Epidemiology of childhood interstitial lung disease in France: the RespiRare cohort.

INTRODUCTION: Interstitial lung disease in children (chILD) are rare and mostly severe lung diseases. Very few epidemiological data are available in limited series of patients. The aim of this study was to assess the prevalence and incidence of chILD in France. METHODS: We performed within the RespiRare network a multicentre retrospective observational study in patients with chILD from 2000 to 2022 and a prospective evaluation of chILD's incidence between February 2022 and 2023. RESULTS: chILD was reported in 790 patients in 42 centres. The estimated 2022 prevalence in France was 44 /million children (95% CI 40.76 to 47.46) and the computed incidence was 4.4 /million children (95% CI 3.44 to 5.56). The median age at diagnosis was 3 months with 16.9% of familial forms. Lung biopsy and genetic analyses were performed in 23.4% and 76.9%, respectively. The most frequent chILD aetiologies in the <2 years group were surfactant metabolism disorders (16.3%) and neuroendocrine cell hyperplasia of infancy (11.8%), and in the 2-18 years group diffuse alveolar haemorrhage (12.2%), connective tissue diseases (11.4%), hypersensitivity pneumonitis (8.8%) and sarcoidosis (8.8%). The management included mainly oxygen therapy (52%), corticosteroid pulses (56%), oral corticosteroids (44%), azithromycin (27.2%), enteral nutrition (26.9%), immunosuppressants (20.3%) and hydroxychloroquine (15.9%). The 5-year survival rate was 57.3% for the patients diagnosed before 2 years and 86% between 2 and 18 years. CONCLUSION: This large and systematic epidemiological study confirms a higher incidence and prevalence of chILD than previously described. In order to develop international studies, efforts are still needed to optimise the case collection and to harmonise diagnostic and management practices.

Non-invasive respiratory support in children and young adults with complex medical conditions in pediatric palliative care.

OBJECTIVE: Dyspnoea and sleep-disordered breathing (SDB) are common in children with life-limiting conditions but studies on treatment with non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) are scarce. The aim of the study was to describe children treated with long-term NIV/CPAP within a paediatric palliative care programme in France. METHODS: Cross-sectional survey on children and young adults with complex medical conditions treated within the French paediatric NIV network with long-term NIV/CPAP. Characteristics of the patients were analysed and patient-related outcome measures of NIV/CPAP benefit were reported. RESULTS: The data of 50 patients (68% boys), median age 12 (0.4-21) years were analysed. Twenty-three (46%) patients had a disorder of the central nervous system and 5 (10%) a chromosomal anomaly. Thirty-two (64%) patients were treated with NIV and 18 (36%) with CPAP. NIV/CPAP was initiated on an abnormal Apnoea-Hypopnoea Index in 18 (36%) of the patients, an abnormal nocturnal gas exchange alone in 28 (56%), and after an acute respiratory failure in 11 (22%) of the patients. Mean objective NIV/CPAP adherence was 9.3±3.7 hours/night. NIV/CPAP was associated with a decrease in dyspnoea in 60% of patients, an increase in sleep duration in 60% and in sleep quality in 74%, and an improvement in parents' sleep in 40%. CONCLUSIONS: In children with life-limiting conditions, long-term NIV/CPAP may be associated with relief of dyspnoea, an improvement of SDB and an improvement in parents' sleep.

Analysis of mandibular jaw movements to assess ventilatory support management of children with obstructive sleep apnea syndrome treated with positive airway pressure therapies.

