Publications by authors named "Riccardo Castagnoli"

62 Publications

BTK inhibitors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Systematic Review.

Res Sq 2021 Mar 22. Epub 2021 Mar 22.

ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes.Evidence ReviewWe searched PubMed, Embase, and Web of Science: Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.FindingsOne hundred twenty-five articles were identified, 6 of which met inclusion criteria. Sample size ranged from 6 to 126 patients. Patient populations included subjects hospitalized with COVID-19 (6/6) and admitted to the intensive care unit (5/6). Patient age ranged between 35 and 98 years. Four studies included patients already receiving BTKinibs for their lymphoproliferative disease, 1 for Waldenstrom's macroglobulinemia and 3 for chronic lymphocytic leukemia (CLL). The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Differences in standard-of-care reflected the date of study and pre-existing conditions in the various patient cohorts. Full-dose acalabrutinib was evaluated in 2 studies, one study evaluated full-dose ibrutinib, and another study evaluated both ibrutinib and acalabrutinib. The remainder 2 studies described outcomes in CLL patients on multiple BTKinibs and other CLL-targeted treatments. Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs. Conclusions and RelevanceBTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration. However, randomized clinical trials are needed to validate the beneficial effects of BTKinibs for acute SARS-CoV-2 infection.
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http://dx.doi.org/10.21203/rs.3.rs-319342/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010740PMC
March 2021

Inborn errors of immunity with atopic phenotypes: A practical guide for allergists.

World Allergy Organ J 2021 Feb 22;14(2):100513. Epub 2021 Feb 22.

Department of Pediatrics, Giovanni XXIII Pediatric Hospital, Bari, Italy.

Inborn errors of immunity (IEI) are a heterogeneous group of disorders, mainly resulting from mutations in genes associated with immunoregulation and immune host defense. These disorders are characterized by different combinations of recurrent infections, autoimmunity, inflammatory manifestations, lymphoproliferation, and malignancy. Interestingly, it has been increasingly observed that common allergic symptoms also can represent the expression of an underlying immunodeficiency and/or immune dysregulation. Very high IgE levels, peripheral or organ-specific hypereosinophilia, usually combined with a variety of atopic symptoms, may sometimes be the epiphenomenon of a monogenic disease. Therefore, allergists should be aware that severe and/or therapy-resistant atopic disorders might be the main clinical phenotype of some IEI. This could pave the way to target therapies, leading to better quality of life and improved survival in affected patients.
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http://dx.doi.org/10.1016/j.waojou.2021.100513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907539PMC
February 2021

Gut Microbiota-Host Interactions in Inborn Errors of Immunity.

Int J Mol Sci 2021 Jan 31;22(3). Epub 2021 Jan 31.

Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.

Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host's innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.
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http://dx.doi.org/10.3390/ijms22031416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866830PMC
January 2021

Epidemiology of rare allergic diseases in children.

Pediatr Allergy Immunol 2020 11;31 Suppl 26:39-42

Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy.

Allergic diseases have different frequencies. In particular, allergic rhinitis and asthma have high frequencies of about 20% and 10%, respectively. Other allergic diseases have lower frequencies; for example, food allergy has a frequency of 1%-4%. There are also rare allergic diseases, with a prevalence of 5 cases per 10 000 people in the general population, and they are included in Orphanet. However, other extremely rare allergic diseases still need to be properly known in order to be possibly recognized as rare diseases and cataloged in Orphanet.
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http://dx.doi.org/10.1111/pai.13359DOI Listing
November 2020

Type-2 inflammatory mediators as targets for precision medicine in children.

Pediatr Allergy Immunol 2020 11;31 Suppl 26:17-19

Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

The prevalence, heterogeneity, and severity of type 2 inflammatory diseases, including asthma and atopic dermatitis, continue to rise, especially in children and adolescents. Type 2 inflammation is mediated by both innate and adaptive immune cells and sustained by a specific subset of cytokines, such as interleukin (IL)-4, IL-5,IL-13, and IgE. IL-4 and IL-13 are considered signature type 2 cytokines, as they both have a pivotal role in many of the pathobiologic changes featured in asthma and atopic dermatitis. Several biologics targeting IL-4, IL-5, and IL-13, as well as IgE, have been proposed to treat severe allergic disease in the pediatric population with promising results. A better definition of type 2 inflammatory pathways is essential to implement targeted therapeutic strategies.
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http://dx.doi.org/10.1111/pai.13340DOI Listing
November 2020

Immunological basis of virus-host interaction in COVID-19.

