Publications by authors named "Zihang Lu"

21 Publications

  • Page 1 of 1

Newly developed multiple-breath washout reference equations from the CHILD Cohort Study: implications of poorly fitting equations.

ERJ Open Res 2021 Jan 25;7(1). Epub 2021 Jan 25.

Division of Respiratory Medicine, Dept of Pediatrics and Program in Translational Medicine, SickKids Research Institute, The Hospital for Sick Children, and University of Toronto, Toronto, Canada.

https://bit.ly/3dcNZ5p.
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http://dx.doi.org/10.1183/23120541.00301-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836672PMC
January 2021

Cardiorespiratory Monitoring Data during Sleep in Healthy Canadian Infants.

Ann Am Thorac Soc 2020 10;17(10):1238-1246

Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

Sleep study interpretation in children needs to be based on age-specific normal values. Although several studies have reported normal cardiorespiratory parameters during sleep in children and adolescents, few have included younger children. To describe cardiopulmonary indices, specifically oxygen saturation and heart rate, as well as frequency of obstructive and central apneas in healthy 1-year-old Canadian infants during sleep. Home sleep cardiorespiratory monitoring was performed among infants participating in the Edmonton subcohort of the CHILD (Canadian Healthy Infant Longitudinal Development) study at their 1-year follow-up visit. A portable sleep monitoring device, which included a nasal pressure cannula, an oronasal thermal airflow sensor, a pulse oximeter, and respiratory inductance plethysmography belts, was used to collect sleep architecture and cardiorespiratory data during one night of monitoring in the home. Sleep scoring was done in blocks of 5 minutes using a novel pilot sleep scoring algorithm. Among the 562 subjects (mean ± standard deviation age 1.1 ± 0.2 yr) who attempted home sleep cardiorespiratory monitoring, 91% provided technically acceptable data with no loss of signal preventing analysis of any parameter. Obstructive and central apneas were rare, with a median obstructive apnea index of 0.0 events/h (10th percentile, 0.0; 90th percentile, 0.5) and a median central apnea index of 2.5 events/h (10th percentile, 0.6; 90th percentile, 7.1). Median oxygen saturation was 97.0% (10th percentile, 95.4; 90th percentile, 97.9). The oxygen desaturation index was 6.7 events/h (10th percentile, 1.4; 90th percentile, 15.8), with infants spending only 0.1% (10th percentile, 0.0; 90th percentile, 0.6) of the time with an oxygen saturation below 92%. These results provide important reference data for healthy infants undergoing cardiorespiratory monitoring during sleep.
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http://dx.doi.org/10.1513/AnnalsATS.201909-703OCDOI Listing
October 2020

Patients With Severe Gastrointestinal Dysmotility Disorders Receiving Home Parenteral Nutrition Have Similar Survival As Those With Short-Bowel Syndrome: A Prospective Cohort Study.

JPEN J Parenter Enteral Nutr 2020 May 8. Epub 2020 May 8.

Toronto General Hospital, University of Toronto, Toronto, Canada.

Introduction: Severe gastrointestinal dysmotility disorder (GID) constitute approximately 20% of patients requiring home parenteral nutrition (HPN), whereas short-bowel syndrome (SBS) remains the most frequent indication for HPN. This study's aim was to characterize GID patients and compare clinical parameters and survival to SBS patients. Similarly, clinical comparisons between sclerodermaand nonscleroderma patients were made.

Methods: Demographic and clinical data for all patients was extracted from the Canadian HPN Registry from January 1, 2003, to November 1, 2018. Kaplan-Meier method was used to estimate the unadjusted survival probability, and log-rank test was used to compare the survival probability between groups.

Result: 270 patients (52 GID and 218 SBS) were included in the analysis. For all patients, higher mortality was associated with age (hazard ratio [HR], 1.02 [1.00-1.04]; P = .05), PN dependence (HR, 1.01 [1.00-1.02]; P = .04), hospitalizations (HR, 1.21 [1.10-1.33]; P < .001), and use of immunosuppressant (HR, 1.97 [1.02-3.82]; P = .04). The 5- and 10-year actuarial survival probabilities between GID and SBS were not significantly different (5-year: 70.0% vs 59.2%; 10-year: 79.6% vs 66.2% [P = .5], respectively). There was no difference in survival between scleroderma and nonscleroderma patients (P = .67).

