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      Proteomic profiling of peripheral blood neutrophils identifies two inflammatory phenotypes in stable COPD patients.

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          Abstract

          COPD is a heterogeneous chronic inflammatory disease of the airways and it is well accepted that the GOLD classification does not fully represent the complex clinical manifestations of COPD and this classification therefore is not well suited for phenotyping of individual patients with COPD. Besides the chronic inflammation in the lung compartment, there is also a systemic inflammation present in COPD patients. This systemic inflammation is associated with elevated levels of cytokines in the peripheral blood, but the precise composition is unknown. Therefore, differences in phenotype of peripheral blood neutrophils in vivo could be used as a read out for the overall systemic inflammation in COPD.

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          Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper

          B.R. Celli, W MacNee, A Agusti … (2004)
          Article 0 comments Cited 467 times – based on 0 reviews     Review now
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            Chronic obstructive pulmonary disease

            Marc DeCramer, Wim Janssens, Marc Miravitlles (2012)
            Summary Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.
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              Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays

              Wilco de Jager, Katarzyna Bourcier, Ger T. Rijkers … (2009)
              Background Growing knowledge about cellular interactions in the immune system, including the central role of cytokine networks, has lead to new treatments using monoclonal antibodies that block specific components of the immune system. Systemic cytokine concentrations can serve as surrogate outcome parameters of these interventions to study inflammatory pathways operative in patients in vivo. This is now possible due to novel technologies such as multiplex immunoassays (MIA) that allows detection of multiple cytokines in a single sample. However, apparently trivial underappreciated processes, (sample handling and storage, interference of endogenous plasma proteins) can greatly impact the reliability and reproducibility of cytokine detection. Therefore we set out to investigate several processes that might impact cytokine profiles such as blood collecting tubes, duration of storage, and number of freeze thawing cycles. Results Since under physiological conditions cytokine concentrations normally are low or undetectable we spiked cytokines in the various plasma and serum samples. Overall recoveries ranged between 80-120%. Long time storage showed cytokines are stable for a period up to 2 years of storage at -80°C. After 4 years several cytokines (IL-1α, IL-1β, IL-10, IL-15 and CXCL8) degraded up to 75% or less of baseline values. Furthermore we show that only 2 out of 15 cytokines remained stable after several freeze-thawing cycles. We also demonstrate implementation of an internal control for multiplex cytokine immunoassays. Conclusion All together we show parameters which are essential for measurement of cytokines in the context of clinical trials.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Respir. Res.
                Title: Respiratory research
                Publisher: Springer Nature
                ISSN (Electronic): 1465-993X
                ISSN (Print): 1465-9921
                Publication date (Electronic): May 22 2017
                Volume: 18
                Issue: 1
                Affiliations
                [1 ] Departments of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
                [2 ] Departments of Respiratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.
                [3 ] Departments of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. l.koenderman@umcutrecht.nl.
                [4 ] Department Respiratory Medicine and Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3583CX, Utrecht, The Netherlands. l.koenderman@umcutrecht.nl.
                Article
                Publisher Item ID: 10.1186/s12931-017-0586-x
                DOI: 10.1186/s12931-017-0586-x
                PMC ID: 5440930
                PubMed ID: 28532454
                SO-VID: 8bc943d4-136a-4ed5-a8f1-6667cc28abb3
                History

                Keywords: COPD,Inflammatory phenotype,Neutrophil,Proteomics profile,Systemic inflammation
                Data availability:
                Keywords: COPD, Inflammatory phenotype, Neutrophil, Proteomics profile, Systemic inflammation

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