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.