BACKGROUND: The polysomnography (PSG) is the gold-standard for obstructive sleep apnea (OSA) syndrome diagnosis and assessment under positive airway pressure (PAP) therapies in children. Recently, an innovative digital medicine solution, including a mandibular jaw movement (MJM) sensor coupled with automated analysis, has been validated as an alternative to PSG for pediatric application. OBJECTIVE: This study aimed to assess the reliability of MJM automated analysis for the assessment of residual apnea/hypopnea events during sleep in children with OSA treated with noninvasive ventilation (NIV) or continuous PAP (CPAP). METHODS: In this open-label prospective non-randomized multicentric trial, we included children aged from 5 to 18 years with a diagnosis of severe OSA. The children underwent in-laboratory PSG with simultaneous MJM monitoring and at-home recording with MJM monitoring 3 months later. Agreement between PSG and MJM analysis in measuring the residual apnea-hypopnea index (AHI) was evaluated by the Bland-Altman method. The treatment effect on residual AHI was estimated for both PSG and MJM analysis. RESULTS: Fifteen (60% males) children were included with a median age of 12 years [interquartile range 8-15]. Two (17%) were ventilated with NIV and 13 (83%) with CPAP. There was a good agreement between MJM-AHI and PSG-AHI with a median bias of -0.25 (95% CI: -3.40 to +2.04) events/h. The reduction in AHI under treatment was consistently significant across the three measurement methods: in-laboratory PSG and MJM recordings in the laboratory and at home. CONCLUSION: Automated analysis of MJM is a highly reliable alternative method to assess residual events in a small population treated with PAP therapies.

Persistent and symptomatic periodic breathing beyond the neonatal period in full-term infants: A case series.

INTRODUCTION: Periodic breathing (PB) is considered physiological in the neonatal period and usually disappears in the first months of life. There are few data available on persistent PB after the neonatal period. The objective of this study was to characterize infants born at term with persistent PB after the age of 1 month through polysomnography (PSG) performed during symptoms. METHODS: This retrospective case series included infants born at term between 2012 and 2021, without an underlying disease, who presented with symptoms of persistent PB during a PSG. Persistent PB was defined as more than 1 % of total sleep time (TST) of PB after 1 month of life, and PB was defined as a succession of at least three episodes of central apnea lasting more than 3 s and separated by less than 20 s of normal breathing. RESULTS: A total of 10 infants born at term were included. They underwent PSG for brief resolved unexplained events, desaturation, pauses in breathing, cyanosis, and/or signs of respiratory distress. The percentage of TST spent with PB was 18.1 % before 3 months of age (n = 7), and 4.7 % between 3 and 6 months of age (n = 10). During the first PSG, ≥3 % of desaturation events were observed in 77-100 % of the PB episodes. At the first PSG, nine of the 10 infants had an obstructive apnea-hypopnea index of >10/h and five of 10 infants had a central apnea index of >5/h. Gastroesophageal reflux (GER) was suspected in eight infants. All infants showed improvement in the initial symptoms during the first year of life. CONCLUSION: This study presents cases of persistent and symptomatic PB after 1 month of life in infants born at term. The interesting finding was the presence of obstructive sleep apnea syndrome and/or central apnea syndrome in the majority of children, along with GER.

Gas exchange parameters for the prediction of obstructive sleep apnea in infants.

STUDY OBJECTIVES: Sleep laboratory polysomnography is the gold standard for obstructive sleep apnea (OSA) diagnosis in infants, but its access remains limited. Oximetry-capnography is another simple and widely used tool that can provide information on the presence of desaturations and alveolar hypoventilation. However, its reliability is debated. This study aimed at examining its use in determining OSA severity in infants. METHODS: This retrospective study was conducted in a sleep unit in a tertiary hospital in infants < 4 months old with clinical signs of OSA or Pierre Robin sequence who underwent a 1-night polysomnography coupled with oximetry-capnography. RESULTS: Among the 78 infants included (median [interquartile range] age: 61 [45-89] days at polysomnography), 44 presented with Pierre Robin sequence and 34 presented with isolated airway obstruction. The clinical, sleep, and respiratory characteristics were not significantly different between the 2 subgroups. In the entire cohort, 63.5% had severe OSA. The median obstructive apnea-hypopnea index was 14.5 (7.4-5.9) events/h, peripheral oxygen saturation (SpO2) was 97.4% (96.5-98.1%), and transcutaneous carbon dioxide pressure (PtcCO2) was 41.1 mmHg (38.3-44.9). The optimal threshold to predict an obstructive apnea-hypopnea index > 10 events/h was 6 events/h for an oxygen desaturation index ≥ 3% (sensitivity, 95.7%; specificity, 51.9%) and 2 events/h for an oxygen desaturation index ≥ 4% (sensitivity, 95.7%; specificity, 48.1%). CONCLUSIONS: Whereas transcutaneous capnography does not appear to be sufficient in predicting severe OSA in infants < 4 months old with Pierre Robin sequence or clinical signs of OSA, oximetry may be a useful alternative for the screening of severe OSA in infants in the absence of polysomnography. CITATION: Gyapay R, Ioan I, Thieux M, et al. Gas exchange parameters for the prediction of obstructive sleep apnea in infants. J Clin Sleep Med. 2024;20(7):1059-1067.

