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.

Age-related immune cell dynamics influence outcomes after allogeneic haematopoietic cell transplantation.

An efficient immunological reconstitution construes the pillar for the success of allogeneic haematopoietic cell transplantation (HCT) in haematological disorders. Factors influencing post-transplant immune recovery have been largely investigated across multiple cohorts issuing heterogeneous results. Differences in outcomes in adult and paediatric populations suggest an age-related contribution to post-transplant immune reconstitution; however, it is unclear how recipient and donor age may affect the dynamics of single immune cells. Here, we retrospectively collected and analysed immunological data of 174 patients (58 children and 116 adults) consecutively transplanted for haematological disorders in our centre. We show that trajectories of specific immune cells were strictly dependent on recipient age and pretransplant virus exposure, with the strongest effect seen on T CD4+ and B-cell counterparts, while donor age and transplant platforms had a minimal impact. This mirrored different kinetics of immune reconstitution in adult and paediatric patients, with major divergences in immune cell composition in late post-transplant phases, featuring better survival, relapse-free survival and cumulative incidence of pathogen-specific infections in younger patients. Altogether, these findings underpin the importance of recipient age on post-transplant immune cell recovery and define the basic dynamics of the immune reconstitution in paediatric and adult populations as a benchmark for future studies.

Procalcitonin is associated with sudden unexpected death in infancy due to infection.

Infection is an important cause of death during infancy worldwide and is a frequent etiology of sudden unexpected death in infancy (SUDI). Procalcitonin (PCT) is a useful marker to diagnose infection in patients, and several studies report the stability of PCT after death. The added value of a biological marker, such as the PCT level in the blood, remains controversial in investigating SUDI. The aim of this study was to determine if PCT can help clinicians determine whether infection caused SUDI. We conducted a retrospective, multicenter study with the French SUDI registry (Observatoire National des Morts Inattendues du Nourrisson; OMIN). We collected data from this registry on children who died between May 2015 and June 2021. The levels of PCT in the blood of 540 SUDI patients were measured. We compared PCT and other biological tests performed in terms of infection status, autopsy results, and cause of death using clinical and biological data compiled by pediatricians at the SUDI referral center. PCT levels were significantly higher in the children who died from infection than in those who did not (0.12 µg/L vs. 0.08 µg/L, p < 0.001). A PCT blood level exceeding 0.2 µg/L was more frequently observed when infection was present than in the absence of infection (44.3% vs. 15.4%, p < 0.001). The same data were obtained with a 0.5 µg/L cut-off (36.1% with infection vs. 9.2% without, p < 0.001).  Conclusions: PCT is a sensitive biomarker for detecting infections postmortem; thus, additional samples may be necessary during autopsy. What is known: • PCT is a stable marker postmortem and increases earlier than CRP, i.e., 2-4 h after the beginning of an infection vs. 6 h. • PCT can be measured up to 140 h after death. What is new: • PCT is a sensitive marker for detecting infection in SUDI patients postmortem. • This test can reveal an infection from non-standardized samples obtained during autopsy if such an infection was not determined before death.

Relevance of sensitization to legumes in peanut-allergic children.

BACKGROUND: Legume consumption has increased during the two past decades. In France, legumes are responsible for 14.6% of food-related anaphylaxis in children, with peanut as the main allergen (77.5%). Few studies have demonstrated cross-reactivities between peanut and other legumes. The aim of this study was to determine prevalence and relevance of sensitization to legumes in peanut-allergic children. METHODS: All children, aged of 1-17 years, admitted to the Pediatric Allergy Department of the University Hospital of Nancy between January 1, 2017 and February 29, 2020 with a confirmed peanut allergy (PA) and a documented consumption or sensitization to at least one other legume were included. Data were retrospectively collected regarding history of consumption, skin prick tests, specific immunoglobulin E (IgE), prior allergic reactions, and oral food challenges for each legume. RESULTS: Among the 195 included children with PA, 122 were sensitized to at least one other legume (63.9%). Main sensitizations were for fenugreek (N = 61, 66.3%), lentil (N = 38, 42.2%), soy (N = 61, 39.9%), and lupine (N = 63, 34.2%). Among the 122 sensitized children, allergy to at least one legume was confirmed for 34 children (27.9%), including six children who had multiple legume allergies (4.9%). Lentil, lupine, and pea were the main responsible allergens. Half of allergic reactions to legumes other than peanut were severe. CONCLUSION: The high prevalence of legume sensitization and the frequent severe reactions reported in children with PA highlight that tolerated legume consumption should be explored for each legume in the case of PA, and sensitization should be investigated if not.

