Upper airway lymphoid tissue size in children with sickle cell disease.
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ABSTRACT:
SUBMITTER: Strauss T
PROVIDER: S-EPMC3419377 | biostudies-other | 2012 Jul
REPOSITORIES: biostudies-other
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Project description:Desaturation of hemoglobin (Hb) in cerebral tissue, a physiologic marker of brain vulnerable to ischemic injury, can be detected non-invasively by transcranial oximetry. Absolute cerebral oximetry has not been studied in sickle cell disease (SCD), a group at very high risk of cerebral infarction in whom prevention of brain injury is key.We measured absolute Hb saturation in cerebral tissue (S(CT)O(2)) in children with SCD using near-infrared spectrophotometry and investigated the contributions of peripheral Hb saturation (S(P)O(2)), hematologic measures, cerebral arterial blood flow velocity, and cerebral arterial stenosis to S(CT)O(2). We also assessed the effects of transfusion.We studied 149 children with SCD (112 HbSS/S?(0); 37 HbSC/S?(+)). S(CT)O(2) was abnormally low in 75% of HbSS/S?(0) and 35% of HbSC/S?(+) patients. S(CT)O(2) (mean ± SD) was 53.2 ± 14.2 in HbSS/S?(0) and 66.1 ± 9.2% in SC/S?(+) patients. S(CT)O(2) correlated with age, sex, Hb concentration, reticulocytes, Hb F, and S(P)O(2), but not transcranial Doppler arterial blood flow velocities as continuous measures. In multivariable models, S(P)O(2), Hb concentration, and age were significant independent determinants of S(CT)O(2). Cerebral vasculopathy was associated with ipsilateral cerebral desaturation. Transfusion increased S(CT)O(2) and minimized the inter-hemispheric differences in S(CT)O(2) due to vasculopathy.Cerebral desaturation, a physiologic marker of at-risk brain, is common in SCD, more severe in HbSS/S?(0) patients, and associated with peripheral desaturation, more severe anemia, and increasing age. Cerebral oximetry has the potential to improve the identification of children with SCD at highest risk of neurologic injury and possibly serve as a physiologic guide for neuroprotective therapy.
| S-EPMC3534844 | biostudies-literature
Project description:BackgroundThe high prevalence of airway hyperresponsiveness (AHR) among children with sickle cell anemia (SCA) remains unexplained.MethodsTo determine the relationship between AHR, features of asthma, and clinical characteristics of SCA, we conducted a multicenter, prospective cohort study of children with SCA. Dose response slope (DRS) was calculated to describe methacholine responsiveness, because 30% of participants did not achieve a 20% decrease in FEV1 after inhalation of the highest methacholine concentration, 25 mg/mL. Multiple linear regression analysis was done to identify independent predictors of DRS.ResultsMethacholine challenge was performed in 99 children with SCA aged 5.6 to 19.9 years (median, 12.8 years). Fifty-four (55%) children had a provocative concentration of methacholine producing a 20% decrease in FEV1<4 mg/mL. In a multivariate analysis, independent associations were found between increased methacholine responsiveness and age (P<.001), IgE (P=.009), and lactate dehydrogenase (LDH) levels (P=.005). There was no association between methacholine responsiveness and a parent report of a doctor diagnosis of asthma (P=.986). Other characteristics of asthma were not associated with methacholine responsiveness, including positive skin tests to aeroallergens, exhaled nitric oxide, peripheral blood eosinophil count, and pulmonary function measures indicating airflow obstruction.ConclusionsIn children with SCA, AHR to methacholine is prevalent. Younger age, serum IgE concentration, and LDH level, a marker of hemolysis, are associated with AHR. With the exception of serum IgE, no signs or symptoms of an allergic diathesis are associated with AHR. Although the relationship between methacholine responsiveness and LDH suggests that factors related to SCA may contribute to AHR, these results will need to be validated in future studies.
| S-EPMC3047289 | biostudies-literature
Project description:Early identification of infants with sickle cell disease (SCD) by newborn screening, now universal in all 50 states in the US, has improved survival, mainly by preventing overwhelming sepsis with the early use of prophylactic penicillin. Routine transcranial Doppler screening with the institution of chronic transfusion decreases the risk of stroke from 10% to 1% in paediatric SCD patients. Hydroxyurea decreases the number and frequency of painful crises, acute chest syndromes and number of blood transfusions in children with SCD. Genetic research continues to be driven toward the prevention and ultimate cure of SCD before adulthood. This review focuses on clinical manifestations and therapeutic strategies for paediatric SCD as well as the evolving topic of gene-focused prevention and therapy.
