•TC is simple to measure, non-invasive and reproducible in extremely fragile infants.•The rib cage is underdeveloped in infants with SMA 1 from the first weeks of life.•TC/HC ratio appears to reflect ...disease progression, regardless of age.•There is a threshold value of TC/HC ratio (0.85) below which infants with SMA 1 die within weeks.
Since respiratory insufficiency is the first cause of morbidity and mortality in spinal muscular atrophy type 1 (SMA 1), specific respiratory outcome measures are needed to evaluate changes and assess innovative therapies. In this study, thoracic circumference (TC) was used as a proxy for chest growth and an indirect measurement of respiratory function. The anthropometric parameters including TC and head-circumference (HC) were evaluated from birth to 13 months in 19 infants with SMA 1 and 124 control infants. TC was significantly decreased in the SMA 1 group from the first weeks of life. The control group TC/HC ratio = 1 (± 0.04), and was not found to be associated with age. By contrast, it decreased with time in all infants with SMA 1 and those with a TC/HC ratio <0.85 died within 3 months. TC is a simple measurement that provided an index of chest growth and was used as evidence of early, progressive respiratory failure and under-development of the rib-cage in SMA 1. The TC/HC ratio decreased in all patients over time, reflecting the progression of the disease suggesting that TC/HC ratio could be a new measure for SMA 1 for measuring disease severity and prognosis.
Airway clearance (ACT) and lung volume recruitment (LVR) techniques are used to manage bronchial secretions, increase cough efficiency and lung/chest wall recruitment, to prevent and treat ...respiratory tract infections. The aim of the study was to review the prescription of ACT/LVR techniques for home use in children in France.
All the centers of the national pediatric noninvasive ventilation (NIV) network were invited to fill in an anonymous questionnaire for every child aged ≤20 years who started a treatment with an ACT/LVR device between 2022 and 2023. The devices comprised mechanical in-exsufflation (MI-E), intermittent positive pressure breathing (IPPB), intrapulmonary percussive ventilation (IPV), and/or invasive mechanical ventilation (IMV)/NIV for ACT/LVR.
One hundred and thirty-nine patients were included by 13 centers. IPPB was started in 83 (60 %) patients, MI-E in 43 (31 %) and IPV in 30 (22 %). No patient used IMV/NIV for ACT/LVR. The devices were prescribed mainly by pediatric pulmonologists (103, 74 %). Mean age at initiation was 8.9 ± 5.6 (0.4–18.5) years old. The ACT/LVR devices were prescribed mainly in patients with neuromuscular disorders (n = 66, 47 %) and neurodisability (n = 37, 27 %). The main initiation criteria were cough assistance (81 %) and airway clearance (60 %) for MI-E, thoracic mobilization (63 %) and vital capacity (47 %) for IPPB, and airway clearance (73 %) and repeated respiratory exacerbations (57 %) for IPV. The parents were the main carers performing the treatment at home.
IPPB was the most prescribed technique. Diseases and initiation criteria are heterogeneous, underlining the need for studies validating the indications and settings of these techniques.
•The use of home ACT/LVR devices in children has not been assessed in France.•One hundred and thirty-nine patients were started on ACT/LVR within a 1-year period.•The devices were prescribed mainly for neuromuscular disorders and neurodisability.•Intermittent positive pressure breathing was the most common device used.•The parents were the main carers performing the treatment at home.
Introduction
The recent development of disease‐modifying treatments in spinal muscular atrophy (SMA) type 1 shifted these patients' management from palliative to proactive. The aim of this study was ...to assess patients' nocturnal gas exchanges before noninvasive ventilation (NIV) initiation and their clinical evolution to determine if capnia is a good criterion to decide when to introduce respiratory support.
Patients and Methods
This multicentric retrospective study reports the respiratory management and evolution of 17 SMA type 1 children (10 females) for whom treatment with Nusinersen was initiated between 2016 and 2018.
Results
Median interquartile range—IQR age at diagnosis and at first Nusinersen injection was of 4 3;8 and 4 3;9 months, respectively. Patients were followed during 38 24;44 months. Thirteen (76%) patients were started on NIV at a median IQR age of 12 9;18 months. Repeated hospitalizations and intensive care unit admissions were needed for 11 of them. Blood gas and nocturnal gas exchange recordings performed before NIV initiation were always normal. 9/13 X‐ray performed before NIV showed atelectasis and/or acute lower respiratory tract infections. There was a significant decrease in the total number of hospital admissions between the first and second year of treatment (p = 0.04).
Conclusion
This study shows that patients do not present with nocturnal hypoventilation before respiratory decompensations and NIV initiation, and suggests that a delay in NIV initiation might result in respiratory complications. There is a need for disease‐centered guidelines for the respiratory management of these patients, including NIV indications.
To describe the characteristics of children treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in France.
Cross-sectional national survey.
Paediatric ...CPAP/NIV teams of 28 tertiary university hospitals in France.
Children aged <20 years treated with CPAP/NIV since at least 3 months on June 1st, 2019.
