Bronchopulmonary dysplasia: infl ammation induced by exogenous factors and myeloid cells
PULMONOLOGY
Abstract
Inflammation in the immature lung, triggered by oxygen toxicity and the formation of reactive oxygen
species early on, is the primary cause of bronchopulmonary dysplasia in premature infants. Inflammation is
characterized by activation of the innate immune response, with migration of predominantly macrophages and
neutrophils and the release of proinflammatory cytokines. The degree of damage and disruption of subsequent lung
development determine the severity of bronchopulmonary dysplasia, which leads to limited lung function. Based on
observational studies of premature infants and experimental work in preclinical models, it has been demonstrated
that excessive stimulation of proinflammatory signaling pathways leads to lung injury, but at the same time, the
physiological activation of these pathways underlies physiological lung growth. This pathophysiological concept
explains why suppression of individual pathways leads to an imbalance in the complex signaling network in
the immature lung, with more severe inflammation and lung injury affecting the alveolar, mesenchymal, and
vascular compartments. Therefore, the number of available drugs with proven efficacy for the prevention of
bronchopulmonary dysplasia is currently limited. Evidence is accumulating that global suppression of the
inflammatory response with corticosteroids leads to more severe limitations in lung function later in life, despite its
high short-term effectiveness in improving gas exchange. Therefore, a detailed analysis of the immunophenotypes
of myeloid cells and their associated gene and immune signatures will be useful for understanding the cellular
and molecular genetic mechanisms of disease development and progression.
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