Clinical correlates of acute pulmonary events in children and adolescents with sickle cell disease

Abstract

Objectives We aimed to identify risk factors for acute pulmonary events in children and adolescents in the Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study. Methods Patients with hemoglobin SS (n=376) and other sickle cell genotypes (n=127) aged 3-20 years were studied at four centers in a cross-sectional manner. A sub-group (n=293) was followed for a median of 21 months (range 9-35). Results A patient-reported history of one or more acute pulmonary events, either acute chest syndrome (ACS) or pneumonia, was obtained in 195 hemoglobin SS patients (52%) and 51 patients with other genotypes (40%). By logistic regression, history of acute pulmonary events was independently associated with patient-reported history of asthma (p<0.0001), older age (p=0.001), >3 severe pain episodes in the preceding 12 months (p=0.002), higher tricuspid regurgitation velocity (TRV) (p=0.028), and higher white blood cell (WBC) count (p=0.043) among hemoglobin SS patients. History of acute pulmonary events was associated with >3 severe pain episodes (p=0.009) among patients with other genotypes. During follow-up, 43 patients (15%) had at least one new ACS episode including 11 without a baseline history of acute pulmonary events. History of acute pulmonary events (odds ratio 5.4; p<0.0001) and younger age (odds ratio 0.9; p=0.010) were independently associated with developing a new episode during follow-up. Conclusions Asthma history, frequent pain and higher values for TRV and WBC count were independently associated with history of acute pulmonary events in hemoglobin SS patients and frequent pain was associated in those with other genotypes. Measures to reduce pain episodes and control asthma may help to decrease the incidence of acute pulmonary events in SCD.

Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease

“…One hundred thirty seven patients were enrolled at Children's National Health System [8]. Repository DNA was obtained from 67 patients participating in the Pulmonary Hypertension and the Hypoxic Response in the SCD (PUSH) study [27] from the following medical centers: Howard University Hospital (n=38), University of Michigan (n=16) and Fairfax Hospital in Northern Virginia (n=13). Blood samples were collected at the time of consent and DNA was extracted using a Qiagen DNA extraction kit (Qiagen, CA).…”

Prevalence of pulmonary hypertension in children with sickle cell disease

“…[9][10] In Sickle cell anemia and other haemolytic disorders, intravascular haemolysis releases red blood cell Hemoglobin and arginase into the plasma. Plasma Hemoglobin scavenges and destroys nitric oxide while arginase interferes with further nitric oxide production by depleting arginine, an important substrate in nitric oxide production.…”

Airway inflammation in sickle cell disease—A translational perspective

“…Since most of these studies were cross‐sectional or retrospective, a more scientific way of estimating the disease prevalence should be based on the few prospective epidemiological studies among SCD cohorts, in which patients were enrolled and prospectively followed over time regardless of their baseline symptoms and diagnosis. Data from three such large cohorts of SCD children report asthma prevalence rates of 17% (The Cooperative Study of Sickle Cell Disease, “CSSCD”‐291 participants followed for a mean of 11 years), 28% (The Sleep and Asthma Cohort Study, “SAC”‐243 participants followed over 10 years), and 24% (The Pulmonary Hypertension and Hypoxic Response study, “PUSH”‐376 children followed up to 4 years) suggesting that there may have been over‐diagnosis of asthma in some of the cross sectional and retrospective cohorts …”