Hari P. R. Bandla

Reproducibility of a scoring system for computed tomography scanning in cystic fibrosis.

Introduction Computerized tomography (CT) scanning shows promise as an outcome surrogate for cystic fibrosis (CF) lung disease progression. The scoring system used to convert the CT image to numeric data is an essential determinant of the performance of CT scanning. Methods Three radiologists independently scored 16 high-resolution CT scans performed on children in the Wisconsin CF Neonatal Screening Project. The test scans were selected to provide a broad range of disease severity. The scoring system provided subscores for the presence and severity of 5 findings of CF lung disease. The sum of the subscores provided a total score. The CT scans were then read again by each of the radiologists at least 11 months later. Using Mixed Effects Linear Model Analysis, the sources of error (scan-to-scan variation, interrater variance, and intrarater variance) were calculated. Results For the total score, the scan-to-scan variation was 14.48, interrater variance was 0.28, and intrarater variance was 0.45, with an overall reproducibility of 95%. The square root of scan-to-scan variance, a measure of sensitivity, was 3.81. Evaluation of the subscores showed higher reproducibility for bronchiectasis and hyperinflation (95% and 88%, respectively). The bronchiectasis score was more sensitive than the air-trapping score (1.46 vs. 0.89). Discussion This system was developed to provide a reproducible method that could be used to evaluate the lobar location, severity, and extent of a broad spectrum of CT features of CF lung disease, especially in children. This study demonstrates that the overall score is both sensitive to variation in the severity of lung disease and reproducible.

Sleep and Obesity in Preschool Children

OBJECTIVEnTo examine the relationship between sleep and obesity in children 3 to 4 years old in Shanghai, China.nnnSTUDY DESIGNnA total of 1311 Chinese children from 10 kindergarten classes in Shanghai, aged 3 to 4 years, who were participating in the kindergarten entrance health examination in 2000, were included in the study. Body weight and height were measured, and a questionnaire was given to the childrens parents about sleep and physical and social characteristics of the children and their family. The main outcome measure was obesity, defined as body mass index (kg/m2) > or = 95th percentile for the children.nnnRESULTSnCompared with children reporting > or = 11 hours of sleep per night, the odds ratio for childhood obesity was 4.76 (95% CI, 1.28-17.69) for children with <9 hours of sleep, and 3.42 (95% CI, 1.12-10.46) for children with 9.0 to 9.4 hours of sleep, after adjustment for age, sex, and other risk factors. Children with caregivers who slept less, who had mothers with higher education, or who co-slept with caregivers had less nighttime sleep than other children.nnnCONCLUSIONnShort sleep duration is positively associated with obesity in preschool children, and short nighttime sleep duration is significantly related to bedtime and co-sleeping with caregivers.

Dynamic changes in EEG spectra during obstructive apnea in children

Children are less likely to demonstrate EEG arousal during obstructive sleep apnea (OSA) than adults. We hypothesized that changes in spectral EEG characteristics occur during REM‐associated OSA in the absence of arousal. Eight snoring children underwent overnight polysomnography. OSA events during REM periods not associated with EEG or behavioral arousal were identified. EEG signals from C3A2 and C4A1 leads corresponding to 1) ≤10‐sec epochs preceding OSA (PRE), 2) the obstructed period (OSA), and 3) ≤10‐sec epochs following airflow resumption (POST) were subjected to fast Fourier transform (FFT) routines. Seventy‐two isolated OSA, and 14 clusters of > 4 OSA events were analyzed.

Overnight polysomnography versus respiratory polygraphy in the diagnosis of pediatric obstructive sleep apnea.

