The proliferation of algal blooms (ABs) in lakes and reservoirs (L&Rs) poses a threat to water quality and the ecological health of aquatic communities. With global climate change, there is a concern that the frequency and geographical expansion of ABs in L&Rs could increase. China has experienced rapid economic growth and major land-use changes over the last several decades and therefore provides an excellent context for such an analysis. About 289,600 Landsat images were used to examine the spatiotemporal distribution of ABs in L&Rs (>1 km(2)) across China (1983-2017). Results showed significant changes in the temporal slope of the sum of normalized area (0.26), frequency (2.28), duration (6.14), and early outbreak (-3.48) of AB events in L&Rs across China. Specifically, AB-impacted water bodies expanded longitudinally, and the time range of AB observation has expanded starting in the 2000s. Spearman correlation and random forest regression analyses further indicated that, among climatic factors, wind speed and temperature contributed the most to AB expansion. Overall, anthropogenic forces have overridden the imprints of climatic factors on the temporal evolution of ABs in China's L&Rs and therefore could inform policy decisions for the management of these resources.

Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso-occlusive pain episodes among children with sickle cell anaemia (SCA). Aeroallergen sensitization is a risk factor for asthma. We hypothesized that aeroallergen sensitization is associated with an increased incidence of hospitalizations for ACS and pain. Participants in a multicentre, longitudinal cohort study, aged 4-18 years with SCA, underwent skin prick testing to ten aeroallergens. ACS and pain episodes were collected from birth until the end of the follow-up period. The number of positive skin tests were tested for associations with prospective rates of ACS and pain. Multivariable models demonstrated additive effects of having positive skin tests on future rates of ACS (incidence rate ratio (IRR) for each positive test 1·23, 95% confidence interval [CI] 1·11-1·36, P < 0·001). Aeroallergen sensitization was not associated with future pain (IRR 1·14, 95%CI 0·97-1·33, P = 0·11). Our study demonstrated that children with SCA and aeroallergen sensitization are at increased risk for future ACS. Future research is needed to determine whether identification of specific sensitizations and allergen avoidance and treatment reduce the risk of ACS for children with SCA.

Affiliations: Department of Pediatrics and Rainbow Babies and Children’s Hospital, Case Western Reserve University School of Medicine, Cleveland OH, USA; Vanderbilt University School of Medicine and Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN, USA; Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO; Department of Medicine, Brigham and Women’s Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Heart and Vascular Institute, Cleveland Clinic Foundation, Cleveland, OH, USA; Department of Paediatric Respiratory Medicine, Great Ormond Street Hospital, London, UK; North Middlesex Hospital NHS Trust, London, UK; Evelina Children’s Hospital, Guy’s and St Thomas Hospital, London, UK; Department of Paediatrics, Imperial College and Imperial College Healthcare NHS Trust, London, UK; Independent statistician, Chicago, IL; University College London Institute of Child Health, London UK

Rationale: Maintaining optimal symptom control remains the primary objective of asthma treatment. Better understanding of the biologic underpinnings of asthma control may lead to the development of improved clinical and pharmaceutical approaches.Objectives: To identify molecular pathways and interrelated genes whose differential expression was associated with asthma control.Methods: We performed gene set enrichment analyses of asthma control in 1,170 adults with asthma, each with gene expression data derived from either whole blood (WB) or unstimulated CD4(+) T lymphocytes (CD4), and a self-reported asthma control score representing either the preceding 6 months (chronic) or 7 days (acute). Our study comprised a discovery WB cohort (n = 245, chronic) and three independent, nonoverlapping replication cohorts: a second WB set (n = 448, acute) and two CD4 sets (n = 300, chronic; n = 77, acute).Measurements and Main Results: In the WB discovery cohort, we found significant overrepresentation of genes associated with asthma control in 1,106 gene sets from the Molecular Signatures Database (false discovery rate, <5%). Of these, 583 (53%) replicated in at least one replication cohort (false discovery rate, <25%). Suboptimal control was associated with signatures of eosinophilic and granulocytic inflammatory signals, whereas optimal control signatures were enriched for immature lymphocytic patterns. These signatures included two related biologic processes related to activation by TREM-1 (triggering receptor expressed on myeloid cells 1) and lipopolysaccharide.Conclusions: Together, these results demonstrate the existence of specific, reproducible transcriptomic components in blood that vary with degree of asthma control and implicate a novel biologic target (TREM-1).

