Premature Birth- and BPD-related Obstructive Lung DiseaseLUNAPRENCT02923648
Lung Obstruction in Adulthood of Prematurely Born (LUNAPRE)
An observational study of Premature Birth- and BPD-related Obstructive Lung Disease, run by Karolinska Institutet at 2 sites in Sweden.
Trial summary
Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population. Smoking is the main and most well studies risk factor for developing COPD. Read more about this study
- Who is it for?
- Ages 18 to 23 yearsHealthy volunteers can take part
- Conditions the study is for
- Premature Birth- and BPD-related Obstructive Lung Disease
- How many people
- 96 participants
- Where
- 2 sitesSweden
- Study dates
- 1 Mar 2013to Dec 2035
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 23 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Participants from the two prematurely born groups are recruited from cohort sfollowed since birth at Sach's Children's Hospital, Stockholm. Participants in the full term born groups are recruited from the general population through advertisements.
Who may be able to join
- Spirometry of postbronchodilator forced expiratory volume in 1 second (FEV1) >50% of predicted level for premature groups
Who cannot join
- Smoking
- Other lung diseases
- Received antibiotics in the 3 months prior to study entry
- Treatment with oral or inhaled glucocorticoids within past 3 months prior to study entry
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Karolinska Institutet/Karolinska University Hospital Solna
Stockholm, Sverige, 17176
Stockholm Southern General Hospital
Stockholm
About this study
Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population. Smoking is the main and most well studies risk factor for developing COPD. However, chronic airway obstruction also in never-smoking populations has recently been recognized as an increasing health problem. Prematurely born children, particularly survivors of bronchopulmonary dysplasia (BPD), defined as the need for oxygen therapy up to the 28th day of life for children born prior to gestational week 32, have an increased incidence of both airway obstruction and hyper-reactivity, both representing major risk factors for developing COPD, or asthma, later in life. The purpose of this study is to perform in-depth clinical and molecular characterizations of of the lungs of survivors of BPD as they enter adulthood, and compare these profiles to relevant control groups (individuals with mild asthma, healthy prematurely born, and healthy individuals born at full term). Specifically, alterations at the epigenetic, mRNA, microRNA, protein and metabolite level as well as associated molecular pathways critical in the pathological mechanisms of obstructive lung disease related to premature birth and BPD will be identified.
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. Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population, and predicted by WHO to become the 5th leading cause of morbidity and disability worldwide by year 2020. Smoking is the main and most well studies risk factor for developing COPD. However, chronic airway obstruction also in never-smoking populations has recently been recognized as an increasing health problem: An estimated 10% of patient diagnosed with COPD have never smoked, representing 1% of the general public. Low birth weight and premature birth represent important risk factors for developing pulmonary obstruction in adulthood. Particularly prematurely born children with bronchopulmonary dysplasia (BPD), defined as the need for oxygen therapy up to the 28th day of life for children born prior to gestational week 32, have an increased incidence of both airway obstruction and hyper-reactivity, both representing major risk factors for developing COPD, or asthma, later in life. The purpose of the LUNAPRE study is to perform in-depth clinical and molecular characterizations of of the lungs of survivors of BPD as they enter adulthood, and compare these profiles to relevant control groups. The study encompasses profiling of epigenetic alterations, mRNA, miRNA, proteomes, metabolomes and lipid mediators 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 very prematurely born subjects with- and without BPD in the neonatal period as they enter adulthood, as well as healthy subjects with mild asthma born at term. The primary objective of the study is to identify molecular alterations that persist into adulthood that are related to early onset obstructive lung disease, specifically by correlating clinical phenotypes with multi-molecular 'omics profiling from several lung compartments of the study groups. Secondary goals involve identification of subsets of prognostic/diagnostic biomarkers for classification of the defined subgroups, as well as relevant pharmaceutical targets.