Conclusion: T5- and 10- year survival probabilities were similar between GID and SBS patients. The diagnosis of scleroderma had no effect on survival. Use of immunosuppressant, older age, PN dependence, and number of hospitalizations per PN duration are risk factors for mortality in both the GID and SBS groups.
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http://dx.doi.org/10.1002/jpen.1866DOI Listing
May 2020

Family functioning among adolescents with narcolepsy.

Paediatr Child Health 2019 Dec 11;24(8):490-494. Epub 2019 Jan 11.

Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Ontario.

Background: Narcolepsy is a sleep disorder with no cure with onset typically during adolescence. Caring for an adolescent with a lifelong medical condition can negatively impact family structure, cohesion, relationships, and overall functioning. The primary objective of this study was to evaluate family functioning in a cohort of adolescents with narcolepsy using the PedsQL Family Impact Module. The secondary objective was to compare family functioning in adolescents with narcolepsy to adolescents with chronic pain based on published data.

Methods: This was a cross-sectional study of adolescents (aged 10 to 18 years) with narcolepsy. The narcolepsy group was recruited from The Hospital for Sick Children in Toronto, Canada. Family functioning was assessed by the PedsQL family impact module total scores, which was completed by the patient's caregiver. The PedsQL family impact module yields a total scale which encompasses parent health-related quality of life, daily activities, family relationships, communication, and worry subscales. Lower scores suggest poorer family functioning. Secondary data analyses were used to compare participants' family functioning to a cohort of adolescents with chronic pain.

Results: Thirty adolescents with narcolepsy participated (mean age=13.8 ± 2.2 years, 76.7% male). Family functioning was impaired in this cohort of adolescents with narcolepsy and similar to adolescents with chronic pain (64.0 ± 19.8 versus 64.7 ± 19.5; P=0.849).

Conclusion: Family functioning is impaired in adolescents with narcolepsy. Clinical teams should assess family functioning at routine clinic visits by asking about concerns and challenges related to caring for an adolescent with narcolepsy and providing resources and support as needed.
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http://dx.doi.org/10.1093/pch/pxy192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901168PMC
December 2019

Early life exposure to phthalates in the Canadian Healthy Infant Longitudinal Development (CHILD) study: a multi-city birth cohort.

J Expo Sci Environ Epidemiol 2020 01 22;30(1):70-85. Epub 2019 Oct 22.

University of Toronto, 223 College Street, Toronto, ON, M5T 1R4, Canada.

Background: Few studies have examined phthalate exposure during infancy and early life, critical windows of development. The Canadian Healthy Infant Longitudinal Development (CHILD) study, a population-based birth cohort, ascertained multiple exposures during early life.

Objective: To characterize exposure to phthalates during infancy and early childhood.

Methods: Environmental questionnaires were administered, and urine samples collected at 3, 12, and 36 months. In the first 1578 children, urine was analyzed for eight phthalate metabolites: mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-3-carboxypropyl phthalate (MCPP). Geometric mean (GM) concentrations were calculated by age, together with factors that may influence concentrations. Trends with age were examined using mixed models and differences within factors examined using ANOVA.

Results: The highest urinary concentration was for the metabolite MBP at all ages (GM: 15-32 ng/mL). Concentrations of all phthalate metabolites significantly increased with age ranging from GM: 0.5-15.1 ng/mL at 3 months and 1.9-32.1 ng/mL at 36 months. Concentrations of all metabolites were higher in the lowest income categories except for MEHP at 3 months, among children with any breastfeeding at 12 months, and in urine collected on dates with warmer outdoor temperatures (>17 °C), except for MBzP at 3 months and MEHP at 3 and 12 months. No consistent differences were found by gender, study site, or maternal age.

Conclusions: Higher phthalate metabolite concentrations were observed among children in lower income families. Examination of factors associated with income could inform interventions aimed to reduce infant phthalate exposure.
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http://dx.doi.org/10.1038/s41370-019-0182-xDOI Listing
January 2020

Depressive symptoms, sleep patterns, and physical activity in adolescents with narcolepsy.

Sleep 2019 08;42(8)

Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.

