Examining the predictive value of fetal fraction on hypertensive disorders of pregnancy.

BACKGROUND: Cell-free fetal DNA (cffDNA) screening is routinely performed in pregnancy. Abnormal fetal fraction has been associated with adverse pregnancy outcomes, including hypertensive disorders of pregnancy, which are associated with severe maternal and neonatal morbidity and mortality. OBJECTIVE: This study examined whether abnormal fetal fraction, defined in this study as fetal fraction either <6 or >15 on the basis of restricted-cubic-spline-plot within our study population, was associated with HDP in a retrospective sample, as well as whether fetal fraction improves the prediction of hypertensive disorders of pregnancy (HDP). We hypothesized that abnormal fetal fraction would be associated with HDP and that adding fetal fraction to a model would significantly improve its strength to predict HDP. STUDY DESIGN: This was a retrospective cohort study of 729 patients delivering singleton, non-anomalous pregnancies with conclusive cffDNA screening. The primary outcome was HDP. Logistic regression models tested associations between fetal fraction and HDP. We evaluated the impact of including fetal fraction on the prediction of hypertensive disorders of pregnancy (HDP) by comparing the area under the receiver operating characteristic (ROC) curve (AUC) between predictive models with and without fetal fraction. RESULTS: Among the study sample, there was an HDP rate of 11.5 %. Abnormal fetal fraction was defined as <6 % percentile and >15 %, HDP incidence was significantly higher in patients with fetal fraction <6 % compared to patients with fetal fraction in normal range (fetal fraction 6-15 %) (19.5 % vs 10.7 %, p = 0.006 on post hoc comparison). Model 1 had one predictor (fetal fraction) with an AUC of 0.59, Model 2 had three predictors (BMI, nulliparity, history of HDP) with an AUC of 0.71, and Model 3 had four predictors (BMI, nulliparity, history of HDP, and fetal fraction) with an AUC of 0.73. Models 2 and 3 were not significantly different (p = 0.18). CONCLUSIONS: More patients who developed HDP had low fetal fraction and fewer patients who developed HDP had high fetal fraction compared to those patients who did not develop HDP. Based on results from multivariable regression models, we cannot conclude that fetal fraction improves HDP prediction. However, developing standardized values for abnormal fetal fraction may be clinically useful.

Understanding spatiotemporal effects of food supplementation on host-parasite interactions using community-based science.

Supplemental feeding can increase the overall health of animals but also can have variable effects on how animals defend themselves against parasites. However, the spatiotemporal effects of food supplementation on host-parasite interactions remain poorly understood, likely because large-scale, coordinated efforts to investigate them are difficult. Here, we introduce the Nest Parasite Community Science Project, which is a community-based science project that coordinates studies with bird nest box 'stewards' from the public and scientific community. This project was established to understand broad ecological patterns between hosts and their parasites. The goal of this study was to determine the effect of food supplementation on eastern bluebirds (Sialia sialis) and their nest parasite community across the geographic range of the bluebirds from 2018 to 2021. We received 674 nests from 69 stewards in 26 states in the eastern United States. Nest box stewards reported whether or not they provided mealworms or suet near nesting bluebirds, then they followed the nesting success of the birds (number of eggs laid and hatched, proportion that hatched, number and proportion of nestlings that successfully fledged). We then identified and quantified parasites in the nests. Overall, we found that food supplementation increased fledging success. The most common nest parasite taxon was the parasitic blow fly (Protocalliphora sialia), but a few nests contained fleas (Ceratophyllus idius, C. gallinae and Orchopeas leucopus) and mites (Dermanyssus spp. and Ornithonyssus spp.). Blow flies were primarily found at northern latitudes, where food supplementation affected blow fly prevalence. However, the direction of this effect varied substantially in direction and magnitude across years. More stewards fed bluebirds at southern latitudes than at northern latitudes, which contradicts the findings of other community-based science projects. Overall, food supplementation of birds was associated with increased host fitness but did not appear to play a consistent role in defence against these parasites across all years. Our study demonstrates the importance of coordinated studies across years and locations to understand the effects of environmental heterogeneity, including human-based food supplementation, on host-parasite dynamics.

