Clinical utility of elective paediatric flexible bronchoscopy and impact on the quality of life: protocol for a single-centre, single-blind, randomised controlled trial.

INTRODUCTION: Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there are no randomised controlled trials (RCTs) that have examined its benefits (or otherwise).Our primary aim is to determine the impact of FB on the parent-proxy quality-of-life (QoL) scores. Our secondary aims are to determine if undertaking FB leads to (a) change in management and (b) improvement of other relevant patient-reported outcome measures (PROMs). We also quantified the benefits of elective FB (using 10-point Likert scale). We hypothesised that undertaking elective FB will contribute to accurate diagnosis and therefore appropriate treatment, which will in turn improve QoL and will be deemed to be beneficial from patient and doctor perspectives. METHODS AND ANALYSIS: Our parallel single-centre, single-blind RCT (commenced in May 2020) has a planned sample size of 114 children (aged <18 years) recruited from respiratory clinics at Queensland Children's Hospital, Brisbane, Australia. Children are randomised (1:1 concealed allocation) within two strata: age (≤2 vs >2 years) and indication for FB (chronic cough vs other indications) to either (a) early arm (intervention where FB undertaken within 2 weeks) or (b) delayed (control, FB undertaken at usual wait time). Our primary outcome is the difference between groups in their change in QoL at the T2 timepoint when the intervention group has had the FB and the control group has not. Our secondary outcomes are change in management, change in PROMs, adverse events and the Likert scales. ETHICS AND DISSEMINATION: The human research ethics committee of the Queensland Children's Hospital granted ethical clearance (HREC/20/QCHQ/62394). Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation. Results will be disseminated through conference presentations, teaching avenues, workshops, websites and publications. REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12620000610932.

Managing moderate-to-severe paediatric asthma: a scoping review of the efficacy and safety of fluticasone propionate/salmeterol.

BACKGROUND: Fluticasone propionate/salmeterol xinafoate (FP/SAL) is an inhaled corticosteroid (ICS) and long-acting ß2-agonist (LABA) combination, indicated for the regular treatment of children (aged >4 years) with asthma that is inadequately controlled with ICS monotherapy plus as-needed short-acting ß2-agonists, or already adequately controlled with ICS/LABA. OBJECTIVE: Compared with the adult population, fewer clinical studies have investigated the efficacy of FP/SAL in paediatric patients with moderate and moderate-to-severe asthma. In this review, we synthesise the available evidence for the efficacy and safety of FP/SAL in the paediatric population, compared with other available therapies indicated for asthma in children. ELIGIBILITY CRITERIA: A literature review identified randomised controlled trials and observational studies of FP/SAL in the paediatric population with moderate-to-severe asthma. SOURCES OF EVIDENCE: The Medline database was searched using PubMed (https://pubmed.ncbi.nlm.nih.gov/), with no publication date restrictions. Search strategies were developed and refined by authors. CHARTING METHODS: Selected articles were screened for clinical outcome data (exacerbation reduction, nocturnal awakenings, lung function, symptom control, rescue medication use and safety) and a table of key parameters developed. RESULTS: Improvements in asthma outcomes with FP/SAL include reduced risk of asthma-related emergency department visits and hospitalisations, protection against exercise-induced asthma and improvements in measures of lung function. Compared with FP monotherapy, greater improvements in measures of lung function and asthma control are reported. In addition, reduced incidence of exacerbations, hospitalisations and rescue medication use is observed with FP/SAL compared with ICS and leukotriene receptor antagonist therapy. Furthermore, FP/SAL therapy can reduce exposure to both inhaled and oral corticosteroids. CONCLUSIONS: FP/SAL is a reliable treatment option in patients not achieving control with ICS monotherapy or a different ICS/LABA combination. Evidence shows that FP/SAL is well tolerated and has a similar safety profile to FP monotherapy. Thus, FP/SAL provides an effective option for the management of moderate-to-severe asthma in the paediatric population.

