Lung Obstruction in Adulthood of Prematurely Born (LUNAPRE)

Premature Birth- and BPD-related Obstructive Lung Disease Clinical Trial

— LUNAPRE  

Official title:

Lung Obstruction in Adulthood of Prematurely Born (LUNAPRE)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02923648
• Other study ID #: 2012/1872-31/4
• Status: Active, not recruiting
• Start date: March 1, 2013
• Est. completion date: December 2025

Study information

• Verified date: November 2022
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 96
• Est. completion date: December 2025
• Est. primary completion date: September 30, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 23 Years

Eligibility

Inclusion Criteria:

• Spirometry of postbronchodilator forced expiratory volume in 1 second (FEV1) >50% of predicted level for premature groups

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Lung Diseases
• Lung Diseases, Obstructive
• Premature Birth
• Premature Birth- and BPD-related Obstructive Lung Disease

Locations

Country	Name	City	State
Sweden	Karolinska Institutet/Karolinska University Hospital Solna	Stockholm	Sverige
Sweden	Stockholm Southern General Hospital	Stockholm

Sponsors (9)

Lead Sponsor	Collaborator
Karolinska Institutet	Göteborg University, Kyoto University, Region Stockholm, Stockholm South General Hospital, Swedish Heart Lung Foundation, The Swedish Research Council, University of California, San Francisco, University of Oulu

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

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. — View Citation

Um-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 — View Citation

Um-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;6 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 at baseline
Primary	Forced Vital Capacity (FVC) including reversibility		Measured at baseline
Primary	Impulse oscillometry		Measured at baseline
Primary	Airway hyper-reactivity (methacholine test)		Measured at baseline
Primary	Emphysema and airway wall thickness, as shown on low radiation chest CT scan		Measured at baseline
Secondary	COPD status (according to GOLD initiative standards as well as LLN)		Determined at baseline
Secondary	Molecular alterations due to BPD and/or premature birth persisting into adulthood		Determined at baseline
Secondary	Molecular gender differences		Determined at baseline