Acute chest syndrome (ACS) is a severe complication of sickle cell disease in patients hospitalized with a vaso-occlusive crisis. ACS significantly contributes to both increased mortality and hospitalization rates among children and adults with Sickle Cell Disease (SCD) (Paul, R.N. et. al., 2011). Despite advances in preventive health measures and comprehensive follow-up care, the morbidity rates associated with ACS has seen a gradual increase over the years. This persistence highlights the need for improved standardized prevention and management strategies for ACS in SCD patients (Allareddy, V. et al., 2014).
ACS is characterized by new segmental pulmonary infiltrates that are consistent with consolidation on chest radiograph or perfusion lung scan (Boyd J. H. et. al., 2006) accompanied by one or more new respiratory signs or symptoms, such as cough, chest pain, hypoxemia, or tachypnea and possibly fever above 38.5°C (Friend A., et. al., 2023). It is however noteworthy that clinical features of ACS may not be immediately apparent upon hospital admission. This is because almost half of the patients initially admitted for a painful vaso-occlusive crisis (VOC) develop ACS while hospitalized, typically 24-72 hours after the onset of severe pain. Therefore, all patients admitted with a painful crisis should be considered as potentially being in the early stages of ACS. Even patients with minimal clinical signs can rapidly deteriorate, making continuous vigilance throughout their hospital stay crucial, particularly for those presenting with rib or chest pain. Regular monitoring of vital signs and daily chest examinations are also essential (Koehl J. L., et. al., 2022).
The onset of ACS initiates a vicious cycle involving lung infarction, inflammation, and atelectasis. This cycle leads to ventilation-perfusion mismatch, hypoxemia, and acute elevations in pulmonary artery and right ventricular pressures (Mekontso D, et. al., 2008). At the cellular level, low oxygen tension in the alveoli exacerbates the abnormal behavior of sickle-shaped red blood cells. These cells tend to stick to each other, to leukocytes, and to the vascular endothelium, resulting in vaso-occlusion and tissue hypoxia. These interactions cause the release of inflammatory cytokines, promoting acute and chronic inflammation in the airways due to their proximity to the vasculature. Elevated plasma levels of vascular cell adhesion molecule-1 and lower levels of cytoprotective factors such as nitric oxide metabolites in patients with ACS support this pathophysiological mechanism with some of the main identifiable causes being pulmonary vascular occlusion, infection, hypoventilation/atelectasis, pulmonary edema and bronchospasm (Taylor, C et. al., 2004; Bhasin, N. and Sarode, R., 2023).
Various studies have identified the risk factors for the development, recurrence and severity of ACS. These risk factors include young age, low levels of fetal hemoglobin (HbF), high steady-state hemoglobin (Hb) and white blood cell (WBC) counts, homozygous sickle cell disease (HbSS), sickle cell-beta(+) thalassemia (HbSβ° thalassemia) (Castro O., et. al., 1994), asthma or airway hyperactivity (Boyd J. H. et. al., 2006), and tobacco smoke exposure. A history of ACS in early childhood, particularly within the first three years of life, is a significant predictor of recurrent episodes. The highest recurrence rates occur within six months of the initial event and factors such as general anesthesia, asthma or airway hyperactivity, and smoking can trigger ACS development in SCD patients. ACS can occur post-operatively, especially after abdominal surgeries, such as splenectomy and cholecystectomy, and is more likely in patients who have not received a pre-operative blood transfusion (Howard et. al., 2013). Both primary and secondhand tobacco smoke exposure are also known to increase the risk of VOC and ACS, with secondhand smoke contributing to lower airway obstruction in children with SCD (Paul R. N., et. al., 2011).
Hospitalization is necessary for all patients with ACS to ensure careful monitoring of their oxygenation and clinical status. Early and aggressive intervention is particularly beneficial for patients with multilobar involvement and coexisting respiratory diseases. The general management principles for ACS include supportive care with hydration, infection management using antibiotics, oxygen supplementation, and red blood cell transfusion to enhance oxygen delivery. Bronchodilators, incentive spirometry (Bellet, P.S., 1995), and pain control are also crucial components of treatment. However, the efficacy of treatments like inhaled nitric oxide and corticosteroids is still under investigation. In clinical practice, adherence to guidelines can be challenging due to variations in implementation across different healthcare settings (Friend, A. et. al., 2023; Scott T. M., 2011)
Hydration is typically administered through intravenous hypotonic fluids at approximately three-fourths of the maintenance rate to prevent pulmonary edema. Aggressive incentive spirometry while awake helps prevent atelectasis, and mechanical chest physiotherapy maneuvers, such as positive expiratory pressure devices, may be used in younger children or those with chest pain limiting incentive spirometry. Supplemental oxygen is recommended for patients with oxygen saturation levels of 92% or lower and/or tachypnea. It is essential to monitor any decline in oxygen saturation from the patient’s baseline state, which may indicate complications. Empiric antibiotic coverage for pneumococcal infection, commonly using third-generation cephalosporins, is usually initiated in most healthcare settings for ACS patients. Pain management with opioids particularly for thoracic bone infarction, is critical to reduce respiratory splinting and hypoventilation. Effective pain management should however balance analgesia to reduce respiratory compromise while avoiding respiratory depression (Friend A., et al, 2023; Paul R. N., et al, 2011)
Effective ACS management is essential for the long-term health of SCD patients. Each ACS episode increases the risk of event-related mortality and long-term lung injury, and recurrent episodes can contribute to chronic lung disease, pulmonary hypertension, and cor pulmonale. Therefore, comprehensive care strategies that include early intervention, preventive measures, and regular monitoring are necessary for managing SCD patients at risk of ACS (Friend, A, et. al., 2023). Comprehensive care for SCD patients could include routine use of prophylactic penicillin to reduce the incidence of infections caused by Streptococcus pneumoniae. This prophylaxis is generally recommended until the age of five. Discontinuing penicillin at this age is considered safe if the child has not had pneumococcal infections, has not undergone splenectomy, and has received appropriate vaccinations. Vaccination against S. pneumoniae is also a very important aspect of this comprehensive care approach (Gaston M. H., et. al., 1986).
