Analyses of 1,236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype-phenotype correlations.

BACKGROUND: Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterized by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes. METHODS: Genetic variants and clinical findings (age, sex, body mass index, laterality defects, FEV1) were collected from 19 countries using the ERN LUNG International PCD Registry. Genetic data were evaluated according to ACMG guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV1. RESULTS: 1236 individuals carried 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%; 47-100%) and laterality defects (mean 42%; 28-69%) varied widely among the countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV1 z-score (-1.66). In the group of individuals with CCNO (-3.26), CCDC39 (-2.49), and CCDC40 (-2.96) variants, FEV1 z-scores were significantly lower, while the group of DNAH11 (-0.83) and ODAD1 (-0.85) variant individuals had significantly milder FEV1 z-score reductions compared to the whole PCD cohort. CONCLUSION: This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of genetic epidemiology of PCD and provides prediction of diagnostic and phenotypic features such as the course of lung function.

Neonatal diagnosis of primary ciliary dyskinesia in a high consanguinity population: a single tertiary center experience.

Though PCD usually presents after birth in term neonates, diagnosing PCD during the neonatal and infancy stages is uncommon, particularly in children who do not exhibit laterality defects. We report our recent experience with the diagnosis of PCD in the neonatal and early infantile period in a highly consanguine population. This was achieved by implementing a novel genetic-based diagnostic approach based on direct testing for recognized regional genetic variants. We conducted a retrospective analysis of children diagnosed with PCD at Soroka University Medical Center during the neonatal or early infantile period between 2020 and 2023. We included children under 3 months of age who had a genetic confirmation of PCD, as evidenced by the presence of two pathogenic variants in recognized genes. Genetic testing targeted regional genetic variants in previously identified PCD genes. Eight patients were included. The median age at diagnosis was 12.5 days. Three (38%) were born prematurely < 34 weeks gestational age. All patients were presented with respiratory distress and hypoxemia after birth. The median duration of oxygen support was 23 days, and upper lobe atelectasis was present in five patients (63%). Congenital cardiac malformation was present in four patients. Organ laterality defects were present in four patients. Genetic mutations identified were in the DNAAF5, DNAL1, DNAAF3, and DNAH1 genes.     Conclusion: Neonatal diagnosis of PCD is uncommon, especially in atypical presentations such as children without laterality defects or preterms. Focusing on a genetic diagnosis of the local tribal pathogenic variants promotes a potential cost-efficient test leading to earlier diagnosis. There is a need for a standardized protocol for earlier diagnosis of PCD in high-consanguinity areas. What is Known: • Primary ciliary dyskinesia (PCD) typically presents after birth in term neonates. • Diagnosing PCD during neonatal and infancy stages is challenging, particularly in children without laterality defects. What is New: • A novel genetic-based diagnostic approach was implemented on the neonatal population in a highly consanguine community, focusing on direct testing for regional genetic variants, leading to early and rapid diagnosis of PCD.

Foreign body aspiration score (FOBAS)-a prospectively validated algorithm for the management and prediction of foreign body aspiration in children.

Foreign body aspiration (FBA) is a common cause of pediatric morbidity, but a standardized protocol to guide decision-making about bronchoscopy is lacking. We aimed to validate a new Foreign body aspiration score (FOBAS) for the pediatric emergency department (ED). Patients aged 0-18 years referred to the ED for suspected FBA were prospectively enrolled. FOBAS was calculated according to clinical features of a choking episode, sudden cough, exposure to nuts, absence of fever and rhinitis, stridor, and unilateral auscultatory and radiological findings. FBA risk was evaluated based on the total score (low, 1-3; moderate, 4-6; high, 7-10). Low-risk children were discharged from the ED and followed clinically. Moderate-risk children were hospitalized and evaluated by a pediatric pulmonologist, and high-risk children were referred directly for therapeutic bronchoscopy. Among the 100 enrolled children (59% males; median age 20 [interquartile range 11-39] months), a foreign body was diagnosed in 1/49 (2%), 14/41 (34.1%), and 9/10 (90%) with low, moderate, and high FOBAS, respectively (P < .001). Logistic regression indicated a higher risk for FBA with higher scores. The odds ratio for each additional point was 2.75 (95% confidence interval 1.78-4.24), and FOBAS showed a high predictive value for FBA (area under the curve 0.89). FOBAS implementation significantly reduced the rate of negative bronchoscopies, from 67.4% annually during 2016-2019 to 50% in 2020 (P = .042). CONCLUSION: FOBAS reliably predicts FBA in cases of suspected FBA and improves management and in-hospital decision-making. WHAT IS KNOWN: • Foreign body aspiration is a major cause of pediatric morbidity and mortality. • Currently, there is no unified protocol for children referred to the emergency department for suspected FBA, therefore, a well-defined algorithm is needed to improve the decision-making process. WHAT IS NEW: • The pediatric Foreign body aspiration score (FOBAS) is a new, prospectively validated clinical score that shows high sensitivity and specificity for the presence of FBA in children. • FOBAS reduces unnecessary admissions and invasive procedures and leads to better clinical outcomes.