Respiratory management and outcomes in high-risk preterm infants with development of a population outcome dashboard.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is associated with adverse long-term respiratory and neurodevelopmental outcomes. No recent studies examined the changing respiratory management and outcomes, particularly severe BPD, across a whole population. PURPOSE: Evaluate the temporal trends in the respiratory management and outcomes of preterm infants born below 32 weeks gestational age and develop an individualised dashboard of the incidence of neonatal outcome. METHODS: Using the National Neonatal Research Database, we determined changes in respiratory management, BPD rates, postdischarge respiratory support and mortality in 83 463 preterm infants in England and Wales from 2010 to 2020. RESULTS: Between 2010 and 2020, antenatal corticosteroids use increased (88%-93%, p<0.0001) and neonatal surfactant use decreased (65%-60%, p<0.0001). Postnatal corticosteroid use increased, especially dexamethasone (4%-6%, p<0.0001). More recently, hydrocortisone and budesonide use increased from 2% in 2017 to 4% and 3%, respectively, in 2020 (p<0.0001). Over the study period, mortality decreased (10.1%-8.5%), with increases in BPD (28%-33%), severe BPD (12%-17%), composite BPD/death (35%-39%) and composite severe BPD/death (21%-24%) (all p<0.0001). Overall, 11 684 infants required postdischarge respiratory support, increasing from 13% to 17% (p<0.0001), with 1843 infants requiring respiratory pressure support at discharge. A population dashboard (https://premoutcome.github.io/) depicting the incidence of mortality and respiratory outcomes, based on gestation, sex and birthweight centile, was developed. CONCLUSION: More preterm infants are surviving with worse respiratory outcomes, particularly severe BPD requiring postdischarge respiratory support. Ultimately, these survivors will develop chronic respiratory diseases requiring greater healthcare resources.

Does routine spirometry impact on clinical decisions and patient-related outcome measures of children seen in respiratory clinics: an open-label randomised controlled trial.

INTRODUCTION: There is limited evidence on the efficacy of using spirometry routinely in paediatric practice for improving outcomes. OBJECTIVE: To determine whether the routine use of spirometry alters clinical decisions and patient-related outcome measures for children managed by respiratory paediatricians. METHODS: We undertook a parallel open-label randomised controlled trial involving children (aged 4-18 years) able to perform spirometry in a specialist children's hospital in Australia. Children were randomised to either routine use of spirometry (intervention) or clinical review without use of spirometry (control) for one clinic visit. The primary outcomes were the (a) proportion of children with 'any change in clinical decisions' and (b) 'change score' in clinical decisions. Secondary outcomes were change in patient-related outcome measures assessed by State-Trait Anxiety Inventory (STAI) and Parent-Proxy QoL questionnaire for paediatric chronic cough (PC-QoL). RESULTS: Of 136 eligible children, 106 were randomised. Compared with controls, the intervention group had significantly higher proportion of children with 'any change in clinical decisions' (n=54/54 (100%) vs n=34/52 (65.4%), p<0.001) and higher clinical decision 'change score' (median=2 (IQR 1-4) vs 1 (0-2), p<0.001). Also, improvement was significantly greater in the intervention group for overall STAI score (median=-5 (IQR -10 to -2) vs -2.5 (-8.5, 0), p=0.021) and PC-QoL social domain (median=3 (IQR 0 to 5) vs 0 (-1, 1), p=0.017). CONCLUSION: The routine use of spirometry in children evaluated for respiratory issues at clinical outpatient review is beneficial for optimising clinical management and improving parent psychosocial well-being. REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12619001686190.

Pleural and transpulmonary pressures to tailor protective ventilation in children.

