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].