Pediatric thermal epiglottitis: insights from a tertiary center experience.

Thermal epiglottitis, a non-infectious cause of epiglottitis, is a rare entity that shares some clinical features with infectious epiglottitis. This study presents 16 years of experience in diagnosing and managing thermal epiglottitis. A retrospective descriptive study in a tertiary center in southern Israel included confirmed cases of thermal epiglottitis in children (0-18 years) between 2004 and 2020 by endoscopy. Of approximately 600,000 pediatric ER admissions between 2004 and 2020, seven children were diagnosed by endoscopy with thermal epiglottitis (mean age 24 months, 71% males). Clinical presentation included stridor, respiratory distress, and drooling. Four children had fever and elevated inflammatory markers at presentation and were treated with systemic antibiotics. All were treated with systemic steroids. The median length of stay in the PICU was five days, and four patients required intubations. All fully recovered without experiencing any sequelae.  Conclusion: Thermal epiglottitis stands as a potential contributor to acute upper airway obstruction. Although it's rarity, it should be discussed in any child with acute upper airway obstruction. It is essential to inquire directly about the accidental intake of hot beverages, particularly in cases lacking fever or elevated inflammatory markers. What is Known: • Thermal epiglottitis is a rare, non-infectious condition sharing clinical features with infectious epiglottitis. • Common presentations include stridor, respiratory distress, and drooling. What is New: • Thermal epiglottitis is a potential contributor to acute upper airway obstruction, urging consideration even in the absence of fever or elevated markers. • Direct inquiry about hot beverage intake for diagnosis is essential for diagnosis.

Evaluation of Foreign body aspiration score (FOBAS) in children- A retrospective cohort study.

Foreign Body Aspiration (FBA) is a common medical emergency among young children, but the evaluation and management of a suspected FBA case can vary across physicians and centers. We aimed to identify which clinical, laboratory, and radiological findings can predict FBA in children and to evaluate a clinical score to improve FBA prediction. This is a retrospective cohort study of patients aged 0-18 years admitted to Soroka University Medical Center between 2010 and 2020 with suspected FBA. All patients underwent flexible bronchoscopy and were divided into positive and negative FBA groups. A newly developed foreign body aspiration score (FOBAS), based on medical history, physical examination, and chest X-ray findings, was evaluated for its predictability. The study included 412 children (median age 21 months, 56.8% females), of whom 154 (37.4%) had FBA and 258 (62.6%) did not. Multivariate regression analysis showed exposure to nuts/seeds, unilateral wheezing or decreased breath sounds, stridor, and suggestive findings on chest X-ray were significant risk factors for FBA (OR [95%CI] -1.994[1.290-3.082], 1.487[1.206-1.832], 1.883 [1.011-3.509] and 2.386[1.917-2.970], respectively). However, a choking episode, acute cough, and absence of fever and rhinorrhea did not predict FBA. FOBAS showed an increased risk of FBA for each additional point of the score, with an odds ratio of 1.572 (95% CI-1.389-1.799).  Conclusion: FOBAS is a good predictor for the presence of FBA in children. Once prospectively validated, FOBAS could aid in decision-making at the emergency department, enabling more standardized care, reducing unnecessary procedures, and leading to better clinical outcomes. What is Known: • The evaluation and management of a child with suspected foreign body aspiration (FBA) vary across physicians and centers, without a consensus regarding the indications and criteria for performing bronchoscopy. • Flexible bronchoscopy is the standard procedure for the diagnosis and sometimes treatment of FBA in children, but it may hold potential complications. What is New: • We propose a newly developed foreign body aspiration score (FOBAS), based on medical history, physical examination, and chest X-ray findings, for the prediction of FBA in children at the emergency department. • The FOBAS is a good predictor of FBA in children. The score enables more standardized care and may reduce unnecessary procedures.