Pediatr Allergy Immunol 2020 11;31 Suppl 26:75-78

Department of Pediatrics, Giovanni XXIII Pediatric Hospital, Bari, Italy.

COVID-19 is a complex new viral disease, in which a strict balance between anti-viral immune response and the ensuing organ inflammation has a critical role in determining the clinical course. In adults, compelling evidence exists indicating that an uncontrolled inflammatory response ("cytokine storm") is pivotal in determining disease progression and mortality. Children may rarely present with severe disease. Modulating factors related to the host's genetic factors, age-related susceptibility, and the capability to mount appropriate immune responses might play a role in control virus load at an early stage and regulating the inflammatory reaction. Elucidating these mechanisms seems crucial in developing target therapies according to patient's age, immunologic status, and disease evolution in COVID-19.
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http://dx.doi.org/10.1111/pai.13363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753582PMC
November 2020

Updates on new monogenic inborn errors of immunity.

Pediatr Allergy Immunol 2020 11;31 Suppl 26:57-59

Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Inborn errors of immunity (IEI), also referred to as primary immunodeficiencies (PID), are disorders that, for the most part, result from mutations in genes involved in immune host defense and immune regulation. Thanks to the increased availability of high-throughput DNA sequencing and the improvement in genomic data interpretation, the number of newly identified genes associated with IEI has exponentially increased over the last decade. We reviewed four recently described monogenic IEI and discussed the clinical and immunologic features of these new conditions.
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http://dx.doi.org/10.1111/pai.13365DOI Listing
November 2020

An asymptomatic mediastinal cyst in a young child: Case report and summary of the literature.

Clin Case Rep 2020 Nov 26;8(11):2163-2165. Epub 2020 Jun 26.

Department of Pediatrics Fondazione IRCCS Policlinico San Matteo University of Pavia Pavia Italy.

Bronchogenic cyst is a rare congenital chest malformation that mainly presents with wheeze and feeding issues in early life. A multidisciplinary approach and follow-up are pivotal for the improvement of lung function, mostly in cases of mediastinal complications.
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http://dx.doi.org/10.1002/ccr3.3070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669405PMC
November 2020

An immune-based biomarker signature is associated with mortality in COVID-19 patients.

JCI Insight 2021 01 11;6(1). Epub 2021 Jan 11.

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.

Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.
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http://dx.doi.org/10.1172/jci.insight.144455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821609PMC
January 2021

Complete Absence of CD3γ Protein Expression Is Responsible for Combined Immunodeficiency with Autoimmunity Rather than SCID.

J Clin Immunol 2021 Feb 19;41(2):482-485. Epub 2020 Nov 19.

Laboratory of Clinical Immunology and Microbiology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

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http://dx.doi.org/10.1007/s10875-020-00918-zDOI Listing
February 2021

Eosinopenia could be a relevant prognostic biomarker in patients with coronavirus disease 2019.

Allergy Asthma Proc 2020 11;41(6):e80-e82

Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

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http://dx.doi.org/10.2500/aap.2020.41.200079DOI Listing
November 2020

Additional Concerns Regarding Children With Coronavirus Disease 2019-Reply.

JAMA Pediatr 2020 12;174(12):1218-1219

Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

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http://dx.doi.org/10.1001/jamapediatrics.2020.2940DOI Listing
December 2020

Urticaria in childhood.

Acta Biomed 2020 09 15;91(11-S):e2020013. Epub 2020 Sep 15.

UOC Pediatria, Grande Ospedale Metropolitano, Reggio Calabria, Italy.

Histaminergic urticaria-angiodema is a common complaint in children. According to clinical criteria, it is classified as acute and chronic urticaria. A further clinical classification relies on triggering factors. We focus on diagnosis and therapeutic strategies. We report the main progresses in the field and issues that remain to be understood.
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http://dx.doi.org/10.23750/abm.v91i11-S.10317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023062PMC
September 2020

Allergen immunotherapy in children and adolescents with respiratory diseases.

Acta Biomed 2020 09 15;91(11-S):e2020006. Epub 2020 Sep 15.

Allergy Clinic, Casa di Cura Villa Montallegro, Genoa, Italy..

