Clinical trial NCT02923648: Lung Obstruction in Adulthood of Prematurely Born (LUNAPRE)
Official title: Lung Obstruction in Adulthood of Prematurely Born (LUNAPRE)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Premature Birth- and BPD-related Obstructive Lung Disease
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Swedish Heart Lung Foundation
name: The Swedish Research Council
name: Region Stockholm
name: Stockholm South General Hospital
name: University of California, San Francisco
name: Kyoto University
name: Göteborg University
name: University of Oulu
First posted: 2016-10-04
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 23
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
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
timeFrame: Measured at baseline
measure: Forced Vital Capacity (FVC) including reversibility
timeFrame: Measured at baseline
measure: Impulse oscillometry
timeFrame: Measured at baseline
measure: Airway hyper-reactivity (methacholine test)
timeFrame: Measured at baseline
measure: Emphysema and airway wall thickness, as shown on low radiation chest CT scan
timeFrame: Measured at baseline
Secondary outcomes:
measure: COPD status (according to GOLD initiative standards as well as LLN)
timeFrame: Determined at baseline
measure: Molecular alterations due to BPD and/or premature birth persisting into adulthood
timeFrame: Determined at baseline
measure: Molecular gender differences
timeFrame: Determined at baseline
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska Institutet/Karolinska University Hospital Solna
state: Sverige
city: Stockholm
country: Sweden
facility: Stockholm Southern General Hospital
Study officials:
affiliation: Karolinska Institute, Karolinska University Hospital
name: Magnus Skold, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Asa M Wheelock, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institute, Stockholm Southern General Hospital
name: Erik Melén, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stockholm Southern General Hospital
name: Eva Berggren-Brostrom, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institute, Karolinska University Hospital
name: Anders Lindén, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institute, Karolinska University Hospital
name: Sven Nyrén, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Craig E Wheelock, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institute, Karolinska University Hospital
name: Maria J Eriksson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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 asthma. Respir Res. 2019 May 24;20(1):102. doi: 10.1186/s12931-019-1075-1.
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;60(3):2102531. doi: 10.1183/13993003.02531-2021. Print 2022 Sep.