Pediatric long-term noninvasive respiratory support in children with central nervous system disorders.

RATIONALE: The use of long-term noninvasive respiratory support is increasing in children along with an extension of indications, in particular in children with central nervous system (CNS) disorders. OBJECTIVE: The aim of this study was to describe the characteristics of children with CNS disorders treated with long-term noninvasive respiratory support in France. METHODS: Data were collected from 27 French pediatric university centers through an anonymous questionnaire filled for every child treated with noninvasive ventilatory support ≥3 months on 1st June 2019. MAIN RESULTS: The data of 182 patients (55% boys, median age: 10.2 [5.4;14.8] years old [range: 0.3-25]) were collected: 35 (19%) patients had nontumoral spinal cord injury, 22 (12%) CNS tumors, 63 (35%) multiple disabilities, 26 (14%) central alveolar hypoventilation and 36 (20%) other CNS disorders. Seventy five percent of the patients were treated with noninvasive ventilation (NIV) and 25% with continuous positive airway pressure (CPAP). The main investigations performed before CPAP/NIV initiation were nocturnal gas exchange recordings, alone or coupled with poly(somno)graphy (in 29% and 34% of the patients, respectively). CPAP/NIV was started in an acute setting in 10% of the patients. Median adherence was 8 [6;10] hours/night, with 12% of patients using treatment <4 h/day. Nasal mask was the most common interface (70%). Airway clearance techniques were used by 31% of patients. CONCLUSION: CPAP/NIV may be a therapeutic option in children with CNS disorders. Future studies should assess treatment efficacy and patient reported outcome measures.

Long term noninvasive ventilation and continuous positive airway pressure in children with neuromuscular diseases in France.

The aim of the study was to describe the characteristics of children with neuromuscular diseases treated with long term noninvasive ventilation or continuous positive airway pressure in France. On June 1st 2019, 387 patients (63% boys, mean age 11.2 ± 5.5 years) were treated with long term noninvasive ventilation/continuous positive airway pressure. Thirty three percent of patients had spinal muscular atrophy, 30% congenital myopathy/dystrophy, 20% Duchenne muscular dystrophy, 7% Steinert myotonic dystrophy, and 9% other neuromuscular diseases. Ninety-four percent of patients were treated with long term noninvasive ventilation and 6% with continuous positive airway pressure. Treatment was initiated electively for 85% of patients, mainly on an abnormal overnight gas exchange recording (38% of patients). Noninvasive ventilation/continuous positive airway pressure was initiated during a respiratory exacerbation in 15% of patients. Mean duration of noninvasive ventilation/continuous positive airway pressure was 3.3 ± 3.1 years. Mean objective long term noninvasive ventilation/continuous positive airway pressure use was 8.0 ± 3.1 h/24. Spinal muscular atrophy, congenital myopathy/dystrophy, and Duchenne muscular dystrophy represented 83% of children with neuromuscular diseases treated with long term noninvasive ventilation in France. Screening for nocturnal hypoventilation was satisfactory as noninvasive ventilation /continuous positive airway pressure was predominantly initiated electively.