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort.

BACKGROUND: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. METHODS: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. RESULTS: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. CONCLUSION: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.

Predictive factors of allergy to pistachio in children allergic to cashew nut.

BACKGROUND: Cashew nut (CN) allergy prevalence has increased over the last few years. In children allergic to CN, complete avoidance of pistachio is usually recommended, but recent study showed that only one third of children allergic to CN were also allergic to pistachio. The aim of our study was to identify predictive factors of allergy to pistachio in children allergic to CN. METHODS: All children who had a positive oral food challenge (OFC) to CN between November 2013 and October 2017 in the Paediatric Allergy Department of the University Hospital of Nancy were included. Logistic regression models were used to predict the probability of allergy to pistachio. RESULTS: Among the 147 children included, tolerance or allergy to pistachio was known for 51. Out of these, 40 were allergic to pistachio (78.4%). Children allergic to pistachio had a larger weal size of skin prick test to CN (P = .01) and pistachio (P = .0007) and a lower reaction dose to CN (P < .0001). In multivariate analysis, only the reaction dose to CN was significantly associated with allergy to pistachio. Children with a low reaction dose to CN were significantly more at risk to have an allergy to pistachio (P = .01). CONCLUSION: A low reaction dose to CN seems to be a predictive factor of allergy to pistachio in children allergic to CN. In order to limit unnecessary food eviction, a pistachio OFC should be performed in children having high reaction dose whatever the importance of the skin or the specific IgE sensitization to pistachio.

Development of Reliable and Validated Tools to Evaluate Technical Resuscitation Skills in a Pediatric Simulation Setting: Resuscitation and Emergency Simulation Checklist for Assessment in Pediatrics.

OBJECTIVES: To develop a reliable and validated tool to evaluate technical resuscitation skills in a pediatric simulation setting. STUDY DESIGN: Four Resuscitation and Emergency Simulation Checklist for Assessment in Pediatrics (RESCAPE) evaluation tools were created, following international guidelines: intraosseous needle insertion, bag mask ventilation, endotracheal intubation, and cardiac massage. We applied a modified Delphi methodology evaluation to binary rating items. Reliability was assessed comparing the ratings of 2 observers (1 in real time and 1 after a video-recorded review). The tools were assessed for content, construct, and criterion validity, and for sensitivity to change. RESULTS: Inter-rater reliability, evaluated with Cohen kappa coefficients, was perfect or near-perfect (>0.8) for 92.5% of items and each Cronbach alpha coefficient was ≥0.91. Principal component analyses showed that all 4 tools were unidimensional. Significant increases in median scores with increasing levels of medical expertise were demonstrated for RESCAPE-intraosseous needle insertion (P = .0002), RESCAPE-bag mask ventilation (P = .0002), RESCAPE-endotracheal intubation (P = .0001), and RESCAPE-cardiac massage (P = .0037). Significantly increased median scores over time were also demonstrated during a simulation-based educational program. CONCLUSIONS: RESCAPE tools are reliable and validated tools for the evaluation of technical resuscitation skills in pediatric settings during simulation-based educational programs. They might also be used for medical practice performance evaluations.

Breathing-related changes of respiratory resistance in vocal cord dysfunction.

Vocal cord dysfunction induced by exercise in children with uncontrolled asthma was identified by laryngoscopy. The paradoxical adduction of the vocal cords was also indicated by the breathing-related changes of the forced oscillation respiratory resistance showing prominent increase during inspiration and a large positive difference between inspiration and expiration. The breathing-related changes of respiratory resistance offer thus a useful first-line technique to diagnose vocal cord dysfunction.

