New Horizons in Emergency Department Management of Pediatric Sickle Cell Disease.

ABSTRACT: Sickle cell disease (SCD) is an important topic for emergency medicine audiences because complications of the disease account for a large proportion of hematologic emergencies that are seen in the emergency department each year. Early recognition and aggressive management of emergency complications of SCD can help to reduce the morbidity and mortality associated with this disease. Although the treatment recommendations for some complications of SCD are based on expert opinion, there has been advancement in the understanding of the pathogenesis of the disease and evidence regarding the treatment options available for managing acute complications. This continuing medical education article will provide a summary of the clinical manifestation and management of the most common acute complications of SCD: infection, vaso-occlusive episode, acute chest syndrome, splenic sequestration, stroke, and priapism.

Lipid and hemolysis parameters predicting acute chest syndrome in adulthood with sickle cell disease.

Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 people in the United States and is one of the most common monogenic diseases. A serious complication of SCD is acute chest syndrome (ACS). ACS is a condition with a high rate of morbidity and mortality. The aim of the study was to assess hemolysis and lipid parameters in a cohort of confirmed SCD patients to predict ACS development in the following year.Standard lipid were performed (triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol) panel to calculate of non-HDL-C, large buoyant LDL cholesterol (lbLDL-C) and small dense LDL cholesterol (sdLDL-C) with Sampson equation. Hemolysis and hematologic parameters were also evaluated.Among 91 patients included between September 2018 and June 2021, thirty-seven patients had history of ACS and 6 patients developed ACS during following year. In unadjusted logistic regression, total bilirubin was associated with ACS occurrence (RR: 1.2 [1.05-1.51] p = 0.013). Concerning lipid profile, non-HDL-C (RR: 0.87 [0.0.67-0.99] p = 0.04) and sdLDL-C (RR: 0.78 [0.49-0.96] p = 0.03) were associated with ACS occurrence decrease. C-reactive protein was associated with ACS occurrence (RR: 1.27 [1.065-1.85] p = 0.011).Based on these findings, this study demonstrated that several biomarker easily available can be used at steady state to predict ACS in the following year. The validation of these results are required to ensure the reproducibility of the findings.

Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death.

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21-35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.

Risk factors for acute chest syndrome among children with sickle cell anemia hospitalized for vaso-occlusive crises.

Sickle cell anemia (SCA) is a globally prevalent inherited condition, with acute chest syndrome (ACS) being one of its most severe complications. ACS frequently leads to hospitalization, requires intensive care unit (ICU) admission, and can even result in death. This study aimed to discern the early indicators of impending ACS in children with SCA who were initially hospitalized due to painful vaso-occlusive crises (VOC). This was a retrospective, case‒control investigation of 120 patients aged 1-14 years seen at the King Saud Medical City in Riyadh, Saudi Arabia from January 2021 to December 2022. Patients were classified into cases and controls: those who developed and did not develop ACS during hospital stay, respectively. Demographic factors, laboratory results, vital and clinical signs, and treatment protocols were compared between these groups. The following were significant predictors of impending ACS: previous diagnosis of asthma, history of ACS, recent upper respiratory tract symptoms prior to admission, and need for a blood transfusion within the first 24 h of admission due to a drop in hemoglobin levels. Further regression analysis indicated that elevated steady-state mean corpuscular volume, leukocyte count, total bilirubin, and an increased absolute neutrophil count level 24 h after admission also foreshadowed impending ACS among patients admitted for VOC. The location of pain was also significant; the incidence of ACS was higher in patients with back pain, but lower in those with pain confined to the limbs. The ACS group had a longer average duration of hospital stay compared to those with VOC alone, (7.6 vs. 5.8 days). Among patients initially admitted for VOC, 15.7% were diagnosed with ACS. Most ACS cases were managed with transfusions and antibiotics, and nearly one-third of patients needed admission to an ICU or a high-dependency area.