Study Objectives: To evaluate the association between depressive symptoms, sleep patterns (duration and quality), excessive daytime sleepiness (EDS), and physical activity (PA) in adolescents with narcolepsy.

Methods: This cross-sectional study included adolescents (ages 10-18 years) with narcolepsy attending a tertiary care facility (The Hospital for Sick Children, Toronto, Canada). Adolescents with narcolepsy completed questionnaires evaluating depressive symptoms (Children's Depression Inventory-2nd edition [CDI-2]), sleep quality (Pittsburgh Sleep Quality Index), EDS (Epworth Sleepiness Scale), and PA (Godin Leisure-Time Exercise Questionnaire). Wrist-based actigraphy was worn by adolescents for 1 week to measure total sleep time (over 24 hr) and sleep efficiency percentage.

Results: Thirty adolescents with narcolepsy (mean age = 13.8 ± 2.2 years, 76.7% male) participated. In this cohort of adolescents with narcolepsy, 23.3% had CDI-2 total scores in the elevated range. Greater CDI-2 total scores were associated with poor sleep quality (ρ = 0.571; p = 0.02), EDS (ρ = 0.360; p = 0.05), and lower self-reported PA levels (ρ = -0.512; p < 0.01).

Conclusions: Adolescents with narcolepsy report experiencing depressive symptoms, which are associated with poor sleep quality, EDS, and low PA levels. Strategies to improve nocturnal sleep quality and symptoms of EDS as well as promoting increased PA levels in adolescents with narcolepsy may provide an opportunity to improve depressive symptoms in this population. Multidisciplinary care with mental health and sleep specialists for adolescents with narcolepsy is needed.
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http://dx.doi.org/10.1093/sleep/zsz111DOI Listing
August 2019

Lung clearance index is elevated in young children with symptom-controlled asthma.

Health Sci Rep 2018 Aug 19;1(8):e58. Epub 2018 Jun 19.

Division of Respiratory Medicine, Department of Pediatrics Hospital for Sick Children and Research Institute Toronto Ontario Canada.

Background: Pulmonary function testing has been recommended as an adjunct to symptom monitoring for assessment of asthma control. Lung clearance index (LCI) measures ventilation inhomogeneity and is thought to represent changes in the small airways. It has been proposed as a useful early marker of airway disease in asthmatic subjects, and determining it is feasible in preschool children. This study aims to assess whether LCI remains elevated in symptomatically controlled asthmatic children with a history of severe asthma, compared with healthy controls. A secondary aim was to determine whether the results were consistent across the preschool and school-aged populations.

Methods: Using a case-control design, we compared 33 children with currently well-controlled symptoms who had a history of severe asthma, to 45 healthy controls (age 3-15 years) matched by age, height, and sex. We performed multiple breath washout tests using sulfur hexafluoride as a tracer gas, to determine their LCI and S values.

Results: In the overall study, LCI z-score values were on average 0.86 units (95% confidence interval: 0.24-1.47,  = 0.01, t-test) higher in children with a history of severe asthma with current well-controlled symptoms compared with healthy controls. In addition, within the subgroup of preschool children (age ≤ 6), the asthmatic had significantly higher LCI z-score values than their healthy controls peers (mean (SD), 0.57 (2.18) vs -1.10 (1.00),  = 0.03, t-test). Twenty-seven percent (27%; 9/33) of subjects had an LCI value greater than the upper limit of our healthy controls despite being symptom controlled. Amongst preschool children, 5 (42%; 5/12) of the asthmatic children had abnormal LCI at the individual level.

Conclusions: LCI is elevated in children with asthma, which may be driven by differences in the preschool population. LCI may be useful in defining preschool asthma endotypes with persistent ventilation inhomogeneity despite symptomatic control.
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http://dx.doi.org/10.1002/hsr2.58DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266588PMC
August 2018

Shape invariant mixture model for clustering non-linear longitudinal growth trajectories.

Authors:
Zihang Lu Wendy Lou

Stat Methods Med Res 2019 12 10;28(12):3769-3784. Epub 2018 Dec 10.

Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

In longitudinal studies, it is often of great interest to cluster individual trajectories based on repeated measurements taken over time. Non-linear growth trajectories are often seen in practice, and the individual data can also be measured sparsely, and at irregular time points, which may complicate the modeling process. Motivated by a study of pregnant women hormone profiles, we proposed a shape invariant growth mixture model for clustering non-linear growth trajectories. Bayesian inference via Monte Carlo Markov Chain was employed to estimate the parameters of interest. We compared our model to the commonly used growth mixture model and functional clustering approach by simulation studies. Results from analyzing the real data and simulated data were presented and discussed.
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http://dx.doi.org/10.1177/0962280218815301DOI Listing
December 2019

Diagnosing atopic dermatitis in infancy: Questionnaire reports vs criteria-based assessment.

Paediatr Perinat Epidemiol 2018 11 21;32(6):556-567. Epub 2018 Nov 21.

Department of Medicine, McMaster University, Hamilton, Canada.

Background: Persisting atopic dermatitis (AD) is known to be associated with more serious allergic diseases at later ages; however, making an accurate diagnosis during infancy is challenging. We assessed the diagnostic performance of questionnaire-based AD measures with criteria-based in-person clinical assessments at age 1 year and evaluated the ability of these diagnostic methods to predict asthma, allergic rhinitis and food allergies at age 5 years.

Methods: Data relate to 3014 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study who were directly observed in a clinical assessment by an experienced healthcare professional using the UK Working Party criteria. The majority (2221; 73.7%) of these children also provided multiple other methods of AD ascertainment: a parent reporting a characteristic rash on a questionnaire, a parent reporting the diagnosis provided by an external physician and a combination of these two reports.

Results: Relative to the direct clinical assessment, the area under the Receiver Operating Characteristic curve for a parental report of a characteristic rash, reported physician diagnosis and a combination of both were, respectively, 0.60, 0.69 and 0.70. The strongest predictor of asthma at 5 years was AD determined by criteria-based in-person clinical assessment followed by the combination of parental and physician report.

Conclusions: These findings suggest that questionnaire data cannot accurately substitute for assessment by experienced healthcare professionals using validated criteria for diagnosis of atopic dermatitis. Combining the parental report with diagnosis by a family physician might sometimes be appropriate (eg to avoid costs of a clinical assessment).
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http://dx.doi.org/10.1111/ppe.12525DOI Listing
November 2018

Risk for Maternal Depressive Symptoms and Perceived Stress by Ethnicities in Canada: From Pregnancy Through the Preschool Years.

Can J Psychiatry 2019 03 1;64(3):190-198. Epub 2018 Aug 1.

3 Department of Pediatrics, University of Toronto & Hospital for Sick Children, Toronto, Canada.

Objective: Past cross-sectional studies have reported that mothers from ethnic minorities experience higher levels of prenatal and post-partum psychosocial distress compared with mothers from ethnic majorities. However, no studies have examined how the pattern varies longitudinally in a Canadian population of heterogeneous ethnicity.

Methods: We analyzed data from 3,138 mothers participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, a longitudinal multi-center study incorporating 10 distinct waves of psychosocial data collection from pregnancy until the index child was aged 5 y. Maternal self-identified ethnicity was grouped as White Caucasian, First Nations, Black, Southeast Asian, East Asian, South Asian, Middle Eastern, Hispanic and mixed ethnicity. We performed a multi-level regression to determine whether mothers of specific minority ethnicities were more likely to experience higher levels of distress (i.e. depressive symptoms and perceived stress) compared to white Caucasian mothers.

Results: Mothers self-identifying as Black or First Nations had consistently higher distress scores than mothers from other ethnicities across all data collection times. After adjusting for relevant variables (history of depression, education, household income, marital status, and social support), First Nations mothers had a 20% increase in the mean scores of depressive symptoms compared to White Caucasian Mothers.

Conclusions: Increased levels of perinatal and post-partum distress were seen in only some ethnic minority groups. Studies should avoid collapsing all categories into ethnic minority or majority and may need to consider how ethnicity interacts with other sociodemographic factors such as poverty.
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http://dx.doi.org/10.1177/0706743718792190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405811PMC
March 2019

Ventilation inhomogeneity in infants with recurrent wheezing.

Thorax 2018 10 15;73(10):936-941. Epub 2018 Jun 15.

Division of Respiratory Medicine and Translational Medicine, Department of Pediatrics & Physiology, Hospital for Sick Children & University of Toronto, Toronto, Ontario, Canada.