Is There Utility in Transvaginal Cervical Length Surveillance After Cerclage Placement for the Prediction of Spontaneous Preterm Birth?

INTRODUCTION: Transvaginal cervical length (TVCL) surveillance post-transvaginal cerclage placement is not universally performed, despite the correlated risk of short TVCL with spontaneous preterm birth (sPTB). This study evaluated if patients with a TVCL <2.5 cm after cerclage placement had higher odds of sPTB than those with a TVCL ≥2.5 cm after cerclage placement. METHODS: This retrospective cohort study included patients with a singleton, non-anomalous gestation with a transvaginal cerclage who had TVCL surveillance post-cerclage placement. The primary outcome was the odds of sPTB among patients with TVCL <2.5 cm vs TVCL ≥2.5 cm after cerclage placement. Transvaginal cerclage placement indications included history indicated, physical exam indicated, and ultrasound indicated. Outcomes were assessed using univariate and multivariate analysis while adjusting for progesterone use, TVCL before cerclage placement, and cerclage indication. RESULTS: The analysis included 210 patients, and the sPTB rate was 46.7%. Those with sPTB underwent cerclage placement at later gestational ages, had higher rates of exam-indicated cerclage, and were more likely to be prescribed vaginal progesterone. Patients with a TVCL of <2.5 cm after cerclage placement did not have significantly increased odds of sPTB (OR: 2.8, 95% CI: 0.9-8.7, p=0.07); however, patients with a TVCL <2.0 cm had significantly increased odds of sPTB (OR: 6.3, 95% CI: 2.2-18.8, p<0.001). CONCLUSION: In patients with transvaginal cerclage, there does not appear to be increased odds of sPTB with TVCL <2.5 cm after cerclage placement; however, there does appear to be an increased odds of sPTB in patients with a TVCL of <2.0 cm after cerclage placement.

Implementation of an Enhanced Prenatal Checklist to Increase Rates of Counseling of Prenatal Fetal Aneuploidy Testing.

Aim This study aims to assess the effect of implementing an enhanced prenatal genetic checklist to guide the provider's discussion on both screening and diagnostic options for fetal aneuploidy testing at the initial prenatal visit. Methods A retrospective quality improvement (QI) project was performed at a single, large, urban academic medical center. The implementation of this project was prospective; however, data was examined retrospectively after the QI initiative was implemented for three months. Patients were included if they were less than 24 weeks gestational age with a live intrauterine gestation at their initial obstetric (OB) visit. Patients less than 18 years old at the initial OB visit were excluded. The results were analyzed using the statistical software R. Chi-squared tests were used to examine proportional differences between the pre- and post-intervention groups with respect to demographic and clinical characteristics and documented genetic counseling discussions. Results A total of 416 patients were included in the final cohort. As measured by documentation, the rate of discussion of diagnostic prenatal genetic testing increased significantly from the pre-intervention proportion of 54% to the post-intervention proportion of 72% (p < 0.001). In the subgroup analysis of patients with advanced maternal age, the rate of discussion of diagnostic prenatal genetic testing increased significantly from the pre-intervention proportion of 53% to the post-intervention proportion of 83% (p = 0.003), and the rate of genetics counseling referrals made at the initial prenatal visit increased significantly from 4% pre-intervention to 38% post-intervention (p < 0.001). Conclusions The use of an enhanced prenatal genetic checklist led to increased discussion of diagnostic fetal aneuploidy testing and increased rates of referral to genetics counseling.

Adjusting models to better predict obstetric anal sphincter injury (OASIS) in forceps-assisted vaginal deliveries: A retrospective cross-sectional trial.

