Background: Recent standards of care mention chest radiography (CR) but not chest computed tomography (CT) in routine annual follow-up of children with cystic fibrosis (CF). To minimise radiation risk, CT or CR should only be performed if they impact clinical decision making. We investigated whether in addition to a wide range of commonly used clinical parameters, chest CT and/or CR in routine follow-up of CF patients influence clinical decisions. Methods: 36 web based clinical vignettes (i.e. case simulations) were designed using clinical data from patients aged 8-18 years, randomly selected from two CF centres in The Netherlands. In a randomized cross-over design, clinicians assessed eight vignettes and suggested therapeutic/diagnostic management on two occasions, with a ten-week interval. Radiological information (CT or CR) was included at only one of the two assessments, in random order. Any differences in management could be attributed to information from CT or CR, and were compared by McNemar analysis. Results: 44 European and Australian clinicians completed a total of 143 CT vignette pairs and 167 CR vignette pairs. CT was associated with a significant increase in antifungal treatment (Risk Ratio (RR) 2.8 (1.3-6.0, p = .02)), bronchoscopies (RR 1.6 (1.1-2.5, p = .04)), mycobacterial cultures (RR 1.3 (1.0-1.5, p = .02)), and `need for hospitalization' (i.e. intravenous antibiotics and/or bronchoscopy) (RR 1.4 (1.0-1.9, p = .03)). CR led to a significant increase in inhaled antibiotics only (RR 1.3 (1.0-1.6, p = .04)). Conclusions: CT but not CR, at routine biennial follow-up was associated with several changes in treatment and/or diagnostic testing, including the need for hospitalization. (C) 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Tobramycin, maximum 2 times a year.For Amikacin we tested every month during the iv course.Results: From January 2016 till December 2018 we tested 80 CF patients who received iv Tobramycin and 9 patients who received iv Amikacin.Preliminary results show no significant clinical effect in most patients who received Tobramycin iv.We did see a mild decrease in dB SPL/Hz in EHF overall.In patients who were treated with Amikacin iv for 2-3 months because of Non-Tuberculous Mycobacteria (NTM)-infection we saw a significant decrease in dB SPL/Hz in EHF.In most cases this did not have a clinical effect; only one patient reported clinical hearing loss, two patients experienced tinnitus.Currently we are (in the process of ) analyzing all data, such as mean age, mean hearing loss (dB SPL/Hz) in EHF and the relation between hearing loss and cumulative dose of antibiotics. Conclusion:The preliminary results underscore that children treated with iv aminoglycosides are at risk for high frequency hearing loss, even without clinical signs of hearing loss.We advocate annual EHF audiometry in all children treated with iv aminoglycosides, especially amikacin.

exacerbations (PEx).New airway clearance techniques (ACTs) adapted to individual needs are still being sought to achieve the best effect of airway clearance.The primary aim of this study was to evaluate the efficacy of Simeox -a new ACT in subjects with CF who were hospitalized due to PEx.Methods: CF Patients aged 10-18 admitted to hospital and requiring intravenous (IV) antibiotic therapy due to PEx were allocated consecutively (1:1) to Simeox arm or classical CP arm (without Simeox).Patients performed spirometry and multiple breath nitrogen washout (N 2 MBW) for Lung Clearance Index (LCI) assessment on admission and prior to discharge.Results: Fourty eight CF patients were included in the study: 24 treated with Simeox and 24 using usual CP.In both groups the spirometry parameters increased significantly after IV antibiotic therapy.Significant improvement in MEF 25 was observed only in patients treated with Simeox ( p < 0.01).A similar trend was observed towards lowering LCI ratio in both.No side effect was observed for each therapy.Drainage with Simeox was not painful for any of the patients and about 80% of them did not feel any fatigue.All patients felt comfortable and >80% learned quickly the use of new ACT.Conclusion: Spirometry parameters increased significantly in CF patients treated for PEx with IV antibiotic therapy and intensive CP.Simeox may improve the drainage of the central and peripheral airways.This new ACT was safe, well-tolerated method of CP and can be considered an option in treatment of PEx.

