DISCUSSION
This study explores several early predictors of pulmonary function via
spirometry at six years of age in a group of premature patients with
bronchopulmonary dysplasia. Following initial hospital discharge, we
found that both the need for supplemental oxygen and the presence of a
Nissen fundoplication was associated with lower FVC% predicted at six
years of age. At two years of age, lower median household income and
higher weight percentile, but not height percentile, were associated
with lower FEV1% predicted at six years of age. This
study demonstrates that several factors at hospital discharge and at 2
years of age are associated with lung function at 6 years of age. This
difference could be attributed to reduced lung growth rates, early-onset
or faster decline in lung function, or a combination of both factors.
The traditional model of lung growth and development suggests that lung
growth begins in utero and continues through early adulthood,
with maximal FEV1 and FVC values occurring around
twenty-five years of age followed by a slow decline throughout the
remaining lifespan18. For individuals born premature
as with term infants, postnatal alveolar “catch up” growth is thought
to occur most rapidly in the first two years of life, around the time
when most children with bronchopulmonary dysplasia are able to wean from
supplemental oxygen13. For healthy term individuals
who do not smoke and avoid other sources of lung damage, normal decline
in lung function occurs with age but seldom is associated with
significant morbidity or disability. Our data supports previous studies
that have reported lower lung function in select groups of individuals,
including those with a history of prematurity19-20.
Indeed, a study from Bui et al. 20, found that
individuals with lower lung function in childhood continued to have
lower lung function during adult life. While our results cannot comment
on the potential for continued accelerated lung function decline in
preterm children with BPD, our findings do suggest that these children
are at an increased risk for not achieving optimal peak lung function
values in their twenties. This highlights the importance of close
pulmonary monitoring and follow-up for preterm patients and especially
those with bronchopulmonary dysplasia throughout childhood and into
adulthood.
Our data also found that airflow obstruction, represented by a reduced
FEV1% predicted, was associated with a lower median
household income. This finding suggests that children born into lower
income households are more likely to have airflow obstruction, similar
to an asthma phenotype. This could be attributed to an increase in
environmental allergen exposures, potential second-hand smoke exposure,
and a more crowded living environment, factors that can adversely affect
lung function, particularly in children born premature. Exposure to such
environmental insults has been suggested to complicate, and potentially
prolong, the resolution of bronchopulmonary dysplasia and prolong risks
of pulmonary morbidity21-22. Additionally, non-white
ethnicity was associated with an increased use of public insurance (p
< 0.0001) and lower median household income (p <
0.0001), surrogate markers of lower socioeconomic status, suggesting
that non-white children with BPD may be disproportionately at risk for
lower lung function in part due to their lower socioeconomic status. The
presence of a Nissen fundoplication at initial hospital discharge was
also associated with a lower FEV1% predicted at six
years of age. The presence of a Nissen could be a marker for infants
with previous swallowing difficulties and microaspiration events; both
comorbidities that can exacerbate lung damage and interfere with lung
injury repair during a critical period of lung growth.
A diminished lung volume or capacity, represented by decreased FVC%
predicted, was associated with an increase in the amount of supplemental
oxygen required at discharge from the NICU. The need for higher
supplemental oxygen at initial hospital discharge likely represents that
these children had more severe lung injury than those requiring less or
no supplemental oxygen. Interestingly, the severity of BPD, as defined
by supplemental oxygen requirement at 36 weeks post-menstrual age did
not correlate with lung function values at six years of age, indicating
that the need for supplemental oxygen or respiratory support at time of
discharge is more predictive of lung function at six years of life.
Alternatively, children discharged on supplemental oxygen may be more
susceptible to post-NICU home environmental exposures, thus preventing
adequate postnatal lung catch-up growth. Furthermore, exposure to a
higher fraction of inspired oxygen (FiO2) in children
with BPD may impair alveolar growth during a rapid period of
alveologenesis that occurs during the first two years of
life13,23. In addition to lower FEV1%
predicted, the presence of a Nissen fundoplication (NF) also predicted a
decreased FVC% predicted.
Interestingly, a lower weight percentile for age at two years of age was
associated with an improved FEV1% predicted and an
improved FVC% predicted. While childhood obesity has been associated
with a decrease in all lung function parameters24, it
may not be the etiology of the observed association given the lack of
significance of body mass index, a better indicator of obesity in the
pediatric population.
Limitations :
This study was limited by the use of an already recruited study
population and clinical information obtained primarily via chart review,
some of which may have been missing. Additionally, it was limited by its
relatively low sample size (n=88) due to multiple patients who were lost
to follow-up prior to age six. While there was initially concern that
the study population could be skewed towards a ‘healthier’ subset of the
registry population given that it includes only patients who are capable
of performing pulmonary function testing, the argument was also made
that the study population may have captured a ‘more affected’ population
who are still being seen in follow-up in a Pediatric Pulmonary Clinic
later in childhood. Overall, the study population does not significantly
differ from the registry population on any of the factors included in
the analysis (Supplemental Table 1 ).
There are several other factors that may influence lung function,
especially in survivors of preterm birth, that were not accounted for in
this study due to its retrospective design including frequent
respiratory infections in early childhood which can result in airway
inflammation and additional injury in an already compromised lung and
other potential damaging environmental insults including exposure to
cigarette smoke in-utero, etc.