Acute Chest Syndrome In Children Research Articles

Sputum interleukin-6 level as a marker of severity during acute chest syndrome in children with sickle cell disease.

Acute chest syndrome (ACS) is a leading cause of morbimortality in sickle cell disease (SCD). In this prospective observational study, we investigated sputum interleukin-6 (IL-6) level as an ACS severity marker during 30 ACS episodes in 26 SCD children. Sputum IL-6 levels measured within the first 72 h of hospitalisation for ACS were significantly higher in patients with oxygen requirement ≥2 L/min, ventilation (invasive and/or non-invasive) length ≥5 days, bilateral and/or extensive opacities on chest X-ray or erythrocytapheresis requirement. Sputum IL-6 could serve as an ACS severity marker to help identify patients requiring targeted anti-inflammatory treatments such as tocilizumab.

The Role of Neighborhood Disadvantage, Systemic Inflammation, and Acute Chest Syndrome in Children with Sickle Cell Disease

Introduction: Acute chest syndrome (ACS) is a frequent pulmonary complication of sickle cell disease (SCD) and is a leading cause of morbidity and mortality in both children and adults with SCD. In addition to biological factors, there is increasing recognition that social and environmental factors, such as low socioeconomic status and air pollution, respectively, play a role in disease processes. Current evidence suggests that neighborhood disadvantage influences cardiopulmonary outcomes in non-SCD populations. The disproportionate presence of polluting industries and major roadways near disadvantaged neighborhoods could impact lung health in children with SCD, and exposure to toxic metals has also been linked to worsening systemic inflammation. Yet, the impact of neighborhood disadvantage on inflammation in ACS has not been assessed. The goal of this study is to investigate the effects of neighborhood disadvantage on inflammatory markers in children presenting with ACS. Methods: We enrolled children in our institution with SCD (all genotypes) aged 2-21 years of age with and without a history of ACS. We abstracted clinical information including sex, age, number of ACS episodes up to enrollment, and residential address. In addition, blood samples were collected during routine hematology appointments and hospitalizations for ACS. Plasma cytokine levels were measured using multiplex assays on a subset of participants. Using census tract-level data on poverty, education, housing and employment from the US Census, we computed the area deprivation index (ADI) for census tracts across the greater Houston area and assigned an ADI score to each study subject based on their geocoded address at the time of visit. We dichotomized ADI at the median value (99.0; minimum 42.4, maximum of 156.5) across the study area into “high” and “low” deprivation categories. Results: Forty-four participants met inclusion criteria with complete ADI, clinical and cytokine data. Mean age was 11.6 years (SD 5.1), 52% were male, and 66% lived in a high ADI tract. In children over 10 years of age (n=24), there were higher levels of IL-4, IL-6, IL-8, and IL-13 in those from high ADI areas compared to those from low ADI areas [median concentrations (pg/mL): 139.2 vs 75.7, p=0.53; 17.18 vs 11.92, p=0.67; 15.85 vs 5.38, p=0.20; 19.28 vs 8.30, p=0.38, respectively]. Similarly, IL-4, IL-6, and IL-13 levels were higher in children 10 years and younger from high ADI areas, though not statistically significant. There were no differences between median ADI for patients without a history of ACS and those with recurrent ACS (107.7 vs 108.1, p=0.9). Conclusion: In Houston children with SCD, especially 10 years and older, there were overall higher levels of systemic inflammation in those from high ADI areas compared to those from low ADI areas. However, these findings did not reach statistical significance. There was also no significant difference in ADI scores based on frequency of admissions for ACS. Future studies are needed to analyze cytokines from a larger cohort of patients with SCD and compare ACS outcomes to other regions for a more powered, comprehensive investigation.

Acute chest syndrome in children with sickle cell disease: Data from a national AIEOP cohort identify priority areas of intervention in a hub-and-spoke system.

Acute chest syndrome (ACS) is a frequent cause of hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings still lack knowledge about ACS best practices. After the AIEOP Guidelines were published in 2012, suggesting standardized management in Italy, a retrospective study was performed to assess the diagnostic and therapeutic pathways of ACS in children. From 2013 to 2018, 208 ACS episodes were presented by 122/583 kids in 11 centres. 73 were male, mean age 10.9 years, 85% African, 92% HbSS or Sβ°. In our hub-and-spoke system, a good adherence to Guidelines was documented, but discrepancies between reference centres and general hospitals were noted. Improvement is needed for timely transfer to reference centres, use of incentive spirometry, oxygen therapy and pain management.