Background: The care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing.

Objective: To assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls.

Methods: This is a case-control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography.

Results: LCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (-0.11 to 0.63) vs -0.58 (-0.79 to 0.36), p<0.001)). Nineteen percent of recurrently wheezing infants had LCI values that were above the upper limit of normal (>1.64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05).

Conclusions: Ventilation inhomogeneity is present in clinically stable infants with recurrent wheezing.
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http://dx.doi.org/10.1136/thoraxjnl-2017-211351DOI Listing
October 2018

Reference equations for the interpretation of forced expiratory and plethysmographic measurements in infants.

Pediatr Pulmonol 2018 07 23;53(7):907-916. Epub 2018 May 23.

Division of Respiratory Medicine, Department of Pediatrics, and Program in Translational Medicine, SickKids Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Canada.

Background: Pulmonary function testing is commonly performed for diagnosis and clinical management of respiratory diseases. It is important to use appropriate reference equations from healthy subjects for interpretation of data from infants with lung disease. This study aimed to determine if published reference equations were similar to forced flow measures and plethysmographic infant pulmonary function testing data collected in the Canadian Healthy Infant Longitudinal Development (CHILD) Study.

Methods: Reference equations for five pulmonary function variables (FEV , FVC, FEF , FEV /FVC ratio and plethysmography (FRC )) were developed using data from the nSpire system. New reference equations developed using healthy data from the CHILD Study were compared to previously published reference equations for forced flow and plethysmographic measures.

Results: The current analysis included 131 infants (on 181 test occasions) with forced flow measures and 161 infants (on 246 test occasions) with plethysmography measures, aged 3-24 months. Age and length were major determinants of both forced flow and plethysmography measures. In addition, ethnicity (Caucasian vs non-Caucasian) was significantly associated with FEV /FVC and FEF measures. We found that the published reference equations based on custom-built equipment or commercially available systems provided poor fit to our current pulmonary function testing data, resulting in placing a large proportion of our healthy population outside the normal ranges.

Conclusions: Our current data support the need for population and device specific reference data for infant pulmonary function studies. By deriving new equipment-specific reference equations for our healthy population, we provide normative data to other centers utilizing this equipment.
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http://dx.doi.org/10.1002/ppul.24063DOI Listing
July 2018

Evaluating the effects of general anesthesia on sleep in children undergoing elective surgery: an observational case-control study.

Sleep 2018 08;41(8)

Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON.

Study Objectives: Previous research has suggested that general anesthetics can disturb postoperative sleep patterns by affecting the sleep-wake cycle. The objective was to identify the effects of general anesthetics on sleep quality and related behavioral changes in children.

Methods: This was a prospective, observational case-control study with children, aged 18 months to 8 years, undergoing general anesthesia for elective surgery. Participants wore an actigraph for 7 days on three occasions: prior to surgery, the immediate postoperative period, and 3 months after surgery. Data regarding behavior patterns were collected using behavioral assessments at baseline, the first postoperative week, and 3 months following surgery.

Results: Thirty-one participants (mean age 4.8 ± 2.0 years, 81% male) underwent urologic or otolaryngologic surgery. The median (interquartile range) anesthetic duration was 132.0 (80.0-184.0) min. No significant differences were found in sleep efficiency, total sleep time, wake time after sleep onset, or sleep onset latency between baseline, 7 day postoperative period, and the 3 month follow-up. No significant differences were found in sleep-related behavioral metrics including internalizing and externalizing behaviors, and executive functioning. Data were compared with a control group of 18 participants (mean age 5.3 ± 1.8 years, 61% male). No significant differences were found in sleep patterns and related behavioral metrics between both groups.

Conclusions: In this study, general anesthesia did not result in disturbed sleep or associated negative behavioral changes in otherwise healthy children undergoing elective surgeries of low complexity. Physicians can advise parents that a child's surgery and associated general anesthetic exposure may not result in significant changes in postoperative sleep patterns.
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http://dx.doi.org/10.1093/sleep/zsy094DOI Listing
August 2018

Intermittent nocturnal hypoxia and metabolic risk in obese adolescents with obstructive sleep apnea.

Sleep Breath 2018 Dec 22;22(4):1037-1044. Epub 2018 Jan 22.

Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.

Purpose: There is conflicting data regarding the independent associations of obstructive sleep apnea (OSA) with metabolic risk in obese youth. Previous studies have not consistently addressed central adiposity, specifically elevated waist to height ratio (WHtR), which is associated with metabolic risk independent of body mass index.

Objective: The objective of this study was to determine the independent effects of the obstructive apnea-hypopnea index (OAHI) and associated indices of nocturnal hypoxia on metabolic function in obese youth after adjusting for WHtR.

Methods: Subjects had standardized anthropometric measurements. Fasting blood included insulin, glucose, glycated hemoglobin, alanine transferase, and aspartate transaminase. Insulin resistance was quantified with the homeostatic model assessment. Overnight polysomnography determined the OAHI and nocturnal oxygenation indices.

Results: Of the 75 recruited subjects, 23% were diagnosed with OSA. Adjusting for age, gender, and WHtR in multivariable linear regression models, a higher oxygen desaturation index was associated with a higher fasting insulin (coefficient [standard error] = 48.076 [11.255], p < 0.001), higher glycated hemoglobin (coefficient [standard error] = 0.097 [0.041], p = 0.02), higher insulin resistance (coefficient [standard error] = 1.516 [0.364], p < 0.001), elevated alanine transferase (coefficient [standard error] = 11.631 [2.770], p < 0.001), and aspartate transaminase (coefficient [standard error] = 4.880 [1.444], p = 0.001). However, there were no significant associations between OAHI, glucose metabolism, and liver enzymes.

Conclusion: Intermittent nocturnal hypoxia rather than the OAHI was associated with metabolic risk in obese youth after adjusting for WHtR. Measures of abdominal adiposity such as WHtR should be considered in future studies that evaluate the impact of OSA on metabolic health.
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http://dx.doi.org/10.1007/s11325-018-1631-9DOI Listing
December 2018

Motor and sensory morbidity associated with the anterolateral thigh perforator free flap.

Laryngoscope 2018 05 6;128(5):1057-1061. Epub 2017 Nov 6.

Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Objective: To quantify changes in motor function, sensation, and lower extremity quality of life following anterior lateral thigh free flap (ALT) resection.

Methods: This mixed methods study contained both a prospective cohort arm (n = 20) and retrospective cross-sectional arm (n = 20). In both arms, patients underwent formal motor and sensation testing of the ipsilateral and contralateral thigh by sphygmomanometry and monofilament testing. In the prospective arm, data was collected preoperatively and at the 6-month and 1-year follow-up visits. In the retrospective arm, consecutive patients with a minimum of 6-month postoperative follow-up were enrolled.

Results: Postoperatively, 82% of participants endorsed some degree of numbness and tingling at the donor site. On monofilament testing, patients from the prospective arm showed decreased sensibility of the midthigh at both the 6- and 12-month assessment (P < 0.01). Two-point discrimination scores were moderately correlated with the cross-sectional surface area of the flap. Donor thighs demonstrated a similar peak isometric quadriceps contraction (retrospective [retro]: 47 ± 24 mmHg, prospective [pro]: 90 ± 36 mmHg) to the unoperated thighs (retro: 43 mmHg ± 22, pro: 69 ± 35.3 mmHg, P = 0.49). When stratified by perforator anatomy, no significant differences were noted. Subjective donor site morbidity measured with the lower extremity function scale demonstrated no statistically significant difference between the preoperative and 12-month postoperative assessment.

Conclusion: The ALT flap offers minimal donor site morbidity. Reduced sensibility of the ALT flap is a common complaint among patients. Quadriceps strength is not significantly affected by an ALT free flap harvest.

Level Of Evidence: 4. Laryngoscope, 128:1057-1061, 2018.
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http://dx.doi.org/10.1002/lary.26865DOI Listing
May 2018

Prevalence of obstructive sleep apnea among obese toddlers and preschool children.

Sleep Breath 2018 05 13;22(2):511-515. Epub 2017 Oct 13.

Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.