| S-EPMC3899685 | biostudies-other
Project description:Hydroxyurea therapy offers promise for ameliorating the clinical course of children with sickle cell disease (SCD). Hydroxyurea is a prototypic therapeutic option; it can be administered with minimal side effects, has a relatively wide therapeutic window, and has mechanisms of action that address pathophysiologic pathways of sickling, vaso-occlusion, hemolysis, and organ damage. There are limited data regarding hydroxyurea's ability to prevent or diminish organ dysfunction, and the long-term risks of hydroxyurea therapy remain incompletely defined. Although clinical trials are underway to address long-term issues, hydroxyurea remains an effective but underutilized therapy for SCD.
| S-EPMC4765496 | biostudies-other
Project description:Rationale: Asthma is a common comorbid condition in sickle cell disease (SCD). However, obstructive lung disease is prevalent in SCD, independent of a diagnosis of asthma. It is speculated that the heightened state of inflammation in SCD, involving pathways distinct from allergic asthma, may underlie the SCD-specific obstructive disease. Objective: The objective of the study was to compare airway and systemic inflammatory markers between SCD patients with pulmonary manifestations and patients with allergic asthma, and correlate the discriminating inflammatory markers with clinical measures of pulmonary disease. Materials and Methods: In a pilot translational study conducted at the Children's Hospital at Montefiore, 15 patients with SCD, and history of asthma, airway obstruction, or airway hyper-reactivity, and 15 control patients with allergic asthma 6-21 years of age were recruited. Inflammatory markers, including peripheral blood T helper cell subsets, serum and exhaled breath condensate (EBC) cytokines and chemokines of the Th-1/Th-17, Th-2, and monocytic pathways, and serum cysteinyl leukotrienes B4 (LTB4), were quantified, compared between the study groups, and correlated with atopic sensitization, pulmonary function tests, and markers of hemolysis. Results: White blood cells (P?<?0.05) and monocytes (P?<?0.001) were elevated in the SCD group, while atopic characteristics were higher in the control asthma group. Tumor necrosis factor-alpha (P?<?0.01), interferon gamma inducible protein (IP)-10 (P?<?0.05), and interleukin-4 (P?<?0.01) in serum and monocyte chemotactic protein (MCP)-1 in EBC were higher in the SCD group (P???0.05). Forced vital capacity (FVC) and forced expiratory volume in 1?s (FEV1) in patients with SCD inversely correlated with serum IP-10 and LTB4 levels. Conclusions: Compared with atopic asthmatic patients, inflammatory markers involving Th-1, Th-2, and monocytic pathways were higher in the SCD group, among which Th-1 measures correlated with pulmonary function deficits.
| S-EPMC6761598 | biostudies-literature
Project description:We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS.Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle.We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively).Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor.
| S-EPMC2718463 | biostudies-other
Project description:Background:Children with sickle cell disease (SCD) face unique problems that attendance at a camp with their peers is well suited to address. However, because the staff members at ordinary summer camps are not accustomed to accommodating children with chronic diseases, the potential for significant health consequences exists.Methods:We searched the literature in PubMed and CINAHL using the keywords summer camp, camp, sickle, and anemia to identify the unique characteristics of camps for children with SCD and the recommendations for care and/or lessons learned.Results:Published data are limited. Accommodations to avoid triggering sickle vaso-occlusive pain have been developed empirically and extrapolated from other settings. Camp experiences provide peer learning opportunities, positive role models, and a safe area to explore personal growth. The supportive atmosphere of the camp and escape from social stigma are welcome changes from the daily routine. Camp experiences can help with education on self-care and the transition from adolescent to adult healthcare.Conclusion:Camp offers unique opportunities for care coordination. Camps for children with SCD provide a setting for dissemination of best practices for the disease. Community-based organizations should partner in recruiting young adults with SCD as counselors. Educational material now available could be modified for use in the camp setting. All stakeholders in the care of children with SCD should work in unison to ensure these children enjoy the benefits of summer camp.
