Gene

Intensive care medicine

Biology

Cohort

Genetics

Pediatrics

Retrospective cohort study

Bronchopulmonary dysplasia

Gestational age

Internal medicine

Confidence interval

Odds ratio

Medicine

Lung disease

Disease

Lung

Pregnancy

Phenotype

Pathology

American Journal of Respiratory and Critical Care Medicine

Rationale: Bronchopulmonary dysplasia (BPD) is a heterogenous condition with poorly characterized disease subgroups.Objectives: To define the frequency of three disease components: moderate–severe parenchymal disease, pulmonary hypertension (PH), or large airway disease, in a referral cohort of preterm infants with severe BPD. The association between each component and a primary composite outcome of death before hospital discharge, tracheostomy, or home pulmonary vasodilator therapy was assessed.Methods: This was a retrospective, single-center cohort study of infants born at <32 weeks’ gestation with severe BPD who underwent both chest computed tomography with angiography (CTA) and echocardiography between 40 and 50 weeks postmenstrual age between 2011 and 2015. Moderate–severe parenchymal lung disease was defined as an Ochiai score ≥8 on CTA. PH was diagnosed by echocardiogram using standard criteria. Large airway disease was defined as tracheomalacia or bronchomalacia on bronchoscopy and/or tracheoscopy or CTA.Measurements and Main Results: Of 76 evaluated infants, 73 (96%) were classifiable into phenotypic subgroups: 57 with moderate–severe parenchymal disease, 48 with PH, and 44 with large airway disease. The presence of all three disease components was most common (n = 23). Individually, PH and large airway disease, but not moderate–severe parenchymal disease, were associated with increased risk for the primary study outcome. Having more disease components was associated with an incremental increase in the risk for the primary outcome (2 vs. 1: odds ratio, 4.9; 95% confidence interval, 1.4–17.2 and 3 vs. 1: odds ratio, 12.8; 95% confidence interval, 2.4–70.0).Conclusions: Infants with severe BPD are variable in their predominant pathophysiology. Disease phenotyping may enable better risk stratification and targeted therapeutic intervention.

Characterization of Disease Phenotype in Very Preterm Infants with Severe Bronchopulmonary Dysplasia