Wamkpah Nneoma, Shrestha Anuj, Salzman Gary, Simon Stephen, Suman Sahil, Poisner Alan, Molteni Agostino
Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, Saint Louis, USA.
Hematology and Oncology, University of Missouri-Kansas City, Kansas City, USA.
Cureus. 2022 Mar 28;14(3):e23567. doi: 10.7759/cureus.23567. eCollection 2022 Mar.
Rationale Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Current treatment is supportive-supplemental oxygen, transfusions, and antibiotics. Prevention of ACS may reduce morbidity and mortality in patients with SCD. Acute chest syndrome appears similar to pulmonary fat embolism (PFE), a complication of severe skeletal trauma or orthopedic procedures from pulmonary micro-vessel blockage by bone marrow fat. Vascular obstruction and bone marrow necrosis occur in PFE and ACS. Pulmonary fat embolism rat models have shown that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) mitigate damage in PFE. These medications could work similarly in ACS. We hypothesize that time to readmission after one hospitalization for ACS will be reduced in patients taking ACEI or ARB compared to patients who are not. Methods This is a retrospective cohort study. Inclusion criteria are adults (18 to 100 years) with sickle cell anaemia (HbSS), hemoglobin SC (HbSC) disease, sickle cell thalassemia (HbSβThal), hospitalized with ACS over 16 years (January 1, 2000, to March 31, 2016); patients who take and don't take ACEI or ARB. Children (<18 years old), elderly adults (>100 years old), pregnant patients, and patients with sickle cell trait were excluded. Data was collected from the Health Facts database, which contains de-identified information from the electronic medical records of hospitals in which Cerner© has a data use agreement. Kaplan-Meier estimates explored a time-to-event model of ACS readmission. Multivariable analysis (age, gender, smoking history) was conducted using Cox proportional hazards regression. Results were reported around a 95% confidence interval. Results There were 6972 patients in total. Of which, 9.6% (n = 667) reported taking ACEI or ARB. Results for the covariates were: average age of 38 years old; 63% female (n = 4366/6969); 16% smokers (n = 1132). Readmission rates were higher for patients not taking ACEI/ARB than those who did: 0.44 (95% CI 0.43, 0.46) versus 0.28 (95% CI 0.24, 0.31) at one year, and 0.56 (95% CI 0.55, 0.58) versus 0.33 (95% CI 0.29, 0.37) at two years. Age had the strongest effect on readmission rates for patients taking ACEI/ARB (adjusted hazards ratio 0.78 [95% CI 0.68, 0.91]). Conclusion Patients with SCD who reported taking ACEI or ARB had lower readmission rates for ACS; age was the strongest covariate. Our results may have a significant impact on the prevention of ACS. Prospective studies comparing ACEI or ARB therapy versus placebo are needed to confirm this preventative effect.
理论依据 急性胸部综合征（ACS）是镰状细胞病（SCD）的一种危及生命的并发症。目前的治疗方法是支持性治疗——补充氧气、输血和使用抗生素。预防ACS可能会降低SCD患者的发病率和死亡率。急性胸部综合征与肺脂肪栓塞（PFE）相似，后者是严重骨骼创伤或骨科手术的一种并发症，由骨髓脂肪阻塞肺微血管所致。PFE和ACS都会发生血管阻塞和骨髓坏死。肺脂肪栓塞大鼠模型显示，血管紧张素转换酶抑制剂（ACEI）和血管紧张素II受体阻滞剂（ARB）可减轻PFE中的损伤。这些药物在ACS中可能有类似作用。我们假设，与未服用ACEI或ARB的患者相比，服用ACEI或ARB的患者因ACS住院一次后的再入院时间会缩短。方法 这是一项回顾性队列研究。纳入标准为16年间（2000年1月1日至2016年3月31日）因ACS住院的镰状细胞贫血（HbSS）、血红蛋白SC（HbSC）病、镰状细胞地中海贫血（HbSβThal）成年患者（18至100岁）；服用和未服用ACEI或ARB的患者。排除儿童（<18岁）、老年人（>100岁）、孕妇和镰状细胞性状患者。数据从健康事实数据库收集，该数据库包含来自Cerner©拥有数据使用协议的医院电子病历的去识别信息。Kaplan-Meier估计探索了ACS再入院的事件发生时间模型。使用Cox比例风险回归进行多变量分析（年龄、性别、吸烟史）。结果以95%置信区间报告。结果 总共有6972名患者。其中，9.6%（n = 667）报告服用ACEI或ARB。协变量结果为：平均年龄38岁；63%为女性（n = 4366/6969）；16%为吸烟者（n = 1132）。未服用ACEI/ARB的患者再入院率高于服用者：一年时为0.44（95% CI 0.43, 0.46）对0.28（95% CI 0.24, 0.31），两年时为0.56（95% CI 0.55, 0.58）对0.33（95% CI 0.29, 0.37）。年龄对服用ACEI/ARB的患者再入院率影响最大（调整后风险比0.78 [95% CI 0.68, 0.91]）。结论 报告服用ACEI或ARB的SCD患者因ACS的再入院率较低；年龄是最强的协变量。我们的结果可能对ACS的预防有重大影响。需要进行比较ACEI或ARB治疗与安慰剂的前瞻性研究来证实这种预防效果。