| S-EPMC6292478 | biostudies-other
Project description:PurposeSickle cell disease (SCD) is an inherited hemoglobinopathy that causes stroke and silent cerebral infarct (SCI). Our aim was to identify markers of brain injury in SCD.Experimental designPlasma proteomes were analyzed using a sequential separation approach of hemoglobin (Hb) and top abundant plasma protein depletion, followed by reverse phase separation of intact proteins, trypsin digestion, and tandem mass spectrometry. We compared plasma proteomes of children with SCD with and without SCI in the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) to age-matched, healthy non-SCD controls.ResultsFrom the SCD group, 1172 proteins were identified. Twenty-five percent (289/1172) were solely in the SCI group. Twenty-five proteins with enriched expression in the human brain were identified in the SCD group. Neurogranin (NRGN) was the most abundant brain-enriched protein in plasma of children with SCD. Using a NRGN sandwich immunoassay and SIT Trial samples, median NRGN levels were higher at study entry in children with SCD (0.28 ng/mL, N = 100) compared to control participants (0.12 ng/mL, N = 25, p < 0.0004).Conclusions and clinical relevanceNRGN levels are elevated in children with SCD. NRGN and other brain-enriched plasma proteins identified in plasma of children with SCD may provide biochemical evidence of neurological injury.
| S-EPMC8666096 | biostudies-literature
Project description:BackgroundThe contribution of environmental tobacco smoke (ETS) exposure to pulmonary morbidity in children with sickle cell anemia (SCA) is poorly understood. We tested the hypothesis that children with SCA and ETS exposure would have an increased prevalence of obstructive lung disease and respiratory symptoms compared with children with SCA and no ETS exposure.MethodsParent reports of ETS and respiratory symptom frequency were obtained for 245 children with SCA as part of a multicenter prospective cohort study. One hundred ninety-six children completed pulmonary function testing. Multivariable regression models were used to evaluate the associations between ETS exposure at different time points (prenatal, infant [birth to 2 years], preschool [2 years to first grade], and current) and lung function and respiratory symptoms.ResultsAmong the 245 participants, a high prevalence of prior (44%) and current (29%) ETS exposure was reported. Of the 196 children who completed pulmonary function testing, those with parent-reported infant and current ETS exposure were more likely to have airway obstruction (defined as an FEV1/FVC ratio below the lower limit normal) compared with unexposed children (22.0% vs 3.1%, P < .001). Those with ETS exposure also had a lower forced expiratory flow, midexpiratory phase/FVC ratio (0.82 vs 0.97, P = .001) and were more likely to have evidence of bronchodilator responsiveness (23% vs 11%, P = .03). Current and prior ETS exposure and in utero smoke exposure were associated with increased frequency of respiratory symptoms.ConclusionsETS exposure is associated with evidence of lower airway obstruction and increased respiratory symptoms in SCA.
| S-EPMC3787918 | biostudies-literature
Project description:Sickle cell disease (SCD) is caused by a pathogenic hemoglobin (Hb) mutation, yet patients can have dramatically variable clinical manifestations. Here we address the genetic basis of this clinical heterogeneity. Using a systems genetics approach, we performed whole blood gene expression analysis and eQTL analysis on different clinical phenotypes in SCD patients. We generated whole blood gene expression profiles for 311 West-African children recruited from the National Sickle Cell Disease Centre in Cotonou, Benin which included 250 patients with varying degrees of SCD severities and 61 age-matched controls. SCD is caused by a point-mutation in the beta-hemoglobin gene that changes the normal HbAA protein into, most often, an abnormal HbSS or HbSC protein. The SCD patients recruited in the study either had HbSS or HbSC phenotypes and were categorized into different 3 clinical states based on follow-up status (Rahimy, MC, et al. Effect of a comprehensive clinical care program on disease course in severely ill children with sickle cell anemia in sub-Saharan African setting. Bood 102, 834-838. 2002). When patients are refered to the clinic, they are enrolled when they are in steady-state condition, and are labeled as entry (E). Patients followed at the SCD clinic are labeled as FU. Control patients were recruited and are labeled as C. Patients were also assigned a severity score (Sebastiani, P. et al. A network model to predict the risk of death in sickle cell disease. Blood 110, 2727-2735, 2007). Hemoglobin protein status (Hb phenotype) was confirmed for each patient using standard electrophoretic techniques. We generated genotypes for 263 of these individuals and performed principal component analysis (PCA) which identified 2 signigicant genotypic principal components (gPC1 and gPC2). Using the gene expression and genotyping data, we performed an eSNP analysis. . Gene expression data presented in this study.
2014-07-01 | E-GEOD-35007 | biostudies-arrayexpress