Familial Hypercholesterolemia Biomarker Distribution in Dried Blood Spots.

OBJECTIVE: To evaluate distribution profiles of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) as candidate markers of familial hypercholesterolemia in newborns, taking into consideration potential confounding factors, such as gestational age, birth weight, sex, and race. STUDY DESIGN: TC, LDL-C, and apoB were measured from 10 000 residual deidentified newborn dried blood spot cards. Concentrations for each biomarker were reported as multiples of the median, with emphasis on describing the 99th percentile values based on birth weight, gestational age, sex, and race. Seasonal variation of biomarkers was also explored. RESULTS: LDL-C and apoB had distribution curves with tails showing extreme elevation, whereas the distribution of TC was less elevated and had the smallest range. Neonates born at early gestational age and low birth weight had significantly greater 99th percentile of multiples of the median values for apoB but not TC or LDL-C. Differences in biomarker concentration based on sex and race were minimal. All biomarkers showed greatest concentrations in the winter as compared with summer months. CONCLUSIONS: LDL-C and apoB had distribution curves supporting candidacy for neonatal familial hypercholesterolemia screening. Future studies are needed to correlate newborn screening results with molecular testing to validate these 2 biomarkers, along with measured cholesterol levels later in childhood.

Preventive Medicine in Pediatric Cardiology Practice.

OBJECTIVES: The objective of the study was to assess contemporary practice patterns of pediatric cardiologists with respect to cholesterol disorders and smoking-related illness. STUDY DESIGN: We sent 2 anonymous surveys to the members of the American Academy of Pediatrics Section on Cardiology and Cardiac Surgery and the Pediheart online community. The surveys addressed training in and management of cholesterol disorders and smoking-related illness. RESULTS: There were 97 responses to the cholesterol disorders survey. A total of 51.6% reported little or no formal training on cholesterol disorders. A total of 56.4% underestimated the prevalence of familial hypercholesterolemia by at least twofold. A total of 54.7% were at least somewhat comfortable prescribing statins. In 5 clinical vignettes, respondents frequently gave clinical recommendations in line with the 2019 American Heart Association guidelines although both undertreatment and overtreatment were recommended. There were 90 responses to the survey on smoking-related illness. Little or no formal training in nicotine addiction (52.3%) or smoking cessation (60.5%) was reported by respondents. Respondents screened for tobacco use in less than a one-third of hospitalizations and less than two-thirds of outpatient clinic visits. Screening for exposure to secondhand smoke was even less common. Twenty-seven percent of respondents never recommend a household smoking ban for their patients. A total of 83.3% were uncomfortable prescribing medications for their patients for smoking cessation, and 65.5% rarely or never refer patients for smoking cessation assistance. CONCLUSION: Although positioned to address the childhood origins of adult heart disease, those cardiologists surveyed placed a limited emphasis on cholesterol disorders and smoking-related disease in their clinical practice.

Phenotypic Variability in Atherosclerosis Burden in an Old-Order Amish Family With Homozygous Sitosterolemia.

Sitosterolemia is a rare atherogenic sterol storage disease with variability in its presentation requiring a high degree of clinical suspicion. We present 8 cases of sitosterolemia from an Amish kindred that, despite a background of decreased genetic and lifestyle variability, still had markedly variable presentations. (Level of Difficulty: Advanced.).

Safety of and cellular response to segmental bronchoprovocation in allergic asthma.

RATIONALE: Despite its incorporation into research studies, the safety aspects of segmental allergen bronchoprovocation and differences in cellular response among different allergens have received limited consideration. METHODS: We performed 87 segmental challenges in 77 allergic asthma subjects. Allergen dose was based on each subject's response to whole lung allergen challenge. Bronchoalveolar lavage was performed at 0 and 48 hours. Safety indicators included spirometry, oxygen saturation, heart rate, and symptoms. RESULTS: Among subjects challenged with ragweed, cat dander, or house dust mite, there were no differences in safety indicators. Subjects demonstrated a modest oxygen desaturation and tachycardia during the procedure that returned to normal prior to discharge. We observed a modest reduction in forced vital capacity and forced expiratory volume in one second following bronchoscopy. The most common symptoms following the procedure were cough, sore throat and fatigue. Total bronchoalveolar lavage fluid cell numbers increased from 13±4 to 106±108×10(4) per milliliter and eosinophils increased from 1±2 to 44±20 percent, with no significant differences among the three allergens. CONCLUSIONS: In mild allergic asthma, segmental allergen bronchoprovocation, using individualized doses of aeroallergens, was safe and yielded similar cellular responses.

Circadian variation of sputum inflammatory cells in mild asthma.

BACKGROUND: Asthma, like many conditions, demonstrates a circadian rhythm with a worsening of lung function in the early morning hours compared with in the late afternoon. OBJECTIVE: Because eosinophilic airway inflammation is a proposed mechanism for worsening asthma, we characterized circadian variation in airway eosinophils and determined its relationship to variability in airway function. METHODS: Pulmonary function testing, sputum induction, and phlebotomy were performed at 7 am and 4 pm in 11 allergic subjects with mild asthma. Sputum was analyzed for cell viability, differential, and eosinophil-derived neurotoxin levels. IL-5 levels in serum were measured by means of ELISA. RESULTS: Subjects had a significant decrease in FEV(1) (median [interquartile range] = 80% [70%-86%] vs 85% [82%-94%], P =.009) and a greater beta-agonist reversibility (median [interquartile range] = 13% [7%-32%] vs 8% [5%-14%], P =.024) in the early morning compared with in the late afternoon. Sputum analysis showed an increase in early morning total sputum leukocytes (median [interquartile range] = 4.3 x 10(6) [2.3 x 10(6) to 6.1 x 10(6)] vs 2.6 x 10(6) [1.7 x 10(6) to 3.6 x 10(6)], P =.044) and eosinophils (median [interquartile range] = 7.0 x 10(4) [2.7 x 10(4) to 18.7 x 10(4)] vs 3.6 x 10(4) [1.0 x 10(4) to 8.2 x 10(4)], P =.024). Furthermore, sputum eosinophils correlated with beta-agonist reversibility (R (s) = 0.665, P =.019). Finally, levels of IL-5 in serum and eosinophil-derived neurotoxin in sputum were significantly increased at 7 am. CONCLUSION: These data suggest that circadian variability in pulmonary function in asthma could be related to changes in airway eosinophil recruitment and activation.