To date, the only disease-modifying treatment strategy for allergic rhinitis and asthma is allergen immunotherapy (AIT). There is evidence that AIT improves allergic rhinitis and asthma, such as reducing symptom severity and medication use and improving of quality of life, with a long-lasting effect after the end of the course. The recent clinical trials evidenced AIT effectiveness and safety in allergic asthma. Consequently, the current version of the GINA (Global Initiative for Asthma) guidelines recommend AIT as an add-on therapy for asthma. There is also evidence that AIT may exert preventive activity on the possible progression from allergic rhinitis to asthma in children and the onset of new sensitizations.
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http://dx.doi.org/10.23750/abm.v91i11-S.10309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023059PMC
September 2020

Timely adaptation of a Pediatric Unit to COVID-19 emergency in Northern Italy: the experience of Fondazione IRCCS Policlinico San Matteo in Pavia.

Acta Biomed 2020 09 15;91(11-S):e2020004. Epub 2020 Sep 15.

Clinica Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; COVID-19 IRCCS San Matteo Pavia Pediatric Task Force.

Italy is one of the most exposed countries worldwide to COVID-19, and Lombardy is the most affected region in Italy. In this context, Fondazione IRCCS Policlinico San Matteo in Pavia, one of the largest University hospitals in the region, has been involved in the management of the outbreak since its inception. Immediately after the communication of the first Italian COVID-19+ patient, the Pediatric Unit has been completely reorganized to face the approaching outbreak. The optimization of the Pediatric Unit resources for COVID-19 emergency is reported as an example to safely preserve health activity during the pandemic.
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http://dx.doi.org/10.23750/abm.v91i11-S.10300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023061PMC
September 2020

SARS-CoV-2 infection in pediatric population.

Acta Biomed 2020 09 15;91(11-S):e2020003. Epub 2020 Sep 15.

Division of Paediatric Infectious Disease, Anna Meyer Children's University Hospital, Department of Health Sciences, University of Florence, Florence, Italy..

n December 2019, in Wuhan (Hubei, China), the first COVID-19 cases due to SARS-COV-2 had been reported. On July 1st 2020, more than 10.268.839 million people had developed the disease, with at least 506.064 deaths. At present, Italy is the third country considering the number of cases (n=240.760), after Spain, and the second for the cumulative number of deaths (n=249.271), after the United States. As regard pediatric COVID-19 cases, more than 4000 cases (have been reported; however, these figures are likely to be underestimated since they are influenced by the number of diagnostic tests carried out. Three pediatric deaths have been reported in Italy to date. We aimed to review the peculiar aspects of SARS-COV-2 infection in the pediatric population.
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http://dx.doi.org/10.23750/abm.v91i11-S.10298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023063PMC
September 2020

Asthma in children and adolescents: the ControL'Asma project.

Acta Biomed 2020 09 15;91(11-S):e2020002. Epub 2020 Sep 15.

Department of Pediatrics, Policlinico Umberto I, Sapienza University, Rome, Italy; “ControL’Asma” Study Group.

The control of asthma is the objective of asthma management. However, it is difficult to obtain in clinical practice. The Italian Society of Allergy and Clinical Immunology promoted the nationwide project "ControL'Asma" to investigate the real situation in a group of children and adolescents with asthma. The preliminary outcomes demonstrated that many asthmatic subjects do not achieve adequate asthma control. Moreover, asthma in Italian children and adolescents was usually more frequent in males, had an early onset and allergic phenotype with very frequent rhinitis comorbidity, uncontrolled and partly controlled asthma affected about the half of subjects. However, this project suggested that the assessment of asthma symptom perception by VAS could be a reliable tool in the asthma management.
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http://dx.doi.org/10.23750/abm.v91i11-S.10295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023065PMC
September 2020

Autoantibodies against type I IFNs in patients with life-threatening COVID-19.