Background: Obstructive sleep apnea (OSA) is a common disorder estimated at 1-5% in the school-aged children. With the obesity prevalence reaching staggering rates globally, OSA in obese adolescents is estimated to be 4-5-folds higher than their lean peers. There is a paucity of data regarding obesity-related OSA in children 6 years and less. This is particularly relevant as OSA is associated with neurocognitive deficits. The aim of this study is to evaluate the prevalence of OSA among obese toddlers and preschool children and further to determine what other factors may be associated with the presence of OSA.

Methods: A retrospective study involving children ≤6 years, identified from two Canadian pediatric tertiary care centers who had an in-lab polysomnography (PSG). Obesity was defined by a BMI of > 95th percentile for age and gender or a z-score of > 2. OSA was diagnosed if the obstructive apnea-hypopnea index (OAHI) was greater than 2 events per hour.

Results: There were 60 participants included; the mean age was 4.4 years (standard deviation [SD] ± 1.7), mean BMI z-score was 3.0 (SD ± 1.2). Of these, 22/60 (36.6%) had OSA. Compared with the non-OSA group, the OSA group had a higher Epworth sleepiness score (p = 0.03) and were more likely to snore (p = 0.01).

Conclusion: Young obese children should be assessed for OSA. A history of snoring and daytime sleepiness may be useful indicators to facilitate triage for a PSG, especially in resource-limited settings.
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http://dx.doi.org/10.1007/s11325-017-1576-4DOI Listing
May 2018

Breastfeeding, maternal asthma and wheezing in the first year of life: a longitudinal birth cohort study.

Eur Respir J 2017 05 1;49(5). Epub 2017 May 1.

Dept of Medicine, McMaster University, Hamilton, ON, Canada.

The impact of breastfeeding on respiratory health is uncertain, particularly when the mother has asthma. We examined the association of breastfeeding and wheezing in the first year of life.We studied 2773 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Caregivers reported on infant feeding and wheezing episodes at 3, 6 and 12 months. Breastfeeding was classified as exclusive, partial (supplemented with formula or complementary foods) or none.Overall, 21% of mothers had asthma, 46% breastfed for at least 12 months and 21% of infants experienced wheezing. Among mothers with asthma, breastfeeding was inversely associated with infant wheezing, independent of maternal smoking, education and other risk factors (adjusted rate ratio (aRR) 0.52; 95% CI 0.35-0.77 for ≥12 <6 months breastfeeding). Compared with no breastfeeding at 6 months, wheezing was reduced by 62% with exclusive breastfeeding (aRR 0.38; 95% CI 0.20-0.71) and by 37% with partial breastfeeding supplemented with complementary foods (aRR 0.63; 95% CI 0.43-0.93); however, breastfeeding was not significantly protective when supplemented with formula (aRR 0.89; 95% CI 0.61-1.30). Associations were not significant in the absence of maternal asthma (p-value for interaction <0.01).Breastfeeding appears to confer protection against wheezing in a dose-dependent manner among infants born to mothers with asthma.
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http://dx.doi.org/10.1183/13993003.02019-2016DOI Listing
May 2017

Changes in multiple breath washout measures after raised volume rapid thoracoabdominal compression maneuvers in infants.

Pediatr Pulmonol 2016 Feb 18;51(2):183-8. Epub 2015 Sep 18.

Department of Pediatrics and Program in Physiology and Experimental Medicine, Division of Respiratory Medicine, SickKids Research Institute, The Hospital for Sick Children and University of Toronto, Toronto, Canada.

Multiple breath inert gas washout (MBW) measurements in infants are performed supine and often obtained under sedation and thus are combined with other lung function tests such as raised volume rapid thoracoabdominal compression (RVRTC). In this study, we sought to determine the effects of RVRTC maneuvers on MBW measures. Compared with tests performed prior to RVRTC, MBW measured after RVRTC was associated with a small reduction in functional residual capacity and a more pronounced decrease in cumulative expired volume in both healthy children and children with obstructive lung disease (cystic fibrosis or recurrent wheeze) indicating a more efficient washout after the raised volume maneuvers. Lung Clearance Index (LCI) decreased significantly in infants with respiratory disease (change in LCI of -0.24 units post RVRTC; standard error (SE) ± 0.07 units; P = 0.0004), but not in healthy infants (change in LCI of -0.08 units; SE ± 0.11 units; P = 0.44). As the RVRTC maneuver affects MBW measurements in infants, the timing of testing procedures needs to be standardized in longitudinal studies.
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http://dx.doi.org/10.1002/ppul.23220DOI Listing
February 2016

Higher nocturnal and awake oxygen saturations in children with sickle cell disease receiving hydroxyurea therapy.