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

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). What is the respective role of respiratory pathogens in ACS epidemiology? This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All childrenaged < 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. 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. 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.

603 - Biomarkers to determine the onset and severity of acute chest syndrome in children with sickle cell disease

603 - Biomarkers to determine the onset and severity of acute chest syndrome in children with sickle cell disease

Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France

Acute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown. To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD. This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included. PCV13 implementation. Monthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes. Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age, 8 [4-12] years; 2228 [55.6%] boys). PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (-0.9% per month; 95% CI, -1.4% to -0.4%; P < .001), with an estimated cumulative change of -41.8% (95% CI, -70.8% to -12.7%) by 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period. PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.

Clinical Characteristics of Severe Acute Chest Syndrome in Children with Sickle Cell Disease

Background: Acute chest syndrome (ACS) is a form of acute lung injury that is a leading cause of morbidity and mortality in children and adults with sickle cell disease (SCD). Despite advances in health maintenance and disease-modifying therapies for SCD, ACS remains a common and often severe complication. There is still limited understanding of why some patients suffer more severe ACS episodes. Few studies have specifically investigated clinical parameters associated with severe ACS in the pediatric population. The purpose of this study is to determine the association between hematologic and radiologic clinical findings and severe ACS in children and adolescents with SCD.Methods: We conducted a single-institution retrospective chart review of 120 pediatric patients with HbSS or HbSβ 0 thalassemia and at least one documented episode of ACS, and then further classified patients by their most severe ACS event. We extracted laboratory and radiologic data to compare clinical findings. Infections reported in patient encounters were verified by documented viral PCR and blood cultures. Continuous variables were analyzed using Welch's t-test; categorical variables were analyzed using Fisher's exact test.Results: Eighty patients in the moderate ACS group were excluded for this analysis. Twenty patients (median age 5.6 years, SD 4.20) had mild ACS defined by no supplemental oxygen requirement, only one segmental or lobar infiltrate on chest radiography, and transfusion of less than 3 units (or 15 cc/kg) of red blood cells. Twenty patients (median age 7.6 years, SD 4.01) had severe ACS characterized by acute respiratory failure requiring mechanical (invasive or non-invasive) ventilation and/or exchange transfusion. Median length of stay for patients with severe ACS was longer than for the mild cohort (mean: 8 days vs 2 days, p <0.001). The median absolute neutrophil count (ANC) was significantly higher in the severe ACS cohort (19.8 x 10 3µL vs. 9.4 x 10 3 µL, p = 0.004). The median platelet count nadir was significantly lower in the severe ACS group compared to the mild group (165 x 10 3 µL vs. 309 x 10 3 µL, p <0.001). Review of radiologic data showed that the median number of lobes affected in the severe ACS group were 3, compared to 1 lobe in the mild group (p <0.001). Approximately 65% of patients with mild ACS had left-sided disease (p = 0.18), while 85% of patients with severe ACS had bilateral disease (p = 0.002). The risk of pleural effusions was also significantly increased with severe ACS [OR 76.00 (95% CI 9.235-825.6), p <0.001]. When we analyzed infection at time of ACS, the proportion of laboratory-confirmed viral infections were twice as high in the mild ACS cohort (41.2%), compared to the severe ACS cohort (20.0%, p = 0.279). There were no bloodstream bacterial infections found in either cohort.Conclusion: Severe ACS in children is a clinically distinct phenotype associated with longer length of stay, higher ANC and lower platelet nadir counts during active ACS, increased involvement of 3 or more lung lobes, and presence of pleural effusions. A lower proportion of confirmed viral infections were found in the severe ACS cohort compared to mild ACS patients, although did not reach statistical significance. Future prospective studies investigating the utility of these specific laboratory and radiographic parameters as components of an ACS severity prediction score are warranted. DisclosuresTubman: Forma Pharmaceuticals: Consultancy; Novartis Pharmaceuticals: Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Perkin Elmer: Honoraria. Fasipe: Emmaus: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Other: Grant Review Committee ; Novartis: Consultancy; Pfizer: Research Funding.

Respiratory pathogens and acute chest syndrome in children with sickle cell disease

BackgroundAcute chest syndromes (ACS) may be associated with upper respiratory tract infections, but the epidemiology of viral and intracellular respiratory pathogens in children with sickle cell disease (SCD) is not...

