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BACKGROUND: Total serum IgE (tIgE) is an important intermediate phenotype of allergic disease. Whole genome genetic association studies across ancestries may identify important determinants of IgE. OBJECTIVE: By leveraging data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) and the Atopic Dermatitis Research Network (ADRN), we aim to increase understanding of genetic variants affecting tIgE production across the ancestry and allergic disease spectrum (N=21,901). METHODS: We performed genome-wide association within strata of study, disease, and ancestry groups, and combined results via a meta-regression approach that models heterogeneity attributable to ancestry. We also tested for association between HLA alleles called from whole genome sequence data and tIgE, assessing replication of associations in HLA alleles called from genotype array data. For details, please see the Methods section in this article’s Online Repository at www.jacionline.org. RESULTS: We identified six loci at genome-wide significance (P

Acute pulmonary problems in sickle cell disease (SCD) patients, in particular acute chest syndrome (ACS), cause significant mortality and morbidity. It is important to differentiate ACS from pneumonia to avoid inappropriate or inadequate treatment. Asthma may increase the risk of ACS and co-morbid asthma and SCD are associated with worse patient outcomes and, in preclinical models, more severe inflammation. Recurrent wheezing, however, can occur in the absence of a diagnosis of asthma; it is likely due to SCD related inflammation and additional therapies than those that treat asthma may be required. Further research is merited to clarify these issues.

Objectives: To examine the clinical features and epidemiology of invasive pneumococcal disease in homozygous sickle cell (SS) disease and the efficacy of pneumococcal prophylaxis. Study design: A retrospective study of 80 episodes in 68 patients in the Jamaican Sickle Cell Clinic in a 25-year period (1973-1997). Results: Clinical features included a history of fever (94%), vomiting (70%), an ill appearance (80%), fever (89%), abnormal chest signs (43%), and meningismus (39%). There were 14 deaths—13 among 68 initial episodes (6 of which were deaths on arrival) and one death during a recurrence. Thirteen episodes occurred in patients who should have been receiving antibiotic prophylaxis. Ten were due to failure to adhere to protocols, and 3 occurred during prophylaxis; one patient was receiving oral erythromycin, and two had received injections of benzathine penicillin 4 and 24 days before the episode. All but one of the pneumococcal isolates were susceptible to penicillin. The 32 patients who received pneumococcal vaccine had more mild clinical courses as indicated by a greater chance of being treated as outpatients or surviving after admission (Mann-Whitney U test, P =.03). Conclusions: Penicillin remains the mainstay of prophylaxis, although breakthroughs occur and will become more common with the increasing frequency of penicillin-resistant organisms. Pneumococcal immunization appears to ameliorate the course of invasive disease. (J Pediatr 2001; 138:65-70)

Caraballo; J Knight-Madden and Kathleen C. Barnes. Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University (JHU), Baltimore, MD 21224; College of Medicine, National Genome Center at Howard University, Washington, DC.; Department of Epidemiology, Bloomberg School of Public Health, JHU, Baltimore, MD 21205; Servico de Imunologia, Hospital Universitario Professor Edgard Santos, Salvador, Bahia, Brazil; 5 ProAR – Faculdade de Medicina, Federal University of Bahia, Salvador, Bahia, Brazil; Servico de Imunologia, Hospital Universitario Professor Edgard Santos, Salvador, Bahia, Brazil; 7 Faculty of Medicine, University of the West Indies, Cave Hill Campus, Barbados; 8 Institute for Immunological Research, University of Cartagena, Cartagena, Colombia; 9 Tropical Medicine Research institute, The University of the West Indies, Mona Kingston 7, Jamaica, West Indies.