Recurrent ACS episodes in childhood can lead to long-term complications such as obstructive or restrictive lung abnormalities, fibrosis, chronic hypoxemia, and early mortality. Therefore, the importance of reducing the frequency of future ACS episodes through preventive measures cannot be overstated. Avoiding tobacco smoke exposure and prophylactic administration of antibiotics, such as Penicillin VK, and annual influenza vaccinations can help decrease the risk of ACS. Again, patients hospitalized for painful crises should be closely monitored as they may be in the prodromal phase of ACS and those admitted for surgery should also be monitored carefully due to the increased risk of postoperative ACS. Preoperative transfusions for significant surgical procedures, careful intraoperative anesthesia management, and postoperative incentive spirometry are essential preventive measures that could contribute immensely to the overall health and wellness of patients presenting with ACS (Bhasin, N. and Sarode, R., 2023).
Acute chest syndrome is a significant and frequent cause for hospitalization in individuals with sickle cell disease. Its complex pathophysiology complicates the development of standardized, targeted therapies. The symptoms can be subtle and the condition usually manifests after hospitalization for VOC or seemingly unrelated issues. Therefore, maintaining a high level of suspicion is necessary for timely diagnosis as this leads to better outcomes.
REFERENCES
Allareddy, V., Roy, A., Lee M.K., Nalliah, R.P., Rampa, S., and Rotta, A.T., 2014. Outcomes of acute chest syndrome in adult patients with sickle cell disease: predictors of mortality. PloS one, 9(4), p.e94387.
Bellet P.S., Kalinyak, K.A., Shukla, R., Gelfand, M.J. and Rucknagel, D.l., 1995.Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases. New England Journal of Medicine, 333(11), pp699-703.
Bhasin N, Sarode R. Acute Chest Syndrome in Sickle Cell Disease. Transfusion Medicine Reviews, p. 150755.
Castro O, Brambilla DJ, Thorington B, Reindorf CA, Scott RB, Gillette P, Vera JC, Levy PS; The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. Blood 1994; 84 (2): 643-649. doi: https://doi.org/10.1182/blood.V84.2.643.643
Friend A, Settelmeyer TP, Girzadas D. Acute Chest Syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441872/
Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J, Presbury G, Zarkowsky H, Vichinsky E, Iyer R, Lobel JS and Diamond S, 1986. Prophylaxis with oral penicillin in children with sickle cell anemia. New England Journal of Medicine, 314(25), pp. 1593-1599.,
Howard, J., Malfroy, M., Llewelyn, C., Choo, L., Hodge, R., Johnson, T., Purohit, S., Rees, D. C., Tillyer, L., Walker, I., Fijnvandraat, K., Kirby-Allen, M., Spackman, E., Davies, S.C. & Williamson, L. M., (2013) The Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS) study: a randomized, controlled, multi-centre clinical trial. Lancet, 381, 930-938.
Jessica H. Boyd, Eric A. Macklin, Robert C. Strunk, Michael R. DeBaun; Asthma is associated with acute chest syndrome and pain in children with sickle cell anemia. Blood 2006; 108 (9): 2923-2927. doi: https://doi.org/10.1182/blood-2006-01-011072
Koehl, J. L., Koyfman, A., Hayes, B. D. and Long, B., 2022. High risk and low prevalence diseases: Acute chest syndrome in sickle cell disease. The American Journal of Emergency Medicine, 58, pp.235-244.
Mekontso Dessap, Armand, Rusel Leon, Anoosha Habibi, Ruben Nzouakou, Francoise Rouddot-Thoraval, Serge Adnot, Bertrand Godeau et al., 2008. Pulmonary hypertension and cor pulmonale during severe cute chest syndrome in sickle cell disease. American journal of respiratory and critical care medicine, 177(6), pp.646-653.
Paul R.N, Castro O.L., Aggarwal A and Oneal P.A, 2011. Acute chest syndrome: sickle cell disease. European journal of hematology, 87(3), pp. 191-207
Scott T. M.: How I treat acute chest syndrome in children with sickle disease. Blood 2011; 117 (20): 5297-5305. doi: https://doi.org/10.1182/blood-2010-11-261834
Taylor C, Carter F, Poulose J, Rolle S, Babu S, Crichlow S, Clinical presentation of acute chest syndrome in sickle cell disease, Postgraduate Medical Journal, Volume 80, Issue 944, June 2004, Pages 346-349, https://doi.org/10.1136/pgmj.2003.012781
By Anita Antwi Assessed and Endorsed by the MedReport Medical Review Board