Pei-Lin Lee

Patient mortality of active pulmonary tuberculosis requiring mechanical ventilation

Mortality remains high among patients with pulmonary tuberculosis requiring mechanical ventilation (TBMV). This study was carried out to establish the mortality rates of TBMV and to identify factors that contribute to in-hospital mortality. From January 1996–April 2001, there were 825 patients with active pulmonary tuberculosis at the National Taiwan University Hospital, Taipei, Taiwan. Of these, 41 suffered acute respiratory failure and required mechanical ventilation in the intensive care unit (ICU). Of these 41 patients, 38 were followed up for 180 days. In-hospital deaths were documented in the medical records and all possible parameters contributing to mortality were collected. Of the 41 patients, 27 died in the hospital and 14 were discharged alive (in-hospital mortality rate 65.9%), with (mean±sd) 40.7±35.4 admission days before death. Of the 27 that died, 25 died during ICU admission and two died after being transferred to the ward. The mortality rate for the 180-day monitoring period was 79%. Factors contributing to in-hospital mortality included consolidations on chest radiographs and multiple organ failure. The mortality rate in the patients with pulmonary tuberculosis requiring mechanical ventilation is very high, with two factors affecting in-hospital mortality. These factors were multiple organ failure and consolidation on chest radiographs.

Body weight status and obstructive sleep apnea in children

Objective:The relationship between weight status, adenotonsillar hypertrophy and obstructive sleep apnea (OSA) in children has not yet been well studied. As the sleep parameters may show a disparity in different weight statuses, this study examined the relationship between the data of over-night polysomnography and different weight statuses, as well as the impact of adenotonsillar hypertrophy on children with OSA.Methods:Children with sleep disturbances were recruited from our clinics. Standard physical examinations, history taking, lateral neck roentgenography, and full-night polysomnography were obtained. Children were divided into four groups based on the age- and gender-corrected body mass index (BMI): underweight, normal weight, overweight and obese. An adenoidal/nasopharyngeal ratio of more than 0.67 was considered adenoidal hypertrophy. Tonsillar hypertrophy was defined as having Grade III tonsils or above.Results:From July 2006 to January 2009, 197 children were included in this study. Obese children had a significantly higher apnea–hypopnea index (AHI), obstructive apnea index and lower minimum oxygen saturation (MinSaO2) than those of the other groups. Underweight children had the second highest AHI. A negative correlation was also found between BMI z scores and MinSaO2 (r=−0.194; P=0.007). Children with tonsillar hypertrophy (P=0.001) were associated with a higher risk of having OSA. The risk of having OSA was significantly higher in obese children (P=0.001) and underweight children (P=0.043) than in those with a normal weight.Conclusion:Obesity, underweight status and tonsillar hypertrophy are associated with children having OSA, and obese children have a significantly higher risk than children with underweight status.

Associations between Adenotonsillar Hypertrophy, Age, and Obesity in Children with Obstructive Sleep Apnea

Objective To investigate the contributions of adenoid and tonsil size to childhood obstructive sleep apnea (OSA) and the interactions between adenotonsillar hypertrophy, age, and obesity in children with OSA. Methods In total, 495 symptomatic patients were recruited. The patients were assigned to four groups according to age：toddler (age 1-3, n=42), preschool (age 3-6, n=164), school (age 6-12, n=200), and adolescence (age 12-18, n=89). All subjects had tonsil size graded by otolaryngologists, adenoid size determined on lateral radiographs (Fujioka method), and a full-night polysomnography. The apnea-hypopnea index (AHI), adenoid size, and tonsil size were compared in obese and non-obese children in the four age groups. Adjusted odds ratios (ORs) and 95% confidence interval (CI) of adenotonsillar hypertrophy and OSA risk were estimated by multi-logistic regression. Results The AHI was positively related to tonsil grade (r=0.33, p <0.001) and adenoid size (r=0.24, p <0.01) in all patients. Tonsil grade was positively related to AHI in all four age groups. Adenoid size was positively related to AHI in the toddler, preschool, school groups, but not in the adolescent group (r=0.11, p=0.37). Tonsil grade and adenoid size were both positively related to AHI in obese and non-obese children. In the regression model, obesity (OR=2.89; 95% CI 1.47-5.68), tonsillar hypertrophy (OR=3.15; 95% CI 2.04-4.88), and adenoidal hypertrophy (OR=1.89; 95% CI 1.19-3.00) significantly increased OSA risk. Conclusions Adenotonsillar hypertrophy and obesity are the major determinants of OSA in children. However, the influence of adenoid size decreases in adolescence.