Paediatric long term continuous positive airway pressure and noninvasive ventilation in France: A cross-sectional study.

OBJECTIVE: To describe the characteristics of children treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in France. DESIGN: Cross-sectional national survey. SETTING: Paediatric CPAP/NIV teams of 28 tertiary university hospitals in France. PATIENTS: Children aged <20 years treated with CPAP/NIV since at least 3 months on June 1st, 2019. INTERVENTION: An anonymous questionnaire was filled in for every patient. RESULTS: The data of 1447 patients (60% boys), mean age 9.8 ± 5.8 years were analysed. The most frequent underlying disorders were: upper airway obstruction (46%), neuromuscular disease (28%), disorder of the central nervous system (13%), cardiorespiratory disorder (7%), and congenital bone disease (4%). Forty-five percent of the patients were treated with CPAP and 55% with NIV. Treatment was initiated electively for 92% of children, while 8% started during an acute illness. A poly(somno)graphy (P(S)G) was performed prior to treatment initiation in 26%, 36% had a P(S)G with transcutaneous carbon dioxide monitoring (PtcCO2), while 23% had only a pulse oximetry (SpO2) with PtcCO2 recording. The decision of CPAP/NIV initiation during an elective setting was based on the apnea-hypopnea index (AHI) in 41% of patients, SpO2 and PtcCO2 in 25% of patients, and AHI with PtcCO2 in 25% of patients. Objective adherence was excellent with a mean use of 7.6 ± 3.2 h/night. Duration of CPAP/NIV was 2.7 ± 2.9 years at the time of the survey. CONCLUSION: This survey shows the large number of children treated with long term CPAP/NIV in France with numerous children having disorders other than neuromuscular diseases.

A national internet-linked based database for pediatric interstitial lung diseases: the French network.

BACKGROUND: Interstitial lung diseases (ILDs) in children represent a heterogeneous group of rare respiratory disorders that affect the lung parenchyma. After the launch of the French Reference Centre for Rare Lung Diseases (RespiRare®), we created a national network and a web-linked database to collect data on pediatric ILD. METHODS: Since 2008, the database has been set up in all RespiRare® centres. After patient's parents' oral consent is obtained, physicians enter the data of children with ILD: identity, social data and environmental data; specific aetiological diagnosis of the ILD if known, genetics, patient visits to the centre, and all medical examinations and tests done for the diagnosis and/or during follow up. Each participating centre has a free access to his own patients' data only, and cross-centre studies require mutual agreement. Physicians may use the system as a daily aid for patient care through a web-linked medical file, backed on this database. RESULTS: Data was collected for 205 cases of ILD. The M/F sex ratio was 0.9. Median age at diagnosis was 1.5 years old [0-16.9]. A specific aetiology was identified in 149 (72.7%) patients while 56 (27.3%) cases remain undiagnosed. Surfactant deficiencies and alveolar proteinosis, haemosiderosis, and sarcoidosis represent almost half of the diagnoses. Median length of follow-up is 2.9 years [0-17.2]. CONCLUSIONS: We introduce here the French network and the largest national database in pediatric ILDs. The diagnosis spectrum and the estimated incidence are consistent with other European databases. An important challenge will be to reduce the proportion of unclassified ILDs by a standardized diagnosis work-up. This database is a great opportunity to improve patient care and disease pathogenesis knowledge. A European network including physicians and European foundations is now emerging with the initial aim of devising a simplified European database/register as a first step to larger European studies.

[Bronchial carcinoid tumors in children]. / Tumeurs carcinoïdes bronchiques de l'enfant.

Carcinoid tumors are the most common endobronchial tumors in the pediatric population, and represent a rare cause of airway obstruction. Clinical manifestations are unspecific, and diagnosis is often delayed due to low clinical suspicion. These tumors are considered low-grade malignant neoplasms, and their evolution is usually favorable after surgery. However, local recurrence and/or metastases can occur with both typical and atypical carcinoid tumors, justifying the need of prompt diagnosis and long-term follow-up.