DISCUSSION
To our knowledge, this is the first study to evaluate LCI in the
childhood sickle cell population. In this study, LCI did not
differentiate SCD from healthy controls in children between the ages of
6 and 18 years of age at baseline health. Furthermore, we saw no
cross-sectional differences in LCI with increasing age. Additionally,
neither a history of asthma nor ACS was associated with a significantly
higher LCI among the SCD participants compared to healthy controls.
There was a high correlation between
FEV1, FVC, RV and TLC with LCI amongst
all subjects, although some of these associations lose statistical
significance when looking at only the sickle cell group likely due to
small sample size.
In the SCD only group, the only significant association with LCI was
TLC. There was no correlation between LCI values and past episodes of
ACS or diagnosis of asthma in our study. TLC was significantly higher in
healthy controls compared to SCD subjects and was highly correlated with
LCI in the SCD group only. This may suggest that TLC is a much more
sensitive measure of early lung disease in the adolescent group (ages
13-18yrs) before any obvious obstructive or restrictive patterns emerge.
Future studies focusing on plethysmography may bring better
understanding to the potential use of LCI for detecting lung disease in
this population.
Our data support previous studies33,34that have reported decreased baseline oxygen saturation in the SCD
population. In children between the ages of 13 and 18 years of age, TLC
and FEV1 were significantly higher in the healthy
subjects compared to those with SCD. This would further support existing
literature that lung disease in sickle cell patients worsens over time,
and that identifying an early screening technique to differentiate the
higher risk SCD populations before they have recurrent ACS and recurrent
VOC is critical.
Three (9%) of our patients demonstrated an obstructive disease pattern
on spirometry and only 1 (3) % had a mixed obstructive/restrictive
disease pattern. This is similar to previous
studies35 with the
majority of SCD patients having normal lung function or some type of
mixed picture. The number of SCD patients with asthma based on physician
diagnosis was 19 (56%). There was likely some recruitment bias as
subjects who were approached for the study and agreed to participate
were often patients seen in Pediatric Pulmonology clinic. LDH values
differed significantly with a mean of 447 in the “asthma” group versus
306 in the “no asthma” group. These values may reflect treatment and
adherence to hydroxyurea. Our data revealed that 80% of the SCD
“asthma” group verbalized having hydroxyurea as a current prescription
medication versus 6 % in the “no asthma” group. This was not part of
our aims or hypotheses but interesting for future research into
potential protective effects of hydroxyurea in SCD patients with
pulmonary diagnoses other than ACS such as asthma, wheezing or chronic
hypoxia.
Study limitations include the inability to reach our goal enrollment of
42 participants in each of the SCD and control study groups. We were
able to report data on 69 total participants, and due to the lack of
normative LCI data for African American participants, our power
calculation was performed based on LCI in pediatric asthma. However, our
research allowed the opportunity to collect LCI data in an African
American normative cohort. Pritchard et al36 studied the basic
biologic processes behind lung disease in SCD animal models, however,
the in-vivo pathophysiology of lung disease in SCD, especially in the
“healthy” SCD pediatric population is still not well understood. The
current understanding of pathophysiology in SCD led to the proposed
hypothesis to test LCI where perhaps using other non-invasive methods
such as FOT (forced oscillation technique) would be more appropriate.
The other limitation is the nature of the study design such that the
patients were not followed longitudinally to assess future frequency of
ACS, and other SCD complications. Future studies in the use of LCI in
the SCD population might focus on LCI values during and after acute
complications such as ACS, wheezing episode, asthma exacerbation. The
other population of interest would be the adult SCD group where the
incidence of respiratory disease and abnormal PFT’s is much higher.
In conclusion, there was no significant difference in LCI measures
between SCD and healthy controls at baseline health. Furthermore, TLC
may be an important pulmonary function measure to follow longitudinally
in the pediatric SCD population. Future studies at time of ACS recovery,
or in the adult population may bring better understanding to the
potential use of LCI for detecting lung disease in this population.