Browsing by Author "Borzutzky Schachter, Arturo José"

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    Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial
    (2024) Borzutzky Schachter, Arturo José; Iturriaga Ortiz, Carolina Alejandra; Pérez Mateluna, Guillermo Andres; Cristi, Francisca; Cifuentes Aguila, Lorena Isabel; Silva‐Valenzuela, Sergio; Vera Kellet, Cristian Andres; Cabalín Arenas, Carolina Andrea; Hoyos Bachiloglu, Rodrigo Andres; Navarrete Dechent, Cristian Patricio; Cossio Traverso, Maria Laura; Le Roy, Catalina; Camargo, Jr, Carlos A.
    Background: Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients.Objectives: To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers.Methods: We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD).Results: Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation.Conclusions: Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).
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    Interferon β-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial
    (Elsevier Ltd, 2023) Castro Rodríguez, José Antonio; Fish, Eleanor; Montgomery, Samuel T.; Kollmann, Tobias R.; Iturriaga Ortiz, Carolina Alejandra; Shannon, Casey; Karpievitch, Yuliya; Ho, Joseph; Chen, Virginia; Balshaw, Robert; Ben-Othman, Rym; Aniba, Radhouane; Gidi Yunge, Francisca Andrea; Hartnell, Lucy; Hancock, David G.; Perez Mateluna, Guillermo Andrés; Urzua, Marcela; Tebbutt, Scott J.; Garcia-Huidobro, Munita Diego Nicolas; Perret, Perez Cecilia; Borzutzky Schachter, Arturo José; Stick, Stephen M.
    © 2023 The Author(s)Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNβ-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 μg subcutaneous pegylated IFNβ-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNβ-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNβ-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = −0.2%, 95% CI = −8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = −3.6% to 11.3%). Treatment with IFNβ-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNβ-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as ‘Plegridy (peginterferon beta-1a).’ The study was substantially funded by BHP Holdings Pty Ltd.
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    Vernix caseosa reveals mechanistic clues linking maternal obesity to atopic dermatitis pathogenesis
    (2023) Arenas Cabalín, Carolina Andrea; Dibarrart Duhalde, Marisol; Núñez Rosales, Juan José; Faunes Pérez, Miriam Elizabeth; Avaca Bengochea, Mónica; Ávalos Odano, Patricia De Las Mercedes; Fabres Biggs, Jorge Guillermo Eduardo; Álvarez Figueroa, María Javiera; Vera Kellet, Cristián Andrés; Silva Valenzuela, Sergio; Sáez Steeger, Claudia; Borzutzky Schachter, Arturo José
    Background Maternal overweight and obesity have been associated with an increased risk of atopic dermatitis (AD) in the offspring, but the underlying mechanisms are unclear. Vernix caseosa (VC) is a proteolipid material covering the fetus produced during skin development. However, whether maternal prepregnancy weight excess influences fetal skin development is unknown. Characterizing the VC of newborns from mothers with prepregnancy overweight and obesity might reveal AD-prone alterations during fetal skin development.ObjectiveWe sought to explore AD biomarkers and staphylococcal loads in VC from the offspring of mothers who were overweight/obese (O/O) before pregnancy versus in those from offspring of normal weight mothers.MethodsThe VC of newborns of 14 O/O and 12 normal weight mothers were collected immediately after birth. Biomarkers were determined by ELISA and staphylococcal species by quantitative PCR.ResultsThe VC from the O/O group showed decreased expression of skin barrier proteins (filaggrin and loricrin) and increased levels of proinflammatory biomarkers (IgA, thymic stromal lymphopoietin [TSLP], S100A8, IL-25, and IL-33). No differences in concentrations of antimicrobial peptides and enzymes were detected. The VC from the O/O group had a lower Staphylococcus epidermidis and Staphylococcus hominis commensal bacterial load, whereas Staphylococcus aureus bacterial load was not significantly different between the 2 groups. Maternal body mass index was negatively correlated with VC filaggrin expression and S epidermidis load and was positively associated with TSLP concentration. One-year follow-up established that the offspring of O/O mothers had a higher incidence of AD that was specifically linked with decreased VC filaggrin expression and lower S epidermidis load.ConclusionsVC from neonates of mothers with prepregnancy overweight and obesity exhibit skin barrier molecular alterations and staphylococcal dysbiosis that suggest early mechanistic clues to this population’s increased risk of AD.