Comparison of chest X-ray interpretation by pediatric pulmonologists, pediatric radiologists, and pediatric residents in children with suspected foreign body aspiration-a retrospective cohort study.

Chest X-ray (CXR) is an important tool in the assessment of children with suspected foreign body aspiration (FBA), although it can falsely be interpreted as normal in one-third of the cases. The aim of this study is to evaluate the positive predictive value of CXR in children hospitalized with suspected FBA, when interpreted by three disciplines: pediatric pulmonology, pediatric radiology, and pediatric residents. This is a retrospective study that included children aged 0-18 years, admitted with suspected FBA, between 2009 and 2020 in one tertiary center. All patients underwent CXR and a flexible/rigid bronchoscopy for the definitive diagnosis of FBA, up to 1 week apart. Two physicians from each discipline interpreted the CXR, independently. Intra-raters' and inter-raters' agreements were assessed. Sensitivity, specificity, and area under the curve (AUC) were calculated for each discipline. Four hundred seventy-three children were included in the study, 175 (37%) with FBA and 298 (63%) without FBA on flexible/rigid bronchoscopy. The most common radiological findings, as interpreted by a pediatric pulmonologist, were unilateral hyperinflation (47%), radiopaque FB (37.6%), lobar atelectasis (10.3%), unilateral hyperinflation with atelectasis (3.4%), and lobar consolidation (1.7%). Intra-raters' agreement ranged from 0.744 (p < 0.001) among pediatric pulmonologists to 0.326 (p < 0.001) among pediatric radiologists. AUC for predicting FBA based on a CXR was 0.81, 0.77, and 0.7 when interpreted by pediatric pulmonologists, pediatric residents, and radiologists, respectively (p < 0.001). CONCLUSIONS: CXR has a high positive predictive value and independently predicts FBA in children; however, normal CXR should not rule out FBA. Predictability is variable among different disciplines. WHAT IS KNOWN: • Chest X-ray is an important tool in the assessment of children with suspected foreign body aspiration (FBA). • Chest X-ray can be interpreted as normal in one-third of the cases. WHAT IS NEW: • Chest X-ray independently predicts FBA in children, with a high positive predictive value. • The ability of chest x-ray to predict FBA in children differs between pediatric residents, pediatric radiologists, and pediatric pulmonologists.

From rigid to flexible bronchoscopy: a tertiary center experience in removal of inhaled foreign bodies in children.

Rigid bronchoscopy is the procedure of choice for removal of inhaled foreign bodies. In this retrospective study, we assessed the safety and efficacy of flexible bronchoscopy use in the removal of inhaled foreign bodies in children. One hundred eighty-two patients (median age of 24 months, 58% males) underwent an interventional bronchoscopy for the removal of inhaled foreign body between 2009 and 2019, 40 (22%) by flexible, and 142 (78%) by rigid bronchoscopy. 88.73% of rigid and 95% of flexible bronchoscopies were successful in foreign bodies removal (p value = 0.24). Complication rate was higher among rigid bronchoscopy (9.2% vs. 0%, p = 0.047). From 2017 onwards, following the implementation of flexible bronchoscopy for foreign bodies removal, 64 procedures were performed, 33 (51.6%) flexible, and 31 (48.4%) rigid. Procedure length was shorter via flexible bronchoscopy (42 vs 58 min, p = 0.016). Length of hospital stay was similar.Conclusion: In our hands, flexible bronchoscopy is an efficient and safe method for removal of inhaled foreign bodies in children, with shorter procedure time and minimal complication rate. Flexible bronchoscopy could be considered as the procedure of choice for removal of inhaled foreign bodies in children, by an experienced multidisciplinary team. What is Known: • Rigid bronchoscopy is currently the gold standard for removal of inhaled foreign bodies in children. • Rigid bronchoscopy has a relatively high complication rate compared to flexible bronchoscopy. What is New: • Flexible bronchoscopy is a short, safe, and efficient procedure to remove inhaled foreign bodies in children, compared to rigid bronchoscopy. • Flexible bronchoscopy could be proposed as the procedure of choice for removal of inhaled foreign bodies in children, if an experienced operator is available.

