Physiologic Pulmonary Phenotyping of Infants Born Preterm and Post-Discharge Respiratory Morbidity.

Objectives: To determine whether airway and parenchymal function identifies subgroups of infants born preterm according to the predominant pulmonary pathophysiology, and whether these subgroups have different risks for respiratory disease during infancy.

Study design: We prospectively enrolled a cohort of 125 infants born preterm with planned clinical follow-up after NICU discharge. The study included monthly questionnaires for wheeze and visits to a physician or care provider for any respiratory illness. In addition, infant lung function testing near 5-months corrected-age included measures of airways and parenchymal function using forced expiratory flows, alveolar volume (V_A), and the carbon monoxide transfer constant (D_L/V_A). Phenotypes were defined using two approaches: an a priori defined phenotypes based on FEF₇₅ and D_L/V_A z-scores, and an unbiased approach to classifying infants using k-means clustering. Results We identified four pulmonary physiologic phenotypes that distinguished participants with predominantly decreased airway and/or parenchymal function. Although the worst physiologic phenotypes were associated with a lower gestational age (GA) at birth, these phenotypes had a better predictive value than GA, sex, and diagnosis of BPD for increased respiratory morbidity during infancy (AUC = 0.71 vs 0.63 for respiratory illness and 0.69 vs 0.63 for wheeze).

Conclusions: Physiologic pulmonary phenotypes of infants born preterm were associated with differential risks for respiratory morbidities as infants, which may identify heterogeneous risks for long-term respiratory sequelae to individualize therapeutic strategies.