Plasma sphingolipids in patients with sickle cell disease: Multiple-site vaso-occlusive crises could be associated with lower sphingolipid levels.

Although sickle cell disease (SCD) and its manifestations have been associated with various lipid alterations, there are a few studies exploring the impact of sphingolipids in SCD. In this study, we determined plasma ceramide (Cer) and sphingomyelin (CerPCho) species and investigated their association with the crisis in SCD. SCD patients (N = 27) suffering from vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) were involved in this study. Blood samples were drawn at crisis and later at steady state periods. Clinical history, white blood cell count (WBC), C-reactive protein and lactate dehydrogenase (LDH) levels were recorded. 16:0, 18:0, 20:0, 22:0 Cer and 16:0, 18:0, 24:0 CerPCho were measured via LC-MS/MS. All measured Cer and CerPCho levels of SCD patients at crisis and steady-state were found to be similar. Inflammation-related parameters were significantly higher in patients with ACS compared to single-site VOC. Patients with multiple-site VOC were found to have significantly lower sphingolipid levels compared with those with single-site VOC, at crisis (16, 18, 24 CerPCho and 18, 22 Cer) and at steady-state (24:0 CerPCho and 18 Cer). Our results show that sphingolipid levels in SCD patients are similar during crisis and at steady state. However, lower sphingolipid levels appear to be associated with the development of multiple-site VOC. Since the differences were observed at both crisis and steady-state, sphingolipid level could be an underlying factor associated with crisis characteristics in patients with SCD.

Factors Associated with Overt Stroke in Children and Adolescents with Sickle Cell Disease: A Retrospective Cohort Study.

Sickle cell disease (SCD) is associated with a high occurrence of complications due to vaso-occlusive phenomenon such as stroke. This retrospective cohort study aimed to examine the clinical and laboratory characteristics of 120 children and adolescents with SCD and analyze the factors associated with overt stroke incidence. All relevant data were obtained from patient medical records. Survival analysis was used to compare the demographic, clinical, and laboratory characteristics between patients with and those without overt stroke. The patients were 52.5% female with a mean (SD) age of 11.2 (4.3) years. The incidence of overt stroke in this cohort was nine out of 956.7 patient-years, resulting in an incidence density of 0.94 cases/100 patient-years. Reports of greater than or equal to two previous attacks of dactylitis and greater than or equal to three episodes of acute chest syndrome (ACS)/pneumonia were associated with overt stroke and an increase in reticulocyte count and red blood cell distribution width (RDW). In conclusion, a history of a high number of dactylitis, ACS/pneumonia, increased RDW, and reticulocytosis was associated with overt stroke occurrence in children and adolescents with SCD. Future studies with a higher stroke incidence in the evaluated sample are necessary to confirm this hypothesis.

Oxygen saturation thresholds in managing sickle cell disease at US children's hospitals.

BACKGROUND: Adequate oxygen saturation (SpO2 ) is crucial for managing sickle cell disease (SCD). Children with SCD are at increased risk for occult hypoxemia; therefore, understanding SpO2 threshold practices would help identify barriers to oxygen optimization in a population sensitive to oxyhemoglobin imbalances. We investigated SpO2 cutoff levels used in clinical algorithms for management of acute SCD events at children's hospitals across the United States, and determined their consistency with recommended national guidelines (SpO2  > 95%). METHODS: Clinical pathways and algorithms used for the management of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) in SCD were obtained and reviewed from large children's hospitals in the United States. RESULTS: Responses were obtained from 94% (140/149) of eligible children's hospitals. Of these, 63 (45%) had available clinical algorithms to manage VOC and ACS. SpO2 cutoff was provided in 71.4% (45/63) of clinical algorithms. Substantial variation in SpO2 cutoff levels was noted, ranging from ≥90% to more than 95%. Only seven hospitals (5% of total hospitals and 15.6% of hospitals with clinical algorithms available) specified oxygen cutoffs that were consistent with national guidelines. Hospitals geographically located in the South (46.8%; n = 29/62) and Midwest (54.8%; n = 17/31) were more likely to have VOC and ACS clinical algorithms, compared to the Northeast (26.5%; n = 9/34) and West (36.4%; n = 8/22). CONCLUSION: There is inconsistency in the use of clinical algorithms and oxygen thresholds for VOC and ACS across US children's hospitals. Children with SCD could be at risk for insufficient oxygen therapy during adverse acute events.