An anonymous questionnaire was filled in for every patient.
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.
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.
•1447 children were treated with long term CPAP or NIV in France on June 2019.•The number of children treated with CPAP or NIV in France has increased 14-fold between 2000 and 2019.•The most frequent disorders were upper airway obstruction (46%) and neuromuscular disease (28%).•45% of the children were treated with CPAP and 55% with NIV.
The introduction of triple combination therapy with elexacaftor–tezacaftor–ivacaftor (ETI), a highly effective CFTR modulator drug, has revolutionised the prognosis for people with cystic fibrosis ...carrying at least one p.Phe508del (F508del) allele.1 ETI restores chloride transport through the F508del-CFTR channel, which is associated with significant improvement in lung function and sweat chloride concentration in patients older than 6 years.2 A placebo-controlled study showed that ETI improves lung clearance, bodyweight, and sweat chloride concentration after 6 months of treatment in children with cystic fibrosis aged 2–6 years, with an overall acceptable safety profile.3 In France, children with cystic fibrosis (age ≥2 years) have had access to ETI since December, 2023.4 In this context, 197 preschool-age children (ie, aged 2–5 years) were enrolled from 34 paediatric cystic fibrosis referral centres across France in the real-world study MODUL-CF (NCT04301856) and underwent an evaluation at baseline and at follow-up visits at 1 month and 3 months. In an in-vivo murine depression model, ivacaftor resulted in improvement in locomotor activity, similar to fluoxetine, and a non-controlled study showed a decreased prevalence of depression in patients treated with ivacaftor.11 In 14 randomised controlled trials in individuals older than 6 years, mainly in adolescents and adults, no alarming adverse events have been observed.6 Ramsey and colleagues6 reported a similar exposure-adjusted rate of depression-related adverse events in a pooled group of patients aged 6 years and older treated with ETI (3·32 per 100 person-years; 1711 patients) compared with the placebo group (3·24 per 100 person-years; 1369 patients), as well as for suicidal ideation (0·23 per 100 person-years in the ETI group vs 0·28 per 100 person-years in the placebo group) and suicide attempt (0·08 per 100 person-years vs 0·14 per 100 person-years).6 We searched the literature for depression or depression-related events in phase 4 or real-world post-marketing studies of ETI that used validated instruments to evaluate depression symptoms, such as the Patient Health Questionnaire, and we did not identify any studies reporting an increase in depression events with ETI, apart from in specific subgroups (the search strategy for literature review and results are in the appendix pp 2–3, 5, 7–9).6 Patients who undergo successful treatment for cystic fibrosis might have difficulties adapting to their new life paradigm, in terms of the shift from a status of patient to that of asymptomatic healthy individual. In addition to this shift, some behavioural issues might also be discovered that were not previously recognised or not considered while they had symptomatic cystic fibrosis. ...the patients who are aware of the potential adverse events of ETI might experience a so-called nocebo effect. ...our observations, the first to our knowledge in preschool-age children, raise the possibility of an iatrogenic effect.
Introduction
When children require supplemental oxygen due to acute hypoxemic respiratory distress (AHRD), manual control of the oxygen flow is often difficult and time‐consuming, and carries the ...risk of unrecognized hypoxia and hyperoxia. To date, no automatic oxygen titration system has been developed and evaluated in spontaneously breathing children.
Methods
Children between 1 month and 15 years of age receiving supplemental oxygen due to AHRD were recruited within 24 hours following the onset of the O2 administration in a French University Department of Paediatrics. Patients were randomized to receive either automated oxygen administration using the FreeO2 device, or conventional manual oxygen administration over a maximum period of 6 hours. Stratification was performed to classify the patients into two age groups: 1 month to 2 years of age and 2 to 15 years of age. The primary outcome was % time spent within the SpO2 target range (92%‐98%).
Results
60 patients (30 infants, 30 children) were randomized and 55 could be analyzed for the primary outcome (28 automated, 27 manual). The automated O2 delivery using the FreeO2 device significantly increased the time spent within the predefined SpO2 range (94.6% ± 6% vs 76.3% ± 22%, difference 95% confidence interval {CI} 18.4 10.1; 26.7) with less time spent with hypoxemia (1% ± 1.1% vs 15.1% ± 21.8%, difference 95% CI −14.4 −22.2; −6.7). This difference was greater among (2‐15 years of age) children, compared to (1 month‐2 years of age) infants.
Conclusions
The present randomized controlled pilot study indicates that the tested automated closed‐loop O2 titration technology was safe and yielded improved oxygen parameters among spontaneously breathing children. Based on our pilot data, a full randomized controlled trial will be required to verify the potential clinical benefits.
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.
•In 2019, 387 children were treated at home with noninvasive ventilation in France.•Most children had spinal muscular atrophy or congenital myopathy/dystrophy.•Ninety-four percent of children were ...treated with noninvasive ventilation.•Treatment was initiated electively for 85% of children.•Mean objective noninvasive ventilation use was 8.0 ± 3.1 h/night.
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.
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