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.

Keywords: acute chest syndrome; associated factors; sickle cell disease; vaso-occlusive episodes.

Figure 1

Dynamics of (A) clinical parameters (B) laboratory data in VOE versus ACS group and (C) hemolytic variables in VOE versus ACS group, by evolution of VOE in hospitalized children with sickle cell disease. VOE: vaso-occlusive episode; ACS: acute chest syndrome. * p < 0.05, ** p < 0.01, ***p < 0.001, ns: not significant. FPS, face pain score; SpO2, peripheral capillary oxygen saturation; CRP, C-reactive protein; LDH, lactate dehydrogenase; AST, aspartate aminotransferase.

Figure 1

Dynamics of (A) clinical parameters (B) laboratory data in VOE versus ACS group and (C) hemolytic variables in VOE versus ACS group, by evolution of VOE in hospitalized children with sickle cell disease. VOE: vaso-occlusive episode; ACS: acute chest syndrome. * p < 0.05, ** p < 0.01, ***p < 0.001, ns: not significant. FPS, face pain score; SpO2, peripheral capillary oxygen saturation; CRP, C-reactive protein; LDH, lactate dehydrogenase; AST, aspartate aminotransferase.

Figure 1

Dynamics of (A) clinical parameters (B) laboratory data in VOE versus ACS group and (C) hemolytic variables in VOE versus ACS group, by evolution of VOE in hospitalized children with sickle cell disease. VOE: vaso-occlusive episode; ACS: acute chest syndrome. * p < 0.05, ** p < 0.01, ***p < 0.001, ns: not significant. FPS, face pain score; SpO2, peripheral capillary oxygen saturation; CRP, C-reactive protein; LDH, lactate dehydrogenase; AST, aspartate aminotransferase.