Acute Chest Syndrome in Children with Sickle Cell Disease: Current Perspectives on Pathogenesis and Treatment

Acute chest syndrome (ACS) is the most prominent cause of mortality in children with sickle cell disease. Its cause was initially not clearly understood, but there are now established concepts regarding its aetiopathogenesis. This narrative review discusses the current perspectives on sickle cell disease pathogenesis and treatment. The PubMed database was searched for articles that met the review objective. The major causative factors are pulmonary infections, pulmonary infarction, and pulmonary fat embolism from bone marrow necrosis. These factors initiate events that result in ACS, in which a vicious cycle of infarction, inflammation, and lung collapse occurs, leading to ventilation-perfusion mismatch and hypoxaemia. ACS is best managed in hospital settings because intensive care of the patient may be required. Despite its complex management, the primary treatment modalities are supportive care, transfusion therapy, and pharmacotherapy. Although the efficacy of several modalities in attenuating or preventing ACS are well established, the outcomes from instituting others are not convincing. More research is, therefore, needed to strengthen the evidence for their therapeutic efficacy.

Acute Thoracic Syndrome in Sickle Cell Children at the Pediatrics Department of Donka National Hospital

Introduction: Acute thoracic syndrome is the appearance of a new pulmonary infiltrate on radiology associated with fever, desaturation or respiratory signs. It is the second leading cause of hospitalization and the first cause of death in sickle cell patients. It is an acute pulmonary complication whose pathophysiological mechanisms are still poorly understood. This study aims to study the epidemiological, clinical, therapeutic and evolutionary aspects of Acute Chest Syndrome in children at the Pediatrics Department of Donka National Hospital. Method: This is a prospective study of descriptive type for a period of 6 months from February 19 to August 19, 2019 on patients with sickle cell disease who developed an ATS in the pediatrics department of Donka National Hospital. Epidemiological, clinical, therapeutic and evolutionary data were studied and proportionate data were calculated. Results: The frequency of ATS was 39%. The mean age of our patients was 9.83 years with the extremes of 4 and 16 years. The age group from 6 to 10 years with a frequency of 66.7% was the most affected. Fever was the main clinical manifestation, followed by hepatomegaly. All our patients were homozygous SS and undergoing folic acid prophylaxis. 96% of our patients did not receive any specific vaccine. Antibiotic therapy, hyperhydration and analgesics were administered to all our patients. 96% of our patients were transfused with red blood cell concentrate. 96% of our patients were transfused with packed red blood cells. 96% of our patients were transfused with packed red blood cells and 96% of them had a favorable outcome. Conclusion: ATS is an acute complication of sickle cell disease responsible for significant mortality and morbidity in the pediatric population. Its treatment is symptomatic and must be started early. Emphasis must be placed on prevention to prevent or limit its occurrence.

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&lt;95%; transfer to reference centers was not always timely. During 75% of ACS episodes a simple red cell transfusion was required for Hb&gt;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. Disclosures Colombatti: AddMedica: Consultancy; Global Blood Therapeutics: Consultancy; Novartis: Consultancy.

Low-risk factors for severe bacterial infection and acute chest syndrome in children with sickle cell disease.

The rate of bacterial infections in children with sickle cell disease (SCD) has decreased in recent years, mainly due to penicillin prophylaxis and vaccination. To determine the rate of severe bacterial infection (SBI) in a cohort of children with SCD and to describe low-risk factors for confirmed SBI (CSBI) and acute chest syndrome (ACS). This 11-year retrospective cohort study included children with febrile SCD admitted to a reference hospital in Spain. A case-control study was performed comparing patients diagnosed with SBI to those without SBI, and subanalyses for groups with CSBI and ACS were carried out. A total of 316 febrile episodes were analyzed; 69 (21.8%) had confirmed or possible SBI. Thirteen of those had CSBI (4.1%), eight urinary tract infection, and five bacteremia/sepsis. Among the cases of possible SBI, the majority had ACS (54/56; 96.4%). Age >3 years, absence of central venous catheter, hemodynamic stability, and procalcitonin <0.6ng/ml were low-risk factors for CSBI, whereas normal oxygen saturation and C-reactive protein <3mg/dl were low-risk factors for ACS, with negative predictive values (NPV) of 98.3%, 97.4%, 96%, 97.2%, 87.5%, and 85.8%, respectively. In this cohort of children with SCD who were well vaccinated and received adequate prophylaxis, we found a low rate of bacteremia and CSBI. We described several low-risk factors for CSBI and ACS, all of them with a high NPV. These findings may help to develop a risk score to safely select the patients that could be managed with a more conservative approach.

