The role of sleep laboratory polygraphy in the evaluation of obstructive sleep apnea syndrome in Robin infants.

OBJECTIVE/BACKGROUND: Currently, obstructive sleep apnea syndrome (OSAS) management in Robin sequence (RS) infants has not been standardized. Sleep laboratory polysomnography (PSG) is the gold standard for OSAS diagnosis, however, access is restricted. This study aimed to compare the respiratory indexes measured in a sleep laboratory using PSG as well as a possible alternative, polygraphy (PG). PATIENTS/METHODS: This retrospective study was conducted between 2015 and 2017 in a tertiary hospital. PSG performed in RS infants in the sleep laboratory was analysed by a single reviewer. After sleep data removal, anonymized raw data were analysed to obtain only PG data. Respiratory indexes were compared for (i) PSG and PG and (ii) patients with or without OSAS clinical signs. RESULTS: Among the 20 RS (median [IQR] age: 43 [25-114] days at evaluation), 70% of the patients had OSAS clinical signs but all of them had severe OSAS. The median mixed obstructive apnea hypopnea index was not significantly different between PSG and PG (27/h [18-38] versus 26/h [18-56], p = 0.43). The median obstructive apnea index was higher with no significant difference between PG and PSG (19/h [15-31] versus 7/h [4-25], p = 0.05). The median obstructive hypopnea index was significantly lower on PG than on PSG (2/h [0-3] versus 8/h [8-19], p = 0.01). No difference on PSG or PG was observed for patients with and without clinical signs of OSAS. CONCLUSION: Although PSG remains the gold standard for OSA evaluation, a PG seems to be a useful alternative to measure OSA in RS infants because of their OSAS severity. This evaluation should be recommended in all RS infants, even in the absence of OSAS clinical signs. CLINICAL TRIAL REGISTRATION: Not applicable.

Neonatal low respiratory tract chlamydia trachomatis infection: Diagnostic and treatment management.

Maternal infection during pregnancy by Chlamydia trachomatis (Chlamydia t.) can result in neonatal interstitial lung disease. It remains difficult for physicians to establish this diagnosis and to select the best treatment, as there is no recommendation. In these two cases of neonatal low respiratory tract Chlamydia t. infection, we proposed successfully a diagnosis method based on Chlamydia t. determination by PCR, on any type of sampling, but more specifically on urinary and pharyngeal specimens; and a management based on oral antibiotic therapy, Josamycin 50mg/kg/day during 14 days which is commonly well accepted and not invasive.

Impact of prone positioning in infants with Pierre Robin sequence: a polysomnography study.

OBJECTIVE/BACKGROUND: Obstructive sleep apnea syndrome (OSA) is frequent in Pierre Robin sequence (PRS) infants. Prone positioning (PP) is commonly recommended but has never been studied by polysomnography (PSG). This study aimed to evaluate the impact of the PP on sleep and breathing outcomes measured by PSG. PATIENTS/METHODS: Retrospective study conducted between 2015 and 2017 in a tertiary hospital. A PSG with pulse oximetry and transcutaneous carbon dioxide was performed in PRS infants in the supine position (SP) and the PP. Sleep and breathing outcome measures were compared between SP and PP. RESULTS: Among the 18 PRS (mean ± SD age: 44 ± 26 days at evaluation), 11 had clinical manifestations of OSA. All had severe OSA diagnosed on PSG. In the PP, infants had a significantly higher sleep efficiency (median [IQR]: 83% [69-90]) than in the SP (70% [55-77], p = 0.04). During REM, there was a trend towards lower OAHI in the PP (50/h [28-82] versus 61/h [40-103], p = 0.05). For 13, the PP was the best sleep position (72%), and for four the SP was the best sleep position (22%; p < 0.01). The PP was sufficient alone to decrease OSA index <10 events/hour in three infants. CONCLUSION: Positioning infants in the PP led to an improvement of sleep quality and an incomplete correction of OSAS in the vast majority of PRS infants. A nocturnal sleep recording seems to be indicated systematically in the early evaluation of these young patients to choose the best therapeutic option for OSAS. CLINICAL TRIAL REGISTRATION: Not applicable.

Children and adolescents with cystic fibrosis display moderate bone microarchitecture abnormalities: data from high-resolution peripheral quantitative computed tomography.