Authors:
Paul Bastard Lindsey B Rosen Qian Zhang Eleftherios Michailidis Hans-Heinrich Hoffmann Yu Zhang Karim Dorgham Quentin Philippot Jérémie Rosain Vivien Béziat Jérémy Manry Elana Shaw Liis Haljasmägi Pärt Peterson Lazaro Lorenzo Lucy Bizien Sophie Trouillet-Assant Kerry Dobbs Adriana Almeida de Jesus Alexandre Belot Anne Kallaste Emilie Catherinot Yacine Tandjaoui-Lambiotte Jeremie Le Pen Gaspard Kerner Benedetta Bigio Yoann Seeleuthner Rui Yang Alexandre Bolze András N Spaan Ottavia M Delmonte Michael S Abers Alessandro Aiuti Giorgio Casari Vito Lampasona Lorenzo Piemonti Fabio Ciceri Kaya Bilguvar Richard P Lifton Marc Vasse David M Smadja Mélanie Migaud Jérome Hadjadj Benjamin Terrier Darragh Duffy Lluis Quintana-Murci Diederik van de Beek Lucie Roussel Donald C Vinh Stuart G Tangye Filomeen Haerynck David Dalmau Javier Martinez-Picado Petter Brodin Michel C Nussenzweig Stéphanie Boisson-Dupuis Carlos Rodríguez-Gallego Guillaume Vogt Trine H Mogensen Andrew J Oler Jingwen Gu Peter D Burbelo Jeffrey I Cohen Andrea Biondi Laura Rachele Bettini Mariella D'Angio Paolo Bonfanti Patrick Rossignol Julien Mayaux Frédéric Rieux-Laucat Eystein S Husebye Francesca Fusco Matilde Valeria Ursini Luisa Imberti Alessandra Sottini Simone Paghera Eugenia Quiros-Roldan Camillo Rossi Riccardo Castagnoli Daniela Montagna Amelia Licari Gian Luigi Marseglia Xavier Duval Jade Ghosn John S Tsang Raphaela Goldbach-Mansky Kai Kisand Michail S Lionakis Anne Puel Shen-Ying Zhang Steven M Holland Guy Gorochov Emmanuelle Jouanguy Charles M Rice Aurélie Cobat Luigi D Notarangelo Laurent Abel Helen C Su Jean-Laurent Casanova

Science 2020 10 24;370(6515). Epub 2020 Sep 24.

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
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http://dx.doi.org/10.1126/science.abd4585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857397PMC
October 2020

Human inborn errors of immunity caused by defects of receptor and proteins of cellular membrane.

Minerva Pediatr 2020 Oct 22;72(5):393-407. Epub 2020 Sep 22.

Department of Molecular and Translational Medicine, A. Nocivelli Institute for Molecular Medicine, University of Brescia, Brescia, Italy.

Inborn errors of immunity are diseases of the immune system resulting from mutations that alter the expression of encoded proteins or molecules. Total updated number of these disorders is currently 406, with 430 different identified gene defects involved. Studies of the underlying mechanisms have contributed in better understanding the pathophysiology of the diseases, but also the complexity of the biology of innate and adaptive immune system and its interaction with microbes. In this review we present and briefly discuss Inborn Errors of Immunity caused by defects in genes encoding for receptors and protein of cellular membrane, including cytokine receptors, T cell antigen receptor (TCR) complex, cellular surface receptors or receptors signaling causing predominantly antibody deficiencies, co-stimulatory receptors and others. These alterations impact many biological processes of immune-system cells, including development, proliferation, activation and down-regulation of the immunological response, and result in a variety of diseases that present with distinct clinical features or with overlapping signs and symptoms.
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http://dx.doi.org/10.23736/S0026-4946.20.06000-4DOI Listing
October 2020

An update on the role of chronic rhinosinusitis with nasal polyps as a co-morbidity in severe asthma.

Expert Rev Respir Med 2020 12 2;14(12):1197-1205. Epub 2020 Sep 2.

Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia , Pavia, Italy.

Introduction: Chronic rhinosinusitis and asthma are heterogeneous diseases with complex pathogenesis. The presence of chronic rhinosinusitis with nasal polyps has been associated with increased asthma exacerbation frequency and may represent a predictor of future exacerbations in severe asthma.

Areas Covered: This review provides the clinician with an overview of the prevalence and clinical impact of the chronic rhinosinusitis with nasal polyps in severe asthma and summarizes recommended therapeutic approaches, including innovative biologic therapies. To select relevant literature for inclusion in this review, we conducted a literature search using the PubMed and ClinicalTrials.gov databases, using terms 'chronic rhinosinusitis with nasal polyps' AND 'asthma' OR 'severe asthma.' The literature review was performed for publication years 2010-2020, restricting the articles to humans and English language publications.

Expert Opinion: Biological therapies have opened new perspectives in the treatment of upper and lower airway allergic diseases. Care pathways in severe asthma are almost consolidated, while they still rely on phenotypic rather than endotypic features in chronic rhinosinusitis with nasal polyps. Unveiling the correlation between clinical phenotypes and molecular endotypes will allow better stratification of patients with chronic rhinosinusitis with nasal polyps to identify candidates who benefit most from biological therapy.
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http://dx.doi.org/10.1080/17476348.2020.1812388DOI Listing
December 2020

Novel insights into pediatric allergy and immunology.