Personalized medicine approach in cystic fibrosis (CF) is focusing on detection of cystic fibrosis transmembrane conductance regulator (CFTR) function in single patients and standardized outcomes for CFTR function in vivo. We applied Optical Sweat Rate Beta Adrenergic (OSRBA) test for measuring sweat rates in individual human sweat glands. The results were analyzed according to a multilinear regression model in non- CF, healthy carriers (HTZ), CF patients; two groups of these were tested during treatment with CFTR modulators such as lumacaftor/ivacaftor (Orkambi) or PTC 124 (Ataluren). We found that different sets of statistically significant coefficients of the multilinear regression of the volume of sweat secretory glands characterize different CFTR genotype as well as different responses to different pharmacological treatments.

Objectives: To determine if early chronic MSSA infection is correlated with poorer prognosis at the age of six years.Methods: We conducted a retrospective study in pediatric cystic fibrosis patient screened in Bordeaux CF center between 2002 and 2011, to evaluate the impact of early chronic MSSA infection at the age of one year (Y1).The primary endpoint was the severity of bronchiectasis on CT-scan at the age of six years (Y6).Other end-points included clinical status (clubbing, crackles, nutritional status), lung function tests, and serum IgG.Results: Forty patients were included.Ten patients had early chronic MSSA infection at Y1 and in 30 patients MSSA infection occurred at a later date.Early chronic Y1 MSSA infection had no impact on any clinical symptom or sign, or nutritional status, at any age.In contrast, early chronic Y1 MSSA infection (vs.after Y1) had a significant negative impact on Y6 CT-scan bronchiectasis severity (4.7 ± 0.8 vs 2.3 ± 0.4, p < 0.05) and Bhalla score (7.3 ± 1.1 vs 4.2 ± 0.6, p < 0.05).Y6 lung function was no significantly worsened by early chronic Y1 MSSA infection (FEV1: 83.7 ± 6 vs 92.8 ± 3.4, p = 0.26; FEF25-75: 67.8 ± 8.9 vs 78.2 ± 5.1, p = 0.21).Finally, the Y6 serum IgG, a marker of chronic inflammation was significantly elevated in the early chronic Y1 MSSA infection group vs. later MSSA infection group (11.3 ± 0.7 vs 8.7 ± 0.4, p < 0.05).Conclusion: Early chronic Y1 MSSA in pediatric patients with cystic fibrosis is associated with more severe lung disease at six years.From the time of screening, prophylactic and/or curative anti-Staphylococcal antibiotic treatment should be discussed.

Background: acute bronchiolitis is frequently diagnosed in infants, involves small airways. It’s often followed by recurrent wheeze. Lung Clearance Index(LCI) is a marker of VI derived from MBW test. It’s more sensible than spirometry indices to detect abnormalities inperipheral lung regions and is easy to obtain also in young children. Aims: analyze and compare MBW indices among children previously hospitalized for acute bronchiolitis (PB), age-matched healthy controls (HC) and Cystic Fibrosis (CF) children. Methods: Prospective longitudinal study including PB children hospitalized in our Emergency Department 5-6 years ago, CF with no relevant airway colonization, and HC. Anamnestic and clinical data were collected during follow-up together with LCI, indices of VI arising in the conductive (Scond) and acinar (Sacin) zones, calculated from N2-MBW. Results: 29 PB,20 CF and 15 HC were recruited. PB had higher LCI levels than HC(p<0.001), and lower than CF(p=0.038 within the 3 groups). Severe bronchiolitis(requiring intensive care) had higher LCI than the others(p=0.019). Scond was higher in PB(p=0.013) children with family history of asthma. Conclusion: Bronchiolitis could lead to impaired lung function at preschool age. LCI is an easy-to-use sensible marker of ventilation inhomogeneity, also in asymptomatic and non-chronic patients.

Objectives: To explore associations between LCI and FEV 1 , and IL8 and IL-1β in BAL fluid in closely monitored CF children at steady state conditions and during episode with increased LCI.Influence from BAL culture results on IL-8 and IL-1β was investigated.Methods: Prospective randomized study in 30 CF children.MBW, spirometry and BAL were performed at inclusion and every 3 month, the latter however only in half of the cohort when a predefined increase in LCI of >1 unit above baseline value occurred.BAL fluid from both lungs was analyzed for IL-8 and IL-1β and cultured.Results: Mean age: 10.6 (6.4-16.7)years, baseline LCI: 9.2 (6.2-13.5)and FEV 1 z-score was -0.02 (-2.04-1.32).Since IL8 and IL-1β on right and left side were highly correlated (r = 0.9 p < 0.0001) and (r = 0.6 p < 0.0019) mean values were used.LCI showed significant correlation with IL-1β (r = 0.45 p = 0.03) whereas no correlation was shown with IL8 levels (r = 0.07 p = 0.75).No correlations between FEV 1 z-score and cytokines were found.In patients randomized to additional BAL during first measurement of elevated LCI compared to baseline (mean increase: 2.4 units) there was no significant elevation of IL8 or IL-1β and no significant difference according to positive BAL cultures.Conclusions: In this study with a limited number of children with stable and mild CF, we found that LCI correlated significantly with level of IL-1β, but not with levels of IL8, and surprisingly, neither IL8 or IL-1β increased significantly at times of LCI elevation, nor were they significantly higher in culture positive BAL fluids.

