Identification of Clinical and Laboratory Parameters Associated with the Development of Acute Chest Syndrome during Vaso-Occlusive Episodes in Children with Sickle Cell Disease: A Preliminary Step before Assessing Specific and Early Treatment Strategies

Abstract

This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days, p < 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (p < 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 109/L) and neutrophil (>10 × 109/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74–0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.

Predicting Acute Chest Syndrome Risk in Sickle Cell Anemia Children During Vaso-occlusive Crisis Hospitalizations

“…This differed from the ndings of Madhi et al's observational study, potentially due to dissimilar age groupings between the two. [15] However, our observations aligned with a large multicenter study by Vichinsky et al reporting median ages at rst ACS episode of 5.4-14.6 years in age groups of 0-9 years and 10-19 years, respectively. [7] Notably, our study suggests gender does not in uence post-admission ACS risk on its own within our population.…”

“…[2,17,18] It is well established that vaso-occlusive crises (VOCs) are the commonest reason of hospitalization among SCA patients. [1,2,11,17,18] Previous research has shown that following admission for a VOC, approximately 13-20% of patients will go on to develop ACS in initial 3 days over an indolent clinical course.. [11,12,15,19] The aim of our study was to identify risk factors that could predict the development of ACS among pediatric patients with SCA. This will help clinicians focus monitoring and care efforts on higher-risk patient groups.…”

What is the role of chest X‐ray imaging in the acute management of children with sickle cell disease?

“…When considering final diagnosis, over 80% of the cohort had either a VOC or ACS. Madhi et al 17 . have identified pain score, pain location and neutrophil count as independently associated with ACS.…”

“…When considering final diagnosis, over 80% of the cohort had either a VOC or ACS. Madhi et al 17 have identified pain score, pain location and neutrophil count as independently associated with ACS. Given that the majority of abnormal CXRs revealed new infiltrates, such parameters incorporated into a clinical score could be used to identify those at risk of ACS, hence determining who would benefit from a diagnostic CXR.…”

“…14,15 CXRs offer the benefits of widespread availability, low cost, ease of use and can importantly help to direct patient management. 16 Nonetheless, X-rays are limited by variable and often poor sensitivity (43-85%) 17 and specificity (60-83%) 18,19 ; resulting in delayed or inaccurate diagnosis. Moreover, given the chronic nature of the disease, children with SCD are repeatedly exposed to diagnostic radiation in the form of computed tomography (CT) and nuclear medicine scans, in addition to X-rays.…”