OBJECTIVE: Obesity and maternal age are increasing among pregnant patients. The understood effect of body mass index (BMI), advanced maternal age (AMA), and second stage of labor on obstetric anal sphincter injury (OASIS) at delivery is varied. The objective of this study was to assess whether incorporating BMI, second stage of labor length, and AMA into a model for predicting OASIS among forceps-assisted vaginal deliveries (FAVD) had a higher predictivity value compared to models without these additions. METHOD: This was an IRB-approved retrospective cohort study of singleton gestations who underwent a FAVD between 2017 and 2021. The primary outcome was prediction of OASIS via established models versus models including the addition of new predictive factors. RESULTS: A total of 979 patients met inclusionary criteria and were included in the final analysis. 20.4% of patients had an OASIS laceration, 11.3% of neonates had NICU admissions, 23.7% had a composite all neonatal outcome, and 8% had a composite subgaleal/cephalohematoma outcome. Comparisons of known factors that predict OASIS (nulliparity, race, episiotomy status) to known factors with additional predictors (BMI, AMA, and length of second stage in labor) were explored. After comparing each model's AUC to one another (a total of 3 comparisons made), there was no statistically significant difference between the models (all P > 0.62). CONCLUSION: Including BMI, AMA, and second stage of labor length does not improve the predictivity of OASIS in patients with successful FAVD. These factors should not impact a provider's decision to perform a FAVD when solely considering increased odds of OASIS.

Prevention of postpartum hemorrhage in vaginal deliveries.

Identification of patients at risk for postpartum hemorrhage (PPH) may allow for prompt diagnosis and intervention. Individual risk factors, risk assessment tools and prediction models have been used for determining a patient's risk of PPH. Measures for the prevention of PPH include identification and management of iron deficiency anemia, unit readiness and preparedness through performing regular simulations and having a PPH cart or medication kit readily available, prophylactic uterotonic - carbetocin alone or dual agents such as oxytocin and misoprostol or oxytocin and methylergometrine or antifibrinolytic (oxytocin and tranexamic acid) use in the third stage of labor immediately after fetal head delivery, and controlled cord traction.

Racial and Ethnic Disparities Among Women Undergoing a Trial of Labor After Cesarean Delivery: Performance of the VBAC Calculator with and without Patients' Race/Ethnicity.

The Maternal Fetal Medicine Units Network (MFMU) vaginal birth after cesarean (VBAC) calculator is a clinical tool designed to predict trial of labor after cesarean delivery (TOLAC) success. The calculator has come under scrutiny for its inclusion of race and ethnicity, which systematically predicts a lower likelihood of success for patients who identify as African American or Hispanic. We hypothesized that the calculator would predict VBAC more accurately without the use of race or ethnicity. A retrospective chart review including all patients undergoing TOLAC from 2016 to 2019 was conducted. A multivariate logistic regression was used to compare one model that utilizes the original variables in predicting VBAC (model 1) and another that uses the same variables except for race and ethnicity (model 2). In model 1, race and ethnicity were the only variables not associated with the probability of successful TOLAC (p = 0.065). The area under the curve (AUC) for models 1 and 2 were 0.77 and 0.78, respectively. There was not a statistically significant difference between the predictive abilities of the two models (p = 0.40). Rates of PPH (p = 0.001), abruption (p = 0.04), intra-amniotic infection (p < 0.0001), and other postpartum complications (p = 0.005) differed significantly by race and ethnicity. The use of race and ethnicity did not contribute to the accuracy of VBAC prediction. The use of race and ethnicity in this predictive model should be omitted to prevent inherent bias and discrimination. There were also significant racial and ethnic differences in overall postpartum complication rates.

SARS-CoV-2 Antibody Response among Women Infected during Pregnancy.