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Very/extremely prematurely born with BPD | Very/extremely prematurely born (gestational age [GA]< 32 weeks) with bronchopulmonary dysplasia (BPD) as defined by Jobe and Bancalari 2001, age 18-23 years | |
| Very/extremely prematurely born without BPD | Very/extremely prematurely born (GA< 32 weeks) without BPD in the neonatal period, age 18-23 years | |
| Asthma full-term control group | Subjects with mild atopic asthma, born at term (GA> 37 weeks), age 18-23 years | |
| Healthy full-term control group | Healthy participants, born at term (GA>37 weeks), age 18-23 years |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forced expiratory volume in 1 second (FEV1) including reversibilityForced expiratory volume in 1 second (FEV1) including reversibilityForced expiratory volume in 1 second (FEV1) including reversibility
Measured: Measured at baseline
Forced Vital Capacity (FVC) including reversibility
Measured: Measured at baseline
Impulse oscillometry
Measured: Measured at baseline
Airway hyper-reactivity (methacholine test)
Measured: Measured at baseline
Emphysema and airway wall thickness, as shown on low radiation chest CT scan
Measured: Measured at baseline
Secondary outcomes (3)
COPD status (according to GOLD initiative standards as well as LLN)
Measured: Determined at baseline
Molecular alterations due to BPD and/or premature birth persisting into adulthood
Measured: Determined at baseline
Molecular gender differences
Measured: Determined at baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2016 (estimated)
- Study start1 Mar 2013
- Primary completion30 Sep 2016
- Study completionDec 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Premature Birth- and BPD-related Obstructive Lung DiseaseStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Swedish Heart Lung Foundation, The Swedish Research Council, Region Stockholm, Stockholm South General Hospital, University of California, San Francisco, Kyoto University, Göteborg University, University of Oulu
- Responsible party
- Principal investigator, Asa Wheelock, Karolinska Institutet
- Investigators
- Magnus Skold, MD, PhD, Principal investigator, Karolinska Institute, Karolinska University HospitalAsa M Wheelock, PhD, Principal investigator, Karolinska InstitutetErik Melén, MD, PhD, Principal investigator, Karolinska Institute, Stockholm Southern General HospitalEva Berggren-Brostrom, MD, PhD, Principal investigator, Stockholm Southern General HospitalAnders Lindén, MD, PhD, Principal investigator, Karolinska Institute, Karolinska University HospitalSven Nyrén, MD, PhD, Principal investigator, Karolinska Institute, Karolinska University HospitalCraig E Wheelock, PhD, Principal investigator, Karolinska InstitutetMaria J Eriksson, MD, PhD, Principal investigator, Karolinska Institute, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02923648
- Sponsor's protocol ID
- 2012/1872-31/4
- Acronym
- LUNAPRE
- Status last verified
- Apr 2025
- First submitted
- 3 Oct 2016
- Last updated
- 4 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Brostrom EB, Thunqvist P, Adenfelt G, Borling E, Katz-Salamon M. Obstructive lung disease in children with mild to severe BPD. Respir Med. 2010 Mar;104(3):362-70. doi: 10.1016/j.rmed.2009.10.008. Epub 2009 Nov 10.
PubMed 19906521Um-Bergstrom P, Hallberg J, Pourbazargan M, Berggren-Brostrom E, Ferrara G, Eriksson MJ, Nyren S, Gao J, Lilja G, Linden A, Wheelock AM, Melen E, Skold CM. Pulmonary outcomes in adults with a history of Bronchopulmonary Dysplasia differ from patients with asthma. Respir Res. 2019 May 24;20(1):102. doi: 10.1186/s12931-019-1075-1.
PubMed 31126291Um-Bergstrom P, Pourbazargan M, Brundin B, Strom M, Ezerskyte M, Gao J, Berggren Brostrom E, Melen E, Wheelock AM, Linden A, Skold CM. Increased cytotoxic T-cells in the airways of adults with former bronchopulmonary dysplasia. Eur Respir J. 2022 Sep 29;60(3):2102531. doi: 10.1183/13993003.02531-2021. Print 2022 Sep.
PubMed 35210327
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung Obstruction in Adulthood of Prematurely Born (LUNAPRE)
- ClinicalTrials.gov ID
- NCT02923648
- Acronym / sponsor ID
- LUNAPRE / 2012/1872-31/4
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Swedish Heart Lung Foundation, The Swedish Research Council, Region Stockholm, Stockholm South General Hospital, University of California, San Francisco, Kyoto University, Göteborg University, University of Oulu
- Study start
- 1 Mar 2013 (actual)
- Primary completion
- 30 Sep 2016 (actual)
- Study completion
- Dec 2035 (estimated)
- First posted
- 4 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population. Smoking is the main and most well studies risk factor for developing COPD. However, chronic airway obstruction also in never-smoking populations has recently been recognized as an increasing health problem. Prematurely born children, particularly survivors of bronchopulmonary dysplasia (BPD), defined as the need for oxygen therapy up to the 28th day of life for children born prior to gestational week 32, have an increased incidence of both airway obstruction and hyper-reactivity, both representing major risk factors for developing COPD, or asthma, later in life. The purpose of this study is to perform in-depth clinical and molecular characterizations of of the lungs of survivors of BPD as they enter adulthood, and compare these profiles to relevant control groups (individuals with mild asthma, healthy prematurely born, and healthy individuals born at full term). Specifically, alterations at the epigenetic, mRNA, microRNA, protein and metabolite level as well as associated molecular pathways critical in the pathological mechanisms of obstructive lung disease related to premature birth and BPD will be identified.