BACKGROUNDnSubstantial discrepancies exist in the type of sleep studies performed to diagnose pediatric obstructive sleep apnea (OSA) in different countries. Respiratory polygraphic (RP) recordings are primarily performed in sleep laboratories in Europe, whereas polysomnography (PSG) constitutes the majority in the US and Australia. Home RP show consistent apnea-hypopnea index (AHI) underscoring, primarily because the total recording time is used as the denominator when calculating the AHI compared to total sleep time (TST). However, laboratory-based RP are less likely affected, since the presence of sleep technicians and video monitoring may enable more accurate TST estimates. We therefore examined differences in AHI in PSG and in-lab RP, and whether RP-based AHI may impact clinical decision making.nnnMETHODSnOf all the children assessed for possible OSA who underwent PSG evaluation, 100 were identified and divided into 4 groups: (A) those with AHI < 1/h TST (n = 20), (B) 1 ≤ AHI < 5/h TST (n = 40), (C) 5 ≤ AHI < 10/h TST (n = 20), and (D) AHI ≥ 10/h TST (n = 20). Electroencephalography, electrooculography, and electromyography channels were deleted from the original unscored recordings to transform them into RP, and then rescored in random sequence. AHI-RP were compared to AHI-PSG, and therapeutic decisions based on AHI-RP and AHI-PSG were formulated and analyzed using clinical details derived from the patients clinic letter.nnnRESULTSnBland Altman analysis showed that in lab RP underestimated the AHI despite more accurate estimates of TST. This underestimation was due to missed hypopneas causing arousals without desaturation. Basing the therapeutic management decision on RP instead of PSG results changed the clinical management in 23% of all patients. The clinical management for patients in groups A and D was unaffected. However, 27.5% of patients in group B would have been given no treatment, as they would be diagnosed as having no OSA (AHI < 1/h TST) when they should have received a trial of anti-inflammatory therapy or been referred for ear, nose, and throat (ENT) review. Sixty percent of patients in group C would have received either a trial of medical treatment to treat mild OSA or no treatment, instead of referral to ENT services or commencement of continuous positive airway pressure.nnnCONCLUSIONnApnea-hypopnea index (AHI) is underestimated in respiratory polygraphy (RP), and the disparity in AHI-RP and AHI-polysomnography can significantly affect clinical management decisions, particularly in children with mild and moderate obstructive sleep apnea (1 < AHI < 10/h total sleep time).

Circulating Adropin Concentrations in Pediatric Obstructive Sleep Apnea: Potential Relevance to Endothelial Function

OBJECTIVEnTo test the hypothesis that concentrations of adropin, a recently discovered peptide that displays important metabolic and cardiovascular functions, are lower in obstructive sleep apnea (OSA), especially when associated with endothelial dysfunction.nnnSTUDY DESIGNnAge-, sex-, and ethnicity-matched children (mean age, 7.2 ± 1.4 years) were included into 1 of 3 groups based on the presence of OSA in an overnight sleep study, and on the time to postocclusive maximal reperfusion (Tmax >45 seconds) with a modified hyperemic test. Plasma adropin concentrations were assayed using a commercial enzyme-linked immunosorbent assay kit.nnnRESULTSnAmong controls, the mean morning adropin concentration was 7.4 ng/mL (95% CI, 5.2-16.3 ng/mL). Children with OSA and abnormal endothelial function (EF) (OSA(+)/EF(+) group) had significantly lower adropin concentrations (2.7 ± 1.1 ng/mL; n = 35) compared with matched controls (7.6 ± 1.4 ng/mL; n = 35; P < .001) and children with OSA and normal EF (OSA(+)/EF(-) group; 5.8 ± 1.5 ng/mL; n = 47; P < .001). A plasma adropin concentration <4.2 ng/mL reliably predicted EF status, but individual adropin concentrations were not significantly correlated with age, body mass index z-score, obstructive apnea-hypopnea index, or nadir oxygen saturation. Mean adropin concentration measured after adenotonsillectomy in a subset of children with OSA (n = 22) showed an increase in the OSA(+)/EF(+) group (from 2.5 ± 1.4 to 6.4 ± 1.9 ng/mL; n = 14; P < .01), but essentially no change in the OSA(+)EF(-) group (from 5.7 ± 1.3 to 6.4 ± 1.1 ng/mL; n = 8; P > .05).nnnCONCLUSIONnPlasma adropin concentrations are reduced in pediatric OSA when endothelial dysfunction is present, and return to within normal values after adenotonsillectomy. Assessment of circulating adropin concentrations may provide a reliable indicator of vascular injury in the context of OSA in children.

Antiinflammatory therapy outcomes for mild OSA in children.

BACKGROUNDnOSA is highly prevalent in children and usually initially treated by adenotonsillectomy. Nonsurgical alternatives for mild OSA primarily consisting of antiinflammatory approaches have emerged, but their efficacy has not been extensively assessed.nnnMETHODSnA retrospective review of clinically and polysomnographically diagnosed patients with OSA treated between 2007 and 2012 was performed to identify otherwise healthy children ages 2 to 14 years who fulfilled the criteria for mild OSA and who were treated with a combination of intranasal corticosteroid and oral montelukast (OM) for 12 weeks (ICS + OM). A subset of children continued OM treatment for 6 to 12 months.nnnRESULTSnA total of 3,071 children were diagnosed with OSA, of whom 836 fulfilled mild OSA criteria and 752 received ICS + OM. Overall, beneficial effects occurred in > 80% of the children, with nonadherence being documented in 61 children and adenotonsillectomy being ultimately performed in 12.3%. Follow-up polysomnography in a subset of 445 patients showed normalization of sleep findings in 62%, while 17.1% showed either no improvement or worsening of their OSA. Among the latter, older children (aged > 7 years; OR, 2.3; 95% CI, 1.43-4.13; P < .001) and obese children (BMI z-score > 1.65; OR: 6.3; 95% CI, 4.23-11.18; P < .000001) were significantly more likely to be nonresponders.nnnCONCLUSIONSnA combination of ICS + OM as initial treatment of mild OSA appears to provide an effective alternative to adenotonsillectomy, particularly in younger and nonobese children. These results support implementation of multicenter randomized trials to more definitively establish the role of ICS + OM treatment in pediatric OSA.