Sweat test practice in pediatric pulmonology after introduction of cystic fibrosis newborn screening.

The influence of the generalization of cystic fibrosis newborn screening (CFNBS) in France on sweat test (ST) prescription is unknown. In this French retrospective, descriptive, and multicenter study, we studied the indications, number, methods, and results of STs prescribed by a pediatric pulmonologist in children who had a negative CFNBS and an ST for respiratory symptoms in 2012. We included 502 children with 523 STs, performed with four different methods. The main indication was asthma (71.3 %), then chronic cough (52.4 %), atypical lower airway infections (42.2 %), and bronchiectasis (7 %). Four children had a diagnosis of CF (0.8 %), all presenting with chronic productive cough and recurrent respiratory infections. CONCLUSION: Asthma is the most frequent indication of ST in our cohort. Because of the systematic CFNBS in France, some prescriptions should be avoided, particularly in case of severe or moderate asthma with no other associated symptom. Moreover, methods of STs often do not follow the guidelines and need standardization. WHAT IS KNOWN: • Newborn screening (NBS) has become the most frequent circumstance of the diagnosis of cystic fibrosis (CF) in France after its generalization. • The prescription of sweat test (ST) in children with respiratory symptoms who already had a negative NBS has not been studied. WHAT IS NEW: • In children with a negative CF NBS referred to a university hospital for respiratory diseases, despite important variations of ST methods, only 4 children among 502 have been diagnosed as CF. • Despite recommendations, ST prescription should be avoided in children with moderate to severe asthma and no other associated symptom.

Desensitization of the cough reflex during limb muscle contraction in anesthetized rabbits.

The 'cough network' exhibits plasticity at the sensor and integration levels leading to modulation of the strength or pattern of the cough reflex. Little is known about the interactions between cough and human activities, especially during exercise. The present study was designed to determine whether exercise, mimicked by electrically induced muscle contractions, can modify the incidence and/or strength of cough following mechanical stimulation of the trachea in anesthetized rabbits. Thirteen anesthetized, tracheotomized rabbits were studied by a total of 311 tracheal stimulations: 196 at rest and 115 during exercise. During muscle contractions, the incidence of the cough reflex (CR) decreased and the expiration reflex (ER) increased (p < 0.0001). The sensitivity of the CR and ER both decreased during exercise compared to the sensitivity of the CR at rest (p < 0.02), while the strength of the expulsive response remained unchanged. These results indicate that adjustments occurring during muscle contractions likely downregulate tracheal defensive reflexes in anesthetized rabbits.

Late-onset pulmonary complications following allogeneic hematopoietic cell transplantation in pediatric patients: a prospective multicenter study.

The primary objective of our multicenter prospective study was to describe the incidence of late-onset non-infectious pulmonary complications (LONIPCs) in children undergoing hematopoietic cell transplantation (HCT) using sensitive criteria for pulmonary function test (PFT) abnormalities including the non-specific pattern of airflow obstruction. Secondary objectives were to assess the factors associated with LONIPC occurrence and the sensitivity of the 2014 NIH-Consensus Criteria of bronchiolitis obliterans syndrome (BOS). PFT and clinical assessment were performed prior to HCT and at 6, 12, 24, and 36 months post-HCT. LONIPC diagnosis was validated by an Adjudication Committee. The study comprised 292 children from 12 centers. Thirty-two individuals (11%, 95% CI: 8-15%) experienced 35 LONIPCs: 25 BOS, 4 interstitial lung diseases, 4 organizing pneumonia and 2 pulmonary veno-occlusive diseases. PFT abnormalities were obstructive defects (FEV1/FVC z-score < -1.645; n = 12), restrictive defects (TLC < 80% predicted, FEV1 and FVC z-scores < -1.645; n = 7) and non-specific pattern (FEV1 and FVC z-score< -1.645, FEV1/FVC z-score > -1.645, and TLC > 80% predicted; n = 8). HCT for malignant disease was the only factor associated with LONIPC (P = 0.04). The 2014 NIH-Consensus Criteria would only diagnose 8/25 participants (32%) as having BOS. In conclusion, 11% of children experienced a LONIPC in a prospective design. Clinical Trials.gov identifier (NCT number): NCT02032381.