OBJECTIVES: Novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus has been declared a pandemic by the World Health Organization as of March 11, 2020. Pregnant women naturally have a reduced immune system due to immunological changes and decreased lung capacity due to respiratory adaptations, making them more susceptible to coronavirus complications. Within the Mount Sinai Health system, more than 15,000 deliveries are performed annually. We began to care for pregnant women with known COVID-19 infections in late March of 2020. In early April 2020, a policy was implemented to perform universal COVID-19 testing for all women planning to deliver within the Mount Sinai Health system. We examined the antibody response of postpartum women who delivered at Mount Sinai Hospital with a SARS-CoV-2 infection between the study intervals during March 15, 2020, through April 30, 2020. STUDY DESIGN: This was a prospective observational study examining the immune response of pregnant women who delivered at Mount Sinai Hospital with a polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Women with a SARS-CoV-2 infection were contacted via phone to discuss participation in the study. Patients who consented were scheduled for a phlebotomy visit to assess their antibody titer levels to COVID-19. The COVID-19 enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)-G antibody test was used to evaluate the patients' antibody titers. The assay detects IgG antibodies for the detection of IgG seroconversion in patients following a known recent SARS-CoV-2 infection. RESULTS: A total of 120 patients were identified with a documented SARS-CoV-2 infection who delivered within the prespecified time frame. Of those patients, 25 women agreed to participate and were included. Of them, 64.00% were Caucasian with a mean age of 35 years. The mean body mass index (BMI) was 30 kg/m2 and the majority of patients had commercial insurance (88.00%). The majority of women were asymptomatic for COVID-19 at the time of admission (80.00%) and the average gestational age of delivery and diagnosis of COVID-19 was 39 weeks' gestation. The later the gestational age at the time of diagnosis, the lower the antibody titer response. When examining the interval from diagnosis to antibody titer analysis, patients with the highest titers (2,880) tended to have a shorter interval between their COVID-19 diagnosis and the time at which the titer level was drawn. Patients with symptoms on admission had similar antibody titer levels when compared with women who were asymptomatic. CONCLUSION: The antibody response among women infected with COVID-19 during pregnancy appears to be greater when the patients are diagnosed at an earlier gestational age. KEY POINTS: · COVID-19 antibody status appears to be greater when diagnosed at an earlier gestational age.. · Asymptomatic and symptomatic pregnant women had similar antibody responses.. · Patients with the highest titers tended to have a shorter interval between their COVID-19 diagnoses..

The effect of an oxytocin washout period on blood loss at cesarean delivery.

Objectives Prolonged oxytocin exposure may result in increased blood loss during delivery. Our objective was to determine whether an oxytocin rest period before cesarean delivery had an impact on blood loss. Methods We performed a retrospective cohort study of women who underwent primary cesarean delivery after oxytocin augmentation. The primary outcome was change between pre- and postoperative hematocrit (Hct) in women with less than 60-min oxytocin rest period (<60 min) and greater than 60-min rest period (>60 min). Results There was no difference in demographic characteristics (age, BMI, or gestational age at delivery) between the two groups. Women in the >60 min group had a higher cumulative dose and longer duration of oxytocin administration. There was no significant difference in change in Hct between the two groups when controlling for these factors. Conclusions We did not find a significant correlation between the duration of the oxytocin rest period and blood loss. Oxytocin washout periods of greater than 60 min may not result in decreased blood loss at cesarean delivery, and thus, women may not benefit from such oxytocin washout periods.

Assisted reproductive technologies (ART) and placental abnormalities.

Objectives Assisted reproductive technologies (ART) may be associated with placental abnormalities including placenta previa, umbilical cord abnormalities, and placental abruption. Our study evaluates the relationship between ART and placental abnormalities compared with spontaneously conceived controls. Methods An IRB-approved cohort study was conducted including women who delivered between January 2013 and December 2018. We excluded delivery prior to 23 weeks and known fetal anomalies. Patients were matched with controls (2:1) for parity, age, and mode of delivery. Controls were women who had spontaneously conceived and delivered immediately preceding and following the index delivery. The primary outcome was placental abnormalities found on both antenatal ultrasound and pathology in ART gestations compared with spontaneously conceived gestations. Results There were 120 ART pregnancies and 240 matched control pregnancies identified. The groups were similar for parity, BMI, comorbidities, number of multiples, mode of delivery, and female newborns. The ART group had a higher maternal age (37.1±5 y vs. 30.0±5 y; p<0.001), greater preterm birth (29 vs. 6%; p<0.001), and lower BW (2,928±803 g vs. 3,273±586 g; p<0.001). The ART group had a higher incidence of placenta previa on ultrasound (4.0 vs. 0.4%, p=0.01), adherent placentas at delivery (3 vs. 0% p=0.014), placental abruption (2 vs. 0%; p=0.04), as well as an increased rate of velamentous cord insertion (12 vs. 3%, p<0.001) and marginal cord insertion (28 vs. 15%, p=0.002). ART demonstrated a two-fold likelihood of abnormal placental pathology. Conclusions ART is associated with increased rate of placental abnormalities, including abnormal umbilical cord insertion and increased rates of adherent placentation. This information may be beneficial in planning and surveillance in patients with ART pregnancies.

