Cytokine kinetic profiles in children with acute lower respiratory tract infection: a post hoc descriptive analysis from a randomized control trial

Fuchs, Aline; Gotta, Verena; Decker, Marie-Luise; Szinnai, Gabor; Baumann, Philipp; Bonhoeffer, Jessica M.; Ritz, Nicole; Baer, Gurli; Bérthet, G; Bonhoeffer, Jan; Buettcher, Michael; Gambon, Muriel; Heininger, Ulrich; Müeller, Beat; Schaad, Urs B.; Schuetz, Philipp; Trachsel, Daniel

doi:10.1016/j.cmi.2018.03.016

Cited by 22 publications

(18 citation statements)

References 28 publications

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“…Host-response biomarkers, such as C-reactive protein, interleukin(IL)-6, and procalcitonin, have been increasingly used to assist the diagnosis of a variety of infectious diseases, including pneumonia and sepsis. [66][67][68][69][70][71] A meta-analysis of 6708 adults with acute respiratory infection found that the use of procalcitonin to guide therapy was associated with a 17% reduced risk of mortality and a 2·4-day reduction in antibiotic exposure compared with controls, without increasing adverse outcomes. 72 However, data in children are scarce, and early studies have conflicting results.…”

Section: Host-response Biomarker Testingmentioning

confidence: 99%

Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group

Goodman¹,

Pervaiz²,

McCollum³

et al. 2019

The Lancet Respiratory Medicine

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Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia.

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Section: Host-response Biomarker Testingmentioning

confidence: 99%

Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group

Goodman¹,

Pervaiz²,

McCollum³

et al. 2019

The Lancet Respiratory Medicine

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“…Among host factors, cytokines are known to play important antiviral roles, but they may also cause damage to respiratory tract and lung 11,12 . Therefore, the balance between pro-inflammatory and anti-inflammatory cytokines determines the outcome of an immune response to an infection.…”

Section: Introductionmentioning

confidence: 99%

“…It is well established that persistent chronic inflammation will damage the development of airway and lung tissues, leading to subsequent respiratory diseases such as asthma 11,13–15 . To date, only a limited number of studies investigate cytokine profiles in children with ARTIs, mostly in relation to specific respiratory virus infection (e.g., influenza, rhinovirus) 11,12,16 . No studies are designed to measure cytokine profiles longitudinally among children with multiple ARTIs.…”

Section: Introductionmentioning

confidence: 99%

Altered respiratory virome and serum cytokine profile associated with recurrent respiratory tract infections in children

et al. 2019

Nat Commun

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Recurrent acute respiratory tract infections (ARTIs) affect a large population, yet the specific decisive factors are largely unknown. Here we study a population of 4407 children diagnosed with ARTI, comparing respiratory virome and serum cytokine profiles associated with multiple ARTIs and single ARTI during a six-year period. The relative abundance of Propionibacterium phages is significantly elevated in multiple ARTIs compared to single ARTI group. Serum levels of TIMP-1 and PDGF-BB are markedly increased in multiple ARTIs compared to single-ARTI and non-ARTI controls, making these two cytokines potential predictors for multiple ARTIs. The presence of Propionibacterium phages is associated with higher levels of TIMP-1 and PDGF-BB. Receiver operating characteristic (ROC) curve analyses show that the combination of TIMP-1, PDGF-BB and Propionibacterium phages could be a strong predictor for multiple ARTIs. These findings indicate that respiratory microbe homeostasis and specific cytokines are associated with the onset of multiple ARTIs over time.

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“…It can be secreted by almost all stromal cells and cells of the immune system at an early stage of in ammation (with rapid elevation in 1-3 hours), and further promote the synthesis and release of CRP by the liver [21,22]. IL-6 has been previously described as a marker of different types of SBI (alone or in combination with other biomarkers) [23,24] such as early-onset neonatal sepsis [25,26], sepsis and septic shock [21,23,27] bacteremia in patients with febrile neutropenia [28,29] or pneumococcal pneumonia [30][31][32][33]. The early elevation of IL-6 that occurs in the presence of SBI is an important advantage of this cytokine over other biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 6 as a Marker of Severe Bacterial Infection in Children with Sickle Cell Disease and Fever: A Case-Control Study

Rincón-López

Gómez

Matos

et al. 2021

Preprint

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BackgroundEtiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI).MethodsA prospective, case-control study of febrile and steady-state SCD children was carried out during 3 years. Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed.ResultsA total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI) and 33 no proven infection (NPI). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences, respectively).ConclusionWe found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.

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Cytokine kinetic profiles in children with acute lower respiratory tract infection: a post hoc descriptive analysis from a randomized control trial

Abstract: We observed an earlier decrease of elevated cytokines compared to PCT or CRP. Both pro- and anti-inflammatory cytokines may serve as markers for severity of LRTI.

Cited by 22 publications

References 28 publications

Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group

Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group

Altered respiratory virome and serum cytokine profile associated with recurrent respiratory tract infections in children

Interleukin 6 as a Marker of Severe Bacterial Infection in Children with Sickle Cell Disease and Fever: A Case-Control Study

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