We investigated whether bone microstructure assessed by high-resolution peripheral quantitative tomography (HR-pQCT) could be altered in children and teenagers with cystic fibrosis (CF). In comparison to their healthy counterparts, bone microstructure was mildly affected at the tibial level only. INTRODUCTION: Cystic fibrosis-related bone disease (CFBD) may alter bone health, ultimately predisposing patients to bone fractures. Our aim was to assess bone microstructure using high-resolution peripheral quantitative tomography (HR-pQCT) in a cohort of children and teenagers with CF in comparison to age-, puberty-, and gender-matched healthy volunteers (HVs). METHODS: In this single-center, prospective, cross-sectional study, we evaluated the HR-pQCT bone parameters of CF patients and compared them to those of the healthy volunteers. RESULTS: At a median age of 15.4 [range, 10.5-17.9] years, 37 CF patients (21 boys) with 91% [range, 46-138%] median forced expiratory volume in 1 s were included. At the ultradistal tibia, CF patients had a smaller bone cross-sectional area (579 [range, 399-1087] mm2) than HVs (655 [range, 445-981] mm2) (p = 0.027), related to a decreased trabecular area, without any significant differences for height. No other differences were found (trabecular number, separation, thickness, or distribution) at the radial or tibial levels. Bone structure was different in patients receiving ursodeoxycholic acid and those bearing two F508del mutations. CONCLUSION: In our cohort of children and teenagers with good nutritional and lung function status, bone microstructure evaluated with HR-pQCT was not severely affected. Minimal microstructure abnormalities observed at the tibial level may be related to the cystic fibrosis transmembrane conductance regulator defect alone; the long-term consequences of such impairment will require further evaluation.

[Disseminated actinomycosis treated with clindamycin]. / Actinomycose disséminée traitée par clindamycine.

Actinomycosis is a rare bacterial disease caused by Actinomyces spp., an anaerobic bacteria from the oropharynx, digestive, and female genital tracts. Initial clinical presentation often mimics malignancy, which can lead to a delay in diagnosis. Cervico-facial, genitourinary, digestive, and respiratory features are the most frequent. Few cases are reported in children and risk factors are not well known in this population. We report on the case of an 8-year-old boy with disseminated actinomycosis with cervico-facial, pulmonary, and bone involvement caused by Actinomyces israelii. The infiltrative appearance initially suggested malignancy and the patient was started on chemotherapy for presumed histiocytosis. Evaluation of subsequent tissue samples demonstrated the presence of filamentous structures consistent with fungal or filamentous bacterial infection. Prolonged culture yielded the correct diagnosis. The patient had a severe allergic reaction to piperacillin/tazobactam and was therefore transitioned to clindamycin to complete a 9-month course. This treatment, which has not been reported in children, led to a favorable clinical, biological, and radiological response, with a good clinical tolerance.

[Insights into cystic fibrosis-related bone disease]. / Maladie osseuse liée à la mucoviscidose : mise au point.

With the increasing life expectancy of patients with cystic fibrosis (CF), prevalence of late complications such as CF-related bone disease (CFBD) has increased. It was initially described in 24% of the adult population with CF and has also been reported in the pediatric population. CFBD is multifactorial and progresses in different steps. Both decreased bone formation and increased bone resorption (in different amounts) are observed. CFBD is likely primitive (directly related to the CFTR defect itself), but is also worsened by acquired secondary factors such as lung infections, chronic inflammation, denutrition, vitamin deficiency, and decreased physical activity. CFBD may be clinically apparent (i.e., mainly vertebral and costal fractures), or clinically asymptomatic (therefore corresponding to abnormalities in bone density and architecture). CFBD management mainly aims to prevent the occurrence of fractures. Prevention and regular monitoring of bone disease as early as 8 years of age is of the utmost importance, as is the control of possible secondary deleterious CFBD factors. New radiological tools, such as high-resolution peripheral quantitative computed tomography, allow an accurate evaluation of cortical and trabecular bone micro-architecture in addition to compartmental density; as such, they will likely improve the assessment of the bone fracture threat in CF patients in the near future.

[Early lung disease in infants with cystic fibrosis. Diagnostic tools and possible therapeutic pathways]. / Atteinte respiratoire précoce chez les nourrissons atteints de mucoviscidose. Outils de diagnostic et pistes pour la prise en charge.