Unique Changes in the Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Unravel the Role of Respiratory Pathogens: A Time Series Analysis.

BACKGROUND: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that the incidence of ACS followed the unprecedented population-level changes in respiratory pathogen dynamics after COVID-19-related nonpharmaceutical interventions (NPIs). RESEARCH QUESTION: What is the respective role of respiratory pathogens in ACS epidemiology? STUDY DESIGN AND METHODS: This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All children aged < 18 years with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1,000 children with SCD over time was analyzed by using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen. RESULTS: Among the 55,941 hospitalizations of children with SCD, 2,306 episodes of ACS were included (median [interquartile range] age, 9 [5-13] years). A significant decrease was observed in ACS incidence after NPI implementation in March 2020 (-29.5%; 95% CI, -46.8 to -12.2; P = .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95% CI, 7.2 to 41.6; P = .007). Using population-level incidence of several respiratory pathogens, Streptococcus pneumoniae accounted for 30.9% (95% CI, 4.9 to 56.9; P = .02) of ACS incidence over the study period and influenza 6.8% (95% CI, 2.3 to 11.3; P = .004); other respiratory pathogens had only a minor role. INTERPRETATION: NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiologic situation allowed determination of the contribution of these respiratory pathogens, in particular S pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population.

Comparison of in-hospital mortality in children and adolescents with sickle cell disease in a resource-limited setting before and during the COVID-19 pandemic.

BACKGROUND: COVID-19 in children and adolescents with sickle cell disease (SCD) has variable presentations (from mild to severe disease), and the main symptoms are vaso-occlusive crises (VOC) and acute chest syndrome (ACS). We hypothesized that the desertion of hospitals due to the pandemic would lead to late arrival at the emergency room and an increased mortality. In this study, we sought to measure and compare the mortality of children with sickle cell disease before and during the COVID-19 pandemic. MATERIAL AND METHODS: We conducted a retrospective cohort study at the sickle cell disease management center of Laquintinie Hospital in Douala (Cameroon). The study period was divided into two, i.e., from March 2019 to February 2020 (Pre-COVID-19) and from March 2020 to February 2021 (COVID-19). All administrative and ethical considerations were fully respected. Data were analyzed using SPSS 20.0. RESULTS: Overall, 823 patients were admitted during the study period. Males represented 52.4% of the overall population, giving a sex ratio of 1.1:1. We admitted 479 patients during the pre-COVID-19 period versus 344 patients during the COVID-19 period, which is a 28.2% drop in admissions during the COVID-19 period. The mortality rate was 3.5% during the pre-COVID-19 period and 3.2% during the COVID-19 period (p>0.05). The most common causes of death were ACS (39.3%, n = 11), severe anemia (25.0%, n = 7), and VOC (17.9%, n = 5). ACS (adjusted odds ratio [aOR]=3.628, 95% confidence interval [CI], [1.645-7.005], p<0.001) was significantly associated with mortality. CONCLUSION: During the COVID-19 pandemic, although the consultation frequency decreased, the mortality rate of sickle cell disease patients remained unchanged.

How I treat sickle cell disease in pregnancy.