BACKGROUND:Deregulated immune response fails to control biofilm-forming bacteria, as Pseudomonas aeruginosa, in the lungs of cystic fibrosis (CF) patients. HLA-G is an immune-modulatory molecule involved in respiratory diseases and infections.MATERIALS & METHODS:HLA-G mRNA and protein were analyzed in plasma and exhaled breath condensate from CF patients undergoing intravenous antibiotic treatment, CF cell line and murine model.RESULTS:Therapy normalizes HLA-G plasmatic in CF patients suggesting a systemic anti-inflammatory role while in CF airway system, higher expression of HLA-G is associated with P. aeruginosa infection. CF cell line and murine model expressed higher HLA-G molecules in the presence of P. aeruginosa.CONCLUSION:Plasmatic and lung HLA-G expression suggest a role in reducing systemic inflammation and supporting P. aeruginosa infection.

Introduction: Lung clearance index (LCI) is a very sensitive marker of early lung disease in Cystic Fibrosis (CF). In Cystic Fibrosis Screen Positive Inconclusive Diagnosis (CFSPID) and in compound heterozygotes carrying at least one mutation with indefinite clinical liability (CH), respiratory symptoms are often more mild and they might begin in adulthood. In childhood usually these patients have normal spirometric values. Aims and objectives: Compare LCI among three groups of patients: CFSPID-CH, CF and controls. We wanted to find out whether it is true that CFSPID-CH have normal LCI as healthy controls. Methods: We perform and compare Spirometry test and N2-Multiple Breath Wash Out (N2-MBW, Exhalyzer D, Ecomedix) in a group of CFSPID-CH, a group of CF and a control group. Results: 9 healthy controls (mean age: 5.4 yrs), 17 CFSPID-CH (mean age: 10.4 yrs) and 37 CF patients (mean age: 7.5 yrs) were tested. Basal FEV1 was normal in all groups and it was not statistically different between them. CF had significantly higher mean LCI than CFSPID-CH (9.68 versus 7.23; p=0.004). CFSPID-CH9s LCI was higher than healthy controls but without statistical significance. Conclusions: Our data show that CFSPID-CH have a pattern of LCI that is different from the one of CF patients and is similar to the one of healthy control. LCI could be a promising technique to study pulmonary function of CFSPID-CH and could be use in the follow-up of these patients.

INTRODUCTION Over the last decade the study of pulmonary function by multiple breath washout technique (MBW) has been widely used to detect early pulmonary changes in Cystic Fibrosis. On the contrary there are only few studies that use Lung Clearance Index (LCI) in other chronic lung diseases like asthma. Moreover data regarding bronchodilator response on LCI are contradictory. AIMS AND OBJECTIVES To find out whether LCI was able to detect any early involvement of small airways in stable asthmatic children and if was more sensitive than spirometry to detect bronchoreversibility after salbutamol administration. METHODS We performed spirometry and N2-Multiple Breath Wash Out (N2-MBW, Exhalyzer D, Ecomedix) in a group of stable asthmatic patients and in a group of healthy children. In the first group we repeated spirometry and N2-MBW after administration of 400μg of salbutamol RESULTS 12 asthmatic children (mean age: 6.0 yrs) and 9 healthy controls (mean age: 5.4 yrs) were tested. Basal FEV1 and basal LCI were no statistically different between the 2 groups. After the administration of Salbutamol the increase of FEV1 was of 5%. Among the asthmatic group LCI after the administration of salbutamol showed a statistically significant decrease (p=0.009) CONCLUSIONS Our data showed that basal LCI was not different between the two groups. In asthmatic patients it could be more sensitive then spirometry in detecting bronchoreversibility.