators). This is the first review to summarise all the serum and BAL biomarkers for fHP proposed in the literature. CONCLUSIONS This review summarized the main biomarkers investigated in fibrotic hypersesitivity pneumonitis because an urgent aim of subsequent research will be to validate and standardize them for diagnostic purposes.
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BAL cellularity and lymphocyte immunophenotyping offer insights into lung inflammatory status. Natural killer (NK) cells are efficient effector cells, producing pro-inflammatory cytokines. A better understanding of the biology of NK cells... more
BAL cellularity and lymphocyte immunophenotyping offer insights into lung inflammatory status. Natural killer (NK) cells are efficient effector cells, producing pro-inflammatory cytokines. A better understanding of the biology of NK cells in BAL in the lungs is necessary to improve the pathogenesis of fibrotic ILD and develop prospective targeted treatments. Our aim was to analyse NK and NKT-like cell percentages in BAL from 159 patients with different ILD: f-HP, f-NSIP, IPF and CTD-ILD, to evaluate their potential diagnostic/prognostic role. BAL NK cell percentages showed significantly higher values in IPF than in f-HP and f-NSIP, while BAL NKT-like cells showed significantly lower values in the f-NSIP than the f-HP and IPF. A cut-off of 4%NK cells in BAL of IPF showed a significant difference in survival rate. It suggests a possible new marker of survival and raises the possibility of new targeted approach in treatment and management of IPF.
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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... more
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.
Research Interests: Immunology, Asthma, Eosinophil, Medicine, T Cell, and 4 moreCD, Immune system, Interleukin, and mepolizumab
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,... more
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). We systematically report the published evidence regarding extended FeNO analysis in the management of patients with different ILDs, focusing on its potential role in differential diagnosis, prognostic evaluation and severity assessment of disease. The few available data concerning extended FeNO anal...
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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... more
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. Materials and methods: One hundred and forty-two ILD patients (median (IQR), 69 (63–75) years; 86 males) were retrospectively enrolled. Serial serum samples were collected from IPF patients before starting antifibrotic therapy and after 12 months. Serum KL-6 levels were measured by KL-6 reagent assay (Fujirebio Europe, UK). Results: Increased KL-6 concentrations were identified in IPF-LC patients than IPF, fibrotic hypersensitivity pneumonitis, and pulmonary fibrosis associated with autoimmune disease groups. A cut-off value was calculated to distinguish IPF and IPF-LC patients. IPF patients monitored for 24 months with Nintedan...
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Serum Krebs von den Lungen‐6 (sKL‐6) is an high‐molecular‐weight (200 kDa) glycoprotein predominantly expressed by damaged alveolar type II cells, and it has been proposed as a potential biomarker of different ILD. This is a prognostic... more
Serum Krebs von den Lungen‐6 (sKL‐6) is an high‐molecular‐weight (200 kDa) glycoprotein predominantly expressed by damaged alveolar type II cells, and it has been proposed as a potential biomarker of different ILD. This is a prognostic biomarker for chronic hypersensitivity pneumonitis (cHP) and idiopathic pulmonary fibrosis (IPF), two diseases that share several clinical and radiological features. Little data are available on the potential role of KL‐6 in granulomatous and cystic interstitial lung diseases, including the orphan disease known as pulmonary Langerhans cell histiocytosis (PLCH).
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Background: Sarcoidosis is a systemic granulomatous disease with unknown etiology. Many clinical presentations have been reported and acute disease needs to be distinguished from subacute and chronic disease. The unpredictable clinical... more
Background: Sarcoidosis is a systemic granulomatous disease with unknown etiology. Many clinical presentations have been reported and acute disease needs to be distinguished from subacute and chronic disease. The unpredictable clinical course of the disease prompted us to evaluate the clinical utility of biomarker serum detection in sarcoidosis follow-up. Objectives: To evaluate the potential role of many serum biomarkers in the clinical management of patients with Sarcoidosis. Methods: Serum concentrations of chitotriosidase, ACE, KL-6 and lysozyme were analyzed in a population of 74 patients with Sarcoidosis (46 on steroid therapy at sampling), regularly monitored at Siena Sarcoidosis Regional Referral Centre, and in a group of healthy controls. Clinical data, functional parameters and organ involvement were retrospectively collected in order to evaluate associations between specific features of disease and biomarkers’ overexpression. Results: KL-6 concentrations were significantly elevated in Sarcoidosis patients with lung fibrosis and were correlated with DLCO e Composite Physiological Index score, while chitotriosidase was significantly higher in patients with extrapulmonary localizations of disease. With a cut-off value of 303.5 IU/ml, KL-6 showed the best sensitivity (78%), while chitotriosidase reported the best specificity (85%) among the biomarkers. Conclusions: KL-6 is a reliable biomarker of fibrotic lung involvement, while chitotriosidase may be an indicator of extrapulmonary localizations of disease in Sarcoidosis patients. Among biomarkers, KL-6 and chitotriosidase showed the best sensitivity and the best specificity, respectively, even in patients on chronic steroid-therapy.
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After publication of our article [1] the authors have notified us that one of the names has been incorrectly tagged.