Mechanisms of Wheezing in BPD
Expiratory wheezing on physical exam is an audible manifestation of turbulent airflow through partially obstructed intrathoracic airways. In addition to virus-induced wheezing and asthma, other mechanisms can contribute to wheezing in preterm infants and children. Central airway collapse, such as tracheomalacia and bronchomalacia is common in preterm infants, especially those with severe BPD [2]. Sustained mechanical trauma to the small airways by long-term positive pressure ventilation has been presumed to be a major contributor to intermittent collapse and associated wheeze in BPD. However, despite a more recent trend toward less invasive respiratory support strategies in premature infants, measures of infant lung function have demonstrated the prevalence of lower airways obstruction has not changed over the last two decades [3]. An additional mechanism of diffuse airways collapse and wheeze in children with BPD may derive from the hallmark alveolar simplification and pulmonary hypoplasia seen in this disease process. Impaired alveolar development in BPD may result in loss of necessary airway tethering by the fibroelastic network of adjacent alveoli to maintain airway patency during exhalation [4]. Furthermore, both the airway epithelium and the surrounding smooth muscle of susceptible premature airways may become damaged by a complex inflammatory cascade triggered by two separate but related events: intermittent hypoxemia and sustained exposure to supplemental oxygen. During the very early newborn period some premature infants experience frequent episodes of hypoxemia, and the extent of these events has been shown to correlate with reports of wheezing and use of asthma medications two years later [5].Cellular and animal models suggest broad ranges of hyperoxia from supplemental oxygen administration during the postnatal period can result in significant airway smooth muscle proliferation as well as notable increase in methacholine-induced airway reactivity [6, 7]. Respiratory viral infections are the primary trigger for wheezing in term infants and children [8], and there is evidence that preterm birth or its treatment are associated with altered immune responses to viral infection [9-11].