Exhaled Nitric Oxide in Wheezy Infants Predicts Persistent Atopic Asthma and Exacerbations at School Age.

BACKGROUND: There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FENO) in infants/toddlers with recurrent wheezing for asthma at school age. OBJECTIVES: In a cohort of infants/toddlers with recurrent wheezing determine the predictive values of sedated single-breath FENO (SB-FENO) and awake tidal-breathing mixed-expired FENO (tidal-FENO) for active asthma, severe exacerbations, and lung function at age 6 years. METHODS: In 44 infants/toddlers, SB-FENO was measured under sedation at 50 mL/sec in conjunction with forced expiratory flow and volume measurements, and tidal-FENO was measured during awake tidal breathing. Clinical outcomes and lung function were assessed at age 6 years in 36 subjects. RESULTS: Enrollment SB-FENO was significantly higher among subjects with active asthma at age 6 years than among subjects without asthma (36.4 vs. 16.9 ppb, p < 0.0001), and the odds of asthma was 7.6 times greater (OR 7.6; 95% CI 1.8-31.6) for every 10 ppb increase in enrollment SB-FENO. A ROC analysis demonstrated that an enrollment SB-FENO > 31.5 ppb predicted active asthma at age 6 years with an area under the curve (AUC) of 0.92 (95% CI: 0.82-1). SB-FENO was also higher among subjects who experienced severe asthma exacerbations during the year preceding age of 6 years. SB-FENO at enrollment and lung function measures at age 6 years were modestly correlated (FEV1: r = -0.4; FEF25-75: r = -0.41; FEV1/FVC ratio: r=-0.46), and SB-FENO was significantly higher among subjects with bronchodilator responsiveness (BDR) at age 6 years. Tidal-FENO was not predictive of active asthma, exacerbations, or lung function at age 6 years. CONCLUSION: In wheezy infants/toddlers, SB-FENO was predictive of school-age asthma and associated with lung function measures at age 6 years.

First-trimester maternal serum alpha fetoprotein is associated with ischemic placental disease.