Massive Pneumomediastinum and Subcutaneous Emphysema Secondary to Foreign Body Aspiration.

BACKGROUND: Spontaneous pneumomediastinum (SPM) occurs in cases of mediastinal leaks that are not caused by trauma, mechanical ventilation, or other surgical procedures. In most cases, in the pediatric population a trigger can be identified, most commonly asthma. SPM caused by foreign body aspiration is not a common entity. It is usually a benign condition that generally resolves without severe sequela, but in some cases, severe morbidity and mortality have been documented. Treatment is usually conservative and includes rest, analgesics, and treatment of any underlying pathologies. CASE REPORT: We report a case of a 19-month-old boy who presented to the emergency department with acute facial swelling and wheezing with no history of foreign body aspiration. This misleading presentation led the medical staff in the emergency department to initially treat the patient for anaphylaxis. The diagnosis was made only after imaging modalities demonstrated SPM with a suspected foreign body in the right main stem bronchus. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Providers should consider SPM from an aspirated foreign body in young children with respiratory distress and acute facial swelling, especially when crepitus is present. © 2021 Elsevier Inc.

DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes.

Primary ciliary dyskinesia (PCD) is a recessively inherited disease that leads to chronic respiratory disorders owing to impaired mucociliary clearance. Conventional transmission electron microscopy (TEM) is a diagnostic standard to identify ultrastructural defects in respiratory cilia but is not useful in approximately 30% of PCD cases, which have normal ciliary ultrastructure. DNAH11 mutations are a common cause of PCD with normal ciliary ultrastructure and hyperkinetic ciliary beating, but its pathophysiology remains poorly understood. We therefore characterized DNAH11 in human respiratory cilia by immunofluorescence microscopy (IFM) in the context of PCD. We used whole-exome and targeted next-generation sequence analysis as well as Sanger sequencing to identify and confirm eight novel loss-of-function DNAH11 mutations. We designed and validated a monoclonal antibody specific to DNAH11 and performed high-resolution IFM of both control and PCD-affected human respiratory cells, as well as samples from green fluorescent protein (GFP)-left-right dynein mice, to determine the ciliary localization of DNAH11. IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations. GFP-left-right dynein mice confirmed proximal DNAH11 localization in tracheal cilia. DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). TEM tomography detected a partial reduction of ODAs in DNAH11-deficient cilia. DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography.

Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1.

In primary ciliary dyskinesia (PCD), genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility. The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Although it has long been suspected that mutations in DNAL1 encoding the ODA light chain1 might cause PCD such mutations were not found. We demonstrate here that a homozygous point mutation in this gene is associated with PCD with absent or markedly shortened ODA. The mutation (NM_031427.3: c.449A>G; p.Asn150Ser) changes the Asn at position150, which is critical for the proper tight turn between the ß strand and the α helix of the leucine-rich repeat in the hydrophobic face that connects to the dynein heavy chain. The mutation reduces the stability of the axonemal dynein light chain 1 and damages its interactions with dynein heavy chain and with tubulin. This study adds another important component to understanding the types of mutations that cause PCD and provides clinical information regarding a specific mutation in a gene not yet known to be associated with PCD.

Stepwise genetic approach for the diagnosis of primary ciliary dyskinesia in highly consanguineous populations.

