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Resume Le depistage neonatal (DNN) de la mucoviscidose, grâce a une prise en charge multidisciplinaire tres precoce des nourrissons, est optimal en termes de pronostic pour les patients. Depuis 20 ans, il a connu une expansion internationale spectaculaire. Les performances du DNN national francais realise depuis 2002 sont en accord avec les standards europeens pour la valeur predictive positive (0,31 pour un minimum de 0,30) et la specificite (0,95 pour un minimum de 0,95) ; nous soulignons le nombre tres faible de cas non conclus, un pourcentage tres eleve de test de la sueur realises (95,5 %) et d’identification des mutations (96,6 %), un ratio de cas de mucoviscidose par rapport aux cas de diagnostic incertain de 6,3:1, ainsi qu’une strategie efficace pour reperer les faux negatifs. Une nouvelle organisation du DNN francais vient de se mettre en place, il est capital de maintenir l’efficacite du processus, du nouveau-ne en maternite jusqu’au diagnostic dans des centres de reference ou de competences de la mucoviscidose avec un recueil exhaustif des donnees et leur validation. Par ailleurs, une proposition de changement d’algorithme introduisant le dosage du polypeptide d’activation pancreatique est soumise aux nouvelles instances du DNN. L’annonce d’un diagnostic positif reste difficile et peu standardisee, si bien qu’une plateforme de simulation est en cours de mise en place. Nous detaillons ici les bonnes pratiques et les difficultes de realisation du test de la sueur, avec les seuils de chlorures recemment redefinis, ainsi que les modalites du conseil genetique.

In cystic fibrosis (CF), cystic fibrosis transmembrane regulator (CFTR) dysfunction leads to digestive disorders that promote intestinal inflammation and dysbiosis enhancing gastrointestinal symptoms. In pancreatic insufficiency CF patients, both intestinal inflammation and dysbiosis, are associated with an increase in the fecal calprotectin (FC) level. However, associations between the FC level, gastrointestinal symptoms, and quality of life (QoL) remain poorly studied. We aimed to assess such associations in pancreatic insufficiency CF children. The FC level was measured in pancreatic insufficiency CF children&rsquo, s stool samples. Children and their parents completed two questionnaires: The Gastrointestinal Symptoms Scales 3.0-PedsQLTM and the Quality of Life Pediatric Inventory 4.0-PedsQLTM. Lower scores indicated worse symptomatology or QoL. Thirty-seven CF children were included. A FC level above 250 &micro, g/g was associated with worse gastrointestinal symptoms and QoL scores. The FC level was inversely correlated with several gastrointestinal scores assessed by children (i.e., Total, &ldquo, Heart Burn Reflux&rdquo, &ldquo, Nausea and Vomiting&rdquo, and &ldquo, Gas and Bloating&rdquo, ). Several QoL scores were correlated with gastrointestinal scores. The FC level was weakly associated with clinical parameters. Some gastrointestinal and QoL scores were related to disease severity associated parameters. In CF, the FC level, biomarker previously related to intestinal inflammation and dysbiosis, was associated with worse digestive symptoms and QoL scores.

Background Whereas Burkholderia infections are recognized to impair prognosis in cystic fibrosis (CF) patients, there is no recommendation to date for early eradication therapy. The aim of our study was to analyse the current management of initial colonisations with Burkholderia cepacia complex (BCC) or B. gladioli in French CF Centres and its impact on bacterial clearance and clinical outcome. Methods We performed a retrospective review of the primary colonisations (PC), defined as newly positive sputum cultures, observed between 2010 and 2018 in five CF Centres. Treatment regimens, microbiological and clinical data were collected. Results Seventeen patients (14 with BCC, and 3 with B. gladioli) were included. Eradication therapy, using heterogeneous combinations of intravenous, oral or nebulised antibiotics, was attempted in 11 patients. Six out of the 11 treated patients, and 4 out of the 6 untreated patients cleared the bacterium. Though not statistically significant, higher forced expiratory volume in 1 second and forced vital capacity at PC and consistency of treatment with in vitro antibiotic susceptibility tended to be associated with eradication. The management of PC was shown to be heterogeneous, thus impairing the statistical power of our study. Large prospective studies are needed to define whom to treat, when, and how. Conclusions Pending these studies, we propose, due to possible spontaneous clearance, to check the presence of Burkholderia 1 month after PC before starting antibiotics, at least in the milder cases, and to evaluate a combination of intravenous beta-lactam + oral or intravenous fluoroquinolone + inhaled aminoglycoside.