Revisiting What We Need to Do to Help Urban Minority Children with AsthmaThe Journal of Allergy and Clinical Immunology: In PracticeVol. 5Issue 2PreviewThe article by Garbutt et al1 brings us back once again to the important question of how to help urban minority children with asthma. The lessons from this study are not new, but nonetheless reinforce what providers can do to improve care. Full-Text PDF

BACKGROUND:Overweight/obesity (OW) is linked to worse asthma and poorer inhaled corticosteroid (ICS) response in older children and adults. OBJECTIVE:We sought to describe the relationships between OW and asthma severity and response to ICS in preschool children. METHODS:This post hoc study of 3 large multicenter trials involving 2- to 5-year-old children compared annualized asthma symptom days and exacerbations among normal weight (NW) (body mass index: 10th-84th percentiles) versus OW (body mass index: ≥85th percentile) participants. Participants had been randomized to daily ICS, intermittent ICS, or daily placebo. Simple and multivariable linear regression was used to compare body mass index groups. RESULTS:Within the group not treated with a daily controller, OW children had more asthma symptom days (90.7 vs 53.2, P = .020) and exacerbations (1.4 vs 0.8, P = .009) thanNW children did. Within the ICS-treated groups, OW and NW children had similar asthma symptom days (daily ICS: 47.2 vs 44.0 days, P = .44; short-term ICS: 61.8 vs 52.9 days, P = .46; as-needed ICS: 53.3 vs 47.3 days, P = .53), and similar exacerbations (daily ICS: 0.6 vs 0.8, P = .10; short-term ICS: 1.1 vs 0.8 days, P = .25; as-needed ICS: 1.0 vs 1.1, P = .72). Compared with placebo, daily ICS in OW led to fewer annualized asthma symptom days (90.7 vs 41.2, P = .004) and exacerbations (1.4 vs 0.6, P = .006), while similar protective ICS effects were less apparent among NW. CONCLUSIONS:In preschool children off controller therapy, OW is associated with greater asthma impairment and exacerbations. However, unlike older asthmatic patients, OW preschool children do not demonstrate reduced responsiveness to ICS therapy.

Childhood asthma causes significant morbidity, and medication nonadherence is a major factor. We hypothesized that medication observation by caretakers would be associated with better asthma control in an inner-city population of children. This cross-sectional study evaluated 123 patients with persistent asthma from 15 elementary and middle schools during their initial visits from 2013-2016. Asthma severity was determined by nurses and nurse practitioners using NHLBI criteria. All parents answered a questionnaire which assessed medication observation frequency during the first visit. Level of asthma control was assessed using asthma control test (cACT and ACT) scores. Asthma severity and control were compared with chi-square tests and a logistic regression, respectively. The median participant age was 8 years, with a range of 4-14 years. Overall, 103 (83.4%) children reported that administration of their medications was observed most or all of the time. The frequency of well-controlled asthma (ACT >19) was the same in both groups, after adjusting for age, gender and African-American race (OR = 1.03, 95% CI 0.37 to 2.83, p = 0.962). Asthma severity was associated with observation status (100% of severe persistent, 75% of moderate persistent and 90% of mild persistent asthmatics were observed, p = 0.026). We found no association between medication observation and asthma control in this minority-predominant elementary and middle school population. Children may be able to take ownership of their healthcare at a younger age than what is typically recommended, but further research is indicated.