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. Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population, and predicted by WHO to become the 5th leading cause of morbidity and disability worldwide by year 2020. Smoking is the main and most well studies risk factor for developing COPD. However, chronic airway obstruction also in never-smoking populations has recently been recognized as an increasing health problem: An estimated 10% of patient diagnosed with COPD have never smoked, representing 1% of the general public. Low birth weight and premature birth represent important risk factors for developing pulmonary obstruction in adulthood. Particularly prematurely born children with bronchopulmonary dysplasia (BPD), defined as the need for oxygen therapy up to the 28th day of life for children born prior to gestational week 32, have an increased incidence of both airway obstruction and hyper-reactivity, both representing major risk factors for developing COPD, or asthma, later in life. The purpose of the LUNAPRE study is to perform in-depth clinical and molecular characterizations of of the lungs of survivors of BPD as they enter adulthood, and compare these profiles to relevant control groups. The study encompasses profiling of epigenetic alterations, mRNA, miRNA, proteomes, metabolomes and lipid mediators 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 very prematurely born subjects with- and without BPD in the neonatal period as they enter adulthood, as well as healthy subjects with mild asthma born at term. The primary objective of the study is to identify molecular alterations that persist into adulthood that are related to early onset obstructive lung disease, specifically by correlating clinical phenotypes with multi-molecular 'omics profiling from several lung compartments of the study groups. Secondary goals involve identification of subsets of prognostic/diagnostic biomarkers for classification of the defined subgroups, as well as relevant pharmaceutical targets.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Very/extremely prematurely born with BPD | – | –Very/extremely prematurely born (gestational age [GA]< 32 weeks) with bronchopulmonary dysplasia (BPD) as defined by Jobe and Bancalari 2001, age 18-23 years |
| Very/extremely prematurely born without BPD | – | –Very/extremely prematurely born (GA< 32 weeks) without BPD in the neonatal period, age 18-23 years |
| Asthma full-term control group | – | –Subjects with mild atopic asthma, born at term (GA> 37 weeks), age 18-23 years |
| Healthy full-term control group | – | –Healthy participants, born at term (GA>37 weeks), age 18-23 years |
Who may qualify
- Ages
- 18 to 23 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Participants from the two prematurely born groups are recruited from cohort sfollowed since birth at Sach's Children's Hospital, Stockholm. Participants in the full term born groups are recruited from the general population through advertisements.
Key inclusion criteria (1 listed)
- Spirometry of postbronchodilator forced expiratory volume in 1 second (FEV1) >50% of predicted level for premature groups
Key exclusion criteria (4 listed)
- Smoking
- Other lung diseases
- Received antibiotics in the 3 months prior to study entry
- Treatment with oral or inhaled glucocorticoids within past 3 months prior to study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Forced expiratory volume in 1 second (FEV1) including reversibilityForced expiratory volume in 1 second (FEV1) including reversibilityForced expiratory volume in 1 second (FEV1) including reversibility
Time frame: Measured at baseline
Forced Vital Capacity (FVC) including reversibility
Time frame: Measured at baseline
Impulse oscillometry
Time frame: Measured at baseline
Airway hyper-reactivity (methacholine test)
Time frame: Measured at baseline
Emphysema and airway wall thickness, as shown on low radiation chest CT scan
Time frame: Measured at baseline
3 secondary outcomes
COPD status (according to GOLD initiative standards as well as LLN)
Time frame: Determined at baseline
Molecular alterations due to BPD and/or premature birth persisting into adulthood
Time frame: Determined at baseline
Molecular gender differences
Time frame: Determined at baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
- Background: PubMed 19906521Brostrom EB, Thunqvist P, Adenfelt G, Borling E, Katz-Salamon M. Obstructive lung disease in children with mild to severe BPD. Respir Med. 2010 Mar;104(3):362-70. doi: 10.1016/j.rmed.2009.10.008. Epub 2009 Nov 10.
- Results publication: PubMed 31126291Um-Bergstrom P, Hallberg J, Pourbazargan M, Berggren-Brostrom E, Ferrara G, Eriksson MJ, Nyren S, Gao J, Lilja G, Linden A, Wheelock AM, Melen E, Skold CM. Pulmonary outcomes in adults with a history of Bronchopulmonary Dysplasia differ from patients with asthma. Respir Res. 2019 May 24;20(1):102. doi: 10.1186/s12931-019-1075-1.
- Results publication: PubMed 35210327Um-Bergstrom P, Pourbazargan M, Brundin B, Strom M, Ezerskyte M, Gao J, Berggren Brostrom E, Melen E, Wheelock AM, Linden A, Skold CM. Increased cytotoxic T-cells in the airways of adults with former bronchopulmonary dysplasia. Eur Respir J. 2022 Sep 29;60(3):2102531. doi: 10.1183/13993003.02531-2021. Print 2022 Sep.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Magnus Skold, MD, PhD principal investigator
Karolinska Institute, Karolinska University Hospital
Asa M Wheelock, PhD principal investigator
Karolinska Institutet
Erik Melén, MD, PhD principal investigator
Karolinska Institute, Stockholm Southern General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Premature Birth- and BPD-related Obstructive Lung Disease, run by Karolinska Institutet at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forced expiratory volume in 1 second (FEV1) including reversibilityForced expiratory volume in 1 second (FEV1) including reversibilityForced expiratory volume in 1 second (FEV1) including reversibility (time frame: Measured at baseline). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02923648, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2025.