This review aims to: (1) describe the rationale of pleural (PPL) and transpulmonary (PL) pressure measurements in children during mechanical ventilation (MV); (2) discuss its usefulness and limitations as a guide for protective MV; (3) propose future directions for paediatric research. We conducted a scoping review on PL in critically ill children using PubMed and Embase search engines. We included peer-reviewed studies using oesophageal (PES) and PL measurements in the paediatric intensive care unit (PICU) published until September 2021, and excluded studies in neonates and patients treated with non-invasive ventilation. PL corresponds to the difference between airway pressure and PPL Oesophageal manometry allows measurement of PES, a good surrogate of PPL, to estimate PL directly at the bedside. Lung stress is the PL, while strain corresponds to the lung deformation induced by the changing volume during insufflation. Lung stress and strain are the main determinants of MV-related injuries with PL and PPL being key components. PL-targeted therapies allow tailoring of MV: (1) Positive end-expiratory pressure (PEEP) titration based on end-expiratory PL (direct measurement) may be used to avoid lung collapse in the lung surrounding the oesophagus. The clinical benefit of such strategy has not been demonstrated yet. This approach should consider the degree of recruitable lung, and may be limited to patients in which PEEP is set to achieve an end-expiratory PL value close to zero; (2) Protective ventilation based on end-inspiratory PL (derived from the ratio of lung and respiratory system elastances), might be used to limit overdistention and volutrauma by targeting lung stress values < 20-25 cmH2O; (3) PPL may be set to target a physiological respiratory effort in order to avoid both self-induced lung injury and ventilator-induced diaphragm dysfunction; (4) PPL or PL measurements may contribute to a better understanding of cardiopulmonary interactions. The growing cardiorespiratory system makes children theoretically more susceptible to atelectrauma, myotrauma and right ventricle failure. In children with acute respiratory distress, PPL and PL measurements may help to characterise how changes in PEEP affect PPL and potentially haemodynamics. In the PICU, PPL measurement to estimate respiratory effort is useful during weaning and ventilator liberation. Finally, the use of PPL tracings may improve the detection of patient ventilator asynchronies, which are frequent in children. Despite these numerous theoritcal benefits in children, PES measurement is rarely performed in routine paediatric practice. While the lack of robust clincal data partially explains this observation, important limitations of the existing methods to estimate PPL in children, such as their invasiveness and technical limitations, associated with the lack of reference values for lung and chest wall elastances may also play a role. PPL and PL monitoring have numerous potential clinical applications in the PICU to tailor protective MV, but its usefulness is counterbalanced by technical limitations. Paediatric evidence seems currently too weak to consider oesophageal manometry as a routine respiratory monitoring. The development and validation of a noninvasive estimation of PL and multimodal respiratory monitoring may be worth to be evaluated in the future.

Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1-3.

INTRODUCTION: Nusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown. AIM: To assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment. METHODS: A prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test. RESULTS: Twenty-eight patients (15 male, aged 0.08-18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was -0.58 (95% CI -0.75 to -0.41), and post initiation was -0.25 (95% CI -0.46 to -0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea-Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1-10.1) at initiation to 2.7 events/hour (IQR 0.7-5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen. CONCLUSION: The first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI.

Early NIV is associated with accelerated lung function decline in Duchenne muscular dystrophy treated with glucocorticosteroids.