Asthma is a common chronic respiratory disease characterized by airway hyperresponsiveness (AHR). The genetics of asthma have been widely studied in mouse and human, and homologous genomic regions have been associated with mouse AHR and human asthma-related phenotypes. Our goal was to identify asthma-related genes by integrating AHR associations in mouse with human genome-wide association study (GWAS) data. We used Efficient Mixed Model Association (EMMA) analysis to conduct a GWAS of baseline AHR measures from males and females of 31 mouse strains. Genes near or containing SNPs with EMMA p-values ,0.001 were selected for further study in human GWAS. The results of the previously reported EVE consortium asthma GWAS meta-analysis consisting of 12,958 diverse North American subjects from 9 study centers were used to select a subset of homologous genes with evidence of association with asthma in humans. Following validation attempts in three human asthma GWAS (i.e., Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG) and two human AHR GWAS (i.e., SHARP, DAG), the Kv channel interacting protein 4 (KCNIP4) gene was identified as nominally associated with both asthma and AHR at a geneand SNP-level. In EVE, the smallest KCNIP4 association was at rs6833065 (P-value 2.9e04), while the strongest associations for Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG were 1.5e-03, 1.0e-03, 3.1e-03 at rs7664617, rs4697177, rs4696975, respectively. At a SNP level, the strongest association across all asthma GWAS was at rs4697177 (P-value 1.1e-04). The smallest P-values for association with AHR were 2.3e-03 at rs11947661 in SHARP and 2.1e03 at rs402802 in DAG. Functional studies are required to validate the potential involvement of KCNIP4 in modulating asthma susceptibility and/or AHR. Our results suggest that a useful approach to identify genes associated with human asthma is to leverage mouse AHR association data. PLOS ONE | www.plosone.org 1 February 2013 | Volume 8 | Issue 2 | e56179 Citation: Himes BE, Sheppard K, Berndt A, Leme AS, Myers RA, et al. (2013) Integration of Mouse and Human Genome-Wide Association Data Identifies KCNIP4 as an Asthma Gene. PLoS ONE 8(2): e56179. doi:10.1371/journal.pone.0056179 Editor: Huiping Zhang, Yale University, United States of America Received October 2, 2012; Accepted January 7, 2013; Published February 14, 2013 Copyright: 2013 Himes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The CAMP Genetics Ancillary Study is supported by U01 HL075419, U01 HL65899, P01 HL083069, R01 HL086601, and T32 HL07427 from the NHLBI, National Institutes of Health (NIH). Additional support was provided by NIH U10 HL064287, U10 HL064288, U10 HL064295, U10 HL064305, U10 HL064307, U01 HL064313, RC2 HL101487, R01 HL087699 and U01 HL65899, an NIH Pharmacogenomics Research Network (PGRN) – RIKEN Center for Genomic Medicine (CGM) Global Alliance and by funding from the BioBank Japan project that was supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government. We thank the American Lung Association Asthma Clinical Research Centers (ALA-ACRC) for use of LOCCS and LODO study samples. B.E.H. was supported by NIH K99 HL105663. L.K.W. is funded by the American Asthma Foundation, the Fund for Henry Ford Hospital, and by NIH R01AI079139 and R01AI061774 from the National Institute of Allergy and Infectious Diseases (NIAID). K.C.B. was supported in part by the Mary Beryl Patch Turnbull Scholar Program. S.J.L. is supported by the Division of Intramural Research, National Institute of Environmental Health Sciences. D.A.G. was supported by the Netherlands Asthma Foundation grant AF (AF 95.09, AF 98.48, AF 3.2.02.51 and AF 3.2.07.015) and a grant from the University Medical Center Groningen. GHK was supported by a Ter Meulen Fund grant from the Royal Netherlands Academy of Arts and Sciences. D.S.P. was supported by a Royal Netherlands Academy of Arts and Sciences Honorary Professorship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: blanca.himes@channing.harvard.edu