Atopic Dermatitis, Melatonin, and Sleep Disturbance

BACKGROUND AND OBJECTIVES: Sleep disturbance is common in patients with atopic dermatitis (AD). However, studies have largely been questionnaire-based, and the pathophysiology remains unclear. The aims of this study were to determine objective characteristics of sleep disturbance in children with AD and explore contributing factors and clinical predictors. METHODS: Sleep parameters were measured by actigraphy and polysomnography in 72 patients with AD and 32 controls ages 1 to 18 years. Urinary 6-sulfatoxymelatonin levels, serum cytokines, and total and allergen-specific immunoglobulin E (IgE) levels were also measured. RESULTS: The patients with AD had significantly reduced sleep efficiency, longer sleep onset latency, more sleep fragmentation, and less nonrapid eye movement sleep. Results from actigraphy correlated well with those from polysomnography. The AD disease severity was associated with sleep disturbance (r = 0.55−0.7), and a Scoring Atopic Dermatitis index of ≥48.7 predicted poor sleep efficiency with a sensitivity of 83.3% and a specificity of 75% (area under the curve = 0.81, P = .001). Lower nocturnal melatonin secretion was significantly associated with sleep disturbance in the patients with AD. Other correlates of sleep disturbance included pruritus, scratching movements, higher total serum IgE levels, and allergic sensitization to dust mite and staphylococcal enterotoxins. CONCLUSIONS: Poor sleep efficiency is common in children with AD and can be predicted by the Scoring Atopic Dermatitis index. Melatonin and IgE might play a role in the sleep disturbance. Further studies are required to explore the mechanisms and clinical implications, and actigraphy could serve as a useful evaluating tool.

Impacts of body weight after surgery for obstructive sleep apnea in children

Objective:To investigate the impacts of body weight status on surgical outcomes and shifts of body weight status after adenotonsillectomy(T&A) in children with obstructive sleep apnea (OSA).Methods:From 2009 to 2011, 161 children (mean age, 7.0±3.4 years; 78% boys) were included. All the children had clinical symptoms and preoperative polysomnographic evaluations diagnosis of OSA. Children were divided into four weight status groups (underweight, normal weight, overweight and obese), based on age and gender corrected body mass index (BMI).Results:Following T&A, the four different weight status groups significantly improved in apnea/hypopnea index (AHI) and minimum oxygen saturation. However, 49.1% of the children (79/161) had residual OSA (AHI ⩾1). The incidence of residual OSA (AHI ⩾1) in the obese group was 75%, which was significantly higher than the other three groups (P<0.01). Weight status changes after T&A were documented, and 54% (13/24) of the underweight children shifted to normal weight status within 6 months after surgery.Conclusion:Although sleep parameters improved in all weight statuses, obese children had a higher incidence of residual OSA postoperatively. About half of the underweight children shifted to normal weight status after T&A.

Sex differences in anthropometric and cephalometric characteristics in the severity of obstructive sleep apnea syndrome