Whereas Burkholderia infections are recognized to impair prognosis in cystic fibrosis (CF) patients, there is no recommendation to date for early eradication therapy. The aim of our study was to analyse the current management of initial colonisations with Burkholderia cepacia complex (BCC) or B. gladioli in French CF Centres and its impact on bacterial clearance and clinical outcome. We performed a retrospective review of the primary colonisations (PC) observed between 2010 and 2018 in five CF Centres. Treatment regimens, microbiological and clinical data were collected. Seventeen patients (14 with BCC, and 3 with B. gladioli) were included. Eradication therapy, using heterogeneous combinations of intravenous, oral or nebulised antibiotics, was attempted in 11 patients. Six out of the 11 treated patients, and 4 out of the 6 untreated patients cleared the bacterium. Though not statistically significant, higher FEV1 and FVC at PC and consistency of treatment with in vitro antibiotic susceptibility tended to be associated with eradication. Thus, the management of PC was shown to be heterogeneous, and the statistic power of our study insufficient. Large prospective studies are needed to define who to treat, when, and how. Pending these studies, we propose, due to possible spontaneous clearance, to check the presence of Burkholderia one month after PC before starting antibiotics, at least in the milder cases, and to evaluate a combination of IV beta-lactam + oral or IV fluoroquinolone + inhaled aminoglycoside.

Objectives: In France, chest physiotherapy for cystic fibrosis (CF) patients is partly performed by liberal physiotherapists at home or at the professional's office. The first lockdown, due to the COVID-19 pandemic, impaired the possibility to practice liberal physiotherapy. We aimed to describe, in our paediatric CF centre, the changes in physiotherapy and sport practice induced by this lockdown, and to correlate it with respiratory symptoms and pulmonary function evolution. Methods: During the lockdown, 68 CF patients >6 years old and their parents answered a questionnaire on time spent in physiotherapy, with or without a liberal professional, and sport practice before and during lockdown. Respiratory symptoms and FEV1 were collected at the venues before and after the lockdown. Results: This study showed a clear reduction of time spent with a liberal physiotherapist from 73 min/week before lockdown to 30 min/week during lockdown. Time of physiotherapy practised alone or with parents increased from 2 min/week to 26 min/week. Thus, the overall physiotherapy time per week was only slightly reduced from 90 min/week before lockdown to 80 min/week during lockdown. Time spent in sport practice was not significantly decreased on average (233 min/week before lockdown vs 225 min/week during lockdown). The standard deviation of sport practice evolution was large (–8 min ± 225 min), reflecting a wide variation of sport practice changes from one patient to another. No deterioration in respiratory symptoms nor FEV1 was observed. Conclusions: During the lockdown in France, we noted that our patients drastically decreased their time spent with a liberal physiotherapist, without enough counterbalance with auto-drainage or sport pratice increase. Nevertheless, their respiratory status was not impaired, suggesting some other confounding factors, such as prevention from viral infection, time to rest or improvement of other treatment observance.

International audience; Pseudomonas aeruginosa and Staphylococcus aureus toothbrush contamination in cystic fibrosis (CF) is unknown. This pilot study aimed to determine their prevalence and the potential involvement of toothbrushes in pulmonary infection. Methods. Toothbrush bacteriological analysis for children aged 8–18 years was conducted on 27 CF patients, 15 healthy siblings, and 15 healthy children from the general population. Results : S. aureus was detected on 22% of the patients’ toothbrushes, and 13% of healthy children's toothbrushes and P. aeruginosa on 15% of patients’ toothbrushes and 0–13% of healthy children's toothbrushes. There was no statistical correlation between pulmonary colonization and toothbrush contamination. P. aeruginosa genotyping showed two identical clones on the patients’ toothbrushes and in their sputum, and between one patient's sputum and his sibling's toothbrush. Conclusion : S. aureus and P. aeruginosa can colonize CF patients’ toothbrushes. The impact on pulmonary colonization remains unknown. Toothbrush decontamination methods need to consider these bacteria in CF patients.