BACKGROUND: Use of non-invasive ventilation (NIV) in adolescents with Duchenne muscular dystrophy (DMD) has increased with concomitant extended survival. AIM: To describe lung function (LF) changes with NIV in adolescents with DMD and to assess differences between Steroid Users and Steroid Naïve subjects. METHOD: A retrospective cohort of adolescents with DMD initiating NIV over 10 years was conducted. Serial LF before and after NIV initiation was collated. Use of systemic glucocorticosteroids, adherence to NIV and presence of cardiac disease were assessed. RESULTS: Twenty-nine men started NIV, median age 14.66 years (IQR 2.35, 10.47-17.96). Nine were Steroid Users and eight were Steroid Naïve. Indications for NIV were apnoea-hypopnoea index >5 and/or nocturnal hypoventilation. LF is better (forced vital capacity (FVC) z-score -3.26 vs -5.41, p < 0.02) and decline slower (FVC z-score -0.58 per annum (pa) vs -0.68 pa, p<0.001) in Steroid Users compared with Steroid Naïve subjects. Following NIV initiation, FVC z-score decline slowed for the whole (-0.72 pa (95% CI -0.79 to 0.64) to -0.46 pa (95% CI -0.54 to 0.38) p < 0.001) and Steroid Naïve groups (-0.74 (95% CI -0.85 to 0.63) to -0.44 pa (95% CI -0.56 to 0.32) p < 0.001) but accelerated in the Steroid User group (-0.56 (95% CI -0.70 to 0.42) to -0.75 pa (95% CI -0.89 to 0.61) p < 0.001). Adherence to NIV and cardiac disease did not impact decline. CONCLUSION: Overall, LF decline is reduced on NIV. Steroid Naïve patients have lower LF and faster decline, which slows following NIV initiation. An accelerated LF decline was seen on NIV in Steroid Users which requires further prospective research.

Lung function in children with sickle cell disease from Central Africa.

Lung function in patients with sickle cell anaemia (SCA) living in sub-Saharan Africa is largely unknown. Anthropometry and spirometry were cross-sectionally evaluated in patients with SCA (HbSS) aged 6-18 years and in schoolchildren from the Democratic Republic of the Congo. The Global Lung Initiative 2012 spirometry reference values were used. A total of 112 patients and 377 controls were included. Twenty-six per cent of patients with SCA had spirometry findings suggestive of a restrictive pattern and 41% had a FEV1 z-score <5th percentile. Wasting, increasing age and female sex were independently associated with increased risk of restrictive spirometry pattern in patients with SCA. Longitudinal studies could clarify the prognostic meaning of these findings.

Effect of idiopathic thoracic scoliosis on the tracheobronchial tree.

INTRODUCTION: High prevalence of obstructive lung disease has been reported in patients undergoing surgical correction of thoracic scoliosis. Airway narrowing due to spine morphology is analysed as a contributing factor. METHODS: Preoperative surgical planning CTs of 34 patients with right-sided thoracic scoliosis (age: 17.6±9.0) were retrospectively analysed and compared with 15 non-scoliotic controls (age: 16.3±5.1). Three-dimensional models of spine and airway lumen were reconstructed. Based on thoracic sagittal profile, patients were divided into hypokyphosis (HypoS: <10°), normal kyphosis (NormS: ≥10° and <40°) and hyperkyphosis (HyperS: ≥40°) groups. Lumen area of bronchi, bifurcation angles and minimum spine-airway distance were measured. Pulmonary function tests were correlated to scoliosis, kyphosis and lumen area. RESULTS: Loss of kyphosis led to proximity between bronchus intermedius (BI) and spine. HypoS (NormS) had lumen area reductions in the right main bronchus of 29% (19%), BI of 45% (23%), right middle lobar bronchus of 46% (32%) and right lower lobe bronchus (RLL7) of 66% (37%), respectively (P<0.05). The lower right superior segmental bronchus was reduced across all scoliotic groups (P<0.05). Airways were displaced caudal by 0.65±0.45 vertebra in patients with scoliosis. Loss of kyphosis correlated negatively with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), FVC/(FVC predicted) and FEV1/(FEV1 predicted) (P<0.01). Lumen area of trachea, right upper lobar bronchus, BI and RLL7 correlated negatively with FEV1/FVC. BI and RLL7 narrowing were strong predictors of FVC and FEV1 loss (P<0.001). CONCLUSIONS: Right-sided main stem airways are narrowed in HypoS and NormS. Loss of kyphosis leads to narrowing of BI and its trifurcation. FEV1/FVC correlated negatively with airway narrowing, implying an obstructive element to lung function impairment in patients with scoliosis and hypokyphosis.

Pott's disease: a major issue for an unaccompanied refugee minor.