Laryngeal mask airway facilitated fibreoptic bronchoscopy in infants

PurposeTo assess the efficacy of the laryngeal mask airway (LMA) for fibreoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in infants.MethodsObservations were made in 19 consecutive infants undergoing FOB under general anaesthesia (GA) plus topical local anaesthesia. Anaesthesia was induced with N2O, O2, and halothane or sevoflurane except in two patients who received propofol and one who received thiopentone. Anaesthesia was maintained with oxygen and either sevoflurane, halothane, desflurane, or propofol infusion. No neuromuscular blockers were used. Size #1 or #2 LMAs were used through which a 3.5 mm fibreoptic bronchoscope was introduced. ECG, noninvasive blood pressure, pulse oximetry and, PETCO2 were measured. Intra-and post-procedural complications were recorded.ResultsMean age was 6 months; mean weight was 6.6 kg. Chronic wheezing was the indication for FOB in eight patients. Minor complications occurred in five patients: difficult LMA placement in one patient required changing size from #2 to #1; two patients had laryngospasm and bronchospasm that resolved with deepened anaesthesia and nebulised bronchodilator; one patient had transient arterial O2 desaturation responding to increased FIO2, and one patient required tracheal intubation because ventilation via LMA became inadequate.ConclusionThe minor complications observed were similar to other series and did not result in morbidity or mortality. We feel that GA via LMA facilitates safe FOB in infants. It affords excellent airway management, a quiet patient, and passage of a larger fibreoptic bronchoscope for better imaging and suction channel required for BAL.RésuméObjectifÉvaluer, en pédiatrie, l’efficacité du masque laryngé (ML) pour la bronchofibroscopie (BOF) et la lavage bronchoalvéolaire (LBA).MéthodesLes observations ont porté sur 19 BOF réalisées chez des enfants sous anesthésie générale (AG) complétée par une anesthésie topique. L’anesthésie générale était induite avec du N2O, de l’O2 et de l’halothane ou du sévoflurane à l’exception de deux patients qui ont reçu du propofol et un patient, du thiopental. L’anesthésie était maintenue avec de l’oxygène associé soit à du sévoflurane, de l’halothane, du desflurane, ou une perfusion de propofol. Aucun myorelaxant n’a été administré. On insérait un ML de taille 1 ou 2 par lequel un bronchofibroscope de 3,5 mm était introduit. LÉCG, l’oscillométrie automatisée, l’oxymétrie de pouls et la PETCO2 étaient enregistrés. On notait les complications peret postopératoires.RésultatsHuit patients ont subi la BOF pour du wheezing. Des complications mineures sont survenues chez cinq patients: chez un patient, l’insertion laborieuse du ML a nécessité un changement de masque de taille 2 à taille 1: deux patients ont présenté un laryngospasme et un bronchospasme maîtrisés par l’approfondissement de l’anesthésie et la nébulisation d’un bronchodilatateur; un patient a présenté une désaturation arténelle transitoire résolue par l’augmentation de la FiO2 et un patient a dû être intubé à cause de l’incapacité de ventiler sous ML.ConclusionLes complications mineures observées étaient les mêmes que celles notées dans d’autres études et n’ont provoqué ni morbidité ni mortalité. Nous croyons que l’AG par ML facilite la BOF chez les enfants. Cette méthode procure un excellent contrôle des voies aériennes, l’immobilité du patient et permet l’introduction d’un bronchofibroscope de plus grand calibre pour faciliter une meilleure visualisation et l’aspiration pendant le LBA.

Alterations in circulating T-cell lymphocyte populations in children with obstructive sleep apnea.

