Cystic Fibrosis Reference Center Research Articles

FORAIDMUCO protocol : Pilot implementation of shared decision making in the treatment of diabetes in adult patients with cystic fibrosis: a mixed comparative evaluation of a training program dedicated to cystic fibrosis reference centers (Preprint)

FORAIDMUCO protocol : Pilot implementation of shared decision making in the treatment of diabetes in adult patients with cystic fibrosis: a mixed comparative evaluation of a training program dedicated to cystic fibrosis reference centers (Preprint)

Effect of 18 months elexacaftor-tezacaftor-ivacaftor on body mass index and glycemic control in adults with cystic fibrosis

Malnutrition and cystic fibrosis related diabetes (CFRD) are common comorbidities in cystic fibrosis (CF). Cystic fibrosis transmembrane regulator (CFTR) modulators have shown beneficial effects on respiratory status. This study aims to determine the effect of elexacaftor-tezacaftor-ivacaftor (ETI) on body mass index (BMI) and glycemic control. A retrospective, observational study of a cohort of 17 adult CF patients was conducted at the CF reference center of Ghent University Hospital. BMI evolution was analyzed 18 months before and 0, 3, 6, 12 and 18 months after the start of ETI. The evolution of insulin dependence and the 2h oral glucose tolerance test (OGTT) results were described until 36 months after start of ETI, in a small subgroup of ten patients with CFRD or impaired glucose tolerance (IGT). A significant increase in mean BMI of 1.2kg/m2 (±1.3 SD) was observed. Most weight gain was observed in the first 3 months after starting treatment. This effect was sustained during the observed period of 18 months. Six patients had insulin dependent CFRD, of which three were able to stop insulin after starting ETI. Two patients with CFRD treated with dietary measures showed an initial normalization of the 2h OGTT, but deterioration at 36 month follow-up. After initiation of ETI an increase in BMI was observed in adults with CF. ETI can have a beneficial impact on glucose metabolism in patients with CFRD, leading to a possible need for reduction or cessation of insulin therapy.

Outcome of patients with cystic fibrosis colonized by Scedosporium and Lomentospora species: A longitudinal cohort study.

Scedosporium and Lomentospora species rank second among the filamentous fungi colonizing the airways of cystic fibrosis (CF) patients. These fungi could be responsible for allergic bronchopulmonary mycosis (ABPM) and bronchitis before lung transplantation and invasive infections after. However, their role in CF lung disease is debated. This study aimed to identify clinical or environmental factors associated with an airway colonization by Scedosporium/Lomentospora species in patients with CF over a period of 7 years. A longitudinal cohort study was conducted from 2008 to 2014 in the CF reference centre in Lyon, France, to compare the characteristics of patients with Scedosporium/Lomentospora colonized and non-colonized patients. During the study period, 283 patients completed the clinical and microbiological follow-up. The analysis revealed that a higher number and duration of hospitalizations, an increased number of courses of parenteral antibiotic therapy, a history of ABPA, and treatment by itraconazole were significantly associated with an airway colonization by Scedosporium/Lomentospora species. The rate of decline of forced expiratory volume in the first second was not statistically different between colonized and non-colonized patients. This study provides evidence that patients colonized by Scedosporium/Lomentospora species require more medical care than non-colonized patients. Additional care could be in part explained by the management of Scedosporium/Lomentospora-related diseases such as ABPM or bronchitis. However, we did not demonstrate a faster rate of decline of respiratory function or body mass index in colonized patients, suggesting, as previously reported, that colonization of the airways by these fungi does not play a significant role in the progression of CF disease.

COVID-19 Lockdown Impacts Among Patients with Cystic Fibrosis: An Italian Regional Reference Centre Experience

