mRNA and miRNA Airway Inflammatory Markers

NCT03924843 | Completed

• 1 other identifier: NL 62038.042.17
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates cytokine Messenger (mRNA) and microRNA (miRNA) level expression of interleukin (IL) -6, IL-8, IL-17, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 beta and transforming growth factor (TGF)-beta regarding their reproducibility and responsivity in induced sputum and nasal mucosa of patients with chronic obstructive pulmonary disease (COPD) in order to assess their potential as a biomarker outcome measure.

Conditions

COPD; COPD Exacerbation

Outcome Measures

Primary Outcomes (2)

• Change of mRNA cytokine expression measured in induced sputum samples

  mRNA level expression of IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta

  Change of outcome measures will be assessed during one COPD exacerbation phase, after 42 days and after 44-51 days

• Change of miRNA and mRNA cytokine expression measured in nose mucosa samples

  mRNA and miRNA level expression of IL-6, IL-8, IL-17, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta

  Change of outcome measures will be assessed during one COPD exacerbation phase, after 42 days and after 44-51 days

Secondary Outcomes (1)

• Change of inflammatory cell profiles, LTB4 levels and protein cytokine levels measured in induced sputum samples

  Change of outcome measures will be assessed during one COPD exacerbation phase, after 42 days and after 44-51 days

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Twenty COPD patients with an initial COPD exacerbation will be followed for a period of seven weeks for three consecutive visits

You may qualify if:

• Men/Women age \>40 years.
• Diagnoses of COPD according to criteria of the American Thoracic Society (ATS), a disease state characterized by the presence of chronic airway obstruction due to chronic bronchitis (cough/sputum on most days a week for 3 months in a year for at least two successive years) and/or emphysema
• Diagnosis of moderate or severe COPD exacerbation (see "Definitions")
• FEV1 \> 0.8 L and ability to produce sputum after hypertonic saline production
• Post bronchodilator FEV1/Forced Vital Capacity (FVC) ratio \<70 % and post bronchodilator FEV1\< 80% pred.
• A smoking history of \>10 pack years

You may not qualify if:

• Pneumonia as determined by X-ray
• \> 48 h intake of prednisolon/antibiotics
• Need for mechanical ventilation (either invasive or non-invasive)
• Treatment with immune-modulating agents for any disease
• Experimental interventions for COPD last half year
• Former/concomitant diagnosis of asthma
• Any significant other pulmonary disease or disorder
• Other significant disease or disorder (like alpha-1-antitrypsine deficiency, significant bronchiectasis, cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic (including diagnosed diabetes), malignant, psychiatric, major physical impairment), which, in the opinion of the investigators may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient's ability to participate in the study.
• Existing pregnancy/ current willingness for becoming pregnant

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center; Department of Pulmonary Diseases

Groningen, Netherlands

Location

Related Publications (13)

• Bathoorn E, Liesker J, Postma D, Koeter G, van Oosterhout AJ, Kerstjens HA. Safety of sputum induction during exacerbations of COPD. Chest. 2007 Feb;131(2):432-8. doi: 10.1378/chest.06-2216.

  PMID: 17296644 BACKGROUND

• Brightling CE, Monterio W, Green RH, Parker D, Morgan MD, Wardlaw AJ, Pavord D. Induced sputum and other outcome measures in chronic obstructive pulmonary disease: safety and repeatability. Respir Med. 2001 Dec;95(12):999-1002. doi: 10.1053/rmed.2001.1195.

  PMID: 11778799 BACKGROUND

• Comer DM, Elborn JS, Ennis M. Comparison of nasal and bronchial epithelial cells obtained from patients with COPD. PLoS One. 2012;7(3):e32924. doi: 10.1371/journal.pone.0032924. Epub 2012 Mar 6.

  PMID: 22412951 BACKGROUND

• Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Pare PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004 Jun 24;350(26):2645-53. doi: 10.1056/NEJMoa032158.

