Increased sputum and bronchial biopsy IL-13 expression in severe asthma

Saha, S.; Berry, Michael A.; Parker, Debbie; Siddiqui, Salman; Morgan, Angela; May, Richard; Monk, Phillip; Bradding, Peter; Wardlaw, Andrew J.; Pavord, Ian D.; Brightling, Christopher E.

doi:10.1016/j.jaci.2008.01.005

Cited by 243 publications

(188 citation statements)

References 34 publications

Supporting

Mentioning

177

Contrasting

Unclassified

Order By: Relevance

“…Elevated IL-13 production has been detected in the airways and sputum of patients with asthma [7,8], and mast cell-derived IL-13 (as well as IL-4) has been demonstrated in airway smooth muscle of patients with asthma [5,9]. Animal model data show that IL-13 causes AHR, eosinophilic inflammation and mucus hypersecretion [6,[10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

An open‐label, single‐dose bioavailability study of the pharmacokinetics of CAT‐354 after subcutaneous and intravenous administration in healthy males

Oh¹,

Faggioni²,

Jin³

et al. 2010

Brit J Clinical Pharma

View full text Add to dashboard Cite

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The safety profile and effective dose of CAT-354 have been determined with intravenous (i.v.) administration, but no information is available on subcutaneous (s.c.) administration. WHAT THIS STUDY ADDS• This study characterized the pharmacokinetics of CAT-354 following s.c. administration of 150 mg and 300 mg doses, and indicated a bioavailability of approximately 60%. AIMTo assess the bioavailability and pharmacokinetics of CAT-354, an anti-IL-13 human monoclonal IgG4 antibody, following subcutaneous (s.c.) and intravenous (i.v.) administration. METHODSThis was a single-dose, randomized, open-label, parallel-group bioavailability study. Healthy male subjects aged 20-54 years were randomly assigned to one of three dose groups (n = 10/group) to receive CAT-354: 150 mg i.v.; 150 mg s.c. or 300 mg s.c. (two 150 mg injections). Serum pharmacokinetics, adverse events (AEs), vital signs, electrocardiograms and laboratory parameters were assessed. RESULTSCAT-354 showed bioavailability of 62% and 60% after 150 mg and 300 mg s.c. doses, respectively, and linear pharmacokinetics over the dose range tested. Peak serum concentrations in the s.c. groups occurred after 3-9 (median 5) days, with a mean elimination half-life of 19.2 Ϯ 3.1 days (150 mg) and 19.4 Ϯ 3.59 days (300 mg) after s.c. and 21.4 Ϯ 2.46 days after i.v. administration. Volume of distribution at steady state (Vss) was 4960 Ϯ 1440 ml kg -1 after i.v. (slightly greater than plasma volume). Average apparent clearances (CL/F) were 292 Ϯ 82.3 and 307 Ϯ 109 ml day -1 after 150 and 300 mg s.c., respectively; systemic CL of 188 Ϯ 84.0 ml day -1 after i.v. dosing was consistent with endogenous IgG and reticuloendothelial elimination. No severe or serious AEs occurred. Among 40 reported AEs, 25 were headache, sinus disorders/respiratory symptoms and changes in body temperature perception. CONCLUSIONSCAT-354 exhibited bioavailability of approximately 60% when given s.c. to healthy male subjects.

show abstract

Section: Introductionmentioning

confidence: 99%

An open‐label, single‐dose bioavailability study of the pharmacokinetics of CAT‐354 after subcutaneous and intravenous administration in healthy males

Oh¹,

Faggioni²,

Jin³

et al. 2010

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Interleukin-8 (IL-8) is a neutrophil chemoattractant which has been shown to be increased during asthma exacerbations [25] and in patients with severe persistent asthma [17], suggesting a role for monitoring asthma exacerbations and assessing the effectiveness of a medication in severe asthmatics. IL-13 is another cytokine whose levels were found higher in asthmatics than controls [26]. However it occurred in less than 50% of asthmatics and no correlation with asthma severity was found [26].…”

Section: Fluid-phase Mediatorsmentioning

confidence: 99%

“…IL-13 is another cytokine whose levels were found higher in asthmatics than controls [26]. However it occurred in less than 50% of asthmatics and no correlation with asthma severity was found [26].…”

Section: Fluid-phase Mediatorsmentioning

confidence: 99%

Markers of airway inflammation in pulmonary diseases assessed by induced sputum

Dragonieri

Tongoussouva

Zanini

et al. 2016

Monaldi Arch Chest Dis

View full text Add to dashboard Cite

During recent years there has been a growing interest in using non-invasive biomarkers to understand and monitor the airway inflammation in subjects with respiratory tract disorders. To date, the best validated and performing non-invasive biomarkers are measures of inflammation in induced sputum in both cellular and fluid phase, which can provide biological insights into the pathogenesis of respiratory diseases such as asthma and chronic obstructive pulmonary disease. The purpose of this review is to examine the principal literature on the different markers of inflammation in pulmonary diseases assessed by induced sputum analysis in either cellular or fluid phase.

show abstract

“…Serum levels are elevated in asthma, and this is thought to be a mechanism of steroid resistance [63]. One of the mechanisms by which IL-13 induces airway fibrosis and remodeling is by upregulating the secretion of periostin [64], which has been linked as a systemic biomarker specific for airway eosinophilia [65].…”

Section: Interleukin-13 (Il-13) Is a Pro-inflammatorymentioning

confidence: 99%

Emerging Biological Therapies in Severe Eosinophilic Asthma

2016

View full text Add to dashboard Cite

A small fraction of patients with asthma have severe, persistent disease that is often refractory to standard therapy. To meet this need, a growing emphasis has been placed on the development of alternative, novel therapies and the ability to characterize those patients who are most likely to benefit from these therapies. The eosinophil has been identified as a primary mediator in airway inflammation and as a potential pharmacological target. This narrative review outlines the need for more phenotype-directed therapies in severe asthma, and discusses the supporting evidence for monoclonal antibodies directed against key pro-eosinophilic T-helper 2 (Th2) inflammatory cytokines as additive agents in the treatment of severe asthma with an eosinophilic phenotype.

show abstract

Increased sputum and bronchial biopsy IL-13 expression in severe asthma

Abstract: Background-The importance of IL-13 in the asthma paradigm is supported by increased expression in human subjects, particularly in patients with mild-to-moderate asthma. However, the role of IL-13 in severe asthma needs to be further defined.

Cited by 243 publications

References 34 publications

An open‐label, single‐dose bioavailability study of the pharmacokinetics of CAT‐354 after subcutaneous and intravenous administration in healthy males

An open‐label, single‐dose bioavailability study of the pharmacokinetics of CAT‐354 after subcutaneous and intravenous administration in healthy males

Markers of airway inflammation in pulmonary diseases assessed by induced sputum

Emerging Biological Therapies in Severe Eosinophilic Asthma

Contact Info

Product

Resources

About