Conservative Airway Management Successful in Majority of Infants With Pierre-Robin Sequence at Queensland Children's Hospital: A Retrospective Review.

PURPOSE: Pierre-Robin Sequence (PRS) is a congenital abnormality characterized by micrognathia, glossoptosis, and variable severity upper airway obstruction. Clear management algorithms are lacking, particularly the indications for surgical versus nonsurgical intervention. The authors reviewed the management of these children in Queensland. METHODS: All children diagnosed with PRS at Queensland Children's Hospital from April 2014 to October 2019 were identified (n=45), and their charts were retrospectively reviewed. Three management patterns emerged: prone/lateral positioning, nasopharyngeal airway (NPA) use, and surgery (tracheostomy or mandibular distraction). RESULTS: Most children (n=30; 67%) were managed successfully nonsurgically with an NPA (median age of insertion 0.25 mo, median duration 5.0 mo). Of these, 12 patients (40%) also required supplemental oxygen. The median age of NPA cessation was 5.5 months, with oxygen therapy ceasing at a median 8.25 months, upon which no further support was required. The remaining majority (n=13; 29%) of children were managed without an NPA, using positioning alone (10/13; 77%) or positioning combined with supplemental oxygen (1/13), CPAP (1/13), or both adjunct measures (1/13). Only 2 patients underwent surgical intervention. Feeding supplementation using nasogastric tube was necessary in 78% of patients for a median duration of 4 months. Cleft palate co-existed in all but one patient. CONCLUSION: Management of upper airway obstruction in PRS children is variable between units. Over a 5-year period, 96% of children with PRS were successfully managed without surgical intervention at the Queensland Children's Hospital. These findings contrast with some other literature and may suggest that more careful consideration of surgical intervention in PRS patients is prudent.

Assessing the impact of the 13 valent pneumococcal vaccine on childhood empyema in Australia.

BACKGROUND: Empyema is a serious complication of pneumonia frequently caused by Streptococcus pneumoniae (SP). We assessed the impact of the 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyema after inclusion in the Australian National Immunisation Program. METHODS: For bacterial pneumonia and empyema hospitalisations, we ascertained incidence rates (IRs) using the National Hospital Morbidity Database International Statistical Classification of Disease discharge codes and relevant population denominators, and calculated incidence rate ratios (IRR) comparing the 13vPCV period (June 2012-May 2017) with the 7vPCV period (June 2007-May 2011). Blood and pleural fluid (PF) cultures and PF PCR of 401 children with empyema from 11 Australian hospitals during the 13vPCV period were compared with our previous study in the 7vPCV period. FINDINGS: Across 7vPCV and 13vPCV periods, IRs per million children (95% CIs) were 1605 (1588 to 1621) and 1272 (1259 to 1285) for bacterial pneumonia, and 14.23 (12.67 to 15.79) and 17.89 (16.37 to 19.42) for empyema hospitalisations. IRRs were 0.79 (0.78 to 0.80) for bacterial pneumonia and 1.25 (1.09 to 1.44) for empyema. Of 161 empyema cases with SP serotypes, 147 (91.3%) were vaccine types. ST3 accounted for 76.4% of identified serotypes in the 13vPCV period, more than double than the 7vPCV period (p<0.001); ST19A decreased from 36.4% to 12.4%. No cases of ST1 empyema were identified in the 13vPCV period versus 14.5% in the 7vPCV period. INTERPRETATION: 13vPCV resulted in a significant reduction in all-cause hospitalisations for bacterial pneumonia but empyema hospitalisations significantly increased, with emergence of pneumococcal ST3 as the dominant serotype in empyema. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trial Registry ACTRN 12614000354684.

Ventilatory support at home for children: A joint position paper from the Thoracic Society of Australia and New Zealand/Australasian Sleep Association.

The goal of this position paper on ventilatory support at home for children is to provide expert consensus from Australia and New Zealand on optimal care for children requiring ventilatory support at home, both non-invasive and invasive. It was compiled by members of the Thoracic Society of Australia and New Zealand (TSANZ) and the Australasian Sleep Association (ASA). This document provides recommendations to support the development of improved services for Australian and New Zealand children who require long-term ventilatory support. Issues relevant to providers of equipment and areas of research need are highlighted.

Multidisciplinary approach to paediatric aerodigestive disorders: A single-centre longitudinal observational study.

