Chronic cough is defined as a daily cough that persists longer than 4 weeks. Protracted bacterial bronchitis (PBB) is a common cause of chronic wet cough in preschool children with no symptoms or signs of other specific causes, and resolution usually follows a 2-week course of an appropriate oral antibiotic. The diagnosis is mainly clinical; generally, no instrumental examinations are necessary. The most common bacteria found in the bronchoalveolar lavage (BAL) of subjects with PBB include Haemophilus influenzae, Streptococcus pneumoniae , and Moraxella catarrhalis . Nowadays, there is no certain evidence of the role of viruses in PBB pathogenesis even though different types of viruses have been detected in BAL from children with PBB. Airway malacia is commonly found in children with PBB; conversely, there is no correlation with any type of immunodeficiency. Amoxicillin-clavulanate acid is the most commonly used antibiotic, as first-line, prolonged therapy (longer than 2 weeks) is sometimes required to cough resolution. When the wet cough does not improve despite prolonged antibiotic treatment, an underlying disease should be considered. Moreover, there are several hypotheses of a link between PBB and bronchiectasis, as recent evidences show that recurrent PBB (>3 episodes/years) and the presence of H. influenzae infection in the lower airways seem to be significant risk factors to develop bronchiectasis. This underlines the importance of a close follow-up among children with PBB and the need to consider chest computerized tomography (CT) in patients with risk factors for bronchiectasis. In this brief review, we summarize the main clinical and pathogenetic findings of PBB, a disease that may be related to a relevant morbidity and decreased quality of life during the pediatric age.
Objectives Clinical presentation of pediatric celiac disease (CD) is heterogeneous and ever-evolving. Our aim is to highlight its changes throughout the years. Methods Data about clinical presentation of CD in children diagnosed between 1990 and 2020 at the CD Center of Maggiore Hospital, Bologna, were collected. Patients were stratified into groups based on the date [P1 (1990–2011), P2 (2012–2020)] and age [G1 (< 2 years), G2 (2–5), G3 (6–11), G4 (12–18)] at diagnosis, then investigated by comparing CD clinical presentation in different periods and ages. Results 1081 children were selected. Mean age at diagnosis increases from 5.9 to 6.6 years from P1 to P2. Gastrointestinal Symptoms (GIs) are predominant, with a decline of diarrhea (47%VS30%) and an increase of constipation (4%VS19%) (p < 0.001). Among Extraintestinal symptoms (EIs) a decrease of anemia (76%VS43%, p = 0,001) is observed. Failure to Thrive (FTT) is stable throughout the years (p = 0.03), while screenings show a trend of increment (19%VS23%). GIs’ frequency decline from G1 to G4 (p = 0,001), with reduction of diarrhea (p < 0.001), and rise of recurrent abdominal pain (p = 0,02). EIs are more frequent at older ages, FTT in younger patients. Conclusions Changes in clinical presentation of CD have occurred in the last 30 years. We observe a reduction of severe and classic gastroenterologic symptoms and a rise of atypical ones, together with a growth of serological screenings and higher age at diagnosis. Awareness about CD clinical trends is crucial for a proper approach and early diagnosis.
BackgroundF8-IL10 (Dekavil) is a human immunocytokine composed of the vascular targeting antibody F8, specific to the extradomain A of fibronectin, fused to the cytokine interleukin-10. F8-IL10 is being investigated in a dose-finding, PK phase Ib study and in a randomized, double blind, placebo-controlled phase II study, as a new therapeutic strategy for rheumatoid arthritis (RA).ObjectivesThe primary objective of the phase Ib study is to determine the safety, tolerability and MTD of Dekavil in combination with methotrexate (MTX). The primary objective of the phase II study is to assess the superiority of Dekavil plus MTX over MTX by measuring the mean change from baseline of DAS28-CRP. Immunogenicity of F8-IL10 and its PK and PD profile will also be explored.MethodsPatients with active RA despite MTX therapy and who failed anti-TNFα treatment are the target population of both studies. In the phase Ib, cohorts of 3–6 patients are treated with escalating doses of Dekavil (6, 15, 30, 60, 110, 160, 210, 300, 450 and 600 μg/kg) in combination with a fixed dose of MTX (10–15 mg). In the phase II, patients are randomized to Dekavil 30 or 160 μg/kg plus MTX or placebo plus MTX. Dekavil is administered by s.c. injection once weekly for a maximum of 8 weeks in both studies.ResultsThe first 9 cohorts of the phase Ib study have been completed, 32 patients were treated and 31 are evaluable for DLT. One DLT (G2 purpura) was observed in one patient of the 9th cohort. The same patient had G1 thrombocytopenia and G3 ALT increase. Both events were considered related to the study drug and resolved within ten days. Neither SUSAR nor treatment-related deaths occurred. Mild injection site reactions were reported in 59% of patients and 2 cases of anemia (G2 and G3) were considered related to the study drug. All adverse reactions resolved after the end of treatment. Currently, the MTD has not been reached and the 600 μg/kg dose is ongoing. To date, 59.3% of the 27 patients analyzed for efficacy had ACR and EULAR responses, 29.6% and 11.1% had ACR50 and ACR70, respectively, at the low dosages of 15, 30 and 60 μg/kg. Two patients benefited from ACR70 response for 12 months after the last drug administration. In the phase II study, 13 out of 87 patients have been enrolled so far. To date, neither SUSAR nor treatment-related deaths were recorded.ConclusionsThe promising safety and efficacy results, even at low dosages, of Dekavil in the phase Ib study led to the start of the phase II study to verify the efficacy of Dekavil in combination with MTX in the same patient population. The currently available data suggest that the targeted delivery of IL-10 to the sites of inflammation is a promising therapeutic approach for RA.Disclosure of InterestM. Galeazzi: None declared, R. Voll: None declared, G. Sebastiani: None declared, L. Bazzichi: None declared, O. Viapiana: None declared, J. Dudler: None declared, P. Sarzi-Puttini: None declared, E. Selvi: None declared, A. Iuliano: None declared, M. Pedretti Employee of: Philogen, L. Giovannoni Employ...
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