BACKGROUND:Nutrient trials differ from drug trials because participants have varying circulating levels at entry into the trial. OBJECTIVE:We sought to study the effect of a vitamin D intervention in pregnancy between subjects of different races and the association between 25-hydroxyvitamin D3 (25[OH]D) levels in pregnancy and the risk of asthma/recurrent wheeze in offspring. METHODS:The Vitamin D Antenatal Asthma Reduction Trial is a randomized trial of pregnant women at risk of having children with asthma randomized to 4400 international units/d vitamin D or placebo plus 400 international units/d vitamin D. Asthma and recurrent wheezing until age 3 years were recorded. RESULTS:African American (AA) women (n = 312) had lower initial levels of 25(OH)D (mean [SD], 17.6 ng/mL [8.3 ng/mL]) compared with non-AA women (n = 400; 27.1 ng/mL [9.7 ng/mL], P < .001). No racial difference was found from vitamin D supplementation in pregnancy on asthma/recurrent wheezing in offspring (P for interaction = .77). Having an initial level of greater than 30 ng/mL and being randomized to the intervention group was associated with the lowest risk for asthma/recurrent wheeze by age 3 years compared with having an initial level of less than 20 ng/mL and receiving placebo (adjusted odds ratio, 0.42; 95% CI, 0.19-0.91). CONCLUSIONS:We did not find differences between AA and non-AA mothers in the effect of maternal vitamin D supplementation and asthma/recurrent wheeze in offspring at 3 years. Maternal supplementation of vitamin D, particularly in mothers with initial 25(OH)D levels of greater than 30 ng/mL, reduced asthma/recurrent wheeze in the offspring through age 3 years, suggesting that higher vitamin D status beginning in early pregnancy is necessary for asthma/recurrent wheeze prevention in early life.

The Childhood Asthma Control Test (c-ACT) is a validated tool commonly used to assess asthma control in children. Differences in responses between parent and child regarding symptoms may be due to the child's inability to identify symptoms of poor asthma control. A chart review of data from the St. Louis Children's Hospital Healthy Kids Express Asthma Program (HKEAP) assessed the agreement between parent and child scores on c-ACT questions to determine how accurately children gauge and report their asthma control. Chart review was performed from visits conducted between 2008-2015. Comparisons were made between c-ACT nighttime symptom response of both parent and child. Additionally, parent and child total c-ACT scores were compared with each other and the clinician's assessment of asthma control using contingency tables. 264 unique patient charts of children ages 8-11 years were reviewed. Child and parent assessments of asthma control via nighttime symptom response had poor agreement (κ= 0.09). Children that reported few nighttime symptoms on c-ACT had a strong association with well controlled asthma via clinician assessment (OR 8.84). Additionally, assessment of asthma control via total ACT score reported and clinician assessment after visit were strongly correlated (OR 45.74). The information gained from the c-ACT is best used in its' entirety with both parent and child responses. The childhood portion of the c-ACT should not be used alone to assess asthma control.

BACKGROUND:Maternal asthma, uncontrolled asthma, and low vitamin D levels during pregnancy have been individually linked to increased risk of preeclampsia. OBJECTIVE:To investigate the association of history of physician-diagnosed asthma and uncontrolled asthma status during pregnancy with the risk of preeclampsia and the effects of early pregnancy vitamin D concentrations on this relationship. METHODS:A total of 816 subjects with available pregnancy outcome data and risk factors of interest were analyzed. A group of experienced obstetricians and gynecologists from 3 study centers validated the preeclampsia diagnoses. Vitamin D was measured using the DiaSorin method at 10 to 18 weeks of gestation. The Pregnancy-Asthma Control Test was used to assess asthma control during pregnancy. Criterion-based stepwise variable selection algorithm was applied to investigate the relationships of risk factors of interest (history of asthma diagnosis, uncontrolled asthma during pregnancy, and vitamin D) to preeclampsia. RESULTS:The incidence of preeclampsia was not related to the presence of asthma diagnosis (8.9% with vs 7.4% without). The adjusted odds of preeclampsia controlled for maternal serum 25-hydroxyvitamin D (25OHD) concentrations was higher for women with a higher proportion of uncontrolled asthma months per visit during pregnancy (adjusted odds ratio, 3.55; 95% CI, 1.15-13.0). Adjusting for asthma control status during pregnancy, an additional decrease in the associated preeclampsia risk by 7% was observed for a 10-unit (ng/mL) increase in early pregnancy 25OHD levels (adjusted odds ratio10-unit, 0.60; 95% CI, 0.43-0.82) as compared with the previous risk estimate of preeclampsia associated with low maternal 25OHD unadjusted for asthma control status. CONCLUSIONS:Uncontrolled asthma during pregnancy is associated with an increased risk of preeclampsia. Early pregnancy 25OHD contributes to the association of uncontrolled asthma status with preeclampsia.

