Clinical & Systems Medicine Investigations of Smoking-related Chronic Obstructive Pulmonary Disease

NCT02627872 | Active Not Recruiting

• 1 other identifier: 2006/959-31/1
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic Obstructive Pulmonary Disease (COPD) is an increasing global health problem, which primarily increases among the female population. The purpose of this study is to perform in-depth clinical and molecular characterizations of early stage COPD patients, as well as healthy never-smoker and at-risk smoking control populations to identify molecularly related subgroups patients, including gender-related sub-phenotypes of COPD.

Conditions

Chronic Obstructive Pulmonary Disease; Emphysema; Chronic Bronchitis; Chronic Airways Obstruction; Smoking

Outcome Measures

Primary Outcomes (5)

• Forced expiratory volume in 1 second (FEV1)

  Measured at baseline and up to 10 year follow-up

• Emphysema, as shown on chest CT scan

  Measured at baseline and up to 10 year follow-up

• Airway wall thickness on chest CT scan

  Measured at baseline and up to 10 year follow-up

• COPD status (COPD participants versus control group participants)

  Measured at baseline and up to 10 year follow-up

• Molecular gender differences

  Molecular levels investigated: mRNA, miRNA, proteome, metabolome, lipidome

  Measured at baseline

Study Arms (3)

COPD patients (GOLD I-II)

Participants with mild-to-moderate COPD (GOLD I-II)

Smoker Control Group

Actively smoking participants with normal lung function (do not have COPD)

Healthy Never-smoker Control Group

Healthy participants that never have smoked

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants from all groups are recruited from the general population through advertisements.

You may qualify if:

• For smokers, at least 10 pack-years of cigarette smoking
• For smokers, at least 10 cigarettes/day the past 6 months before study entry Spirometry that meets stage I-II of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (postbronchodilator forced expiratory volume in 1 second (FEV1) of 50%-100% of predicted level and FEV1/forced vital capacity \[FEV1/FVC\] less than 0.7) or normal (postbronchodilator FEV1 greater than 80% of predicted level and forced expiratory volume in 1 second/forced vital capacity \[FEV1/FVC\] greater than 0.7)

You may not qualify if:

• Other lung diseases
• Atopy (defined as positive specific IgE test)
• Asthma
• Received antibiotics for a COPD exacerbation in the 3 months prior to study entry
• Treatment with oral or inhaled glucocorticoids within past 3 months prior to study entry
• Significant ischaemic heart disease or arrhythmia

Sponsors & Collaborators

• Karolinska Institutet: lead
• University of California, San Francisco: collaborator
• Göteborg University: collaborator
• University of Bergen: collaborator
• University of Oulu: collaborator
• Kyoto University: collaborator
• Swedish Heart Lung Foundation: collaborator
• The Swedish Research Council: collaborator
• Region Stockholm: collaborator
• Vinnova: collaborator
• Swedish Foundation for Strategic Research: collaborator
• European Union: collaborator

Study Sites (1)

Karolinska Institutet/Karolinska University Hospital Solna

Stockholm, Sverige, 17176, Sweden

Location

Related Publications (17)

• Sandberg A, Skold CM, Grunewald J, Eklund A, Wheelock AM. Assessing recent smoking status by measuring exhaled carbon monoxide levels. PLoS One. 2011;6(12):e28864. doi: 10.1371/journal.pone.0028864. Epub 2011 Dec 16.

  PMID: 22194931 BACKGROUND

• Forsslund H, Mikko M, Karimi R, Grunewald J, Wheelock AM, Wahlstrom J, Skold CM. Distribution of T-cell subsets in BAL fluid of patients with mild to moderate COPD depends on current smoking status and not airway obstruction. Chest. 2014 Apr;145(4):711-722. doi: 10.1378/chest.13-0873.

  PMID: 24264182 RESULT

• Karimi R, Tornling G, Forsslund H, Mikko M, Wheelock A, Nyren S, Skold CM. Lung density on high resolution computer tomography (HRCT) reflects degree of inflammation in smokers. Respir Res. 2014 Feb 24;15(1):23. doi: 10.1186/1465-9921-15-23.

  PMID: 24564813 RESULT

• Kohler M, Sandberg A, Kjellqvist S, Thomas A, Karimi R, Nyren S, Eklund A, Thevis M, Skold CM, Wheelock AM. Gender differences in the bronchoalveolar lavage cell proteome of patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013 Mar;131(3):743-51. doi: 10.1016/j.jaci.2012.09.024. Epub 2012 Nov 10.

  PMID: 23146379 RESULT

• Mikko M, Forsslund H, Cui L, Grunewald J, Wheelock AM, Wahlstrom J, Skold CM. Increased intraepithelial (CD103+) CD8+ T cells in the airways of smokers with and without chronic obstructive pulmonary disease. Immunobiology. 2013 Feb;218(2):225-31. doi: 10.1016/j.imbio.2012.04.012. Epub 2012 May 4.