BACKGROUND: The American Thoracic Society guidelines for the diagnosis of primary ciliary dyskinesia (PCD) consider the presence of a bi-allelic pathogenic variant confirmatory for the diagnosis of PCD, with genetic testing recommended when other confirmatory diagnostic tests are less accessible. We present our experience with genetic testing as first line with a proposed algorithm for high consanguinity populations. METHODS: Patients with a suspected diagnosis of PCD underwent genetic testing according to a diagnostic algorithm composed of three steps: (1) patients with a previously known causative familial/Bedouin tribal pathogenic variant completed direct testing for a single variant; (2) if the initial test was negative or there was no known pathogenic variant, a PCD genetic panel was completed; (3) if the panel was negative, whole exome sequencing (WES) was completed. RESULTS: Since the implementation of the protocol, diagnosis was confirmed by genetic testing in 21 patients. The majority of them were of Bedouin origin (81%) and had a positive history of consanguinity (65%). Nine patients (43%) had a sibling with a confirmed diagnosis. Most patients (15/21, 71%) were diagnosed by direct pathogenic variant testing and the remainder by genetic panel (19%) and WES (10%). Disease-causing variants were found in nine genes, with DNAL1 (24%) and DNAAF3, DNAAF5, ZMYND10 (14% each) as the most prevalent ones. CONCLUSIONS: In highly consanguineous regions, a stepwise genetic testing approach is recommended. This approach may be particularly useful in areas where the ability to obtain confirmatory diagnostic tests through other modalities is less accessible.

Eradication of Nontuberculous Mycobacteria in People with Cystic Fibrosis Treated with Elexacaftor/Tezacaftor/Ivacaftor: A Multicenter Cohort Study.

BACKGROUND: The prevalence of nontuberculous mycobacteria (NTM) infections is rising in people with cystic fibrosis (pwCF). NTM infection, especially infection with Mycobacterium abscessus complex (MABC), is commonly associated with severe lung deterioration. The current treatment modalities, including multiple intravenous antibiotics, frequently fail to achieve airway eradication. Although treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to modulate the lung microbiome, data regarding its role in eradicating NTM in pwCF is lacking. Our aim was to evaluate the impact of ETI on the rate of NTM eradication in pwCF. METHODS: This retrospective multicenter cohort study included pwCF from five CF centers in Israel. PwCF aged older than 6 who had at least one positive NTM airway culture in the past two years and were treated with ETI for at least one year were included. The annual NTM and bacterial isolations, pulmonary function tests, and body mass index were analyzed before and after ETI treatment. RESULTS: Fifteen pwCF were included (median age 20.9 years, 73.3% females, 80% pancreatic insufficient). In nine patients (66%) NTM isolations were eradicated following treatment with ETI. Seven of them had MABC. The median time between the first NTM isolation and treatment with ETI was 2.71 years (0.27-10.35 years). Eradication of NTM was associated with improved pulmonary function tests (p<0.05). CONCLUSIONS: For the first time, we report successful eradication of NTM, including MABC, following treatment with ETI in pwCF. Additional studies are needed to assess whether treatment with ETI can result in the long-term eradication of NTM.

Maternal and fetal outcomes in multiparous women with Cystic Fibrosis.

BACKGROUND: Quality of life and survival in Cystic Fibrosis (CF) have improved dramatically, making family planning a feasible option. Maternal and perinatal outcomes in women with CF (wwCF) are similar to those seen in the general population. However, the effect of undergoing multiple pregnancies is unknown. METHODS: A multinational-multicenter retrospective cohort study. Data was obtained from 18 centers worldwide, anonymously, on wwCF 18-45 years old, including disease severity and outcome, as well as obstetric and newborn complications. Data were analyzed, within each individual patient to compare the outcomes of an initial pregnancy (1st or 2nd) with a multigravid pregnancy (≥3) as well as secondary analysis of grouped data to identify risk factors for disease progression or adverse neonatal outcomes. Three time periods were assessed - before, during, and after pregnancy. RESULTS: The study population included 141 wwCF of whom 41 (29%) had ≥3 pregnancies, "multiparous". Data were collected on 246 pregnancies, between 1973 and 2020, 69 (28%) were multiparous. A greater decline in ppFEV1 was seen in multiparous women, primarily in pancreatic insufficient (PI) wwCF and those with two severe (class I-III) mutations. Multigravid pregnancies were shorter, especially in wwCF over 30 years old, who had high rates of prematurity and newborn complications. There was no effect on pulmonary exacerbations or disease-related complications. CONCLUSIONS: Multiple pregnancies in wwCF are associated with accelerated respiratory deterioration and higher rates of preterm births. Therefore, strict follow-up by a multidisciplinary CF and obstetric team is needed in women who desire to carry multiple pregnancies.