BACKGROUND: While elevated second-trimester maternal serum alpha fetoprotein has been associated with adverse pregnancy outcomes, the utility of first-trimester maternal serum alpha fetoprotein in predicting these outcomes is limited. Some laboratories have been including maternal serum alpha fetoprotein as part of the first-trimester analyte screening for aneuploidy and preeclampsia, offering its potential utility in predicting pregnancy outcomes. OBJECTIVE: Our primary objective was to determine the association between elevated first-trimester maternal serum alpha fetoprotein and preeclampsia as well as ischemic placental disease (a composite of preeclampsia, fetal growth restriction, and/or placental abruption). Secondary outcomes included early-onset preeclampsia requiring delivery at <34 weeks gestation, fetal growth restriction, placental abruption, preterm delivery, fetal demise, and spontaneous abortion. STUDY DESIGN: An institutional review board-approved multisite retrospective cohort study was performed including all patients with first-trimester maternal serum alpha fetoprotein as part of routine first-trimester aneuploidy screening from April 2015 through January 2017. Pregnancies with multiple gestations, known structural or chromosomal abnormalities, known malignancy, and incomplete delivery records were excluded. Delivery records were reviewed for baseline characteristics and adverse pregnancy outcomes. The optimal cutoff point for first-trimester maternal serum alpha fetoprotein to predict these outcomes was assessed, and an elevated maternal serum alpha fetoprotein was considered >2.0 multiple of the median. A Fisher exact test and odds ratios were used to determine the association between elevated first-trimester maternal serum alpha fetoprotein and adverse pregnancy outcomes. Spearman correlation coefficient assessed the relationship between first- and second-trimester maternal serum alpha fetoprotein. RESULTS: Of 1478 patients with first-trimester maternal serum alpha fetoprotein, 1280 had complete records available for review (86.6%). There was no association demonstrated between elevated first-trimester maternal serum alpha fetoprotein (>2.0 multiple of the median) and the primary outcome, overall preeclampsia (5.8% vs 4.6%, odds ratio, 1.29, 95% confidence interval, 0.58-2.91). However, there was an increased incidence of ischemic placental disease, 15.8% vs 7.7% (odds ratio, 2.26, 95% confidence interval, 1.33-3.87) in those with an elevated alpha fetoprotein. Also, elevated first-trimester maternal serum alpha fetoprotein was associated with a higher incidence of fetal growth restriction (7.5% vs 2.3%, odds ratio, 3.40, 95% confidence interval, 1.56-7.42) and preterm birth (18.3% vs 10.3%, odds ratio, 1.95, 95% confidence interval, 1.18-3.21). Also, a positive correlation between first- and second-trimester maternal serum alpha fetoprotein was demonstrated (rho = 0.46, P < .0001). CONCLUSION: Elevated first-trimester maternal serum alpha fetoprotein is associated with ischemic placental disease, fetal growth restriction, and preterm birth. This suggests that elevated maternal serum alpha fetoprotein may help to identify high risk pregnancies as early as the first trimester of pregnancy. Future studies are necessary to determine whether the addition of first-trimester maternal serum alpha fetoprotein to existing algorithms can improve the early detection of ischemic placental disease.

Home Self-Collection of Nasal Swabs for Diagnosis of Acute Respiratory Virus Infections in Children With Cystic Fibrosis.

BACKGROUND: Understanding the importance of respiratory viruses in children with cystic fibrosis (CF) has been limited because of challenges using clinic- or hospital-based diagnostic testing. We conducted a pilot study to assess feasibility of home self- (or parent-) collection of nasal swabs (NS). METHODS: Cystic fibrosis patients aged 6-18 years with new respiratory illness participated. In clinic, a deep nasal flocked swab was collected by research staff and compared with an anterior foam NS obtained after instillation of saline spray. At home, up to 2 self-collections of paired foam NS (with and without saline) were collected and mailed for real-time polymerase chain reaction (PCR) testing. RESULTS: Paired swabs were collected from 28 patients: 18 sets in clinic (deep nasal vs saline foam NS) and 43 sets at home (saline vs dry foam NS) with 9 (50%) and 35 (81%) virus detections, respectively. Home-collected NS were obtained closer to illness onset, with a mean difference in symptom days of -2.3 between home and clinic collections (95% confidence interval [CI] -3.5, -1.2; P < .001). Rhinovirus comprised 73% of virus detections; the difference in mean PCR cycle threshold values for rhinovirus between swabs collected at home versus clinic was -3.8 (95% CI -6.8, -0.9; P = .014), indicating significantly higher viral load for home-collected swabs. CONCLUSIONS: Home-collected foam NS had a higher positivity rate compared with clinic-collected swabs, likely because collection was closer to illness onset. Home self-collection is feasible and well tolerated for timely respiratory virus diagnosis and provides a novel approach for clinical diagnostics and surveillance of respiratory virus infections among CF patients.