STUDY OBJECTIVESnChanges in lymphocyte phenotype and functionality have been described in adult patients with obstructive sleep apnea (OSA). We hypothesized that OSA is associated with T lymphocyte alterations in children, particularly in T regulatory lymphocytes (T regs), and aimed to characterize circulating T lymphocyte subsets in children with OSA.nnnDESIGNnCross-sectional.nnnSETTINGnKosair Childrens Hospital (Louisville, KY, USA) and Comer Childrens Hospital (Chicago, IL, USA).nnnPARTICIPANTSnConsecutively recruited children being evaluated for habitual snoring.nnnINTERVENTIONSnN/A.nnnMEASUREMENTS AND RESULTSnOvernight polysomnography (PSG) was performed and a fasting blood sample was obtained from the patients. Flow cytometry was performed on peripheral blood mononuclear cells stained for CD3, CD4, CD8, CD25, FOXP3, interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17. Patients were divided into three groups based on their PSG: controls (apnea-hypopnea indices [AHI] < 1/h total sleep time [TST]), mild OSA (1 ≤ AHI < 5/hTST), moderate-severe OSA (AHI ≥ 5/h TST). The percentage of CD4+ and T reg lymphocytes differed across groups. Children with moderate-severe OSA had significantly reduced T reg than control children (median [interquartile range] 4.8 [3.8-5.7% CD4+] versus 7.8 [7.0-9.2% CD4+]; P < 0.001). There were also significant differences in the percentage of T helper 1 (Th1) lymphocytes and in Th1:Th2 ratios between groups. Children with moderate-severe OSA had increased Th1 cells (P = 0.001) and Th1:Th2 ratios (P = 0.0026) compared with children with mild OSA and control children. Associations between AHI and T reg (P = 0.0003; r = -0.46), CD4+ lymphocytes (P = 0.0047; r = -0.37), and Th1:Th2 ratios (P = 0.0009; r = 0.43) emerged. In addition, the percentage of T reg was inversely correlated with Th1:Th2 ratios (P = 0.029; r = -0.29).nnnCONCLUSIONSnPediatric OSA is associated with reduced T reg population and altered Th1:Th2 balance toward Th1 predominance, suggesting a shift to a proinflammatory state. The changes in lymphocytic phenotypes associated with OSA may contribute to the variance in systemic inflammation and downstream morbidities associated with this condition.

Assessing learning outcomes and cost effectiveness of an online sleep curriculum for medical students.

OBJECTIVEnSleep disorders are highly prevalent across all age groups but often remain undiagnosed and untreated, resulting in significant health consequences. To overcome an inadequacy of available curricula and learner and instructor time constraints, this study sought to determine if an online sleep medicine curriculum would achieve equivalent learner outcomes when compared with traditional, classroom-based, face-to-face instruction at equivalent costs.nnnMETHODnMedical students rotating on a required clinical clerkship received instruction in 4 core clinical sleep-medicine competency domains in 1 of 2 delivery formats: a single 2.5-hour face-to-face workshop or 4 asynchronous e-learning modules. Immediate learning outcomes were assessed in a subsequent clerkship using a multiple-choice examination and standardized patient station, with long-term outcomes assessed through analysis of students patient write-ups for inclusion of sleep complaints and diagnoses before and after the intervention. Instructional costs by delivery format were tracked. Descriptive and inferential statistical analyses compared learning outcomes and costs by instructional delivery method (face-to-face versus e-learning).nnnRESULTSnFace-to-face learners, compared with online learners, were more satisfied with instruction. Learning outcomes (i.e., multiple-choice examination, standardized patient encounter, patient write-up), as measured by short-term and long-term assessments, were roughly equivalent. Design, delivery, and learner-assessment costs by format were equivalent at the end of 1 year, due to higher ongoing teaching costs associated with face-to-face learning offsetting online development and delivery costs.nnnCONCLUSIONSnBecause short-term and long-term learner performance outcomes were roughly equivalent, based on delivery method, the cost effectiveness of online learning is an economically and educationally viable instruction platform for clinical clerkships.

Nitric oxide production by monocytes in children with OSA and endothelial dysfunction

OSA (obstructive sleep apnoea) is associated with a higher risk for alterations in post-occlusive hyperaemia, an eNOS (endothelial NO synthase)-dependent endothelial response. However, since not all children manifest endothelial dysfunction, we hypothesized that differences in circulating monocyte subsets and NO production may underlie the vascular phenotype in paediatric OSA. Matched pre-pubertal children with OSA with abnormal endothelial function (OSAab) and with normal endothelial function (OSAn), and controls (CO) were recruited. Peripheral blood mononuclear cells were subtyped into CD14+ and CD16+ cells, and NO production was assessed using flow cytometry. Endothelial dysfunction was defined as Tmax (time to reach maximal reperfusion)>45 s by laser Doppler flowmetry. A total of 11 OSAab, 12 OSAn and 12 CO-matched children completed the study. The OSAab group had increased CD16+ and decreased CD14+ cell numbers. They also had increased CX3CR1 (CX3C chemokine receptor 1) expression in CD16+ monocytes (P<0.01). Furthermore, monocytes from the OSAab group exhibited overall reduced NO production (787±71 compared with 1226±229 and 1089±116 median fluorescence intensity in the OSAn group and CO children respectively; P<0.01). Significant bivariate associations emerged between NO production, monocyte subsets, CX3CR1 in CD16+ monocytes, the CD14+/CD16+ ratio and Tmax. Thus OSA in children is associated with increased numbers of pro-inflammatory monocytes and reduced NO production in circulating monocytes that are closely associated with endothelial function.