Yellow fever vaccine-associated neurologic and viscerotropic disease: a 10-year case series of the French National Reference Center for Arboviruses with clinical and immunological insights.

BACKGROUND: Immunization against the Yellow fever virus (YFV) with the 17D live-attenuated vaccine is the most effective way to prevent the disease. However, unexpected severe adverse events can occur. They consist in a neurological impairment - neurological disease (YEL-AND), a YF-like illness - viscerotropic disease (YEL-AVD) or anaphylaxis. In this article, we describe the epidemiology, clinical and biological features of YEL-AND and YEL-AVD cases reported to the French National Reference Center for Arboviruses (NRCA) in the past 10 years. METHODS: We conducted a national, retrospective study using the database of the NRCA from June 2012 to June 2022. All patients whose biological samples were sent to the NRCA for detection of YFV by serology and/or RT-qPCR for a suspected vaccine-associated adverse event were included. We collected data by reading medical records and conducted complementary neuro-immunological analysis, followed by a search for autoimmunity against type-1-interferon when samples were available at the NRCA. RESULTS: There were 10 cases of YEL-AND and 2 cases of YEL-AVD reported to the NRCA in the past 10 years, which represented an overall incidence of 0.6 for 100 000 doses. A total of 6/12 cases were previously healthy patients (50%, mean age 31 years), and 4/12 cases had cardiovascular co-morbidities (42%, mean age 56 years). The majority of YEL-AND had a favourable outcome at 6 months of follow up. One YEL-AVD patient passed. In secondary analyses, we evidenced a significant blood cerebrospinal fluid (CSF) barrier dysfunction, without intrathecal synthesis of immunoglobulin and without argument for a neuron damage. We further detected a significant rate of anti-type-1alpha interferon antibodies in 3/10 tested patients (2 YEL-AND and 1 YEL-AVD). CONCLUSION: YEL-AND and YEL-AVD are rare events that can underlie defect in the innate immunity of apparently healthy or mild co-morbid subjects. Outcome was generally favourable in the YEL-AND cases of our series, but still life-threatening or even fatal in the YEL-AVD cases.

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.

De novo complex X chromosome rearrangement unmasking maternally inherited CSF2RA deletion in a girl with pulmonary alveolar proteinosis.

We report on a 3-year-old girl with a de novo complex X chromosome rearrangement associated with congenital pulmonary alveolar proteinosis (PAP) and short stature. Array comparative genome hybridization and FISH analyses contributed to characterize the complex rearrangement consisting of a 7.37 Mb terminal deletion of Xp22.33p22.2, a 17.3 Mb interstitial inverted duplication of Xp22.2p21.3, and a 10.14 Mb duplication of Xq27.3q28. PCR analysis of microsatellite markers supported a paternal origin of the X chromosome rearrangement. A pre-meiotic two-step mechanism may explain the occurrence of this complex X rearrangement: an inverted duplication deletion event on Xp, and duplication of the Xq27.3qter region through a telomere capture event stabilizing the broken chromosome Xp end. The girl has also inherited from her healthy mother an X chromosome with a colony stimulating factor 2 receptor, alpha (CSF2RA) gene deletion. Consistent with the recessive mode of inheritance, the de novo paternal Xp22.33p22.2 deletion combined to the maternally inherited CSF2RA gene deletion led to homozygous deletion of CSF2RA and PAP diagnosis in the girl. The Xp deletion encompasses the pseudoautosomal region 1 (PAR1) which contains genes that escape X inactivation. Short stature homeobox (SHOX) haploinsufficiency explains growth retardation. Absence of other symptoms in relation to the X deletion/amplification is most probably due to skewed X inactivation. Finally, inherited deletions may unmask rare pathogenic genomic rearrangement and contribute to clinical phenotypes by a recessive mode of gene action.