Ann Am Thorac Soc 2015 Jul;12(7):1044-9

1 Division of Respiratory Medicine, and.

Rationale: Obstructive sleep apnea and intermittent nocturnal oxygen desaturations are highly prevalent in children with sickle cell disease and have been reported to contribute to associated morbidity, including vasoocclusive disease. Hydroxyurea (HU) is increasingly used to treat children with sickle cell disease and has been shown to decrease the number and severity of vasoocclusive crises. Although there has been an increase in the use of HU, the impact of HU on the prevalence of obstructive sleep apnea and nocturnal hypoxia are not well documented.

Objectives: To evaluate whether the use of HU is associated with a decreased frequency of obstructive sleep apnea and higher nocturnal and awake oxygen saturations (SaO2) in children with sickle cell disease.

Methods: This was a retrospective, cross-sectional review of children with sickle cell disease referred to the sleep laboratory at the Hospital for Sick Children, Toronto, Canada. Polysomnogram data in children with sickle cell disease receiving HU therapy were compared with those not prescribed HU.

Measurements And Main Results: Children with sickle cell disease receiving HU therapy (HU group, n = 37) were matched with children not receiving HU (no-HU group, n = 104). Obstructive sleep apnea was diagnosed in 14 of 37 (38%) and 54 of 104 (52%) in the HU group and no-HU groups, respectively (P = 0.14). The median obstructive apnea-hypopnea index was 0.9 and 1.9 events/h in the HU group and the no-HU group, respectively (P = 0.28). The HU group compared with the no-HU group had a significantly higher median awake SaO2 (98.6 and 96.2%, respectively; P < 0.0001), a significantly higher median sleep SaO2 (98.4 and 96.1%, respectively; P < 0.001), and a significantly higher nadir SaO2 while asleep (91.4 and 85.0%, respectively; P = 0.0002).

Conclusions: In children with sickle cell disease, the use of HU was associated with an increase in awake and nocturnal SaO2, despite there being no difference in the frequency of obstructive sleep apnea and the severity of the obstructive apnea-hypopnea index. Improving nocturnal SaO2 may be an important mechanism of action of HU therapy. The use of HU to improve nocturnal saturations across the severity spectrum of sickle cell disease may be beneficial in decreasing morbidities related to sickle cell disease.
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http://dx.doi.org/10.1513/AnnalsATS.201410-473OCDOI Listing
July 2015

Timely case-fatality risk estimation.

Epidemiology 2015 Mar;26(2):e26-7

Department of Biostatistics School of Public Health and Tropical Medicine Southern Medical University Guangzhou, China SickKids Research Institute Hospital for Sick Children Toronto, ON, Canada Department of Biostatistics School of Public Health and Tropical Medicine Southern Medical University Guangzhou, China

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http://dx.doi.org/10.1097/EDE.0000000000000258DOI Listing
March 2015

[Estimation and application of case fatality rate, using the summarizing data].

Zhonghua Liu Xing Bing Xue Za Zhi 2014 May;35(5):600-5

Department of Biostatistics, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China. Email:

To evaluate five methods in the estimation on the rate of case fatality during the epidemics of diseases based on the summarizing data. Case fatality rates, derived from the simulation data, 2003 SARS epidemic data in Hong Kong, Singapore Beijing and the 2013 H7N9 epidemic data in mainland China were analyzed, using these 5 methods. Results from the simulation analysis discovered that the relative errors and the standard deviations of the Chen [7, 8] (method 3), Chen [9] (method 4)were minor with high accuracy. Data from the analysis on 2003 SARS epidemic was noticed that the estimation from method 3, 4 in Hong Kong and Singapore both showing high veracities. Since the case fatality rate reported in Beijing was not a constant value, method 5 showed low accuracy even though it was close to the final case fatality rate. Data from the 2013 H7N9 epidemic showed that the estimations of method 1, 2, 3, 4 were all higher than that in the method 5, suggesting that method 3, 4 could be used to estimate the case fatality rates of epidemics more precisely.
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May 2014