Sickle cell anemia (SCA) is one of the most common inherited blood disorders in the world, characterized by chronic hemolytic anemia and recurrent vasoocclusive pain episodes. Pulmonary complications are a major cause of morbidity and mortality. Individuals with SCA have been shown to have a high prevalence of asthma, wheezing, and airway hyperresponsiveness (AHR) (1, 2). Increased AHR has been demonstrated in individuals with SCA, both with and without a concomitant diagnosis of asthma (2, 3). Although previous studies have looked at the association between a history of acute chest syndrome (ACS) episodes and AHR to methacholine (4), investigators have not examined whether AHR to methacholine is a risk factor for future SCA-related morbidity (pain and ACS). Therefore, the aim of this study was to examine the association between AHR to methacholine and future rates of hospitalization for pain and ACS.

OBJECTIVE:To determine if parents are receptive to discussing firearm safety with their pediatrician.STUDY DESIGN:Parents completed a self-administered paper survey during a pediatric office visit. Responses of those who confirmed and denied household firearms were compared using Fisher exact test.RESULTS:Between March 23 and May 21, 2015, 1246 of 1363 eligible parents (91.4%) completed the survey (22.6% African American, 79.5% at least some college education); 36% of respondents reported household firearms (owners). An additional 14.3% reported that their child was often in homes that contained firearms. Of the 447 owners, 25.1% reported ≥1 firearm was stored loaded, and 17.9% carried a firearm when leaving the house. Seventy-five percent of parents thought the pediatrician should advise about safe storage of firearms (owners 71.1%, others 77.5%), 16.9% disagreed (owners 21.9%, others 13.4%), and 8.2% were uncertain. Sixty-six percent thought pediatricians should ask about the presence of household firearms (owners 58.4%, others 70.9%), 23.2% disagreed (owners 31.5%, others 17.8%), and 10.5% were uncertain. Differences in parental opinions between owners and other parents were statistically significant. Twenty-two percent of owners would ignore advice to not have household firearms for safety reasons, and 13.9% would be offended by such advice. Only 12.8% of all parents reported a discussion about firearms with the pediatrician.CONCLUSIONS:Avoiding direct questioning about firearm ownership and extending the discussion about why and how to ensure safe storage of firearms to all parents may be an effective strategy to decrease firearm-related injuries and fatalities in children.

OBJECTIVES: Information is lacking regarding recognition and treatment of overweight and obesity in children hospitalized for asthma. The study objectives were to determine the current practice of recognition, diagnosis, and treatment of overweight and obesity for children hospitalized for asthma and to describe demographic, asthma, and weight characteristics for these patients. METHODS: A retrospective record review was conducted for children admitted to the hospital with asthma in 2012. Charts were reviewed for evidence of recognition, diagnosis, and treatment of overweight and obesity. Subjects were classified into age-adjusted Centers for Disease Control and Prevention weight categories based on BMI percentile and chronic asthma severity categories according to National Asthma Education and Prevention Program guidelines. RESULTS: A total of 510 subjects aged 3 to 17 years were studied. Obesity was present in 19.6% and overweight in 13.3% of subjects. BMI percentile was recorded in only 3.3% of all charts, in only 11% of subjects with obesity, and in 0% of subjects with overweight. BMI percentile was documented more often in subjects with severe obesity (P = .013) and with moderate to severe persistent asthma (P = .035). Only 9 of 168 subjects who were overweight or obese (5.6%) were given a discharge diagnosis indicating overweight or obesity, and 14 (8.3%) received treatment. Chronic asthma severity differed by BMI weight category (P < .001), with a significant relationship between obesity status and chronic asthma severity in older subjects (P = .033). There were no differences in severity of acute episodes based on weight group. CONCLUSIONS: Overweight and obesity were underrecognized, underdiagnosed, and undertreated in children hospitalized for asthma.

Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management.

Background: The significance of fractional exhaled nitric oxide (FENO) levels in children with sickle cell anemia (SCA) is unclear, but increased levels can be associated with features of asthma and thus increased morbidity.Objectives: We sought to determine factors associated with FENO and whether FENO levels are associated with increased rates of acute chest syndrome (ACS) and pain.Methods: All participants had SCA, were part of the prospective observational Sleep and Asthma Cohort study, and had the following assessments: FENO levels, spirometry, blood samples analyzed for hemoglobin, white blood cell counts, eosinophil counts and total serum IgE levels, questionnaires about child medical and family history, and review of medical records.Results: The analytic sample included 131 children with SCA (median age, 11.2 years; age range, 6-18 years) followed for a mean of 16.2 years, including a mean of 5.1 years after baseline FENO data measurements. In multivariable analyses higher FENO levels were associated with ln(IgE) levels (P <.001) and the highest quartile of peripheral eosinophil counts (P=.03) but not wheezing symptoms, baseline spirometric indices, or response to bronchodilator. Multivariable analyses identified that the incident rate ofACS was associated with ln(FENO) levels (P=.03), as well as male sex (P =.025), wheezing causing shortness of breath (P=.002), andACSat less than 4 years of age (P<. 001). FENO levels were not associated with future pain episodes.Conclusions: Steady-state FENO levels were not associated with an asthma diagnosis, wheezing symptoms, lung function measures, or prior sickle cell morbidity but were associated with markers of atopy and increased risk of future ACS events.

BACKGROUND: Although specialist asthma care improves children's asthma outcomes, the impact of primary care management is unknown.OBJECTIVE: To determine whether variation in preventive and acute care for asthma in pediatric practices affects patients' outcomes.METHODS: For 22 practices, we aggregated 12-month patient data obtained by chart review and parent telephone interviews for 948 children, 3 to 12 years old, diagnosed with asthma to obtain practice-level measures of preventive (>= 1 asthma maintenance visit/year) and acute (>= 1 acute asthma visit/year) asthma care. Relationships between practice-level measures and individual asthma outcomes (symptom-free days, parental quality of life, emergency department [ED] visits, and hospitalizations) were explored using generalized estimating equations, adjusting for seasonality, specialist care, Medicaid insurance, single-family status, and race.RESULTS: For every 10% increase in the proportion of children in the practice receiving preventive care, symptom-free days per child increased by 7.6 days (P = .02) and ED visits per child decreased by 16.5% (P = .002), with no difference in parental quality of life or hospitalizations. Only the association between more preventive care and fewer ED visits persisted in adjusted analysis (12.2% reduction; P = .03). For every 10% increase in acute care provision, ED visits per child and hospitalizations per child decreased by 18.1% (P = .02) and 16.5% (P < .001), respectively, persisting in adjusted analyses (ED visits 8.6% reduction, P = .02; hospitalizations 13.9%, P = .03).CONCLUSIONS: Children cared for in practices providing more preventive and acute asthma care had improved outcomes, both impairment and risk. Persistence of improved risk outcomes in the adjusted analyses suggests that practice-level interventions to increase asthma care may reduce childhood asthma disparities. (C) 2016 American Academy of Allergy, Asthma & Immunology

BackgroundInterstitial lung disease is common in patients with sickle cell anemia (SCA). Fibrocytes are circulating cells implicated in the pathogenesis of pulmonary fibrosis and airway remodeling in asthma. In this study, we tested the hypotheses that fibrocyte levels are: (1) increased in children with SCA compared to healthy controls, and (2) associated with pulmonary disease.ProcedureCross-sectional cohort study of children with SCA who participated in the Sleep Asthma Cohort Study.ResultsFibrocyte levels were obtained from 45 children with SCA and 24 controls. Mean age of SCA cases was 14 years and 53% were female. In children with SCA, levels of circulating fibrocytes were greater than controls (P<0.01). The fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on the majority of cells and CCR2 and CCR7 expressed on a smaller subset. Almost half of fibrocytes demonstrated -smooth muscle actin activation. Increased fibrocyte levels were associated with a higher reticulocyte count (P=0.03) and older age (P=0.048) in children with SCA. However, children with increased levels of fibrocytes were not more likely to have asthma or lower percent predicted forced expiratory volume in 1sec/forced vital capacity (FEV1/FVC) or FEV1 than those with lower fibrocyte levels.ConclusionsHigher levels of fibrocytes in children with SCA compared to controls may be due to hemolysis. Longitudinal studies may be able to better assess the relationship between fibrocyte level and pulmonary dysfunction. Pediatr Pulmonol. 2016;51:295-299. (c) 2015 Wiley Periodicals, Inc.

