Sputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis

Berry, Michael A.; Parker, Debbie; Neale, Natalie; Woodman, Lucy; Morgan, Angela; Monk, Phillip; Bradding, Peter; Wardlaw, Andrew J.; Pavord, Ian D.; Brightling, Christopher E.

doi:10.1016/j.jaci.2004.08.032

Cited by 146 publications

(114 citation statements)

References 20 publications

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“…Asthma is an eosinophilic inflammatory disease of the airways characterized by increased airway responsiveness to various stimuli, causing chronic inflammation and as a consequence airway remodeling (Juniper et al 2002). Unlike asthma, EB characteristically manifests as chronic cough and sputum eosinophilia without airflow limitation or airway hyperresponsiveness (Gibson et al 1989;Brightling et al 2003;Berry et al 2004). Likewise, the main pathophysiology of AR is nasal mucosal eosinophilic inflammation (Greiff et al 1999;Nielsen et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Expression Levels of Eosinophil Granule Protein mRNAs in Induced Sputum Reflect Airway Hyperresponsiveness and Airflow Limitation

Jung

Kang

Lee

et al. 2014

Tohoku J. Exp. Med.

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Eosinophils are regarded as the major effector cells that produce symptoms in allergic diseases. Activation of eosinophils induces extracellular release of a number of eosinophil granule proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophilderived neurotoxin. The objective of this study was to evaluate the differences and significance of the sputum eosinophil% and expression levels of eosinophilic granule protein mRNAs in allergic airway disease. Induced sputum samples were obtained from non-smokers with 25 asthma, 54 eosinophilic bronchitis, 16 allergic rhinitis, and 19 healthy control subjects. The eosinophil granule protein mRNAs were measured with real time RT-PCR. There was no correlation between the sputum eosinophil% and the mRNA level of any of eosinophil granule proteins. However, the expression levels of MBP and ECP mRNAs were higher in subjects with each of the specified allergic diseases than those in control subjects (P < 0.05). Moreover, in the subjects with allergic sensitization, the expression levels of MBP and EPO mRNAs were significantly higher in those with airway hyperresponsiveness (13 subjects) than in those without airway hyperresponsiveness (32 subjects) (P = 0.004 and 0.010, respectively). In asthma patients, the FEV1% was negatively correlated with ECP mRNA levels (r = −0.510, P = 0.022), but showed no correlation with sputum eosinophil%. In conclusion, mRNA levels of eosinophil granule proteins, rather than sputum eosinophil%, may reflect airway hyperresponsiveness and airflow limitation. In practice, consideration for the eosinophil% as well as the eosinophil granule proteins levels in induced sputum is needed.

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Section: Introductionmentioning

confidence: 99%

Expression Levels of Eosinophil Granule Protein mRNAs in Induced Sputum Reflect Airway Hyperresponsiveness and Airflow Limitation

Jung

Kang

Lee

et al. 2014

Tohoku J. Exp. Med.

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“…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

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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.

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“…Several research groups have investigated modified sputum processing techniques to optimize biomarker recovery [66][67][68]. However, these processing techniques are not fully validated and most of them prevented recovery of other mediators from the samples.…”

Section: Biomarkers In Fluid Phasementioning

confidence: 99%

Biomarkers in asthma and allergic rhinitis

Diamant

Boot

Mantzouranis

et al. 2010

Pulmonary Pharmacology & Therapeutics

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Sputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis

Cited by 146 publications

References 20 publications

Expression Levels of Eosinophil Granule Protein mRNAs in Induced Sputum Reflect Airway Hyperresponsiveness and Airflow Limitation

Expression Levels of Eosinophil Granule Protein mRNAs in Induced Sputum Reflect Airway Hyperresponsiveness and Airflow Limitation

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

Biomarkers in asthma and allergic rhinitis

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