ABSTRACT: Fifty years ago, people with sickle cell disease (SCD) were discouraged from becoming pregnant, but now, most should be supported if they choose to pursue a pregnancy. They and their providers, however, should be aware of the physiological changes of pregnancy that aggravate SCD and pregnancy's unique maternal and fetal challenges. Maternal problems can arise from chronic underlying organ dysfunction such as renal disease or pulmonary hypertension; from acute complications of SCD such as acute anemia, vaso-occlusive crises, and acute chest syndrome; and/or from pregnancy-related complications such as preeclampsia, sepsis, severe anemia, thromboembolism, and the need for cesarean delivery. Fetal problems include alloimmunization, opioid exposure, fetal growth restriction, preterm delivery, and stillbirth. Before and during pregnancy, in addition to the assessment and care that every pregnant patient should receive, patients with SCD should be evaluated and treated by a multidisciplinary team with respect to their unique maternal and fetal issues.

Managing pregnancy in patients with sickle cell disease from a transfusion perspective.

Advances in the management of sickle cell disease (SCD) have made it possible for most female patients (whether homozygous or compound heterozygous) to reach childbearing age and become pregnant. However, even in the less symptomatic forms of SCD a high risk of complications during pregnancy and the postpartum period can occur for both the mother (1% to 2% mortality) and the fetus. Coordinated care from the obstetrician and the sickle cell disease expert is essential, together with the active participation of the patient. Vaso-occlusive complications, such as vaso-occlusive crisis and acute chest syndrome, often increase in frequency when hydroxyurea treatment is interrupted. Obstetric complications, such as pre-eclampsia, fetal growth restriction, and preterm delivery, are more common in women with SCD. Recent meta-analysis-based studies support prophylactic transfusion. However, there have been no randomized trials assessing the benefits of prophylactic transfusion. Given the known risk of transfusion complications, including delayed hemolytic transfusion reaction and hyperhemolysis, transfusion is not systematically performed in pregnant women with SCD. We describe here a case-by-case approach to the management of pregnancy in women with SCD based on the medical and transfusion history of each patient.

Presentation and challenges in management of COVID-19 in sickle cell disease: case report.

Sickle cell has predominantly been a disease in the sub-Saharan Africa. There is scanty data in Africa and none in Tanzania regarding patients with sickle cell disease infected with COVID-19 especially in the paediatric group. This is concerning because a large population of children living with sickle cell disease are found in this part of the world where scarcity of resources also prevail. This is the first paediatric case of sickle cell disease and COVID-19 reported in Tanzania; highlighting the presentation and challenges faced in management. It is also the first case in literature describing secondary infection in a child with COVID-19 and underlying sickle cell disease. Our patient was a female child of African origin with underlying sickle cell disease who had recurrent admissions. She presented with cough, fever, chest and abdominal pain and was managed for acute chest syndrome and vaso-occlusive crisis. During the second admission, she developed respiratory distress, infection with COVID-19 was confirmed and managed accordingly. However, she was re-admitted due to bilateral arm pain and physical findings were suggestive of secondary respiratory bacterial infection. She was then started on a different treatment plan. Despite challenges faced in the management of the patient, the outcome was favourable. It is important to recognize the presentation of COVID-19 in children with sickle cell disease and challenges faced in management so that the epidemiologic characteristics, spectrum of the disease and its outcomes can be understood better in the context of sub-Saharan Africa.

Associating a standardized reporting tool for chest radiographs with clinical complications in pediatric acute chest syndrome.

BACKGROUND: Acute chest syndrome (ACS) is an important cause of morbidity in sickle cell disease (SCD). A standardized tool for reporting chest radiographs in pediatric SCD patients did not previously exist. OBJECTIVE: To analyze the interobserver agreement among pediatric radiologists' interpretations for pediatric ACS chest radiographs utilizing a standardized reporting tool. We also explored the association of radiographic findings with ACS complications. METHODS: This was a retrospective cohort study of pediatric ACS admissions from a single institution in 2019. ICD-10 codes identified 127 ACS admissions. Two radiologists independently interpreted the chest radiographs utilizing a standardized reporting tool, a third radiologist adjudicated discrepancies, and κ analysis assessed interobserver agreement. Clinical outcomes were correlated with chest radiograph findings utilizing Pearsons' χ2 , t tests, and Mann-Whitney U tests. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Interobserver agreement was moderate to near-perfect across variables, with κ analysis showing near-perfect agreement for opacity reported in the right upper lobe (0.84), substantial agreement for right lower lobe (0.63), and vertebral bony changes (0.72), with moderate agreement for all other reported variables. On the initial chest radiograph, an opacity located in the left lower lobe (LLL) correlated with pediatric intensive care unit transfer (p = .03). Pleural effusion on the initial chest radiograph had a 3.98 OR (95% CI: 1.35-11.74) of requiring blood products and a 10.67 OR (95% CI: 3.62-31.39) for noninvasive ventilation. CONCLUSION: The standardized reporting tool showed moderate to near-perfect agreement between radiologists. LLL opacity, and pleural effusion were associated with increased risk of ACS complications.

