Discussion
In ACS, guidelines from the British Society of Hematology recommend that patients presenting with fever, hypoxia, tachypnea, tachycardia and abnormal respiratory exam findings should be treated empirically as well as receive a CXR11. However, radiological signs can be delayed compared to physical signs; a normal CXR does not preclude the diagnosis of ACS if there is clinical suspicion11. Vichinsky’s study of 939 patients found that 35% had normal lung exams and 17% presented with lower extremity pain when they presented with ACS12. Our data demonstrate that clinical findings such as chest pain, tachypnea and hypoxia were most likely to correlate with a diagnosis of ACS. While 69% of our febrile patients received a CXR in the PED, only 13% were ultimately diagnosed with ACS, indicating that more CXRs and radiation exposure occurred in the febrile population than may have been necessary. When adjusting for fever and asthma, the most salient predictors of ACS were hypoxia and chest pain. When present, these findings were significant predictors of ACS; when absent, patients had significantly decreased odds of ACS.
While CXR remains a key diagnostic tool in the diagnosis of ACS, many studies have suggested that lung ultrasound may provide evidence for diagnosis and evolution of ACS. CXR can be normal in up to approximately 66% of early cases of ACS, including CXRs obtained in patients who were hypoxemic on presentation13. Historically, lung ultrasound diagnostic research had been primarily performed in adult patients; however, more recently, lung ultrasound has been evaluated in the pediatric population. Multiple studies in pediatric SCD patients have demonstrated that lung ultrasounds showed a higher number of ACS associated lesions than CXR13. In a study by Vetter et al., lung ultrasound was superior to CXR for diagnosing consolidations and pleural effusions in these patients.13 Future investigations should evaluate whether lung ultrasound is at least equal to, if not superior, to CXR to support the broader use of radiation-sparing bedside alternatives for diagnosing ACS in pediatric patients.
Strengths of our study include a relatively large sample size; the total “n” of 424 was robust enough to allow for significant statistical analysis and supported a meaningful analysis stratifying by risk factors. Our study evaluated SCD in an understudied patient population, with a focus on children aged 2 to 12 years old due to the higher incidence and severity of ACS in this age group. One limitation is that our data may not be generalizable to patients under 2 years or older than 12 years. The retrospective study design can limit results due to risk of bias in documentation, but we evaluated all PED and inpatient notes and laboratory values to increase likelihood of capturing important clinical data. As with any retrospective study, we can only evaluate for associations and not causation, but we performed multivariable modelling, in addition to bivariate analysis, in order to control for confounders and better assess for significant predictors. In addition, we evaluated subjects presenting to the PED in 2016-2018, which is a more modern cohort than many studies on pediatric SCD and ACS diagnosis.
In conclusion, studies have demonstrated that the clinical presentation of ACS differ based on the age of patients. Prior studies have noted that children under the age of 10 tend to present with fever, cough and wheezing, whereas adults typically report chest pain and dyspnea.14 Further research is needed to confirm, but based on our data, incorporating the presence or absence of chest pain and hypoxia in pediatric patients may help focus the use of CXR to the appropriate patient population at risk of developing ACS. By 18 years of age, most children with SCD will have had on average 26.7 (95% CI: 24.1-29.3; range 0-492.1) radiographic tests while 5% of these patients will have had more than 100 radiographic tests15. A high cumulative lifetime of radiation exposure is an established risk factor for serious life-threatening diseases such as cancer16. With advancements in standards of medical care for patients with SCD, the life expectancy for SCD patients has improved to an average of 54 years old8, which makes it even more important to reduce cumulative exposure to diagnostic radiation in this vulnerable population. Thus, this study provides evidence to support a more critical assessment of risk factors and presenting symptoms to better triage which pediatric patients warrant further imaging in the PED at initial presentation to investigate for possible ACS.