Lung Obstruction in Adulthood of Prematurely Born (LUNAPRE)

Overview

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.

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.