Exercise-induced bronchoconstriction in school-age children born extremely preterm.

BACKGROUND: School children born preterm often show airway hyperresponsiveness to methacholine or histamine. Less attention has been paid to their airway response to exercise, an important point because of the role of exercise in the child's daily life. The aim of this study was to describe the characteristics of, and potential determinants to, the airway response to exercise in children born extremely preterm. METHODS: Forty-two nonasthmatic nonatopic children born before 32 wk gestation were compared with 27 healthy nonasthmatic nonatopic term children at age 7. Spirometry and respiratory impedance were measured at baseline and repeated after a single-step 6-min treadmill exercise in a climate-controlled room. RESULTS: The preterm group showed significant broncho-constriction induced by exercise. Prematurity, but not low baseline lung function, neonatal oxygen supplementation, mechanical ventilation, chronic lung disease, or maternal smoking, was a determinant of exercise-induced bronchoconstriction. CONCLUSION: Children born extremely preterm present significant exercise-induced airway obstruction at age 7. The response has different characteristics from that occurring in asthmatics and is likely to express airway noneosinophilic inflammation.

Unattended home sleep studies for the diagnosis of obstructive sleep apnea in a population of French children.

BACKGROUND: Ambulatory exams were preferred in children during the COVID-19 pandemic. Polysomnography (PSG), the gold standard for obstructive sleep apnea (OSA) diagnosis, requires several leads and sensors to be attached to the child's body. Children are more comfortable with respiratory polygraphic (RP) recording, which needs fewer sensors. OBJECTIVE: To compare respiratory parameters obtained by home RP with those obtained by home PSG with the device installed at the child's home by a trained sleep nurse from a national health care provider. METHODS: Data from home PSGs performed in children aged 2-19 years were retrospectively included. The obstructive apnea-hypopnea index (OAHI) was computed in PSG and then in RP after removing the sleep signals. The two indexes were compared using non-parametric paired Wilcoxon rank test, Bland-Altman analysis and sensitivity-specificity analysis. RESULTS: 44 PSGs of 44 children were included with only 34 (77%) PSGs interpretable. Median (min-max) OAHI was significantly underestimated in RP than in PSG (2.2 (0-25) vs 4.0 (0.4-28), p < 0.0001), confirmed also by the Bland-Altman diagram, the magnitude of the difference being mean ± standard deviation -1.7 ± 1.7. The sensitivity and specificity of OAHI in RP to identify an OAHI ≥2/h in PSG was 0.91 for both. CONCLUSION: Unattended ambulatory RP performed at child's house and installed under carefully controlled conditions is a useful exam for diagnosing OSA in children with or without comorbidities. However, RP must be installed in a supervised environment and interpreted with caution as it tends to underestimate OSA severity.

Early exposure to farm dust in an allergic airway inflammation rabbit model: Does it affect bronchial and cough hyperresponsiveness?

INTRODUCTION: Over the past 50 years, the prevalence of allergic respiratory diseases has been increasing. The Hygiene hypothesis explains this progression by the decrease in the bio-diversity of early microbial exposure. This study aims to evaluate the effect of early-life farm exposure on airway hyperresponsiveness and cough hypersensitivity in an allergic airway inflammation rabbit model. METHOD: A specific environment was applied to pregnant rabbits and their offspring until six weeks after birth. Rabbits were housed in a pathogen-free zone for the control group and a calf barn for the farm group. At the end of the specific environmental exposure, both groups were then housed in a conventional zone and then sensitized to ovalbumin. Ten days after sensitization, the rabbit pups received ovalbumin aerosols to provoke airway inflammation. Sensitization to ovalbumin was assessed by specific IgE assay. Cough sensitivity was assessed by mechanical stimulation of the trachea, and bronchial reactivity was assessed by methacholine challenge. The farm environment was characterized by endotoxin measurement. RESULTS: A total of 38 rabbit pups were included (18 in the farm group). Endotoxin levels in the farm environment varied from 30 to 1854 EU.m-3. There was no significant difference in specific IgE values to ovalbumin (p = 0.826) between the two groups. The mechanical threshold to elicit a cough did not differ between the two groups (p = 0.492). There was no difference in the number of cough (p = 0.270) or the intensity of ventilatory responses (p = 0.735). After adjusting for age and weight, there was no difference in respiratory resistance before and after methacholine challenge. CONCLUSION: Early exposure to the calf barn did not affect cough sensitivity or bronchial reactivity in ovalbumin-sensitized rabbits. These results suggest that not all farm environments protect against asthma and atopy. Continuous exposure to several sources of microbial diversity is probably needed.