The incidence of TB in children in Germany has been on a rise since 2008, especially among foreign-born individuals. With rapidly increasing numbers of refugees from the numerous areas of conflict, this increase in incidence is not expected to halt, neither in Germany nor in Europe in general. We report a case of insufficient tracking in a 16-year-old unaccompanied refugee minor from Somalia who had a positive interferon γ release assay on arrival in Germany. No actions were undertaken, until 6 months later, an X-ray showed prominent hilar enlargement. Nine  months later, the patient presented to our hospital with abdominal pain, vomiting and B symptoms. Workup revealed a paravertebral abscess due to Pott's disease, a skeletal manifestation of Mycobacterium tuberculosis disease. The patient made a full recovery after a combination therapy for a total of 9 months.

Respiratory viruses associated with community-acquired pneumonia in children: matched case-control study.

BACKGROUND: Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. A better understanding of the role of virus infections in this condition is needed to improve clinical management and preventive measures. The aim of the study was therefore to assess the association between specific respiratory viruses and childhood CAP. METHODS: A case-control study was conducted during 3 years in Stockholm, Sweden. Cases were children aged ≤5 years with radiological CAP. Healthy controls were consecutively enrolled at child health units during routine visits and matched to cases on age and calendar time. Nasopharyngeal aspirates were obtained and analysed by real-time PCR for 15 viruses. Multivariate conditional logistic regression was used to account for coinfections with other viruses and baseline characteristics. RESULTS: A total of 121 cases, of which 93 cases met the WHO criteria for radiological pneumonia, and 240 controls were included in the study. Viruses were detected in 81% of the cases (n=98) and 56% of the controls (n=134). Influenza virus, metapneumovirus and respiratory syncytial virus were detected in 60% of cases and were significantly associated with CAP with ORs >10. There was no association with parainfluenza virus, human enterovirus or rhinovirus and coronavirus and bocavirus were negatively associated with CAP. CONCLUSIONS: Our study indicates viral CAP is an underestimated disease and points out hMPV as a new important target for the prevention of childhood CAP.

A protocol to determine valid V˙O2max in young cystic fibrosis patients.

OBJECTIVES: Measuring aerobic fitness (V˙O2max) via a maximal cardiopulmonary exercise test is an important clinical tool in cystic fibrosis. This study sought to establish: (1) the validity of traditional criteria to verify maximal efforts during a ramp cardiopulmonary exercise test; and (2) whether V˙O2 measured during an exhaustive cardiopulmonary exercise test represents a valid V˙O2max in paediatric patients, using a subsequent exhaustive supramaximal (Smax) exercise test. DESIGN: Cross-sectional. METHODS: Fourteen patients (7-18 years; 10 males) completed an exhaustive ramp test to determine V˙O2max. Following 15-min recovery, Smax (110% ramp peak power output) was performed. RESULTS: Ramp test V˙O2peak was significantly higher than V˙O2 documented at traditional endpoint criteria, including a RER of 1.00 (0.99±0.47 L min(-1) vs. 1.83±0.78 L min(-1), p<0.001) and 1.10 (1.36±0.59 L min(-1) vs. 1.83±0.78 L min(-1), p<0.001), despite 100% of patients satisfying these two criteria. Only 23% and 75% of patients satisfied the 95% age-predicted heart rate (HR) maximum and 180 b min(-1) criteria. Whilst mean ramp and Smax V˙O2peak were not significantly different (1.83±0.78 L min(-1) vs. 1.82±0.67 L min(-1); p=0.88), at the individual level Smax elicited a 'meaningful' (>9%) increase in V˙O2peak (range 9.9-38.3%) compared with V˙O2peak from the ramp test in 3 of 14 cases (21.4%). CONCLUSIONS: Traditional criteria significantly underestimate V˙O2max in young cystic fibrosis patients. Conversely, Smax can confirm when 'true' V˙O2max is achieved. The use of Smax following cardiopulmonary exercise test represents an appropriate method to measure V˙O2max in young cystic fibrosis patients.