Sputum interleukin‐13 as a biomarker for the evaluation of asthma control

Tsilogianni, Zoi; Hillas, Georgios; Bakakos, Petros; Aggelakis, L.; Konstantellou, Elissavet; Papaioannou, Andriana Ι.; Papaporfyriou, Anastasia; Papiris, Spyros; Koulouris, Nikolaos; Loukides, Stelios; Κostikas, Κonstantinos

doi:10.1111/cea.12729

Cited by 13 publications

(4 citation statements)

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“…Sputum and blood eosinophils have demonstrated sensitivities of 50–79% and specificities of 69–92% for the prediction of responsiveness to oral steroid treatment ( 70 ). Finally, asthma biomarkers, such as blood Il-13 and sputum eosinophils, were also proposed to monitor disease state, with highly variable sensitivities (63–94%) and specificities (55–95%) ( 15 ).…”

Section: Resultsmentioning

confidence: 99%

Diagnostic Accuracy of Liquid Biomarkers in Airway Diseases: Toward Point-of-Care Applications

et al. 2022

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BackgroundLiquid biomarkers have shown increasing utility in the clinical management of airway diseases. Salivary and blood samples are particularly amenable to point-of-care (POC) testing due to simple specimen collection and processing. However, very few POC tests have successfully progressed to clinical application due to the uncertainty and unpredictability surrounding their diagnostic accuracy.ObjectiveTo review liquid biomarkers of airway diseases with well-established diagnostic accuracies and discuss their prospects for future POC applications.MethodologyA literature review of publications indexed in Medline or Embase was performed to evaluate the diagnostic accuracy of liquid biomarkers for chronic obstructive pulmonary disease (COPD), asthma, laryngopharyngeal reflux (LPR), and COVID-19.ResultsOf 3,628 studies, 71 fulfilled the inclusion criteria. Sputum and blood eosinophils were the most frequently investigated biomarkers for the management of asthma and COPD. Salivary pepsin was the only biomarker with a well-documented accuracy for the diagnosis of LPR. Inflammatory blood biomarkers (e.g., CRP, D-dimers, ferritin) were found to be useful to predict the severity, complications, and mortality related to COVID-19 infection.ConclusionMultiple liquid biomarkers have well-established diagnostic accuracies and are thus amenable to POC testing in clinical settings.

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Section: Resultsmentioning

confidence: 99%

Diagnostic Accuracy of Liquid Biomarkers in Airway Diseases: Toward Point-of-Care Applications

et al. 2022

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“…In a multivariate logistic regression analysis comparing findings in patients with controlled versus uncontrolled asthma, inclusion of FeNO levels at the first visit in the model significantly improved the prediction of asthma control (odds ratio [OR] 0.9459 (95% CI, 0.9024; 0.9915); p = 0.021). A cohort study of 170 patients with mild to moderate (72%) or severe (28%) asthma on ICS and/or other treatments found that sputum IL-13 was superior to both FeNO and sputum eosinophils with respect to predicting well-controlled asthma at 6 months [57]. Nevertheless, FeNO levels differed significantly between patients with well-controlled asthma (ACT ≥20) and those with uncontrolled asthma: median (interquartile range [IQR]) 21 (14-28) vs. 45 , p < 0.001.…”

Section: Loss Of Control In Adultsmentioning

confidence: 99%

Fractional exhaled nitric oxide as a determinant for the clinical course of asthma: a systematic review

Ulrik

Lange

Hilberg

2021

European Clinical Respiratory Journal

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Background: Precision medicine means linking the right patient to the right management strategy including best possible pharmacological therapy, considering the individual variability of the disease characteristics, type of inflammation, genes, environment, and lifestyle. For heterogenous diseases such as asthma, reliable biomarkers are needed to facilitate the best possible disease control and reduce the risk of side effects. The present review examines fractional exhaled nitric oxide (FeNO) as a guide for the management strategy of asthma and predictor of its clinical course. Method: The literature included was identified by searching the PubMed database using specific key words and MeSH terms. Studies were not excluded based on their design alone. The search resulted in 212 hits, of which 35 articles were included in this review. Results: Several studies support a potential role for high FeNO levels as a prognostic biomarker for accelerated lung function decline in adults with newly diagnosed asthma. Furthermore, studies report an association between high FeNO levels and excess decline in FEV 1 in adults with long-standing moderate to severe asthma despite optimised therapy, whereas the findings for patients with less severe disease are conflicting. Applying a FeNO-based management algorithm reduces the exacerbation rate in adults with asthma. Similar observations are seen in children, though based on fewer studies. The available studies provide evidence that the level of FeNO may be useful as a predictor of subsequent loss of asthma control in adults, though the evidence is somewhat conflicting in children and young adults. Conclusion: The present review provides evidence of the prognostic value of FeNO as a surrogate biomarker for type 2 inflammation in the airways. FeNO is likely to emerge as an important biomarker in monitoring and tailoring modern asthma treatment, either alone or in combination with other biomarkers.