  PMID: 22652413 RESULT

• Balgoma D, Yang M, Sjodin M, Snowden S, Karimi R, Levanen B, Merikallio H, Kaarteenaho R, Palmberg L, Larsson K, Erle DJ, Dahlen SE, Dahlen B, Skold CM, Wheelock AM, Wheelock CE. Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD. Eur Respir J. 2016 Jun;47(6):1645-56. doi: 10.1183/13993003.01080-2015. Epub 2016 Mar 10.

  PMID: 26965288 RESULT

• Forsslund H, Yang M, Mikko M, Karimi R, Nyren S, Engvall B, Grunewald J, Merikallio H, Kaarteenaho R, Wahlstrom J, Wheelock AM, Skold CM. Gender differences in the T-cell profiles of the airways in COPD patients associated with clinical phenotypes. Int J Chron Obstruct Pulmon Dis. 2016 Dec 20;12:35-48. doi: 10.2147/COPD.S113625. eCollection 2017.

  PMID: 28053515 RESULT

• Karimi R, Tornling G, Forsslund H, Mikko M, Wheelock AM, Nyren S, Skold CM. Differences in regional air trapping in current smokers with normal spirometry. Eur Respir J. 2017 Jan 25;49(1):1600345. doi: 10.1183/13993003.00345-2016. Print 2017 Jan.

  PMID: 28122862 RESULT

• Naz S, Kolmert J, Yang M, Reinke SN, Kamleh MA, Snowden S, Heyder T, Levanen B, Erle DJ, Skold CM, Wheelock AM, Wheelock CE. Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD. Eur Respir J. 2017 Jun 22;49(6):1602322. doi: 10.1183/13993003.02322-2016. Print 2017 Jun.

  PMID: 28642310 RESULT

• Li CX, Wheelock CE, Skold CM, Wheelock AM. Integration of multi-omics datasets enables molecular classification of COPD. Eur Respir J. 2018 May 10;51(5):1701930. doi: 10.1183/13993003.01930-2017. Print 2018 May.

  PMID: 29545283 RESULT

• Naz S, Bhat M, Stahl S, Forsslund H, Skold CM, Wheelock AM, Wheelock CE. Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD. Metabolites. 2019 Oct 1;9(10):212. doi: 10.3390/metabo9100212.

  PMID: 31581603 RESULT

• Fuchs D, Hamberg M, Skold CM, Wheelock AM, Wheelock CE. An LC-MS/MS workflow to characterize 16 regio- and stereoisomeric trihydroxyoctadecenoic acids. J Lipid Res. 2018 Oct;59(10):2025-2033. doi: 10.1194/jlr.D087429. Epub 2018 Jul 31.

  PMID: 30065010 RESULT

• Che KF, Tufvesson E, Tengvall S, Lappi-Blanco E, Kaarteenaho R, Levanen B, Ekberg M, Brauner A, Wheelock AM, Bjermer L, Skold CM, Linden A. The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers. Clin Sci (Lond). 2018 May 20;132(9):959-983. doi: 10.1042/CS20180057. Print 2018 May 23.

  PMID: 29780024 RESULT

• Che KF, Kaarteenaho R, Lappi-Blanco E, Levanen B, Sun J, Wheelock A, Palmberg L, Skold CM, Linden A. Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines. Mol Med. 2017 Oct;23:247-257. doi: 10.2119/molmed.2016.00064. Epub 2017 Aug 29.

  PMID: 28853490 RESULT

• Merikallio H, Kaarteenaho R, Linden S, Padra M, Karimi R, Li CX, Lappi-Blanco E, Wheelock AM, Skold MC. Smoking-associated increase in mucins 1 and 4 in human airways. Respir Res. 2020 Sep 18;21(1):239. doi: 10.1186/s12931-020-01498-7.

  PMID: 32948202 RESULT

• Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, Grunewald J, Berven FS, Magnus Skold C, Wheelock AM. Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD. Respir Res. 2018 Mar 8;19(1):40. doi: 10.1186/s12931-017-0695-6.

  PMID: 29514648 RESULT

• Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, Grunewald J, Berven FS, Nyren S, Magnus Skold C, Wheelock AM. Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype. Respir Res. 2018 Mar 8;19(1):39. doi: 10.1186/s12931-017-0699-2.

  PMID: 29514663 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Bronchoalveolar lavage (BAL) cells, BAL fluid, bronchial biopsies, airway epithelial brushings, serum, plasma, and blood cells have been collected.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema; Bronchitis, Chronic; Smoking

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: December 11, 2015
• Study Start: March 1, 2007
• Primary Completion: December 1, 2021
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

SE (1)