  PMID: 15215480 BACKGROUND

• Huang CC, Wang CH, Fu CH, Huang CC, Chang PH, Chen YW, Wu CC, Wu PW, Lee TJ. Association between cigarette smoking and interleukin-17A expression in nasal tissues of patients with chronic rhinosinusitis and asthma. Medicine (Baltimore). 2016 Nov;95(47):e5432. doi: 10.1097/MD.0000000000005432.

  PMID: 27893686 BACKGROUND

• Kistemaker LE, Oenema TA, Meurs H, Gosens R. Regulation of airway inflammation and remodeling by muscarinic receptors: perspectives on anticholinergic therapy in asthma and COPD. Life Sci. 2012 Nov 27;91(21-22):1126-33. doi: 10.1016/j.lfs.2012.02.021. Epub 2012 Mar 3.

  PMID: 22406302 BACKGROUND

• O'Donnell RA, Peebles C, Ward JA, Daraker A, Angco G, Broberg P, Pierrou S, Lund J, Holgate ST, Davies DE, Delany DJ, Wilson SJ, Djukanovic R. Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD. Thorax. 2004 Oct;59(10):837-42. doi: 10.1136/thx.2003.019349.

  PMID: 15454648 BACKGROUND

• Perng DW, Tao CW, Su KC, Tsai CC, Liu LY, Lee YC. Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD. Eur Respir J. 2009 Apr;33(4):778-84. doi: 10.1183/09031936.00115308. Epub 2009 Jan 7.

  PMID: 19129278 BACKGROUND

• Powrie DJ, Wilkinson TM, Donaldson GC, Jones P, Scrine K, Viel K, Kesten S, Wedzicha JA. Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD. Eur Respir J. 2007 Sep;30(3):472-8. doi: 10.1183/09031936.00023907. Epub 2007 May 15.

  PMID: 17504798 BACKGROUND

• Rutgers SR, Postma DS, ten Hacken NH, Kauffman HF, van Der Mark TW, Koeter GH, Timens W. Ongoing airway inflammation in patients with COPD who Do not currently smoke. Chest. 2000 May;117(5 Suppl 1):262S. doi: 10.1378/chest.117.5_suppl_1.262s. No abstract available.

  PMID: 10843943 BACKGROUND

• Singh D, Edwards L, Tal-Singer R, Rennard S. Sputum neutrophils as a biomarker in COPD: findings from the ECLIPSE study. Respir Res. 2010 Jun 15;11(1):77. doi: 10.1186/1465-9921-11-77.

  PMID: 20550701 BACKGROUND

• Wessler I, Kirkpatrick CJ. Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. Br J Pharmacol. 2008 Aug;154(8):1558-71. doi: 10.1038/bjp.2008.185. Epub 2008 May 26.

  PMID: 18500366 BACKGROUND

• Zhang X, Sebastiani P, Liu G, Schembri F, Zhang X, Dumas YM, Langer EM, Alekseyev Y, O'Connor GT, Brooks DR, Lenburg ME, Spira A. Similarities and differences between smoking-related gene expression in nasal and bronchial epithelium. Physiol Genomics. 2010 Mar 3;41(1):1-8. doi: 10.1152/physiolgenomics.00167.2009. Epub 2009 Dec 1.

  PMID: 19952278 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Induced sputum samples; nasal mucosa samples Main study parameters: * mRNA level expression of IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta * miRNA level expression of IL-6, IL-8, IL-17, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta * inflammatory cell profiles, LTB4 and protein levels of IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta, ECP and TGF-beta

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor pulmonology; Head of department of Pulmonology and Tuberculosis; Principal Investigator

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: April 23, 2019
• Study Start: November 14, 2017
• Primary Completion: February 27, 2021
• Study Completion: March 30, 2021
• Last Updated: July 9, 2021

Record last verified: 2021-07

Locations

NL (1)