AIM: Aerodigestive clinics (ADCs) are multidisciplinary programmes for the care of children with complex congenital or acquired conditions affecting breathing, swallowing and growth. Our objective was to describe the demographic, clinical, etiological and investigational profile of children attending the inaugural ADC at a tertiary paediatric centre in Queensland. METHODS: Children referred to the ADC at Queensland Children's Hospital from August 2018 to December 2019 were included. Data on clinical, growth and lung function parameters, bronchoscopy and upper gastrointestinal endoscopy findings, thoracic imaging and comorbidities were retrospectively analysed. RESULTS: Fifty-six children (median (range) age 4 years (3 months-15 years); 18 female) attended the ADC during this 17-month period. Forty-six (82%) children had previous oesophageal atresia with tracheo-oesophageal fistula; 43 of these were type C. Previous isolated oesophageal atresia, congenital diaphragmatic hernia and congenital pulmonary malformation were the underlying disorder in three (5%) children each, with one child having a repaired laryngeal cleft. Vertebral Anal Tracheo Esophageal Renal Limb anomalies (VACTERL)/Vertebral Anal Tracheo Esophageal renal anomalies (VATER) association was seen in 21 (38%) children. Growth was adequate (median weight and body mass index z-score -0.63 and -0.48, respectively). Thirty-four (61%) children reported ongoing wet cough, with 12 (21%) requiring previous hospital admission for lower respiratory tract infection. Fourteen (25%) had bronchiectasis on computed tomography chest and 33 (59%) had clinical tracheomalacia, apparent on bronchoscopic examination in 21 patients. Dysphagia was reported in 15 (27%) children, 11 (20%) were gastrostomy feed-dependent and 5 (9%) had biopsy-proven eosinophilic oesophagitis. CONCLUSION: High proportion of children attending the ADC have ongoing respiratory symptoms resulting in chronic pulmonary suppuration and bronchiectasis. Potential benefits of this model of care need to be studied prospectively to better understand the outcomes.

Asthma and sleep disturbance in adolescents and young adults: A cohort study.

AIMS: A longitudinal birth cohort provides an opportunity to study the impact of childhood conditions persisting into adulthood. This study examines the cross-sectional association of asthma with sleep quality and snoring in the adolescent and young adult population and the extent to which asthma, sleep quality and snoring at 14 years independently predict themselves or each other at 21 years. METHODS: Data from a 21-year follow-up of mothers and their children recruited into the Mater-University of Queensland Study of Pregnancy (n = 7223). Complete asthma and sleep information (questionnaire data) was available for 5015 participants at 14 years and 3527 at 21 years, with 3237 participants at both 14 and 21 years. RESULTS: Poor sleep quality and snoring were independently associated with asthma at 14 years and 21 years, with stronger associations evident in women. At 21 years, associations were mediated by asthma symptom severity. Asthma, sleep quality and snoring at 14 years each strongly and independently predicted themselves at 21 years. Asthma at 14 years predicted snoring at 21 years, while poor sleep quality and snoring in women predicted asthma at 21 years, the latter partially mediated by body mass index. CONCLUSIONS: The relationship between asthma, sleep quality and snoring varied by gender. Sleep quality and snoring should be considered in the assessment and holistic management of asthma. The predictive relationship seen between 14 and 21 years provides an opportunity to address these issues at a younger age.

Longitudinal tracking of intrabreath respiratory impedance in preschool children.

BACKGROUND: Longitudinal measurements of intrabreath respiratory impedance (Zrs) in preschool-aged children may be able to distinguish abnormal lung function trajectories in children with a history of wheezing compared to healthy ones. METHODS: Children from a prospective, longitudinal community-based cohort performed annual intrabreath oscillometry (IB-OSC) measurements from age 3- to 7-years. IB-OSC was performed using a single 10 Hz sinusoid while clinically asymptomatic. Linear mixed-effects models were developed to explore the effects of wheezing phenotypes, growth, and sex on seven IB-OSC outcome variables over time: resistance at end-expiration (ReE), resistance at end-inspiration (ReI), the tidal change in resistance (∆R=ReE-ReI), reactance at end-expiration (XeE), reactance at end-inspiration (XeI), the tidal change in reactance (∆X=XeE-XeI), and ∆X normalized by tidal volume (∆X/VT). RESULTS: Eighty-five children produced 374 acceptable IB-OSC measurements. Subjects were classified into one of three wheeze groups: never (n = 36), transient (n = 34), or persistent (n = 15). After adjusting for height, children with persistent wheezing, compared to those who never wheezed, had +0.814 hPa s L-1 ReE (95% confidence interval [CI] +0.178 to +1.451, p = 0.015), -0.792 hPa s L-1 XeE (95% CI -1.203 to -0.381, p = 0.003), -0.538 hPa s L-1 ∆X (95% CI -0.834 to -0.242, p = 0.007) and -1.672 hPa s L-2 ∆X/VT (95% CI -2.567 to -0.777, p < 0.001). Increasing height had a significant effect on all IB-OSC resistance and reactance variables when adjusted for the effect of preschool wheezing. CONCLUSIONS: IB-OSC is feasible for tracking lung function growth in preschool-aged children and may allow abnormal lung function to be identified early in asymptomatic preschoolers with a history of persistent wheezing.

