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Case Presentation A 50-year-old woman presented with 3 months of cough, dyspnea, and fatigue. She also reported new fevers, night sweats, and a rash on her face and torso. On presentation she was tachycardic and tachypneic, with oxygen saturation of 81% on 2 L/min of oxygen. She was in mild respiratory distress. Results of the physical examination were remarkable for tender left cervical and axillary adenopathy and bibasilar pulmonary crackles. She had an acneiform rash on her face, chest, and back, consisting of multiple nonblanching erythematous or violaceous macules and papules ( Fig 1 ) and had conjunctival edema. Admission laboratory test results were significant for a WBC count of 56,000, of which 79.5% were lymphocytes. Hemoglobin and platelet levels were normal. She was admitted for further management.

The presentation, pathobiology, and prognosis of asthma are highly heterogeneous and challenging for clinicians to diagnose and treat. In addition to the adaptive immune response that underlies allergic inflammation, innate immune mechanisms are increasingly recognized to be critical mediators of the eosinophilic airway inflammation present in most patients with asthma. Efforts to classify patients by severity and immune response have identified a number of different clinical and immune phenotypes, indicating that the innate and adaptive immune responses are differentially active among patients with the disease. Advances in the detection of these subgroups using clinical characteristics and biomarkers have led to the successful development of targeted biologics. This has moved us to a more personalized approach to managing asthma. Here we review the emerging endotypes of asthma and the biologics that have been developed to treat them.

Severe asthma is a complex and heterogeneous inflammatory disease that encompasses multiple phenotypes that are being targeted with an increasing number of biologic therapies. Our understanding of the mechanisms that drive severe asthma has been rapidly evolving over the last decade, revealing multiple pathologic mechanisms that can result in similar asthma symptoms and disease activity. Concurrently, there has been a dramatic change in the approach to asthma therapies mediated by the availability of new targeted therapies for severe asthma. There are now five biologic therapies and bronchial thermoplasty approved by the Food and Drug Administration (FDA) that are targeted at reducing exacerbations and oral corticosteroid (OCS) exposure and improving asthma control. Identification of responders to these advanced therapies currently relies on surrogate markers of inflammation. These surrogate markers (biomarkers) can be used as phenotyping tools, predictive markers of response, and prognostic markers. Although our understanding of how to use biomarkers to select patients for these therapies has evolved, many limitations remain, and more work needs to be done to improve the accuracy of these markers. Personalized medicine is now a realizable dream when managing severe asthma but faced with increasingly complex decision making surrounding which therapies should be given to a particular patient. It is imperative that we continue to work to improve the precision of our tools if we are ever to fully realize the goal of providing precision medicine to patients that suffer from asthma. In this review, we will discuss the current biomarkers used to phenotype patients with asthma, how they are currently used, their limitations, and future biomarkers.

To identify challenges that disadvantaged adults with asthma face in mitigating social and environmental factors associated with poor symptom control.Using a community-engaged approach, we partnered with a community health center in New Haven, CT to conduct in-person interviews and a written survey of asthmatic adults with poor symptom control. Using the constant comparative method, we analyzed participant interviews to establish emerging themes and identify common barriers to improved outcomes. Through a written survey utilizing clinically validated questions, we assessed information on access to medical care, asthma control, and selected social and environmental risk factors.Twenty-one patients (mean age 47, 62% female, 71% Black, 95% insured by Medicaid) participated. The average Asthma Control Test (ACT) score was 11.6. Seventy-six percent of participants were currently employed and of those, 75% reported work-related symptoms. Among participants currently in housing, 59% reported exposure to domiciliary mice and 47% to mold. We identified three themes that summarize the challenges the study participants face: 1) Lack of knowledge about home and workplace asthma triggers; 2) Lack of awareness of legal rights or resources available to mitigate adverse conditions in the home or work environment; and 3) Fear of retaliation from landlords or employers, including threats of eviction, sexual assault, and job loss.Patients with poorly controlled asthma in a disadvantaged urban northeast community identified common barriers in both the domestic and work environments that impeded attainment of symptom control. These challenges may be best addressed through legal advocacy for those most at risk.

inTroDucTion Tumor lysis syndrome (TLS) is a metabolic disturbance caused by the destruction of rapidly dividing cancer cells following administration of cytotoxic chemotherapy. The subsequent release of intracellular material results in hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. The clinical presentation of TLS, including acute kidney injury, results from these electrolyte abnormalities and can be life-threatening. Here we present the second reported case of TLS in a woman with endometrial cancer.

In B-cell malignancies, the t(11;14)(q13;q32) at the 11q13 BCL1 locus is characterized by a scattering of breakpoint sites along a 100 kb genomic region, between the BCL1 major translocation cluster (MTC) and the PRAD1 (also termed cyclin D1 or CCND1) gene. Recently, the 11q13 breakpoint region was extended on both sides, centromeric to the MTC and telomeric to PRAD1. We report here the molecular cloning of a new t(11;14) breakpoint site, 20 kb centromeric to the MTC, from a patient with prolymphocytic leukemia. We subcloned a non-repetitive DNA fragment near the breakpoint and mapped this new 11q13 probe (pHO11c) relative to already identified breakpoint sites, using long- and short-range physical mapping within the BCL1 locus. Rearrangements in the BCL1 locus are associated with deregulation of the PRAD1 gene, which is often overexpressed, particularly in mantle-cell malignancies. The detectable but weak PRAD1 expression in the case we present suggests that this breakpoint centromeric to the MTC still lies inside the BCL1 locus boundaries. We think that attention should be focused on this region centromeric to the BCL1-MTC, where the investigation of previously unidentified translocations may increase understanding of the PRAD1 gene deregulation in t(11;14) associated pathologies.