Staphylococcus aureus small-colony variants are independently associated with worse lung disease in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) lung disease is associated with diverse bacteria chronically infecting the airways. Slow-growing, antibiotic-resistant mutants of Staphylococcus aureus known as small-colony variants (SCVs) have been isolated from respiratory secretions from European adults and children with CF lung disease using specific but infrequently used culture techniques. Staphylococcus aureus SCVs can be selected either by exposure to specific antibiotics or by growth with another CF pathogen, Pseudomonas aeruginosa. We sought to determine the prevalence, clinical significance, and likely mechanisms of selection of S. aureus SCVs among a US cohort of children with CF. METHODS: We performed a 2-year study of 100 children with CF using culture techniques sensitive for S. aureus SCVs, and evaluated associations with clinical characteristics using multivariable regression models. RESULTS: Staphylococcus aureus SCV infection was detected among 24% of participants and was significantly associated with a greater drop in lung function during the study (P = .007, adjusted for age and lung function at enrollment). This association persisted after adjusting for infection with other known CF pathogens, including P. aeruginosa and methicillin-resistant S. aureus. Evidence indicated that S. aureus SCVs were likely selected in vivo by treatment with the antibiotic trimethoprim-sulfamethoxazole and possibly by coinfection with P. aeruginosa. CONCLUSIONS: Infection with SCV S. aureus was independently associated with worse CF respiratory outcomes in this pediatric cohort. As many clinical microbiology laboratories do not specifically detect S. aureus SCVs, validation and extension of these findings would require widespread changes in the usual laboratory and clinical approaches to these bacteria.

Lung function and biomarkers of airway inflammation during and after hospitalization for acute exacerbations of childhood asthma associated with viral respiratory symptoms.

BACKGROUND: There are limited data assessing relationships between biomarkers of inflammation and lung function after hospitalization for asthma exacerbations in children. OBJECTIVE: To assess the associations in asthmatic children among changes in lung function, fraction of exhaled nitric oxide (FENO), and cysteinyl leukotrienes (CysLTs) in exhaled breath condensate (EBC) after hospitalization for acute asthma. METHODS: Spirometry and FENO were measured and EBC collected for CysLT measurement from 40 children during and 1, 2, and 4 weeks after hospitalization for an asthma exacerbation and during a single-study visit for 40 healthy children. RESULTS: Enrollment FENO and EBC CysLT concentrations were higher in the children with asthma than in healthy individuals (mean FENO, 31.6 vs 7 ppb; P < .0001; mean EBC CysLT, 7.9 vs 4.9 ppb; P = .03). Among children with asthma, improvement in lung function reached a plateau within 2 weeks after hospital discharge. The EBC CysLT concentrations were not associated with changes in lung function, use of albuterol, or use of inhaled corticosteroids (ICSs). Among asthmatic children enrollment FENO was not associated with changes in lung function during follow-up. However, among children who had an elevated enrollment FENO (≥25 ppb), patients who did not use ICSs after hospital discharge had lower end-of-study lung function than those who used ICSs. At 2 and 4 weeks after hospital discharge, FENO was higher among patients who reported albuterol use more than twice weekly and among patients who reported no ICS use. CONCLUSION: FENO measured at hospital discharge among children hospitalized with acute asthma may be useful in identifying patients who will respond to ICS therapy.

Airway epithelial cells from asthmatic children differentially express proremodeling factors.

BACKGROUND: The airway epithelium can express factors that drive subepithelial airway remodeling. TGF-ß2, vascular epithelial growth factor (VEGF), a disintegrin and metalloprotease 33 (ADAM33), and periostin are hypothesized to be involved in subepithelial remodeling and are overexpressed in adult asthmatic airways. Epidemiologic data suggest that lung function deficits in asthmatic patients are acquired in childhood. OBJECTIVES: We sought to determine whether airway epithelial cells (AECs) from asthmatic children differentially express TGF-ß2, VEGF, ADAM33, or periostin compared with cells from atopic nonasthmatic and healthy children intrinsically or in response to IL-4/IL-13 stimulation. METHODS: Bronchial and nasal epithelial cells were obtained from brushings from well-characterized asthmatic (n = 16), atopic nonasthmatic (n = 9), and healthy (n = 15) children after achievement of anesthesia for elective procedures. After differentiation at an air-liquid interface (ALI) for 3 weeks, conditioned media were sampled and RNA was extracted from unstimulated and IL-4/IL-13-stimulated cultures. TGF-ß2 and VEGF levels were measured with ELISA. ADAM33 and periostin expression was assessed by using real-time PCR. RESULTS: TGF-ß2 and VEGF production was significantly greater in bronchial and nasal ALI cultures from asthmatic children than in cultures from atopic nonasthmatic and healthy children. TGF-ß2 levels increased significantly in asthmatic cultures after IL-4/IL-13 stimulation. Within-subject correlation between nasal and bronchial ALI production of TGF-ß2 (r = 0.64, P = .001) and VEGF (r = 0.73, P < .001) was good. Periostin expression was 3.7-fold higher in bronchial cells (P < .001) and 3.9-fold higher in nasal cells (P < .004) from asthmatic children than in cells from atopic nonasthmatic or healthy children. ADAM33 was not differentially expressed by AECs from asthmatic patients compared with that from cells from atopic nonasthmatic or healthy children. CONCLUSION: AECs from asthmatic children differentially express TGF-ß2, VEGF, and periostin compared with cells from atopic nonasthmatic and healthy children. Nasal epithelial cells might be a suitable surrogate for bronchial cells that could facilitate investigation of the airway epithelium in future longitudinal pediatric studies.