Assessment of bronchodilator response in preschoolers: A systematic review.

BACKGROUND: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet. METHODS: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts. RESULTS: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children. CONCLUSION: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.

Sleep disorders in children.

Sleep disorders are very common in childhood and are often amenable to simple advice and parental education. Questions about sleep should be an integral part of every paediatric consultation. Children with underlying syndromes or complex medical conditions often have multiple sleep issues. Excessive sleepiness in children requires careful history-taking and consideration of specialised investigation. Obstructive sleep apnoea (OSA) is a common condition in childhood with important health implications. The high prevalence of OSA warrants rigorous attempts to identify children at higher risk and manage them appropriately. Adenotonsillectomy is a highly efficacious therapy for paediatric OSA. A current major issue is to improve ways of distinguishing mild from severe OSA before a child undergoes adenotonsillectomy, as those with more severe disease are at increased risk of postoperative complications and should undergo adenotonsillectomy in a tertiary centre. Children with obesity and other comorbid conditions are at increased risk of persisting OSA despite adenotonsillectomy. Topical (nasal) steroids and/or anti-inflammatory agents have a role in the non-surgical treatment of mild OSA. Continuous positive airway pressure and orthodontic interventions are treatment options for treatment of persisting OSA in children.

Paediatric foreign body aspiration and endobronchial granuloma.

Paediatric foreign body aspiration can result in pulmonary complications including the formation of endobronchial granuloma, which can be managed conservatively or via surgical or bronchoscopic intervention. This case highlights the importance of having a high index of suspicion for foreign body aspiration in patients with persistent symptoms or abnormal imaging.

Real world impact of 13vPCV in preventing invasive pneumococcal pneumonia in Australian children: A national study.

BACKGROUND: We aimed to assess the direct protective effect of 13 valent pneumococcal conjugate vaccine (13vPCV) against invasive pneumococcal pneumonia (IPP; including pneumonia and empyema) in children using a nation-wide case-control study across 11 paediatric tertiary hospitals in Australia. METHODS: Children < 18 years old admitted with pneumonia were eligible for enrolment. IPP was defined as Streptococcus pneumoniae (SP) cultured or detected by polymerase chain reaction (PCR) from blood or pleural fluid. Causative SP serotype (ST) was determined from blood or pleural fluid SP isolates by molecular methods in PCR positive specimens or else inferred from nasopharyngeal isolates. For each IPP case, 20 population controls matched by age and socio-economic status were sampled from the Australian Immunisation Register. Conditional logistic regression was used to estimate the adjusted odds ratio (aOR) of being fully vaccinated with 13vPCV (≥3 doses versus < 3 doses) among IPP cases compared to controls, adjusted for sex and Indigenous status. RESULTS: From February 2015 to September 2018, we enrolled 1,168 children with pneumonia; 779 were 13vPCV-eligible and were individually matched to 15,580 controls. SP was confirmed in 195 IPP cases, 181 of whom had empyema. ST3 and ST19A were identified in 52% (102/195) and 11% (21/195) of IPP cases respectively. The aOR of being fully vaccinated with 13vPCV was 0.8 (95% CI 0.6-1.0) among IPP cases compared to matched controls. CONCLUSION: We failed to identify a strong direct protective effect of 13vPCV against IPP among Australian children, where disease was largely driven by ST3.

Pleural fluid nucleic acid testing enhances pneumococcal surveillance in children.