Recurrence of acute chest syndrome post stopping Crizanlizumab, the dilemma of stopping vs continuation in patient with sickle cell disease: case report.

Sickle cell disease (SCD) is one of the most common hematological diseases, which results in variable complications. The treatment of SCD is evolving but limited options are available for now. Acute chest syndrome (ACS) is one of the serious complications observed in SCD and a challenging one in prevention. Crizanlizumab is a monoclonal antibody that binds to P-selectin and improves blood flow by preventing sickle cell adhesion to endothelium, resulting in improvement of vaso-oclusive crises (VOC). It is not well evaluated in terms of ACS prevention. Here we report a 23-year-old patient with SCD and recurrent ACS; she was started on Crizanlizumab and she had no more ACS, but once she was off Crizanlizumab she developed ACS again, later Crizanlizumab was re-started, and the patient has improved significantly.

Description of a Colocated Comprehensive Care Model for People With Sickle Cell and Comorbid Pulmonary Disease.

Comorbid pulmonary complications in people with sickle cell disease (pwSCD) are associated with high rates of morbidity and mortality, and poor access to care contributes to poor outcomes among this particularly high-risk pwSCD. Our purpose was to describe the population served and the resources required for hematology, pulmonary, nursing, respiratory therapy, social work, genetics, psychology, and school liaison providers to see these patients in an integrated clinic. We abstracted demographic, medication, clinical, and diagnostics data of the pwSCD seen at least once in this clinic from February 1, 2014 to December 10, 2020 from the electronic medical record and identified 145 unique pwSCD. Abnormal lung function and bronchodilator responsiveness were detected in 31% and 42% of participants respectively. Sleep abnormalities were found in over two-thirds of those screened and 65% had ≥1 previous acute chest syndrome episode. This clinic also allowed for direct provider communication and required relatively limited resources to serve a large number of severely affected pwSCD. Given the degree of abnormal respiratory variables detected and the limited resources required to implement this model, studies are warranted to evaluate whether it has the potential to improve outcomes in high-risk populations.

Early recognition of pulmonary complications of sickle cell disease.

Sickle cell disease (SCD) is an inherited hematological disorder with multiple-organ involvement. The pulmonary complications of SCD are associated with significant morbidity and mortality. This article presents an important review of acute and chronic pulmonary complications, including acute chest syndrome, pneumonia, pulmonary thromboembolism, pulmonary fat embolism, chronic sickle cell lung disease, and pulmonary hypertension, in patients with SCD. Bronchial asthma and obstructive sleep apnea in relation to SCD are discussed in this article. Early recognition of pulmonary complications leads to early therapeutic interventions and improvement of the overall treatment outcome.

