Role of free radicals in the pathogenesis of acute chest syndrome in sickle cell disease

Acute chest syndrome (ACS) of sickle cell disease (SCD) is characterized pathologically by vaso-occlusive processes that result from abnormal interactions between sickle red blood cells (RBCs), white blood cells (WBCs) and/or platelets, and the vascular endothelium. One potential mechanism of vascular damage in ACS is by generation of oxygen-related molecules, such as superoxide (O(2)(-)), hydrogen peroxide (H(2)O(2)), peroxynitrite (ONOO(-)), and the hydroxyl (•OH) radical. The present review summarizes the evidence for alterations in oxidant stress during ACS of SCD, and the potential contributions of RBCs, WBCs and the vascular endothelium to this process

Sickle cell disease: Wheeze or asthma?

Sickle cell disease (SCD) is the most common life-limiting genetic disease among African Americans, affecting more than 100,000 people in the United States. Respiratory disorders in patients with sickle cell disease have been associated with increased morbidity and mortality. Associations between asthma and pain, acute chest syndrome (ACS), and even death have long been reported. More recently wheezing, even in the absence of an asthma diagnosis, has gained attention as a possible marker of SCD severity. Several challenges exist with regards to making the diagnosis of asthma in patients with SCD, including the high prevalence of wheezing, evidence of airway obstruction on pulmonary function testing, and/or airway hyperresponsiveness among patients with SCD. These features often occur in isolation, in the absence of other clinical criteria necessary for an asthma diagnosis. In this review we will summarize: 1) Our current understanding of the epidemiology of asthma, wheezing, airway obstruction, and airway responsiveness among patients with SCD; 2) The evidence supporting associations with SCD morbidity; 3) Our understanding of the pathophysiology of airway inflammation in SCD; 4) Current approaches to diagnosis and management of asthma in SCD; and 5) Future directions

Common Complications of Sickle Cell Disease: A Simulation-Based Curriculum

Introduction: Sickle cell disease (SCD), the most common autosomal recessive genetic disorder worldwide, affects nearly every organ of the body and results in accelerated mortality. Nationally, internal medicine physicians lack a complete understanding of morbidity and mortality in this population leading to health care disparities. Methods: We created a 2-hour curriculum consisting of three SCD case vignettes representing common disease complications (acute stroke, acute chest syndrome, and septic shock) with the goal to increase medicine house staff knowledge and confidence in patient management. Residents completed a pretest to assess baseline knowledge and were divided into groups of four to five. Three simulation cases were completed by each group; learners needed to work through a differential diagnosis and describe key management steps. Each group was graded on achieving the 10 critical actions for each case. Following each case, there was a faculty-led debriefing session. Residents repeated the pretest 30 days after completion of the curriculum (posttest). RESULTS: Thirty-six second year internal medicine residents participated in this curriculum. After completing this curriculum, residents improved their test score from 33% (SD = 12%) to 57% (SD = 18%) (p \u3c .0001). Additionally, self-reported confidence in management scores increased from 2.6 (SD = 0.8) in the pretest to 3.5 (SD = 0.4) in the posttest (p = .02) on a 5-point Likert scale (1 = not very confident, 5 = very confident). Discussion: Use of a simulation curriculum increased knowledge and confidence of internal medicine residents in the management of critical illness in patients with SCD

A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported

Critical Care of Patients With Cardiopulmonary Complications of Sarcoidosis

Sarcoidosis is a systemic inflammatory disease defined by the presence of aberrant granulomas affecting various organs. Due to its multisystem involvement, care of patients with established sarcoidosis becomes challenging, especially in the intensive care setting. While the lungs are typically involved, extrapulmonary manifestations also occur either concurrently or exclusively within a significant proportion of patients, complicating diagnostic and management decisions. The scope of this review is to focus on what considerations are necessary in the evaluation and management of patients with known sarcoidosis and their associated complications within a cardiopulmonary and critical care perspective