BACKGROUND AND OBJECTIVE: National surveillance of invasive pneumococcal disease (IPD) includes serotyping Streptococcus pneumoniae (SP) isolates from sterile site cultures. PCR is more sensitive and can identify more SP serotypes (STs) in culture-negative samples. The aim of this study was to determine whether enhanced surveillance of childhood empyema, using PCR, provides additional serotype information compared with conventional surveillance. METHODS: Pleural fluid (PF) from children with empyema were cultured and tested by PCR to identify SP, targeting the autolysin gene (lytA). Multiplex PCR-based reverse line blot assay was used to identify SP STs. Corresponding IPD surveillance and serotype data were obtained from the National Notifiable Diseases Surveillance System (NNDSS). RESULTS: Eighty-nine children with empyema, aged ≤16 years, were recruited between April 2008 and March 2009, inclusive. SP was isolated from 5/84 (5.9%) PF cultures and by PCR in 43/79 (54.4%) PF samples. Serotypes were unidentifiable in 15 samples. The frequency of six serotypes (or serotype pairs) identified in 28 samples, including one with two serotypes, were: ST1, n = 4/29 (13.8%); ST3, n = 9/29 (31.0%); ST19A, n = 12/29 (41.4%); ST7F/7A, n = 1/29 (3.4%); ST9V/9A, n = 1/29 (3.4%); ST22F/22A, n = 2/29 (6.9%). Over the same period, 361 IPD patients, aged 16 years or less, were notified to NNDSS. Among 331 serotypeable NNDSS isolates (71.5% from blood), the frequencies of ST1 and 3 were significantly lower than in PF samples: ST1, n = 8/331 (2.4%; P < 0.05); ST3, n = 13/331 (3.9%; P < 0.0001). CONCLUSIONS: The use of PCR to identify and serotype SP in culture-negative specimens provides additive information.

Symptom care approach to noninvasive ventilatory support in children with complex neural disability.

STUDY OBJECTIVES: Sleep-disordered breathing is a major cause of morbidity and mortality among pediatric patients with severe neurological disabilities such as cerebral palsy. Despite increasing use of noninvasive ventilation (NIV) in this group, there remains a lack of consensus about its role and indications. We aim to explore the indications, acceptability, and outcomes of a cohort of children with severe, complex neurological disability and sleep-disordered breathing, managed with NIV. METHODS: Data were retrospectively extracted on children with severe neurological disabilities (Gross Motor Function Classification System V equivalent) initiated on NIV in Queensland over a 5-year period. Demographic, clinical, hospitalization, and polysomnography data were collected, as well as caregiver-reported side effects and NIV adherence. RESULTS: Fourteen (median age 9.1 years; 6 female) children were included, 8 with cerebral palsy and 6 with other complex neurological disabilities. Obstructive sleep apnea was the most common indication for NIV (n = 12). The median (interquartile range) apnea-hypopnea index improved on NIV [pre-NIV 21.3 (interquartile range 10.0-28.2) vs post-NIV 12.2 (interquartile range 2.8-15.2)], although this was not statistically significant. There was significant improvement in proportion of time spent with SpO2 < 95% (22.2% pre-NIV vs 7.85% post-NIV; P < .05). Reported side effects were minimal. There was no reduction in hospital admissions in the 12 months post-NIV initiation. CONCLUSIONS: Our findings suggest that NIV improves polysomnography parameters among children with severe neurological disability. Long-term outcomes and overall impact on quality of life remain unclear. Ethical issues and overall benefit must be considered before embarking on this mode of therapy. CITATION: Morrison L, Suresh S, Leclerc MJ, Kapur N. Symptom care approach to noninvasive ventilatory support in children with complex neural disability. J Clin Sleep Med. 2022;18(4):1145-1151.

Central sleep apnea in otherwise healthy term infants.

STUDY OBJECTIVES: To describe the outcomes of central sleep apnea requiring home supplemental oxygen therapy in otherwise healthy term infants. METHODS: All children < 1 year of age undergoing polysomnography between 2015 and 2020 at the Queensland Children's Hospital were retrospectively studied. Children with gestational age < 37 weeks, underlying syndrome, cleft palate, those with obstructive apnea-hypopnea index > 50% of total apnea-hypopnea index, or with underlying cardiac or pulmonary parenchymal pathology were excluded. Polysomnography parameters were extracted for periods both on and off supplemental oxygenation. RESULTS: Fifty-two (mean [standard deviation] age at polysomnography 32.6 [34.7] days; 21 females) term infants were included. There was a statistically significant improvement in apnea-hypopnea index on supplemental oxygen (mean [standard deviation] in room air 50.2 [36.3] vs 11.6 [9], P < .001 on supplemental oxygen), in both rapid eye movement and nonrapid eye movement sleep, as well as in mean oxygen saturations (96.6% in room air to 98.9% on oxygen; P < .001). There was no statistically significant change in transcutaneous carbon dioxide levels or sleep duration. Oxygenation was prescribed for a median (interquartile range) age of 197 (127) days. CONCLUSIONS: Central sleep apnea in term infants who are otherwise healthy generally has a good prognosis, with oxygen therapy prescribed for around 6 months. Oxygen therapy was associated with improved saturations and decrease in apnea-hypopnea index when assessed with polysomnography. CITATION: Hayashi A, Suresh S, Kevat A, Robinson J, Kapur N. Central sleep apnea in otherwise healthy term infants. J Clin Sleep Med. 2022; 18(12):2813-2817.

Comparison of polysomnographic characteristics between low birthweight and normal birthweight children in the Northern Territory of Australia: A case-control study.

OBJECTIVES: To describe the sleep architecture of pediatric patients according to whether they were born low birthweight (birthweight <2500 g, LBW) or normal birthweight (birthweight >2500 g). DESIGN: Case control study. SETTING: Pediatric sleep laboratory in the Northern Territory of Australia during a 5-year study period (2015- 2020). PARTICIPANTS: Pediatric patients (aged <18 years) referred to the specialist sleep service for assessment of clinically suspected sleep disorders. MEASUREMENTS: Sleep onset latency, rapid eye movement (REM) sleep latency, wake time after sleep onset, total sleep time, sleep efficiency, non-rapid eye movement stages N1/N2/N3, and REM sleep duration, total/spontaneous/respiratory/limb related arousal indexes, total/non-rapid eye movement/REM obstructive apnea-hypopnea index and oxygen saturation. RESULTS: One hundred and seventy-two pediatric patients had birthweight data available of whom 19 were LBW. LBW patients showed significantly greater sleep disruption and higher prevalence of poor sleepers (<80% efficiency). In multivariate regression models, increasing birthweight was associated with significantly greater sleep efficiency and total sleep time. After accounting for gestational age LBW was associated with increased odds of obstructive sleep apnea. CONCLUSIONS: Among pediatric patients LBW is associated with increased sleep disruption and reduced sleep efficiency. This is attenuated by gestational age, though both gestational age and LBW significantly influence odds of obstructive sleep apnea. This sleep health deficit may contribute to development of chronic disease in this vulnerable population, and should be monitored to provide avenues for early intervention.

Bacterial causes of empyema in children, Australia, 2007-2009.

An increase in the incidence of empyema worldwide could be related to invasive pneumococcal disease caused by emergent nonvaccine replacement serotypes. To determine bacterial pathogens and pneumococcal serotypes that cause empyema in children in Australia, we conducted a 2-year study of 174 children with empyema. Blood and pleural fluid samples were cultured, and pleural fluid was tested by PCR. Thirty-two (21.0%) of 152 blood and 53 (33.1%) of 160 pleural fluid cultures were positive for bacteria; Streptococcus pneumoniae was the most common organism identified. PCR identified S. pneumoniae in 74 (51.7%) and other bacteria in 19 (13.1%) of 145 pleural fluid specimens. Of 53 samples in which S. pneumoniae serotypes were identified, 2 (3.8%) had vaccine-related and 51 (96.2%) had nonvaccine serotypes; 19A (n = 20; 36.4%), 3 (n = 18; 32.7%), and 1 (n = 8; 14.5%) were the most common. High proportions of nonvaccine serotypes suggest the need to broaden vaccine coverage.

Congenital central hypoventilation syndrome: four families.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare condition that usually presents soon after birth and is potentially life-shortening if not treated. The defining abnormality is hypoventilation during sleep which requires life-long treatment with artificial ventilation. This syndrome may also be associated with generalised dysfunction of the autonomic nervous system and a sub-group with associated Hirschsprung's disease. The genetic basis of CCHS has been identified as mutations in the PHOX2B gene. METHODS: We present four families, three with autosomal dominant inheritance and familial clustering, and one with a de novo mutation resulting in CCHS. CONCLUSIONS: We demonstrate that nasal mask ventilation from birth can provide adequate treatment and improved quality of life for these children. Phenotypic variability in expression of disease is seen in families with the same mutations in PHOX2B gene. The psychosocial costs of the disease and the unrecognised 'morbidity barter' that is part of current management needs to be factored into in all stages of management from childhood to adolescence to adulthood.