Acute Chest Syndrome in Children with Sickle Cell Disease in Italy: Results of a National Survey from the Italian Association of Pediatric Hematology Oncology (AIEOP)

Background: Acute Chest Syndrome (ACS) is the second cause of hospitalization in Sickle Cell Disease (SCD), burdened by significant morbidity and mortality. The guidelines regarding management of ACS are sometimes difficult to follow in the real world and the prevention and treatment strategies of ACS are often applied in an uneven manner in the various settings (community care, regional hospitals, reference university centers). Moreover, epidemiology, clinical phenotype and outcomes as well as risk factors could vary in different populations according to ethnicity, genotype or health care system organization.

Aims and Methods: A retrospective multicenter observational study was conducted to investigate the epidemiology of ACS and to the evaluate the diagnostic and therapeutic pathways of ACS in children with SCD (age 0-18 years) in the 2013-2018 period, after the publication of the Italian Association of Pediatric Hematology Oncology (AIEOP) Guidelines for the Management of SCD in Childhood in Italy in 2012.

Results: 126 children were recruited and 122 included in the analysis, with 208 evaluable episodes of ACS (range: 1-6 episodes /patient) from 11 AIEOP Centers. 73 M, 49 F. Mean age was 10.9 years. 85% patients were of African origin, 92% were HbSS/SB°; mean age at diagnosis of SCD of the entire cohort was 25,3 months (range 0-16,8). 44.2% of patients had more than one episode of ACS during the study period; 37% had had a previous episode before 2013. 58% had comorbidities, mostly respiratory (asthma or allergy). 75% of the patients underwent disease modifying treatment during study period (73% hydroxyurea, 2% chronic transfusion). The seasonality of ACS episodes was important in our country: 75% of episodes occured between October and March. 95% of ACS episodes were secondary to a Vaso-Occlusive Crisis.

76% of the admissions occurred in SCD reference centers, 24% in regional hospitals, but 30% later required transfer to reference centers for worsening of clinical conditions or need of exchange transfusion.

The mean length of hospitalization was 9.6 days (range 1-46); one patient died of pneumococcal sepsis; 6 episodes required transfer to the Intensive Care Unit, mechanical ventilation was required in one episode.

A good adherence to the AIEOP Guidelines was documented for some aspects: 99% of the patients were hospitalized, 98% performed chest X-ray for the diagnosis of ACS and in 99% antibiotic therapy was started. Others aspects were less satisfactory and in need of improvement: incentive spirometry was only performed in 19% of admissions; oxygen therapy was performed only in 75% of patients even if SatO2 was<95%; transfer to reference centers was not always timely. During 75% of ACS episodes a simple red cell transfusion was required for Hb>8g/dl, while in 16% an exchange transfusion was performed for severe respiratory distress (of these 71% were performed in patients transfered from regional hospitals); 38% required inhaled bronchodilators, 6% steroids.

A preliminay evaluation of risk factors for recurrent ACS showed that in our cohort allergy to inhaled allergens (p 0.02) and enuresis (p 0.01) were associated with increased prevalence of recurrent ACS; patients with asthma/wheezing also presented more recurrent ACS compared to patients wihout them (23% vs 13%) but this data did not reach statistical significance.

Conclusion: This study represents the first analysis in Italy of ACS, which is confirmed as a frequent event in our cohort, with a significant proportion of patients who experience recurrent ACS. Steps need to be undertaken to improve management of ACS and adherence to the AIEOP guidelines at a national level: stimulate the application of early preventive measures that are still under-utilized, increase the appropriateness of multidisciplinary specialist approach (transfusion specialist, acute care physicians, pneumologists, hematologists) strengthen the dissemination of information through training events for all the Hospitals of the network.