Acute Chest Syndrome in Children with Sickle Cell Disease: Case Report and Review of the Literature

Sickle cell anemia (SCA) is the most common hemoglobinopathy all over the world. While the overall incidence of sickle cell disease trait in Turkey is %0.3-0.6, especially some places in Çukurova area it reaches the level of 3-44%. Painful vaso- occlusive crisis which is the most important complication of this disease, is predicted to increase in frequency and HbS polymerization is responsible in its pathophysiology. As an acute complication of SCA, acute chest syndrome is the second most common cause of hospitalization and mortality. İnitial approach to patients with an acute chest syndrome includes supportive treatments. Whereas, solely transfusion is not enough for treatment if there is worsening in respiratory signs and chest radiography; deepening of hypoxemia which requires an oxygen support. Therapeutic red cell apheresis can be used with the aim to treat acute complication of sickle cell disease. In this article we present successful therapeutic red cell apheresis and supportive treatments that we practise in our case who developed acute chest syndrome, and followed up by us with the diagnosis of sickle cell disease.

Early Noninvasive Ventilation and Nonroutine Transfusion for Acute Chest Syndrome in Sickle Cell Disease in Children: A Descriptive Study.

To describe the need for transfusion and short- and long-term evolutions of pediatric sickle cell disease patients with acute chest syndrome for whom early continuous noninvasive ventilation represented first-line treatment. Single-center retrospective chart study in PICU. A tertiary and quaternary referral PICU. All sickle cell disease patients 5-20 years old admitted with confirmed acute chest syndrome and not transfused in the previous month were included. None. Demographic data, laboratory and radiologic findings, transfusions, invasive ventilation, oxygen and noninvasive ventilation settings, duration of opioid treatment, length of hospital stay, and severe sickle cell disease complications in the ensuing 2 years were extracted from medical charts. Sixty-six acute chest syndrome in 48 patients were included. Continuous early noninvasive ventilation was well tolerated in 65 episodes, with positive expiratory pressure 4 cm H2O and pressure support 10 cm H2O (median) administered continuously, then discontinued during 7 days (median). No patient necessitated invasive ventilation or died. Twenty-three acute chest syndrome (35%) received transfusions; none received blood exchange. Transfused patients had more frequent upper lobe radiologic involvement, more severe anemia, higher reticulocyte counts, and higher C-reactive protein than nontransfused patients. Their evolution was more severe in terms of length of opioid requirement, length of noninvasive ventilation treatment, overall time on noninvasive ventilation, and length of stay. At 2-year follow-up after the acute chest syndrome episode, no difference was observed between the two groups. Early noninvasive ventilation combined with nonroutine transfusion is well tolerated in acute chest syndrome in children and may spare transfusion in some patients. Early recognition of patients still requiring transfusion is essential and warrants further studies.

Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia.

Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso-occlusive pain episodes among children with sickle cell anaemia (SCA). Aeroallergen sensitization is a risk factor for asthma. We hypothesized that aeroallergen sensitization is associated with an increased incidence of hospitalizations for ACS and pain. Participants in a multicentre, longitudinal cohort study, aged 4-18years with SCA, underwent skin prick testing to ten aeroallergens. ACS and pain episodes were collected from birth until the end of the follow-up period. The number of positive skin tests were tested for associations with prospective rates of ACS and pain. Multivariable models demonstrated additive effects of having positive skin tests on future rates of ACS (incidence rate ratio (IRR) for each positive test 1·23, 95% confidence interval [CI] 1·11-1·36, P<0·001). Aeroallergen sensitization was not associated with future pain (IRR 1·14, 95%CI 0·97-1·33, P=0·11). Our study demonstrated that children with SCA and aeroallergen sensitization are at increased risk for future ACS. Future research is needed to determine whether identification of specific sensitizations and allergen avoidance and treatment reduce the risk of ACS for children with SCA.

Acute Chest Syndrome in Children with Sickle Cell Disease.