The lungs of infants with cystic fibrosis (CF) have been considered to be normal at birth. However, recent data indicates that this is unlikely to be true in most cases. Animal CF-models developed in the early 2000s have shown that constitutional airway narrowing may be present at birth, and is associated with both functional and structural abnormalities. Longitudinal birth cohort studies have shown that 25 % of CF infants followed in specialized centers, while being asymptomatic, showed decreased lung function at 3months of age. Air trapping was present in 68 % and bronchiectasis in 28 % of patients at the same age. The presence of neutrophil elastase in the bronchoalveolar lavage at 3months of age tripled the risk of bronchiectasis at the age of 3years. Currently available tools such as infant pulmonary function tests (both the jacket and multiple breath washout) as well as high-resolution volume controlled chest-computed tomography or functional magnetic resonance imaging will facilitate early intervention trials in the very near future. The role of such tools for the routine follow-up of patients, and the ability of early therapeutic interventions to alter the natural history of CF-lung disease should soon be established.

[Therapeutic advances in cystic fibrosis in 2014]. / La mucoviscidose en 2014 : actualités thérapeutiques.

Twenty-five years after the cystic fibrosis (CF) gene identification, this discovery actually begins to benefit to patients. Increasing our knowledge on CFTR biology, as well as technical progress made in order to screen for new drugs have made therapeutic strategies move an important step forward. It is likely that in the forthcoming years, the panel of molecules available for CF patients will be larger, with new activators and potentiators. The disease by itself may consequently change in its natural history. CF is an example of the so-called personalized medicine, aiming to fit treatment according to patient's genetic background. Ongoing clinical trials may enlarge the actually limited eligible number of CF patients for new drugs such as ivacaftor. Beyond this exciting and promising new therapeutic approach, one may not push symptomatic treatments on the side. Improvements have been made for inhaled antibiotics administration, aiming to simplify patient's life; clinical trials using new molecules able to liquefy mucus or with anti-inflammatory properties are actually underway. One important next step in the care for CF will be to design and conduct early intervention trials in CF infants. Newborn screening program have been widely implanted around the word, and cohorts studies have shown that both functional and structural abnormalities occurred very early, making the therapeutic window of opportunity tight.

[New therapeutic developments in cystic fibrosis]. / Nouvelles thérapeutiques ciblant le canal chlorure dans la mucoviscidose.

Since the discovery of chloride secretion by the Cystic Fibrosis Transport regulator CFTR in 1983, and CFTR gene in 1989, knowledge about CFTR synthesis, maturation, intracellular transfer and function has dramatically expanded. These discoveries have led to the distribution of CF mutations into 6 classes with different pathophysiological mechanisms. In this article we will explore the state of art on CFTR synthesis and its chloride secretion function. We will then explore the consequences of the 6 classes of mutations on CFTR protein function and we will describe the new therapeutic developments aiming at correcting these defects.

[Early lung disease in cystic fibrosis]. / Atteinte respiratoire précoce dans la mucoviscidose.

Recent data has shown that lung inflammation and infection subvene very early in very young infants with Cystic Fibrosis (CF). This leads to impaired lung function and structural damage, even in asymptomatic children. In the CF-pig model constitutional airway narrowing is present at birth, and is associated with defective mucus migration, and impaired bacterial clearance. At the age of 3 months, 25% of screened CF infants show decreased lung function. Air trapping is also present in 68% and bronchiectasis in 28% of patients. At the same age, the presence of neutrophil elastase in the bronchoalveolar lavage is an ominous sign since it triples the risk of bronchiectasis at the age of 3 years. Since only very few drug therapies have been validated in the preschool children, adapted clinical trials are warranted in this age group. Early interventions may have a huge impact on the natural history of CF, on the condition of not interfering with normal lung growth.

[Children exposed to multidrug-resistant tuberculosis: How should we manage? Analysis of 46 child contacts and review of the literature]. / Enfants au contact d'individus atteints d'une tuberculose multi-résistante : quelles stratégies adopter ? Analyse de 46 enfants contacts et revue de la littérature.

