This European Respiratory Society statement provides a comprehensive overview on protracted bacterial bronchitis (PBB) in children. A task force of experts, consisting of clinicians from Europe and Australia who manage children with PBB determined the overall scope of this statement through consensus. Systematic reviews addressing key questions were undertaken, diagrams in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement constructed and findings of relevant studies summarised. The final content of this statement was agreed upon by all members.The current knowledge regarding PBB is presented, including the definition, microbiology data, known pathobiology, bronchoalveolar lavage findings and treatment strategies to manage these children. Evidence for the definition of PBB was sought specifically and presented. In addition, the task force identified several major clinical areas in PBB requiring further research, including collecting more prospective data to better identify the disease burden within the community, determining its natural history, a better understanding of the underlying disease mechanisms and how to optimise its treatment, with a particular requirement for randomised controlled trials to be conducted in primary care.

Rationale: Obstructive sleep apnea syndrome (OSAS) and nonalcoholic fatty liver disease (NAFLD) are frequently encountered in obese children. Whether OSAS and intermittent hypoxia are associated with liver injury in pediatric NAFLD is unknown. Objectives: To assess the relationship of OSAS with liver injury in pediatric NAFLD. Methods: Sixty-five consecutive children with biopsy-proven NAFLD (age, mean ± SD, 11.7 ± 2.1 yr; 58% boys; body mass index z score, 1.93 ± 0.61) underwent a clinical-biochemical assessment and a standard polysomnography. Insulin sensitivity, circulating proinflammatory cytokines, markers of hepatocyte apoptosis (cytokeratin-18 fragments), and hepatic fibrogenesis (hyaluronic acid) were measured. Liver inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3, and CD163, surface markers of leukocytes, T cells, and activated macrophage/Kupffer cells, respectively. OSAS was defined by an apnea/hypopnea index (AHI) greater than or equal to 1 event/h, and severe OSAS was defined by an AHI greater than or equal to 5 events/h. Measurements and Main Results: Fifty-five percent of children with NAFLD had nonalcoholic steatohepatitis (NASH), and 34% had significant (stage F ≥ 2) fibrosis. OSAS affected 60% of children with NAFLD; the presence and severity of OSAS were associated with the presence of NASH (odds ratio, 4.89; 95% confidence interval, 3.08–5.98; P = 0.0001), significant fibrosis (odds ratio, 5.91; 95% confidence interval, 3.23–7.42; P = 0.0001), and NAFLD activity score (β, 0.347; P = 0.029), independently of body mass index, abdominal adiposity, metabolic syndrome, and insulin resistance. This relationship held also in nonobese children with NAFLD. The duration of hemoglobin desaturation (SaO2 < 90%) correlated with increased intrahepatic leukocytes and activated macrophages/Kupffer cells and with circulating markers of hepatocyte apoptosis and fibrogenesis. Conclusions: In pediatric NAFLD, OSAS is associated with biochemical, immunohistochemical, and histological features of NASH and fibrosis. The impact of hypoxemia correction on liver disease severity warrants evaluation in future trials.

Rare variants in the T-box transcription factor 4 gene (TBX4) have recently been recognised as an emerging cause of paediatric pulmonary hypertension (PH). Their pathophysiology and contribution to persistent pulmonary hypertension in neonates (PPHN) are unknown. We sought to define the spectrum of clinical manifestations and histopathology associated withTBX4variants in neonates and children with PH.We assessed clinical data and lung tissue in 19 children with PH, including PPHN, carryingTBX4rare variants identified by next-generation sequencing and copy number variation arrays.Variants included six 17q23 deletions encompassing the entireTBX4locus and neighbouring genes, and 12 likely damaging mutations. 10 infants presented with neonatal hypoxic respiratory failure and PPHN, and were subsequently discharged home. PH was diagnosed later in infancy or childhood. Three children died and two required lung transplantation. Associated anomalies included patent ductus arteriosus, septal defects, foot anomalies and developmental disability, the latter with a higher prevalence in deletion carriers. Histology in seven infants showed abnormal distal lung development and pulmonary hypertensive remodelling.TBX4mutations and 17q23 deletions underlie a new form of developmental lung disease manifesting with severe, often biphasic PH at birth and/or later in infancy and childhood, often associated with skeletal anomalies, cardiac defects, neurodevelopmental disability and other anomalies.

BACKGROUND: Spinal muscular atrophy type 1 (SMA1) is a progressive disease and is usually fatal in the first year of life. METHODS: A retrospective chart review was performed of SMA1 patients and their outcomes according to the following choices: letting nature take its course (NT); tracheostomy and invasive mechanical ventilation (TV); continuous noninvasive respiratory muscle aid (NRA), including noninvasive ventilation; and mechanically assisted cough. RESULTS: Of 194 consecutively referred patients enrolled in this study (103 males, 91 females), NT, TV, and NRA were chosen for 121 (62.3%), 42 (21.7%), and 31 (16%) patients, respectively. Survival at ages 24 and 48 months was higher in TV than NRA users: 95% (95% confidence interval: 81.8%–98.8%) and 67.7% (95% confidence interval: 46.7%–82%) at age 24 months (P < .001) and 89.43% and 45% at age 48 months in the TV and NRA groups, respectively (P < .001). The choice of TV decreased from 50% (1992–1998) to 12.7% (2005–2010) (P < .005) with a nonstatistically significant increase for NT from 50% to 65%. The choice of NRA increased from 8.1% (1999–2004) to 22.7% (2005–2010) (P < .001). CONCLUSIONS: Long-term survival outcome is determined by the choice of the treatment. NRA and TV can prolong survival, with NRA showing a lower survival probability at ages 24 and 48 months.

Long-term noninvasive respiratory support, comprising continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV), in children is expanding worldwide, with increasing complexities of children being considered for this type of ventilator support and expanding indications such as palliative care. There have been improvements in equipment and interfaces. Despite growing experience, there are still gaps in a significant number of areas: there is a lack of validated criteria for CPAP/NIV initiation, optimal follow-up and monitoring; weaning and long-term benefits have not been evaluated. Therapeutic education of the caregivers and the patient is of paramount importance, as well as continuous support and assistance, in order to achieve optimal adherence. The preservation or improvement of the quality of life of the patient and caregivers should be a concern for all children treated with long-term CPAP/NIV. As NIV is a highly specialised treatment, patients are usually managed by an experienced paediatric multidisciplinary team. This statement written by experts in the field of paediatric long-term CPAP/NIV aims to emphasise the most recent scientific input and should open up new perspectives and research areas.