Flexible bronchoscopy in pediatric patients with Down syndrome: A case-control study of the indications, findings, and complications.

BACKGROUND: Children with Down syndrome (DS) often undergo flexible bronchoscopies (FB) due to common respiratory symptoms. OBJECTIVE: To examine the indications, findings, and complications of FB in pediatric DS patients. METHODS: A retrospective case-control study on FB performed in DS pediatric patients between 2004 and 2021 in a tertiary center. DS patients were matched to controls (1:3) based on age, gender, and ethnicity. Data collected included demographics, comorbidities, indications, findings, and complications. RESULTS: Fifty DS patients (median age 1.36 years, 56% males) and 150 controls (median age 1.27 years, 56% males), were included. Evaluation for obstructive sleep apnea and oxygen dependence were more common indications among DS (38% vs. 8%, 22% vs. 4%, p < 0.01, respectively). Normal bronchoscopy was less frequent in DS compared with controls (8% vs. 28%, p = 0.01). Soft palate incompetence and tracheal bronchus were more frequent in DS (12% vs. 3.3%, p = 0.024, 8% vs. 0.7%, p = 0.02, respectively). Complications were more frequent in DS (22% vs. 9.3%, incidence rate ratio [IRR] 2.36, p = 0.028). In DS, cardiac anomalies (IRR 3.96, p < 0.01), pulmonary hypertension (IRR 3.76, p = 0.006), and pediatric intensive care unit (PICU) hospitalization before the procedure (IRR 4.2, p < 0.001) were associated with higher complication rates. In a multivariate regression model, history of cardiac disease and PICU hospitalization before the procedure, but not DS, were independent risk factors for complications with an IRR of 4 and 3.1, respectively (p = 0.006, p = 0.05). CONCLUSION: DS pediatric patients undergoing FB are a unique population with specific indications and findings. DS pediatric patients with cardiac anomalies and pulmonary hypertension are at the highest risk for complications.

High flow nasal cannula therapy in the pediatric home setting.

BACKGROUND: High-flow nasal cannula (HFNC) therapy may be better tolerated than traditional noninvasive ventilation (NIV) and is rapidly gaining acceptance in pediatric acute care. In Israel, HFNC is approved for domestic use. We aim to describe its indications, efficacy, parental satisfaction, and safety. METHODS: Retrospective study of children treated with home HFNC therapy in three pediatric centers. Data included demographic parameters, indication of use, weight and days of hospitalization before and after initiation. Safety, tolerability, and parental satisfaction were assessed via standardized telephone questionnaire. RESULTS: Median (interquartile range [IQR]) age of initiating home HFNC in 75 children was 8.3 (2.2, 29.6) months. Indications were obstructive sleep apnea (33; 44%), airway malacia (19; 25%), chronic lung disease (15; 20%), neuromuscular disease (4; 5%), and postextubation support (4; 5%). Weight standard deviation score rose from -2.3 pre-HFNC to -1.7 at 6.7 months post-HFNC initiation, p < 0.001. Hospital admission days during the 2 months pre- versus post-HFNC initiation were 22 (5.5, 60) and 5 (0, 14.7) respectively, p < 0.008. Median (IQR) parental satisfaction score was 5/5 (4, 5). Fifty of 60 (83%) respondents would recommend home HFNC to other families in a similar situation. There were no serious adverse events. CONCLUSION: In our population, domestic HFNC appeared safe and well tolerated for a variety of indications. Its introduction was associated with improved weight gain, fewer hospitalization days and high parental satisfaction. Further work is required to characterize groups of children most likely to benefit from HFNC, as opposed to traditional modes of NIV.