INTRODUCTION: Tuberculosis-related morbidity and mortality remain important. Emergence and diffusion of multidrug-resistance tuberculosis (MDR-TB) is a global public health concern. Cases of MDR-TB in children are a sentinel event indicating the spread of a mycobacterial strain within a community. Latent TB precedes MDR-TB and screening and follow-up of contact individuals are key points of TB infection control. METHODS: We performed the case-investigation of 20 adult cases of MDR-TB managed in our institution. RESULTS: Forty-six pediatric contact individuals were identified. A high proportion of these children were lost to follow-up (80% at 12 months), showing that monitoring this reservoir population with migrant history is challenging. Five (11%) children presented a secondary infection: one child was diagnosed with active TB infection (positive tuberculin skin test associated with abnormalities on chest computer tomography [CT] scan). Four children were diagnosed with latent TB infection (isolated positive tuberculin skin test with normal CT scan). Two of these children received a treatment adjusted to the strain of the index case. DISCUSSION: In the setting of emerging MDR-TB, tuberculin skin test may be likely replaced by specific interferon-gamma release assays (IGRA), independent of prior BCG vaccination. In addition, chest CT scan is preferred to chest X-ray to detect TB lesions. The management of latent TB infection is controversial: immediate treatment with second-line anti-TB drugs adapted to the index case strain or, consistently with WHO guidelines, a simple follow-up with subsequent treatment in case of active TB.

[Allgrove syndrome]. / Syndrome d'Allgrove.

BACKGROUND: Allgrove syndrome or "Triple A syndrome" involves adrenal insufficiency as a result of resistance to adrenocorticotropic hormone (ACTH), achalasia and alacrima, often associated with neurological signs. Herein, we report a new case of this rare genetic disease, which is of interest because of its dermatological mode of discovery. PATIENTS AND METHODS: A 4-year-old child, born to parents related by first-degree consanguinity, presented oral hyperpigmentation and diffused acquired melanoderma, as well as long-standing dry-eye syndrome. Laboratory tests confirmed low adrenal insufficiency. The combination of alacrima and adrenal insufficiency prompted screening for Allgrove syndrome, which was confirmed by genetic analysis showing homozygous c.1331+1G>A mutation within intron 14 of the gene encoding for ALADIN protein. Both parents were heterozygous for the same mutation. Two years later, the onset of vomiting raised concerns about achalasia, which was confirmed by oesophageal manometry. The child received symptomatic treatment consisting of supplementary hydrocortisone and oesophageal dilatation. DISCUSSION: The present case serves as a reminder that Allgrove syndrome may be diagnosed by dermatologists. Therapy is cross-disciplinary, being based upon medical treatment for adrenal insufficiency with prescription of artificial tears in the event of alacrima. Achalasia is treated by oesophageal dilatation or by surgery.

Lung clearance index: evidence for use in clinical trials in cystic fibrosis.

The ECFS-CTN Standardisation Committee has undertaken this review of lung clearance index as part of the group's work on evaluation of clinical endpoints with regard to their use in multicentre clinical trials in CF. The aims were 1) to review the literature on reliability, validity and responsiveness of LCI in patients with CF, 2) to gain consensus of the group on feasibility of LCI and 3) to gain consensus on answers to key questions regarding the promotion of LCI to surrogate endpoint status. It was concluded that LCI has an attractive feasibility and clinimetric properties profile and is particularly indicated for multicentre trials in young children with CF and patients with early or mild CF lung disease. This is the first article to collate the literature in this manner and support the use of LCI in clinical trials in CF.

[Staphylococcus aureus broncho-pulmonary infections]. / Infections broncho-pulmonaires à Staphylococcus aureus.

Staphylococcus aureus accounts for 2-5% of the etiologies of community-acquired pneumonia. These infections occur mainly in elderly patients with comorbidity, after a respiratory viral infection. S. aureus could also be responsible for necrotizing pneumonia, which occurs in young subjects, also after flu. Necrotizing pneumonia are associated with the production of a particular staphylococcal toxin called Panton-Valentine leukocidin, responsible for pulmonary focal necrosis, occurrence haemoptysis, leucopenia, and death. In Europe, these strains are still predominantly sensitive to anti-staphylococcal penicillin, which must be used at high dosage intravenously in combination with an antibiotic that reduces toxin production such as clindamycin, and intravenous immunoglobulin in severe cases. The mortality rate is estimated at 50%. In addition, S. aureus is one of the pathogens involved in early respiratory infections in cystic fibrosis patients, in whom methicillin resistance plays an important prognostic role. However, the involvement of S. aureus in COPD exacerbations is rare. Finally, S. aureus represents 20 to 30% of cases of hospital-acquired pneumonia, including ventilator-associated pneumonia. In these cases, methicillin-resistance is common and requires the use of glycopeptides or linezolid. The place of new anti-staphylococcal antibiotics such as new generation cephalosporins or tigecyclin remains to be defined.