In advanced cirrhosis, decreased lung transfer for carbon monoxide (TLCO) and increased alveolar-arterial oxygen tension difference (PA-aO2≥15 mmHg while breathing ambient air) are frequently detected. Pulmonary membrane diffusion capacity for CO (DmCO) and pulmonary capillary blood volume (Vcap) can be derived from the simultaneous measurement of TLCO and lung transfer for nitric oxide (TLNO). Measurements of single-breath TLNO and TLCO were performed in 49 cirrhotic patients with advanced liver cirrhosis and in 35 healthy controls to derive Vcap, DmCO, and TLNO:TLCO ratio. Twenty-five patients had increased PA-aO2, of whom 11 had hepatopulmonary syndrome (HPS). Compared with controls, non-HPS patients with normal PA-aO2had a significant ∼10% decrease in TLCO, DmCO, and Vcap but similar TLNO:TLCO ratios. Compared with non-HPS patients with normal PA-aO2, non-HPS patients with increased PA-aO2had lower Vcap and higher TLNO:TLCO ratio but similar DmCO. HPS patients had lower Vcap and higher TLNO:TLCO ratios than both subgroups of non-HPS patients. In cirrhotic patients, TLNO:TLCO ratios correlated positively, and TLCO (percentage of the predicted value) and Vcap (percentage of the predicted value) correlated negatively with PA-aO2( r2= 0.25, P = 0.0003, r2= 0.48, P < 0.0001 and r2= 0.57, P < 0.0001, respectively). We concluded that, in cirrhotic patients, lower TLCO and increased PA-aO2are associated with lower Vcap. In addition, high TLNO:TLCO ratios in patients with increased PA-aO2suggest a decreased thickness of the capillary blood layer in these patients.

In cirrhotic patients, alveolar nitric oxide (NO) concentration is increased. This may be secondary to increased output of NO produced by the alveoli (V'(A,NO)) and/or to decreased lung transfer factor of NO. In advanced liver cirrhosis, NO produced by the alveoli may play a role in abnormalities of pulmonary haemodynamics and gas exchanges. In cirrhotic patients, we aimed to measure V'(A,NO) and to compare V'(A,NO) with pulmonary haemodynamics and gas exchange parameters. Measurements were performed in 22 healthy controls and in 29 cirrhotic patients, of whom eight had hepatopulmonary syndrome. Exhaled NO concentrations were measured at multiple expiratory flow rates to derive alveolar NO concentration. V'(A,NO) was the product of alveolar NO concentration by single breath lung transfer factor for NO. V'(A,NO) was increased in patients (median (range) 260 (177-341) nL x min(-1)) compared with controls (79 (60-90), p0.0001). Alveolar-arterial oxygen tension difference failed to correlate with V'(A,NO). However, cardiac index correlated positively and systemic vascular resistance correlated negatively with V'(A,NO) (r = 0.56, p = 0.001 and r = -0.52, p = 0.004, respectively). In cirrhotic patients, NO was produced in excess by the alveolar compartment of the lungs. Alveolar NO production was associated with hyperdynamic circulatory syndrome but not with arterial oxygenation impairment.

Pseudomonas aeruginosa or Staphylococcus aureus toothbrushes contamination in cystic fibrosis (CF) patients is unknown. The objective of this pilot study was to determine prevalence of those germs on toothbrushes of CF and healthy children, and define if toothbrushes may be involved in pulmonary infection.

