Deconstructing the Way We Use Pulmonary Function Test Race-Based Adjustments.

Race is a social construct. It is used in medical diagnostic algorithms to adjust the readout for spirometry and other diagnostic tests. The authors review historic evidence about the origins of race adjustment in spirometry, and recent attention to the lack of scientific evidence for their continued use. Existing reference values imply that White patients have better lung function than non-White patients. They perpetuate the historical assumptions that human biological functions of the lung should be calculated differently on the basis of racial-skin color without considering the difficulty of using self-identified race. More importantly, they fail to consider the important effects of environmental exposures, socioeconomic differences, health care access, and prenatal factors on lung function. In addition, the use of "race adjustment" implies a White standard to which other non-White values need "adjustment." Because of the spirometric guidelines in place, the current diagnostic prediction adjustment practice may have untoward effects on patients not categorized as "White," including underdiagnosis in asthma and restrictive lung disease, undertreatment with lung transplant, undercompensation in workers compensation cases, and other unintended consequences. Individuals, institutions, national organizations, and policymakers should carefully consider the historic basis, and reconsider the current role of an automated, race-based adjustment in spirometry.

Epidemiology of Anaphylaxis in Critically Ill Children in the United States and Canada.

BACKGROUND: Anaphylaxis is a rapid-onset, multisystem, and potentially fatal hypersensitivity reaction with varied reports of prevalence, incidence, and mortality. There are limited cases reported of severe and/or fatal pediatric anaphylaxis. OBJECTIVE: This study describes the largest cohort of intensive care unit pediatric anaphylaxis admissions with a comprehensive analysis of identified triggers, clinical and demographic information, and probability of death. METHODS: We describe the epidemiology of pediatric anaphylaxis admissions to North American pediatric intensive care units (PICUs) that were prospectively enrolled in the Virtual Pediatric Systems database from 2010 to 2015. One hundred thirty-one PICUs in North America (United States and Canada) were queried for anaphylaxis International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision codes from the Virtual Pediatric Systems database from 2010 to 2015 in the United States and Canada. One thousand nine hundred eighty-nine patients younger than 18 years were identified out of 604,279 total number of patients admitted to a PICU in the database during this time frame. RESULTS: The primary outcome was mortality, which was compared with patient and admission data using Fisher exact test. Secondary outcomes (intubation, length of stay, mortality risk scores, systolic blood pressure, and pupillary reflex) were analyzed using the Kruskal-Wallis test or Wilcoxon rank-sum test, as appropriate. One thousand nine hundred eighty-nine patients with an anaphylaxis International Classification of Diseases code were identified in the database. One percent of patients died because of critical anaphylaxis. Identified triggers for fatal cases were peanuts, milk, and blood products. Peanuts were the most common trigger. Children were mostly male when younger than 13 years, and mostly female when 13 years and older. Average length of stay was 2 days. There was a higher proportion of Asian patients younger than 2 years or when the trigger was food. CONCLUSIONS: This is the largest study to describe pediatric critical anaphylaxis cases in North America and identifies food as the most common trigger. Death occurs in 1% of cases, with intubation occurring most commonly in the first hour. The risk for intensive care unit admission in children underscores the serious nature of anaphylaxis in this population.

Bilayer Effects of Antimalarial Compounds.

Because of the perpetual development of resistance to current therapies for malaria, the Medicines for Malaria Venture developed the Malaria Box to facilitate the drug development process. We tested the 80 most potent compounds from the box for bilayer-mediated effects on membrane protein conformational changes (a measure of likely toxicity) in a gramicidin-based stopped flow fluorescence assay. Among the Malaria Box compounds tested, four compounds altered membrane properties (p< 0.05); MMV007384 stood out as a potent bilayer-perturbing compound that is toxic in many cell-based assays, suggesting that testing for membrane perturbation could help identify toxic compounds. In any case, MMV007384 should be approached with caution, if at all.

Phytochemicals perturb membranes and promiscuously alter protein function.

A wide variety of phytochemicals are consumed for their perceived health benefits. Many of these phytochemicals have been found to alter numerous cell functions, but the mechanisms underlying their biological activity tend to be poorly understood. Phenolic phytochemicals are particularly promiscuous modifiers of membrane protein function, suggesting that some of their actions may be due to a common, membrane bilayer-mediated mechanism. To test whether bilayer perturbation may underlie this diversity of actions, we examined five bioactive phenols reported to have medicinal value: capsaicin from chili peppers, curcumin from turmeric, EGCG from green tea, genistein from soybeans, and resveratrol from grapes. We find that each of these widely consumed phytochemicals alters lipid bilayer properties and the function of diverse membrane proteins. Molecular dynamics simulations show that these phytochemicals modify bilayer properties by localizing to the bilayer/solution interface. Bilayer-modifying propensity was verified using a gramicidin-based assay, and indiscriminate modulation of membrane protein function was demonstrated using four proteins: membrane-anchored metalloproteases, mechanosensitive ion channels, and voltage-dependent potassium and sodium channels. Each protein exhibited similar responses to multiple phytochemicals, consistent with a common, bilayer-mediated mechanism. Our results suggest that many effects of amphiphilic phytochemicals are due to cell membrane perturbations, rather than specific protein binding.