Exhaled nitric oxide, lung function, and exacerbations in wheezy infants and toddlers.

BACKGROUND: There are limited data assessing the relationship between fraction of exhaled nitric oxide and lung function or exacerbations in infants with recurrent wheezing. OBJECTIVES: In a longitudinal pilot study of children less than 2 years old, we assessed whether baseline fraction of exhaled nitric oxide was associated with lung function, bronchodilator responsiveness, changes in lung function, or subsequent exacerbations of wheezing. METHODS: Forced expiratory flows and volumes using the raised-volume rapid thoracic compression method were measured in 44 infants and toddlers (mean age, 15.7 months) with recurrent wheezing. Single-breath exhaled nitric oxide (SB-eNO) was measured at 50 mL/s. Lung function was again measured 6 months after enrollment. RESULTS: At enrollment, forced expiratory volume in 0.5 seconds (FEV(0.5)), forced expiratory flow at 25% to 75% of expiration (FEF(25-75)), and forced expiratory flow at 75% of expiration (FEF(75)) z scores for the cohort were significantly less than zero. There was no correlation between enrollment SB-eNO levels and enrollment lung function measures. SB-eNO levels were higher in infants with bronchodilator responsiveness (46.1 vs 23.6 ppb, P < .001) and was associated with a decrease in FEV(0.5) (r = -0.54, P = .001), FEF(25-75) (r = -0.6, P < .001), and FEF(75) (r = -0.55, P = .001) over 6 months. A 10-ppb increase in SB-eNO level was associated with a 0.4-point z score decrease in FEV(0.5), a 0.4-point z score decrease in FEF(25-75), and a 0.42-point z score decrease in FEF(75). SB-eNO level was superior to lung function and bronchodilator responsiveness in predicting subsequent wheezing treated with systemic steroids. CONCLUSIONS: SB-eNO level might predict changes in lung function and risk of future wheezing and holds promise as a biomarker to predict asthma in wheezy infants and toddlers.

Evaluation of candidate genes for DYX1 and DYX2 in families with dyslexia.

Dyslexia is a common heterogeneous disorder with a significant genetic component. Multiple studies have replicated the evidence for linkage between variously defined phenotypes of dyslexia and chromosomal regions on 15q21 (DYX1) and 6p22.2 (DYX2). Based on association studies and the possibility for functional significance of several polymorphisms, candidate genes responsible for the observed linkage signal have been proposed-DYX1C1 for 15q21, and KIAA0319 and DCDC2 for 6p22.2. We investigated the evidence for contribution of these candidate genes to dyslexia in our sample of multigenerational families. Our previous quantitative linkage analyses in this dataset provided supportive evidence for linkage of dyslexia to the locus on chromosome 15, but not to the locus on chromosome 6. In the current study, we used probands from 191 families for a case control analysis, and proband-parent trios for family-based TDT analyses. The observation of weak evidence for transmission disequilibrium for one of the two studied polymorphisms in DYX1C1 suggests involvement of this gene in dyslexia in our dataset. We did not find evidence for the association of KIAA0319 or DCDC2 alleles to dyslexia in our sample. We observed a slight tendency for an intronic deletion in DCDC2 to be associated with worse performance on some quantitative measures of dyslexia in the probands in our sample, but not in their parents.