Pulse transit time as a diagnostic test for OSA in children with Down syndrome.

STUDY OBJECTIVES: Children with Down syndrome (DS) are at risk of obstructive sleep apnea (OSA), but the access to sleep lab polysomnography (PSG) is limited. Simplified techniques are needed, such as polygraphy coupled with pulse transit time (PTT-PG) that detects respiratory events and the total autonomic arousals index (PTTAI). Our objective was to assess the ability of PTT-PG compared with PSG to diagnose OSA in children with DS. METHODS: In this prospective multicenter study, patients with DS underwent a full-night PSG coupled with PTT. Sleep questionnaires (Sleep Disturbance Scale for Children and Pediatric Sleep Questionnaire) were filled by parents. PSG and PTT-PG results were compared to test their sensibility and specificity to diagnose OSA. RESULTS: A total of 53 patients with DS were included; their median age was 9.3 years. An obstructive apnea-hypopnea index (OAHI) by PSG > 1 event/h was found in 36 (68%) patients, OAHI was > 1 and < 5 events/h in 18 patients (34%), ≥ 5 and < 10 events/h in 11 patients (21%), and ≥ 10 events/h in 7 patients (13%). OAHI was larger on PSG than on PTT-PG (P = .0005). For OSA diagnosis, the sensitivity was excellent for OAHI by PTT-PG if the added total PTTAI was > 1 event/h (1.0) and the specificity was high for the Pediatric Sleep Questionnaire (0.88) and OAHI > 1 event/h on PTT-PG (1.0). CONCLUSIONS: More than two-thirds of children with DS referred for screening by a genetics specialist had OSA diagnosed by PSG. With its excellent sensitivity and specificity, PTT-PG could be a good and simplified alternative to PSG to diagnose OSA in children with DS. CITATION: Ioan I, Weick D, Sevin F, et al. Pulse transit time as a diagnostic test for OSA in children with Down syndrome. J Clin Sleep Med. 2022;18(1):119-128.

Neurocognitive evaluation of children with down syndrome and obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) treatment has been shown to improve cardiac behavioral and cognitive functions in typically developing children. Early OSAS diagnosis in children with Down syndrome (DS) would be important to prevent its complications, especially cognitive ones, but remains overlooked. The main objective of our study was to assess the cognitive function of children with DS, with and without OSAS. The second objective was to determine the impact of the therapeutic intervention on the cognitive function of children with OSAS. This study included 41 children with DS who underwent polysomnography for OSAS diagnosis and a cognitive evaluation. They were aged between 3.4 and 17.3 years and 24 (59%) were boys. Their median OAHI was 2.6 (0-31)/h of sleep, 30 (73%) were diagnosed with OSAS (15 had mild OSAS, and 15 had moderate/severe OSAS). Some scores of the Raven's colored progressive matrices were negatively correlated with the respiratory arousal index, OAHI tended to be positively correlated with Reiss behavioral problems. 24 (59%) patients received a treatment. Even if we were unable to demonstrate this formally due that only 16 children (39%) accepted a follow-up visit, some displayed improvement in their neuropsychological scores, especially those with moderate/severe OSAS after treatment. Children with DS have low intellectual abilities and more risk of developing OSAS compared to the general population, which may lead to further neurocognitive impairment. Early screening and management are important in this population to prevent any further neurocognitive delay in their development.