Minerva Pediatr 2020 10 29;72(5):341-342. Epub 2020 Jul 29.

Department of Pediatrics, Pediatric Clinic, IRCCS San Matteo Polyclinic Foundation, University of Pavia, Pavia, Italy -

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http://dx.doi.org/10.23736/S0026-4946.20.06015-6DOI Listing
October 2020

An update on biological therapies for pediatric allergic diseases.

Minerva Pediatr 2020 Oct 20;72(5):364-371. Epub 2020 Jul 20.

Department of Pediatrics, Pediatric Clinic, IRCCS San Matteo Polyclinic Foundation, University of Pavia, Pavia, Italy.

Allergic diseases represent a global health burden. Patients with allergic diseases may experience disability, reduced quality of life and productivity, emotional distress, and social restrictions, especially in the most severe cases. Current advances in unveiling the pathogenesis of allergic disorders have paved the way for the development of novel therapeutic strategies. Biological drugs have been widely studied in pediatric allergic asthma, with strong evidence of efficacy and safety. Moreover, promising results derive from studies on other conditions such as atopic dermatitis, chronic spontaneous urticaria, and food allergy. This review analyzes recent evidence on the role of biologic therapies for allergic diseases, focusing on the pediatric age.
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http://dx.doi.org/10.23736/S0026-4946.20.05993-9DOI Listing
October 2020

Behavioral issues and quality of life in children with eosinophilic esophagitis.

Minerva Pediatr 2020 Oct 4;72(5):424-432. Epub 2020 Jun 4.

Department of Pediatrics, IRCCS San Matteo Polyclinic Foundation, University of Pavia, Pavia, Italy.

Eosinophilic esophagitis (EoE) is a chronic disease characterized by symptoms related to esophageal dysfunction and eosinophil-predominant inflammation (≥15 eosinophils/high power field). In the last ten years, several epidemiological studies showed a significant increase in the incidence and prevalence of EoE, especially in children in Western Countries. Although EoE often presents with gastrointestinal symptoms, adults and children may develop extraintestinal symptoms and behavioral issues. Also, the chronic nature of the disease, long-term therapies, and strict follow-up may impair the quality of life of patients and their family. This review summarizes current knowledge on the behavioral and psychosocial issues and quality of life of children and adolescents with EoE and their caregivers.
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http://dx.doi.org/10.23736/S0026-4946.20.05913-7DOI Listing
October 2020

Measuring inflammation in paediatric severe asthma: biomarkers in clinical practice.

Breathe (Sheff) 2020 Mar;16(1):190301

Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

Severe asthma in children is a highly heterogeneous disorder, encompassing different clinical characteristics (phenotypes) and immunopathological pathways (endotypes). Research is focusing on the identification of noninvasive biomarkers able to predict treatment response and assist in designing personalised therapies for severe asthma. Blood and sputum eosinophils, serum IgE and exhaled nitric oxide fraction mostly reflect type 2 airway inflammation in children. However, in the absence of available point-of-care biomarkers, the diagnosis of non-type 2 asthma is still reached by exclusion. In this review, we present the most recent evidence on biomarkers for severe asthma and discuss their implementation in clinical practice. We address the methods for guiding treatment decisions and patient identification, focusing on the paediatric age group.

Key Points: Severe asthma in children is a highly heterogeneous disorder, encompassing different clinical characteristics (phenotypes) and immunopathological pathways (endotypes).Research is focusing on the identification of noninvasive biomarkers able to predict treatment response and assist in designing personalised therapies for severe asthma.Blood and sputum eosinophils, serum IgE and exhaled nitric oxide fraction mostly reflect type 2 airway inflammation in children. However, knowledge regarding non-type 2 inflammation and related biomarkers is still lacking.

Educational Aims: To summarise the most recent evidence on biomarkers for severe asthma in children.To discuss their implementation in clinical practice through guiding patient identification and treatment decisions.
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http://dx.doi.org/10.1183/20734735.0301-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249787PMC
March 2020

COVID-19 in the Pediatric Population Admitted to a Tertiary Referral Hospital in Northern Italy: Preliminary Clinical Data.

Pediatr Infect Dis J 2020 07;39(7):e160

From the Department of Child and Woman Health, Pediatrics Clinic, IRCCS Fondazione Policlinico San Matteo and University of Pavia, Pavia, Italy.

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http://dx.doi.org/10.1097/INF.0000000000002730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359913PMC
July 2020

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review.