INTRODUCTION Craniofacial anatomic abnormalities related to structural narrowing of the upper airway have been reported in patients with obstructive sleep apnea syndrome (OSAS). The purpose of this study was to test whether there are sex differences in the relative contributions of specific anthropometric and cephalometric measurements of OSAS severity. METHODS The subjects were Taiwanese patients who visited the Ear, Nose, and Throat Department of National Taiwan University Hospital with complaints of snoring or sleep apnea. The anthropometric, cephalometric, and overnight polysomnographic records of 109 subjects were evaluated. RESULTS There are obvious sex differences in the craniofacial skeletal characteristics that contribute to OSAS severity. Male patients with the following risk factors are likely to have more severe type OSAS: increased neck size, inferiorly positioned hyoid bone, and greater anterior lower facial height. The risk factors related to the severity of OSAS in female patients include smaller posterior facial height and anteriorly positioned hyoid bone. CONCLUSIONS To evaluate OSAS severity, different anthropometric and cephalometric measurements should be used for men and women. The craniofacial skeletal characteristics that contribute to OSAS severity were in the anterior lower portion of the profile in men and in the posterior portion of the profile in women.

Quality of life after adenotonsillectomy for children with sleep-disordered breathing: A linear mixed model analysis

OBJECTIVE To study changes in quality of life (QoL) after adenotonsillectomy (T&A) in children with sleep-disordered breathing (SDB), and to elucidate discrepancies in QoL improvements after T&A in children of different gender, age, adiposity status, and disease severity. MATERIALS AND METHODS Children aged 2-18 years were recruited. All children had SDB-related symptoms and underwent preoperative full-night polysomnography (PSG). Caregivers completed the first obstructive sleep apnea 18-items questionnaire (OSA-18) prior to T&A and the second OSA-18 survey within 3 months after surgery. Disease severity was defined as primary snoring (apnea/hypopnea index, AHI < 1), mild obstructive sleep apnea (OSA) (5 > AHI ≥ 1), and moderate-to-severe OSA (AHI ≥ 5). Discrepancies in OSA-18 score changes after T&A for different groups were assessed using the linear mixed model. RESULTS In total, 144 children were enrolled (mean age, 7.0 ± 3.6 years; 76% boy). The OSA-18 total score changes after surgery were not significantly different by gender (boys vs. girls), age group (≥ 6 years vs. < 6 years), or adiposity (obese vs. non-obese). The OSA-18 total score changes after surgery differed by disease severity (primary snoring vs. moderate-to-severe OSA, P = 0.004; mild OSA vs. moderate-to-severe OSA, P = 0.003). Children with moderate-to-severe OSA had greater improvement in OSA-18 total score after surgery than those with mild OSA or primary snoring. CONCLUSIONS Children with SDB had QoL improvement after T&A, as documented by OSA-18 score changes. The QoL improvement after T&A for SDB children increased as disease severity increased, and the improvement was not affected by gender, age, or adiposity.

PHOX2B Mutation-Confirmed Congenital Central Hypoventilation Syndrome in a Chinese Family: Presentation From Newborn to Adulthood

BACKGROUND Congenital central hypoventilation syndrome (CCHS) is characterized by compromised chemoreflexes resulting in sleep hypoventilation. We report a Chinese family with paired-like homeobox 2B (PHOX2B) mutation-confirmed CCHS, with a clinical spectrum from newborn to adulthood, to increase awareness of its various manifestations. METHODS After identifying central hypoventilation in an adult man (index case), clinical evaluation was performed on the complete family, which consisted of the parents, five siblings, and five offspring. Pulmonary function tests, overnight polysomnography, arterial blood gas measurements, hypercapnia ventilatory response, and PHOX2B gene mutation screening were performed on living family members. Brain MRI, 24-h Holter monitoring, and echocardiography were performed on members with clinically diagnosed central hypoventilation. RESULTS The index patient and four offspring manifested clinical features of central hypoventilation. The index patients had hypoxia and hypercapnia while awake, polycythemia, and hematocrit levels of 70%. The first and fourth children had frequent cyanotic spells, and both died of respiratory failure. The second and third children remained asymptomatic until adulthood, when they experienced impaired hypercapnic ventilatory response. The third child had nocturnal hypoventilation with nadir pulse oximetric saturation of 59%. Adult-onset CCHS with PHOX2B gene mutation of the + 5 alanine expansions were confirmed in the index patient and the second and third children. The index patient and the third child received ventilator support system bilevel positive airway pressure treatment, which improved the hypoxemia, hypercapnia, and polycythemia without altering their chemosensitivity. CONCLUSIONS Transmission of late-onset CCHS is autosomal-dominant. Genetic screening of family members of CCHS probands allows for early diagnosis and treatment.