Diagnostic Test Accuracy of Lung Ultrasound for Acute Chest Syndrome in Sickle Cell Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Acute chest syndrome (ACS) is a leading cause of death in patients with sickle cell disease. Lung ultrasound (LUS) is emerging as a point-of-care method to diagnose ACS, allowing for more rapid diagnosis in the ED setting and sparing patients from ionizing radiation exposure. RESEARCH QUESTION: What is the diagnostic accuracy of LUS for ACS diagnosis, using the current reference standard of chest radiography? STUDY DESIGN AND METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed for this systematic review and meta-analysis. Embase, MEDLINE, Web of Science, and Google Scholar were used to compile all relevant studies. Two reviewers screened the studies for inclusion in this review. Cases of discrepancy were resolved by a third reviewer. Meta-analyses were conducted using both metadta and midas STATA software packages to retrieve summary receiver operating characteristic curves, sensitivities, and specificities. Three reviewers scored the studies with QUADAS-2 for risk of bias assessment. RESULTS: From a total of 713 unique studies retrieved, six studies were included in the final quantitative synthesis. Of these, five studies were in pediatric EDs. Two studies were conference abstracts and not published manuscripts. Data were available for 625 possible ACS cases (97% of cases in patients aged ≤ 21 years) and 95 confirmed ACS diagnoses (pretest probability of 15.2%). The summary sensitivity was 0.92 (95% CI, 0.68-0.98) and the summary specificity was 0.89 (95% CI, 0.69-0.97) with an area under the curve of the summary receiver operating characteristic curve of 0.96 (95% CI, 0.94-0.97). INTERPRETATION: LUS has excellent sensitivity and very good specificity for ACS diagnosis and may serve as an initial point-of-care test to facilitate rapid treatment of ACS and spare pediatric patients from ionizing radiation; however, further research is warranted to improve the generalizability to the adult sickle cell disease population.

SARS-CoV-2 Infection Presenting as Acute Chest Syndrome in a Child With Hemoglobin SD-Los Angeles Disease: A Case Report and Review of Literature.

Hemoglobin D-Los Angeles is a variant of hemoglobin that can polymerize in the deoxygenated state. When co-inherited with Hemoglobin S (HbSD-Los Angeles disease) a severe sickling syndrome similar to HbSS can result. Corona virus infectious disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome-corona virus-2. It has been associated with acute chest syndrome (ACS) in individuals with sickle cell disease (SCD), but this complication has not previously been reported in patients with HbSD-Los Angeles. Dexamethasone has been shown to improve outcomes in non-SCD patients with severe acute respiratory syndrome-corona virus-2 pneumonia or acute respiratory distress syndrome; however, its use in SCD patients with ACS is controversial due to a reported increased risk of complications including vaso-occlusive painful episodes. Herein, we reported a patient with HbSD-Los Angeles and COVID-19-associated ACS whom we treated with dexamethasone without transfusion. The patient experienced a rapid recovery without sequelae from steroid use. To further evaluate the use of steroids, we conducted a literature review focusing on the management of pediatric SCD patients with COVID-19-associated ACS. We identified a total of 39 pediatric patients with SCD and COVID-19, of whom 21 (54%) had ACS. Packed red blood cell transfusion (n=11), exchange transfusion (n=4), or a combination of exchange transfusion and packed red blood cell transfusion (n=4) were the most frequently reported treatment, with hydroxychloroquine (n=5), remdesivir (n=1), and tocilizumab (n=1) also being reported. Three patients were treated with dexamethasone. All patients recovered and no adverse outcomes from steroid use were reported. Even though transfusion is considered the standard of care for children with ACS and steroids are not routinely recommended, our experience suggested that COVID-19-associated ACS may be an important exception, especially for patients who refuse transfusion or are in resource-poor nations where blood transfusions may not be readily available. Further studies are warranted to confirm these observations.

Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease.

BACKGROUND: Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. This is an update of a previously published Cochrane Review. OBJECTIVES: The aim of the review is to determine whether the use of inhaled, short-acting bronchodilators for acute chest syndrome reduces morbidity and mortality in people with sickle cell disease and to assess whether this treatment causes adverse effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional searches were carried out on MEDLINE (1966 to 2004) and Embase (1981 to 2004) and ongoing trial registries (28 September 2022). Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 25 July 2022. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials. Trials using quasi-randomisation methods will be included in future updates of this review if there is sufficient evidence that the treatment and control groups are similar at baseline. DATA COLLECTION AND ANALYSIS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. MAIN RESULTS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease.