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Active, not recruitingNCT02627872COSMICUpdated Mar 28, 2025

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

An observational study in Chronic Obstructive Pulmonary Disease, Emphysema and Chronic Bronchitis, sponsored by Karolinska Institutet. Active, not recruiting at 1 site in Sweden. Open to participants aged 45 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-03-28.

Sponsored by Karolinska Institutet · Observational

Study type
Observational
Model
Cohort
Time perspective
Cross-sectional
Enrollment
120
Ages
45 Years to 65 Years
Sex
All
01

Study 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.

Read the detailed description

Chronic Obstructive Pulmonary Disease (COPD) is an umbrella diagnosis defined by obstructive lung function impairments, and is likely to be caused by a multitude of etiologies including environmental exposures, genetic predispositions and developmental factors. Due to the heterogeneity of the disease, molecular and mechanistic sub-phenotyping of COPD represents an essential step to facilitate the development of relevant diagnostic and treatment options for this constantly growing patient group. In the Karolinska COSMIC study, the investigators are investigating molecular sub-phenotypes of smoking-induced COPD. A particular focus relates to recent epidemiological indications of gender differences in both incidence and severity of disease, with post-menopausal women being at greatest risk. The study encompasses profiling of mRNA, miRNA, proteomes, metabolomes and lipid mediators of from multiple lung compartments (airway epithelium, alveolar macrophages, exosomes, and bronchoalveolar exudates) using a range of 'omics platforms, in combination with extensive clinical phenotyping of early stage COPD patients, never-smokers, and smokers with normal lung function from both genders. The primary objective of the study is to identify molecular sub-phenotypes of patients with COPD, specifically by correlating clinical phenotypes multi-molecular 'omics profiling from multiple lung compartments of early stage COPD patients compared to healthy and at-risk control populations. Secondary goals involve identification of subsets of prognostic/diagnostic biomarkers for classification of the defined subgroups, as well as relevant pharmaceutical targets.

02

Conditions studied

  • Chronic Obstructive Pulmonary Disease
  • Emphysema
  • Chronic Bronchitis
  • Chronic Airways Obstruction
  • Smoking
03

Who can participate

Ages eligible
45 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

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

Inclusion criteria

  • 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)

Exclusion criteria

Exclusion Criteria:

  • 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
04

Study design

Observational model
Cohort
Time perspective
Cross-sectional
Enrollment
120 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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

05

What researchers measure

Primary outcomes

  1. Forced expiratory volume in 1 second (FEV1)

    Time frame: Measured at baseline and up to 10 year follow-up

  2. Emphysema, as shown on chest CT scan

    Time frame: Measured at baseline and up to 10 year follow-up

  3. Airway wall thickness on chest CT scan

    Time frame: Measured at baseline and up to 10 year follow-up

  4. COPD status (COPD participants versus control group participants)

    Time frame: Measured at baseline and up to 10 year follow-up

  5. Molecular gender differences

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

    Time frame: Measured at baseline

06

Study locations

1 site
  • Karolinska Institutet/Karolinska University Hospital Solna
    Stockholm, Sverige 17176, Sweden
07

References and documents

Publications

  • 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. PubMed 22194931 ↗
  • 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. PubMed 24264182 ↗
  • 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. PubMed 24564813 ↗
  • 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. PubMed 23146379 ↗
  • 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. PubMed 22652413 ↗
  • 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. PubMed 26965288 ↗
  • 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. PubMed 28053515 ↗
  • 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. PubMed 28122862 ↗
  • 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. PubMed 28642310 ↗
  • 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. PubMed 29545283 ↗
  • 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. PubMed 31581603 ↗
  • 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. PubMed 30065010 ↗
  • 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. PubMed 29780024 ↗
  • 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. PubMed 28853490 ↗
  • 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. PubMed 32948202 ↗
  • 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. PubMed 29514648 ↗
  • 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. PubMed 29514663 ↗

Individual participant data

Plan to share: Yes — The deidentified clinical phenotype data has been disseminated through peer reviewed publication

08

Registry details

Key details

Study ID
NCT02627872
Lead sponsor
Karolinska Institutet
Collaborators
University of California, San Francisco, Göteborg University, University of Bergen, University of Oulu, Kyoto University, Swedish Heart Lung Foundation, The Swedish Research Council, Region Stockholm, Vinnova, Swedish Foundation for Strategic Research, European Union
Responsible party
Asa Wheelock (Associate professor, Karolinska Institutet) — Principal investigator
First posted
Dec 11, 2015
Start date
Mar 2007
Primary completion
Dec 2021
Completion
Dec 2030 (estimated)
Last update
Mar 28, 2025

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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