RATIONALE:Patient factors associated with development of abnormal lung function in children with sickle cell anemia (SCA) have not been fully characterized.OBJECTIVES:To characterize lung function abnormalities among children with SCA and to determine whether these steady-state lung function results were associated with morbidity before or after testing among children with SCA.METHODS:This study was part of the prospective National Institutes of Health-funded Sleep and Asthma Cohort Study. Children with HbSS or Hb Sβ(o) (SCA) were enrolled without regard for sickle cell-related comorbidities or diagnosis of asthma. Lung function was measured by spirometry and plethysmography on the same day, when free of acute disease. Standardized asthma symptom questionnaires and review of the medical records were also performed.MEASUREMENTS AND MAIN RESULTS:A total of 149 children aged 6 to 19 years completed lung function testing, of whom 139 participants had retrospective morbidity data from birth to the test date, and 136 participants were followed prospectively for a median of 4.3 years from the test date. At baseline, percentages with normal, obstructive, restrictive, nonspecific, and mixed lung function patterns were 70, 16, 7, 6, and 1, respectively. Neither retrospective rates of pain nor acute chest syndrome was associated with lung function patterns. Furthermore, baseline lung function pattern was not predictive of future pain or acute chest syndrome episodes.CONCLUSIONS:The majority of children with SCA have lung function that is within the normal range. Abnormal lung function patterns were not associated with prior vasoocclusive pain or acute chest syndrome episodes, and baseline lung function patterns did not predict future vasoocclusive pain or chest syndrome episodes.

BACKGROUNDLow vitamin D status in pregnancy was proposed as a risk factor of preeclampsia.METHODSWe assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (10-18 weeks), on the development of preeclampsia. The effects of serum vitamin D (25-hydroxyvitamin D [25OHD]) levels on preeclampsia incidence at trial entry and in the third trimester (32-38 weeks) were studied. We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin D-associated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia.RESULTSOf 881 women randomized, outcome data were available for 816, with 67 (8.2%) developing preeclampsia. There was no significant difference between treatment (N = 408) or control (N = 408) groups in the incidence of preeclampsia (8.08% vs. 8.33%, respectively; relative risk: 0.97; 95% CI, 0.61-1.53). However, in a cohort analysis and after adjustment for confounders, a significant effect of sufficient vitamin D status (25OHD ≥30 ng/ml) was observed in both early and late pregnancy compared with insufficient levels (25OHD <30 ng/ml) (adjusted odds ratio, 0.28; 95% CI, 0.10-0.96). Differential expression of 348 vitamin D-associated genes (158 upregulated) was found in peripheral blood of women who developed preeclampsia (FDR <0.05 in the Vitamin D Antenatal Asthma Reduction Trial [VDAART]; P < 0.05 in a replication cohort). Functional enrichment and network analyses of this vitamin D-associated gene set suggests several highly functional modules related to systematic inflammatory and immune responses, including some nodes with a high degree of connectivity.CONCLUSIONSVitamin D supplementation initiated in weeks 10-18 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm. However, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia. Differentially expressed vitamin D-associated transcriptomes implicated the emergence of an early pregnancy, distinctive immune response in women who went on to develop preeclampsia.TRIAL REGISTRATIONClinicalTrials.gov NCT00920621.FUNDINGQuebec Breast Cancer Foundation and Genome Canada Innovation Network. This trial was funded by the National Heart, Lung, and Blood Institute. For details see Acknowledgments.