Acute chest syndrome (ACS) is a frequent cause of acute lung disease in children with sickle cell disease (SCD). Patients may present with ACS or may develop this complication during the course of a hospitalization for acute vaso-occlusive crises (VOC). ACS is associated with prolonged hospitalization, increased risk of respiratory failure, and the potential for developing chronic lung disease. ACS in SCD is defined as the presence of fever and/or new respiratory symptoms accompanied by the presence of a new pulmonary infiltrate on chest X-ray. The spectrum of clinical manifestations can range from mild respiratory illness to acute respiratory distress syndrome. The presence of severe hypoxemia is a useful predictor of severity and outcome. The etiology of ACS is often multifactorial. One of the proposed mechanisms involves increased adhesion of sickle red cells to pulmonary microvasculature in the presence of hypoxia. Other commonly associated etiologies include infection, pulmonary fat embolism, and infarction. Infection is a common cause in children, whereas adults usually present with pain crises. Several risk factors have been identified in children to be associated with increased incidence of ACS. These include younger age, severe SCD genotypes (SS or Sβ0 thalassemia), lower fetal hemoglobin concentrations, higher steady-state hemoglobin levels, higher steady-state white blood cell counts, history of asthma, and tobacco smoke exposure. Opiate overdose and resulting hypoventilation can also trigger ACS. Prompt diagnosis and management with intravenous fluids, analgesics, aggressive incentive spirometry, supplemental oxygen or respiratory support, antibiotics, and transfusion therapy, are key to the prevention of clinical deterioration. Bronchodilators should be considered if there is history of asthma or in the presence of acute bronchospasm. Treatment with hydroxyurea should be considered for prevention of recurrent episodes. This review evaluates the etiology, pathophysiology, risk factors, clinical presentation of ACS, and preventive and treatment strategies for effective management of ACS.

Regional- and Age-Related Differences in Pain in Children with Sickle Cell Anemia: Results from the Multinational DOVE Study

Background: Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) was a multi-national Phase 3 trial to assess the efficacy of prasugrel for the prevention of vaso-occlusive crisis (VOC) as a composite endpoint of painful crisis or acute chest syndrome in children and adolescents aged 2-18 years with sickle cell anemia (SCA). Despite a trend toward fewer VOCs in the prasugrel-treated oldest age group (12-18 years), DOVE did not meet its primary endpoint. This was the first multinational prospective study of diary-reported pain rate and intensity in children and adolescents with SCA.Aim of current study: This sub-study evaluated VOC events (as defined by DOVE), analgesic use, and the rate, intensity, and perception of pain by geographical region and age group.Data: During the DOVE study, participants who were 4 years or older used daily diaries to report pain rate and intensity, and analgesic use. Rates of pain and analgesic use were calculated for each patient by summing the number of days with any pain or analgesic use reported divided by the number of non-missing diary entries from randomization to 9 months. Mean pain intensity was calculated similarly, but days in which participants reported pain of "0" were not included. Pain rate and intensity were evaluated only for participants 7 years or older. Type of analgesic use (opioid vs non-opioid) was also evaluated in all participants. Treatment arms (prasugrel-treated and untreated patients) were combined for the current analysis, as justified by the lack of a statistically significant treatment effect. Data were analyzed by univariable and multivariable methods.Results: There was no association between baseline hematology labs or lactic dehydrogenase levels and pain rate or intensity. In multivariable analysis, older participants (aged ≥12 years) reported more frequent pain than younger participants (p=0.0320). Hydroxyurea (HU) use at baseline did not affect pain rate or pain intensity. The regions of the Americas and West Europe showed higher pain rate and intensity scores than Africa and the Middle East. (Table 1) Opioid use was much higher in the Americas compared with other regions p=0.0002. (Table 2)Conclusions: Pain rates were higher in older children, demonstrating a worsening of pain during the lifespan, which is consistent with previous literature. Pain rate and intensity were similar irrespective of HU treatment; whether this finding reflects increased baseline pain in participants on HU or other causality is unclear. Regional differences in pain rate and intensity were seen. Pain intensity and opioid use were significantly higher in the Americas than in other regions. In contrast, the lowest reported pain rates and intensities were found in Africa. These findings suggest cultural and/or regional differences in SCA pain perception and reporting that require further exploration. The relationship between pain intensity and analgesic treatment practices also needs further study. [Display omitted] DisclosuresKanter:Novartis: Consultancy. Heath:Eli Lilly and Company: Employment. Zhou:Eli Lilly and Company: Employment, Other: Minor Shareholder. Colombatti:Eli Lilly and Company: Research Funding. Dampier:Eli Lilly and Company: Consultancy, Research Funding. Hassab:Eli Lilly and Company: Research Funding. Brown:Eli Lilly and Company: Employment, Other: Minor Shareholder. Jakubowski:Eli Lilly and Company: Employment, Equity Ownership. Yao:Eli Lilly and Company: Employment. Knorr:Eli Lilly and Company: Employment, Equity Ownership. Hoppe:Eli Lilly and Company: Consultancy.