Objectives: Oxidative stress is associated with the condition of cystic fibrosis (CF), but no guidelines exist for its assessment or treatment. Our aim was to evaluate a test that measures the blood antioxidant capability in CF children. Methods: This antioxidant capability was assessed by the Kit Radicaux Libres (KRL) test in 44 CF children (24 boys). We recorded also anthropometric measures, pulmonary function, CF severity scores, and plasma nutritional and inflammatory parameters (proteins, vitamins, erythrocyte fatty acids, and micronutrients). We performed univariate and multivariate analyses with linear regression models. Results: The mean age at the first KRL assessment was 12.2 ± 3.8 years. Factors that correlated with decreased antioxidant capacity were mostly related to the severity of pulmonary disease [ forced expiratory volume at 1 second (FEV1), acute exacerbation, and congestion. In multivariate analysis, the correlation between Brasfield score and erythrocyte antioxidant potential remained significant (β = - 0.611, p < 0.001). Among nutritional factors, the ω6/ω3 ratio was significantly correlated to erythrocyte antioxidant potential (β = - 1.213, p = 0.01). Conclusion: The blood antioxidant capability, measured by the KRL test, appears to be an interesting biomarker to evaluate oxidative stress in CF. This study suggests that the ω6/ω3 ratio should be regarded as a nutritional marker in antioxidant management in CF children.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a common complication among patients with CF that produces significant respiratory morbidity. Standard therapy for ABPA includes systemic corticosteroids for a prolonged period of time with potentially severe side effects and use of antifungal agents. Omalizumab is a humanized monoclonal antibody directed against IgE that prevents its binding to receptors on effector cells. It has been shown to be effective in improving asthma control in patients with a strong allergic component. Recently, sporadic reports of omalizumab use against ABPA have been reported. Methods: We present our long term experience of omalizumab in three children with CF and ABPA who were steroid dependent. Results: Five (3.4%) out of 148 children and adolescents with CF followed in our Unit over a seven year period, developed ABPA (75% females, mean age at start of therapy 14.3 years). Omalizumab was given to 3 of them (2 males, mean age 17.1 years, mean FEV1 35%). All three were already experiencing significant side effects from chronic steroid therapy (invasive aspergillosis, diabetes mellitus, depression, relapse of ABPA and severe osteoporosis) and received regular antifugal therapy. Omalizumab treatment was given for a period of 12−18 months. Oral steroids were gradually stopped. Omalizumab resulted in significant improvement of respiratory symptoms and lung function (mean FEV1 52%, p: 0.01). Conclusion: According to our results in a small number of patients, omalizumab has a significant potential as a strategy to control ABPA in steroid dependent patients. However, more studies are needed to confirm these findings.

Introduction: Physical activity is beneficial for cystic fibrosis (CF) patients. This induces to stimulate their habitual physical activity (HAP) from childhood. Thus, for HAP evaluation, we need methods that are simple, reliable, objective and well accepted by the patients. Accelerometry is one of the possibilities for evaluating HAP. We studied its feasibility, acceptability and correlation with other HAP evaluation methods in a population of paediatric CF patients. Methods: 34 CF patients, aged between 9 and 18 years, were proposed to wear accelerometers. The reasons for not wearing the accelerometer were evaluated. A correlation was measured between the data produced by accelerometry, the answers to HAES and Veerschuur questionnaires, and evaluations by medical staff. Results: – 14 children out of 34 (41%) did not wear the accelerometer, 5 of them simply refused it; 6 children (17%) have worn the accelerometer less than 5 days. Finally, 14 recordings were interpretable, i.e. 41% of the 34 children to whom the measurement was proposed. – The answers to the questionnaires appeared not to be correlated to the accelerometry data. But there was a good correlation of 62.1% (p = 0.017) between the data obtained by accelerometry and the medical evaluation. Conclusion: The feasibility of the HAP evaluation by accelerometry in a pediatric CF population is only around 40%. Therefore it cannot be used in every-day clinical practice. However, in clinical trials, the objective evaluation by accelerometry should be preferred because of the discrepancies observed with answers to standardized questionnaires on physical activity.