[Late onset Ondine syndrome: literature review on a case report]. / Syndrome d'Ondine à révélation tardive : revue de la littérature à propos d'un cas.

Ondine syndrome is the central congenital hypoventilation syndrome (CCHS) caused by the mutation of the PHOX2B gene. In late onset cases, the symptomatology often appears after an acute event (infection, general anesthesia, drug intake), increasing hypoventilation. We report a case of late onset Ondine curse in a 9-year-old girl. The diagnosis was made based on a hypercapnic coma complicating a respiratory infection caused by Mycoplasma pneumoniae and was confirmed by genetic testing. In the patient's history we found symptoms that had not been noted (e.g., enuresis, morning headache, adynamia), attesting to chronic hypoventilation. Through this observation, we review the literature on CCHS, notably late onset cases, which are rare and insidious, emphasizing the pre-existing hypoventilation symptoms in this child. This case underlines the need for all practitioners not to trivialize these symptoms so as to decrease the current delay in diagnosis for late onset CCHS and to introduce optimal care as soon as possible.

[Intrafamilial transmission of Staphylococcus aureus Panton-Valentine leukocidin responsible for two cases of neonatal necrotizing pneumonia]. / Transmission intrafamiliale de Staphylococcus aureus sécréteur de toxine leucocidine Panton-Valentine responsable de deux cas de pneumopathies nécrosantes néonatales.

Necrotizing Staphylococcus aureus Panton-Valentine leukocidin (SA-PLV+) accounts for less than 1% of community-acquired lung diseases in children and young adults. Neonatal cases are exceptional. We report the observations of two newborn female twins, who were not breastfed, presenting a necrotizing lung disease due to the same strain of SA-PVL+ despite nasal decolonization measures taken. These two cases are informative and bring to light (1) the possibility of severe SA-PVL+ lung infections in young infants and (2) their strictly intrafamilial mode of transmission for which eradication measures were ineffective.

[Screening and management of glucose metabolism disorders in cystic fibrosis patients. Practices survey in 4 French reference centers]. / Dépistage et prise en charge des troubles du métabolisme glucidique chez les patients atteints de mucoviscidose. Etude de pratiques au sein du réseau EMERA.

OBJECTIVE: Glucose metabolism disorders are a new point of interest in cystic fibrosis (CF) management. Cystic fibrosis-related diabetes mellitus (CFRD) increases alteration of pulmonary function as well as patients' morbidity and mortality. In France, CF patients are exclusively followed up in reference centers. We conducted a practices survey on screening and diagnosis of glucose metabolism disorders at 4 French CF centers. The objective of this study was to assess adherence to practice guidelines developed in 2002 at these centers. METHODS: This study was conducted in 2 sessions: 60 medical records were randomly selected in 2005 and in 2007 for patients aged over 10 years followed up at 4 CF centers. A questionnaire survey was completed for each patient with questions on CFRD screening, diagnosis, monitoring and treatment. Our guidelines recommend random blood glucose (RBG) at each standard biological test, annual glycosylated haemoglobin and an oral glucose tolerance test (OGTT) at 10, 15 and 18 years of age, then every 2 or 3 years. RESULTS: An annual RBG was performed in 82% of patients in 2005 and 91.5% in 2007. HbA1c screening was performed annually for 77% of patients in the 1st session and for 90% of patients for the 2nd session (p<0.10). Adherence to OGTT guidelines was better for adults than children: 96% had an OGTT during the 3 years of the first session and 79% during the second session, while fewer than 50% of children had their OGTT at 15 and 18 years of age. Taking the OGTT at 10 years of age could not be assessed because no patients were 10 years old during the study period. Screening for neurological complications of CFRD was assessed in the majority of diabetic patients, while half or less than half had annual fundus oculi or microalbuminuria dosage. DISCUSSION: There was an improvement in screening for CFRD and glucose metabolism disorders between 2005 and 2007, even though practices could still be improved. This shows that clinical guidelines can be implemented and followed. However, screening and management criteria for glucose metabolism disorders must be consensus-based with higher evidence in order to limit the variability of practices and prevent CFRD-related complications.