Poor Sensitivity of Physician Assessment to Predict Acute Chest Syndrome in Children with Sickle Cell Disease and Fever

▪Background: Acute chest syndrome (ACS) is a common complication of sickle cell disease (SCD) detected by chest radiography (CXR) with significant morbidity and mortality. Previousstudies show that many children with ACS present without obvious signs or symptoms. We evaluate the sensitivity of clinical assessment for predicting ACS in children with SCD and fever.Methods: This is a prospective cross-sectional, observational study that took place from June 2014-March 2015. Consented providers in 2 CHOA EDs caring for patients aged 0-18 years with SCD and fever 38.0 C completed a questionnaire including vital signs, past history of ACS or asthma, clinical signs, symptoms, physical exam (PE) findings and whether the provider suspected pneumonia/ACS on CXR. CXRs were read by a blinded pediatric radiologist. CXRresults were compared to questionnaire responses completed prior to CXR. Sensitivity, specificity, positive and negative predictive value and accuracy of clinical assessment for predicting ACS compared to CXR was determined. Signs, symptoms, PE findings, and clinical course was compared in cases with positive versus negative CXRs as well as suspected versus unsuspected ACS.Results: 111 SCD fever events with CXR were evaluated over 10 months. Thirteen patients (12%) had evidence of ACS on CXR. Based on MD questionnaires, only 46% of ACS cases were predicted by clinical assessment alone. Physician assessment sensitivity to identify ACS was low at only 50%. (Table 1). An abnormal lung exam, history of ACS, lack of rhinorrhea and a trend towards chest pain were more common in ACS cases compared to children with a negative CXR. However, 62% of children with ACS had a normal lung exam. Cases of unsuspected ACS had a lower degree of fever at presentation to the ED, but ultimately required more packed red blood cell transfusions during hospitalization than suspected ACS cases. There were no other significant differences in signs, symptoms, PE findings or clinical course in suspected vs. unsuspected ACS cases. The recently published NIH guidelines forincluding CXR in a fever work-up for children with SCD (risks include presence of cough, tachypnea, shortness of breath or abnormal lung exam) performed poorly in our cohort, with an Area under the Curve (AUC) = 0.725Conclusions: Clinical impression alone is a poor predictor of ACS in children with SCD and fever. We and others have identified clinical criteria to help identify a high risk group, however many children with ACS lack signs and symptoms of ACS and may be missed based on clinical assessment alone. Given the high mortality and morbidity associated with ACS, empiric CXR may still be indicated in children with SCD. Due to radiation exposure risks with CXR, our team is studying lung ultrasound as an alternative modality for ACS imaging. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Red blood cell storage duration is not associated with clinical outcomes for acute chest syndrome in children with sickle cell disease.

Providers commonly transfuse sickle cell disease (SCD) patients with fresh red blood cells (RBCs) as treatment for acute chest syndrome (ACS). The objective of this study was to determine if there is an association between the storage duration of RBCs and length of hospitalization and oxygen requirement after transfusion in pediatric SCD patients with ACS. This is a retrospective cohort study of pediatric SCD patients with ACS treated with a simple RBC transfusion over 8.5 years at a single institution. Multivariate generalized estimation equation analysis was used to identify associations between storage duration of RBCs and outcome measures. A total of 234 ACS episodes in 131 subjects were included. The median storage duration of the oldest unit of transfused RBCs was 17 days (interquartile range, 11-26). The majority of ACS episodes, 77.4%, were treated with 1 unit of transfused RBCs; 20.9% received 2 units; and 1.7% received 3 or more units of RBCs. There was no association between the storage duration of the oldest unit of transfused RBCs and either duration of hospitalization or supplemental oxygen requirement after transfusion in multivariate analyses. This retrospective study is one of the first to investigate the role of the storage lesion in children with SCD and does not support the preferential transfusion of fresh RBCs for ACS. Ultimately, a randomized controlled trial is necessary to determine whether the storage age of RBCs affects outcomes for patients with SCD and ACS.

Age-dependent pathophysiology of acute chest syndrome in children with sickle cell disease.

Age-dependent pathophysiology of acute chest syndrome in children with sickle cell disease.