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“…One such is interleukin (IL)-13 [ 6 ] that signals primarily through the type 2 IL-4 receptor (IL-4R; composed of IL-13Rα1 and IL-4Rα subunits [ 7 ]) and contributes to many key features of asthma, including mucus production, eosinophilic airway inflammation, immunoglobulin E synthesis, bronchial fibrosis, and airway hyper-responsiveness [ 8 ]. IL-13 is overexpressed in the sputum of patients with asthma, particularly those with severe disease [ 9 ], and was recently proposed as a biomarker for evaluating asthma control [ 10 ]. Elevated IL-13 levels in patients with uncontrolled asthma despite corticosteroid treatment also support the notion of a potential association between IL-13 and treatment resistance [ 9 ], implicating IL-13 signaling as a therapeutic target in severe asthma.…”

Section: Introductionmentioning

confidence: 99%

Randomized study of the safety and pharmacodynamics of inhaled interleukin-13 monoclonal antibody fragment VR942

et al. 2018

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Background Interleukin-13 (IL-13) is a key mediator of T-helper-cell-type-2 (Th-2)-driven asthma, the inhibition of which may improve treatment outcomes. We examined the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of VR942, a dry-powder formulation containing CDP7766, a high-affinity anti-human-IL-13 antigen-binding antibody fragment being developed for the treatment of asthma. Methods We conducted a phase 1, randomized, double-blind, placebo-controlled, ascending-dose study at Hammersmith Medicines Research, London, UK, which is now complete. Healthy adults aged 18–50 years (n = 40) were randomized 3:1 to a single inhaled dose of VR942 0.5, 1.0, 5.0, 10, or 20 mg, or placebo. Adults aged 18–50 years who were diagnosed with asthma for ≥6 months before screening, and had forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) values ≥70% of the predicted values at screening (n = 45), were randomized to once-daily inhaled VR942 0.5 or 10 mg, or placebo (2:2:1), or VR942 20 mg or placebo (3:2), for 10 days. All participants were randomized to receive VR942 or placebo based on a randomization list prepared by an independent HMR statistician using SAS® software ( , Cary, NC). The primary outcome was safety and tolerability of VR942 (safety population, defined as all who received at least one dose of VR942 or placebo). This study is listed on ClinicalTrials.gov (NCT02473939). Findings In the VR942 and placebo groups, treatment-emergent adverse events (TEAEs) were reported in 10/30 (33%) and 0/10 (0%) healthy participants, and in 16/29 (55%) and 9/16 (56%) participants with asthma, respectively. Mild intermittent wheezing occurred in 7 participants (VR942 20 mg, n = 4; corresponding placebo, n = 3), resolving spontaneously within 1 h. All TEAEs were mild or moderate; there were no deaths, serious adverse events, or clinically significant changes in vital signs, electrocardiograms, or laboratory parameters. There was no clinically significant immunogenicity, with only one participant with asthma considered positive for treatment-related immunogenicity for CDP7766. Interpretation This study, considered to be the only example of a dry powder anti-IL-13 fragment antibody being administered via inhalation, demonstrated that single and repeat doses were well tolerated over a period of up to 10 days in duration. Rapid and durable inhibition of fractional exhaled nitric oxide (FeNO) (secondary outcome) provided evidence of pharmacological engagement with the IL-13 target in the airways of participants diagnosed with mild asthma. These data, together with the numerical improvements observed for predose FEV 1 , justify further clinical evaluation of VR942 in a broader population of patients with asthma, and continue to support the development of an inhaled anti-IL-13 antibody fragment as a potential...

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Sputum interleukin‐13 as a biomarker for the evaluation of asthma control

Abstract: The diagnostic performance of sputum IL-13 was superior to both sputum eosinophils and FeNO levels for the identification of well-controlled asthma. Sputum IL-13 levels could serve as a useful biomarker for asthma control assessment.

Cited by 13 publications

References 30 publications

Diagnostic Accuracy of Liquid Biomarkers in Airway Diseases: Toward Point-of-Care Applications

Diagnostic Accuracy of Liquid Biomarkers in Airway Diseases: Toward Point-of-Care Applications

Fractional exhaled nitric oxide as a determinant for the clinical course of asthma: a systematic review

Randomized study of the safety and pharmacodynamics of inhaled interleukin-13 monoclonal antibody fragment VR942

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