Melatonin Supplementation for Children With Atopic Dermatitis and Sleep Disturbance: A Randomized Clinical Trial

IMPORTANCE Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical management for this problem is lacking. Reduced levels of nocturnal melatonin were found to be associated with sleep disturbance and increased disease severity in children with AD. Melatonin also has sleep-inducing and anti-inflammatory properties and therefore might be useful for the management of AD. OBJECTIVE To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial used a double-blind, placebo-controlled crossover design to study 73 children and adolescents aged 1 to 18 years with physician-diagnosed AD involving at least 5% of the total body surface area. The study was conducted at the pediatric department of a large tertiary care hospital in Taiwan from August 1, 2012, through January 31, 2013. Forty-eight children were randomized 1:1 to melatonin or placebo treatment, and 38 of these (79%) completed the cross-over period of the trial. Final follow-up occurred on April 13, 2013, and data were analyzed from January 27 to April 25, 2014. Analyses were based on intention to treat. INTERVENTIONS Melatonin, 3 mg/d, or placebo for 4 weeks followed by a 2-week washout period and then crossover to the alternate treatment for 4 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was AD severity evaluated using the Scoring Atopic Dermatitis (SCORAD) index, with scores ranging from 0 to 103 and greater scores indicating worse symptoms. Secondary outcomes included sleep variables measured by actigraphy, subjective change in sleep and dermatitis, sleep variables measured by polysomnography, nocturnal urinary levels of 6-sulfatoxymelatonin, and serum IgE levels. RESULTS After melatonin treatment among the 48 children included in the study, the SCORAD index decreased by 9.1 compared with after placebo (95% CI, -13.7 to -4.6; P < .001), from a mean (SD) of 49.1 (24.3) to 40.2 (20.9). Moreover, the sleep-onset latency shortened by 21.4 minutes after melatonin treatment compared with after placebo (95% CI, -38.6 to -4.2; P = .02). The improvement in the SCORAD index did not correlate significantly with the change in sleep-onset latency (r = -0.04; P = .85). No patient withdrew owing to adverse events, and no adverse event was reported throughout the study. CONCLUSIONS AND RELEVANCE Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01638234.

Quality of life after adenotonsillectomy in children with obstructive sleep apnea: Short-term and long-term results

OBJECTIVE To assess short-term and long-term changes in quality of life after adenotonsillectomy (T&A) in children with obstructive sleep apnea (OSA). MATERIALS AND METHODS Children aged 2-18 years old were enrolled. All subjects had clinical symptoms, overnight polysomnography diagnosis of OSA, and received T&A as treatment. Caregivers were asked to complete the OSA-18 survey before surgery, within 6 months after surgery (short-term), and more than 6 months after surgery (long-term). RESULTS A total of 114 children were included (mean age, 7.0±3.5 years; 75% boys). The mean OSA-18 total score was 71.5±16.0 before surgery. After surgery, the mean OSA-18 total score was significantly decreased in both the short-term (40.3±12.2, p<0.001) and the long-term (42.0±13.7, p<0.001). All five OSA-18 domains were also significantly decreased during short-term and long-term postoperative follow up (p<0.001). Short-term and long-term outcomes were compared. Mean OSA-18 total scores, sleep disturbance score, emotional distress score, daytime function score, and caregiver concerns score did not differ significantly between the short-term and long-term periods, while the physical symptom score was slightly higher in the long-term than the short-term period (9.7±3.3 vs. 8.7±3.0, p=0.02). Additionally, the physical symptoms score was higher in the long-term period in the female (p=0.01), older age (>6 years) (p=0.03), and non-obese (p=0.04) subgroups. CONCLUSION T&A improves short-term and long-term quality of life in children with OSA. Nevertheless, caregivers observed children with aggravation of physical symptoms of quality of life during long-term follow up, especially in the female, older, and non-obese subgroups.