JAMA Pediatr 2020 Sep;174(9):882-889

Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Importance: The current rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection justifies the global effort to identify effective preventive strategies and optimal medical management. While data are available for adult patients with coronavirus disease 2019 (COVID-19), limited reports have analyzed pediatric patients infected with SARS-CoV-2.

Objective: To evaluate currently reported pediatric cases of SARS-CoV-2 infection.

Evidence Review: An extensive search strategy was designed to retrieve all articles published from December 1, 2019, to March 3, 2020, by combining the terms coronavirus and coronavirus infection in several electronic databases (PubMed, Cochrane Library, and CINAHL), and following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Retrospective cross-sectional and case-control studies, case series and case reports, bulletins, and national reports about the pediatric SARS-CoV-2 infection were included. The risk of bias for eligible observational studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.

Findings: A total of 815 articles were identified. Eighteen studies with 1065 participants (444 patients were younger than 10 years, and 553 were aged 10 to 19 years) with confirmed SARS-CoV-2 infection were included in the final analysis. All articles reflected research performed in China, except for 1 clinical case in Singapore. Children at any age were mostly reported to have mild respiratory symptoms, namely fever, dry cough, and fatigue, or were asymptomatic. Bronchial thickening and ground-glass opacities were the main radiologic features, and these findings were also reported in asymptomatic patients. Among the included articles, there was only 1 case of severe COVID-19 infection, which occurred in a 13-month-old infant. No deaths were reported in children aged 0 to 9 years. Available data about therapies were limited.

Conclusions And Relevance: To our knowledge, this is the first systematic review that assesses and summarizes clinical features and management of children with SARS-CoV-2 infection. The rapid spread of COVID-19 across the globe and the lack of European and US data on pediatric patients require further epidemiologic and clinical studies to identify possible preventive and therapeutic strategies.
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http://dx.doi.org/10.1001/jamapediatrics.2020.1467DOI Listing
September 2020

Pediatric use of omalizumab for allergic asthma.

Expert Opin Biol Ther 2020 07 13;20(7):695-703. Epub 2020 Apr 13.

Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia , Pavia, Italy.

Introduction: Severe pediatric asthma is associated with significant morbidity as well as with a high economic burden. It represents a heterogeneous disease with multiple clinical phenotypes. Currently, physicians are facing the challenge to provide a 'personalized medicine approach', which is tailored to the diverse pathomechanisms underlying clinical presentations. Three main endotypes of airway inflammation have been described in children with severe asthma. While neutrophilic and paucigranulocytic inflammatory patterns are quite uncommon in childhood, type Th2 inflammation asthma with elevated IgE is the most prevalent in pediatric asthma. Considering the pivotal role of IgE in type Th2 inflammation asthma, the blockade of IgE using anti-IgE therapy represents a potent therapeutic option for severe pediatric asthma in children.

Areas Covered: This review aims to focus on the role of omalizumab as a treatment option in pediatric patients (aged six years and above) with severe allergic asthma.

Expert Opinion: The clinical efficacy and safety of omalizumab for the treatment of pediatric asthma is well documented in clinical trials and observational studies. Further studies are still required to characterize the potential benefit of anti-IgE therapy in airway remodeling, identify additional biomarkers of clinical response and address current unmet needs, including the limit on omalizumab use in children younger than six years.
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http://dx.doi.org/10.1080/14712598.2020.1751115DOI Listing
July 2020

Dupilumab to Treat Type 2 Inflammatory Diseases in Children and Adolescents.

Paediatr Drugs 2020 Jun;22(3):295-310

Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, viale Golgi 19, 27100, Pavia, Italy.

During the past decade, significant therapeutic progress has been made in the field of allergic diseases, mainly concerning the pathogenic role of type 2 inflammation. Biologics targeting specific key cytokines, such as interleukin (IL)-4, IL-5, and IL-13, as well as IgE, have emerged as promising innovative therapies for allergic disorders. In this context, dupilumab has emerged as one of the most successful therapies targeting the IL-4R axis. Dupilumab is a human IgG4 antibody anti-IL-4 receptor (IL-4R) α-subunit that blocks IL-4R signaling induced by both IL-4 and IL-13, downregulating the molecular pathways that drive type 2 inflammatory diseases, including atopic dermatitis, allergic rhinitis, allergic asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. This review presents the most recent evidence on dupilumab for the treatment of type 2 inflammatory diseases and discusses the future perspective, focusing on the pediatric age group and adolescents.
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http://dx.doi.org/10.1007/s40272-020-00387-2DOI Listing
June 2020