Serum KL‐6 levels as a biomarker of lung injury in respiratory syncytial virus bronchiolitis

Kawasaki, Yukihiko; Aoyagi, Yoshimichi; Abe, Yusaku; Go, Hayato; Imamura, Takashi; Kaneko, Mari; Ito, Masaki; Katayose, Masahiko; Hashimoto, Koichi

doi:10.1002/jmv.21634

Cited by 23 publications

(22 citation statements)

References 22 publications

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“…KL‐6 serum levels in ARDS may reflect the alveolar epithelial cell damage induced by mechanical ventilatory support 5 . High peripheral levels of this protein have also been reported in Legionella , Pneumocystis jivorecii infections, 6,7 and measles‐associated pneumonia, 8 as well as in viral pneumonia 9 …”

Section: Introductionmentioning

confidence: 92%

Serum KL‐6 concentrations as a novel biomarker of severe COVID‐19

d’Alessandro

Cameli

Refini

et al. 2020

Journal of Medical Virology

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Severe acute respiratory syndrome coronavirus 2–induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen‐6 (KL‐6) is mainly produced by damaged or regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL‐6 in patients with coronavirus disease (COVID‐19) to verify its potential as a prognostic biomarker of severity. Twenty‐two patients (median age [interquartile range] 63 [59‐68] years, 16 males) with COVID‐19 were enrolled prospectively. Patients were divided into mild‐moderate and severe groups, according to respiratory impairment and clinical management. KL‐6 serum concentrations and lymphocyte subset were obtained. Peripheral natural killer (NK) cells/µL were significantly higher in nonsevere patients than in the severe group (P = .0449) and the best cut‐off value was 119 cells/µL. KL‐6 serum concentrations were significantly higher in severe patients than the nonsevere group (P = .0118). Receiver operating characteristic analysis distinguished severe and nonsevere patients according to KL‐6 serum levels and the best cut‐off value was 406.5 U/mL. NK cell analysis and assay of KL‐6 in serum can help identify severe COVID‐19 patients. Increased KL‐6 serum concentrations were observed in patients with severe pulmonary involvement, revealing a prognostic value and supporting the potential usefulness of KL‐6 measurement to evaluate COVID‐19 patients' prognosis.

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Section: Introductionmentioning

confidence: 92%

Serum KL‐6 concentrations as a novel biomarker of severe COVID‐19

d’Alessandro

Cameli

Refini

et al. 2020

Journal of Medical Virology

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“…The mechanisms underlying RSV-induced lung disease and the associated long-term consequences remain incompletely understood, although lung inflammatory responses likely play a central role in promoting pathogenesis 16 17 . RSV infection can progress to ARDS, the most severe form of ALI that further contributes to morbidity 18 in infants 19 20 21 . Notably, our recent study showed that ACE2 is involved in influenza H7N9-induced lung injury and that use of a recombinant ACE2 protein alleviates the severity of ALI 15 .…”

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confidence: 99%

Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus

Xie

et al. 2016

Sci Rep

231

237

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Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory illness in infants and young children, but the underlying mechanisms responsible for viral pathogenesis have not been fully elucidated. To date, no drugs or vaccines have been employed to improve clinical outcomes for RSV-infected patients. In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. Moreover, ACE2 deficiency aggravated RSV-associated disease pathogenesis, mainly by its action on the angiotensin II type 1 receptor (AT1R). Furthermore, administration of a recombinant ACE2 protein alleviated the severity of RSV-induced lung injury. These findings demonstrate that ACE2 plays a critical role in preventing RSV-induced lung injury, and suggest that ACE2 is a promising potential therapeutic target in the management of RSV-induced lung disease.

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“…Primary Hypothesis 2, Nested Case-Control Study: Preliminary data from previous studies provide estimates of selected biomarkers, including leukotrienes, CC-16, KL-6, IL-18, TNF-α, and HNE. Estimates of minimal detectable differences (two sided α = 0.05) are given in Table 4, for different numbers of asthma cases identified [46][47][48][49][50].…”

Section: Power Calculationsmentioning

confidence: 99%

Objectives, design and enrollment results from the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE)

et al. 2015

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BackgroundRespiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infancy has been consistently associated with an increased risk of childhood asthma. In addition, evidence supports that this relationship is causal. However, the mechanisms through which RSV contributes to asthma development are not understood. The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) study objectives are to: 1) characterize the host phenotypic response to RSV infection in infancy and the risk of recurrent wheeze and asthma, 2) identify the immune response and lung injury patterns of RSV infection that are associated with the development of early childhood wheezing illness and asthma, and 3) determine the contribution of specific RSV strains to early childhood wheezing and asthma development. This article describes the INSPIRE study, including study aims, design, recruitment results, and enrolled population characteristics.Methods/designThe cohort is a population based longitudinal birth cohort of term healthy infants enrolled during the first months of life over a two year period. Respiratory infection surveillance was conducted from November to March of the first year of life, through surveys administered every two weeks. In-person illness visits were conducted if infants met pre-specified criteria for a respiratory illness visit. Infants will be followed annually to ages 3-4 years for assessment of the primary endpoint: wheezing illness. Nasal, urine, stool and blood samples were collected at various time points throughout the study for measurements of host and viral factors that predict wheezing illness. Nested case-control studies will additionally be used to address other primary and secondary hypotheses.DiscussionIn the INSPIRE study, 1952 infants (48% female) were enrolled during the two enrollment years and follow-up will continue through 2016. The mean age of enrollment was 60 days. During winter viral season, more than 14,000 surveillance surveys were carried out resulting in 2,103 respiratory illness visits on 1189 infants. First year follow-up has been completed on over 95% percent of participants from the first year of enrollment.With ongoing follow-up for wheezing and childhood asthma outcomes, the INSPIRE study will advance our understanding of the complex causal relationship between RSV infection and early childhood wheezing and asthma.

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Serum KL‐6 levels as a biomarker of lung injury in respiratory syncytial virus bronchiolitis

Cited by 23 publications

References 22 publications

Serum KL‐6 concentrations as a novel biomarker of severe COVID‐19

Serum KL‐6 concentrations as a novel biomarker of severe COVID‐19

Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus

Objectives, design and enrollment results from the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE)

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