Coronavirus pandemic has influenced our society with social distancing and management of chronic disease such as cystic fibrosis (CF). During the Italian lockdown from March to May 2020, CF patients reduced the number of outpatient visits, limited social interactions and spent more time at home. The aim of this study is to evaluate the impact of the lockdown on body mass index (BMI) and lung function tests on CF patients. We retrospectively reviewed clinical data about 111 CF patients followed in our Regional Cystic Fibrosis Reference Centre (Policlinico Umberto I, Rome) according to two periods: pre-lockdown (from October 2019-March 2020) and post-lockdown (from May 2020-October 2020). We collected data on nutritional (BMI and body weight) and lung function status; we chose the best values of the 'pre-lockdown' and 'post-lockdown' period for each patient. Patients were divided into 3 groups according to FEV1 value (Forced Expiratory Volume in the 1st second): group 1 (FEV1 <40%), group 2 (FEV1 40-70%), group 3 (FEV1 >70%). All patients received a telephone interview asking for the number of hours per week devoted to physical activity, number of pulmonary acute exacerbations and subjective evaluation of adherence to medical therapy, respiratory physiotherapy and diet, during the two periods. Comparing weight, BMI and respiratory function between pre and post lockdown periods, we noticed an increase in weight during among overall patients. Male patients improved weight, BMI, FEF 25-75% (Forced Expiratory flow between 25% and 75% of vital capacity) and Tiffenau index more than female patients. The most severely compromised patients (group 1), showed a significant loss of both weight and BMI. Instead, patients with moderate respiratory function (group 2) showed a significant increase of both weight and BMI and a slightly reduced CVF (Forced Vital capacity). We found no differences among patients with good respiratory function (group 3). Comparing each clinical sub-groups, we noticed a significative improvement of weight (p = 0.018) and BMI (p = 0.030) among patients with moderate respiratory function compared to patients with compromised respiratory function. During lockdown, patients reported less physical activity, no variation in food amount and composition, more adherence to therapy (43%) and more consistent daily respiratory physiotherapy (47.6%). Lockdown period had benefit among CF patients in terms of weight in particular in male patient. The greatest benefit on nutritional state was observed in patients with moderate reduction of respiratory function. In addition, we noted a stabilization and sometimes a slight improvement of lung function, instead of a continuous and steady decline that is normally observed in CF patients. These beneficial effects are slight but significative, bearing in mind the general worsening that CF patients experience annually.

Frequency of CFTR variants in southern Brazil and indication for modulators therapy in patients with cystic fibrosis.

This is a descriptive cross-sectional study that aims to determine the distribution of the CFTR causing variant in a group of patients at a cystic fibrosis (CF) center in southern Brazil, as well as to describe causing variants that are treatable with mutation-specific drugs. Ninety-two patients from a CF reference center were assessed in this research, all of them with a clinical diagnosis of CF and both alleles identified with pathogenic variants. The most prevalent causing variants were F508del, R1162X, G542X, and N1303K. As for patients with a mutation-specific drug indication, 69.6 % were candidates for the use of Elexacaftor/Tezacaftor/Ivacaftor (Trikafta®), 44.6 % for the use of Tezacaftor/Ivacaftor (Symdeko ®), and 35.9 % for the use of Lumacaftor/Ivacaftor (Orkambi®). For the use of Ivacaftor (Kalydeco®), only two patients (2.2 %) were candidates following the Brazilian agency approval. According to the FDA, 10 patients would be candidates for Ivacaftor (10.9 %). Causing variants of classes I and II, which are related to a major severity of the illness, were identified in 135 of 184 alleles (73.3 %). In this study, more than 2/3 of the patients were candidates for the use of CFTR modulators therapy.

Colonic Transit Time and Fecal Impaction in Children and Adolescents With Cystic Fibrosis-associated Constipation.

Constipation is prevalent in pediatric cystic fibrosis (CF) patients and colonic motility has not been studied in this population. In this study, we aimed to evaluate the total and segmental colonic transit time in children and adolescents with CF based on the presence of constipation and radiological fecal impaction. In this case series, all patients aged 3 to 20 years of a CF reference center were invited to participate. CF-associated constipation was diagnosed based on the European Society for Paediatric Gastroenterology Hepatology and Nutrition criteria. Total and segmental colonic transit time was determined using radiopaque markers. Fecal impaction on plain abdominal radiography was assessed based on the Barr score. Of the 43 eligible patients, 34 (79%) agreed to participate. Constipation was found in 44.1% of children and adolescents, predominantly in girls. The total colonic transit time (medians of 42 and 24 hours, respectively, P = 0.028) and the segmental right colon transit time (medians of 8 and 2 hours, respectively, P = 0.012) were significantly longer in CF-associated constipation group than in the group of patients without constipation. The frequency of radiological fecal impaction was similar in patients with (50.0%) and without (64.2%) CF-associated constipation (P = 0.70). There was no relationship between radiological fecal impaction and the total and segmental colonic transit time. Children and adolescents with CF-associated constipation had a longer total and segmental right colon transit time. Colonic transit time was similar in patients with and without radiological fecal impaction.

MO512THE RENAL CONSEQUENCES OF LUNG TRANSPLANTATION IN ADULT CYSTIC FIBROSIS PATIENTS

Abstract Background and Aims Cystic fibrosis patients are at high risk for chronic kidney disease (CKD), because of chronic aminoglycoside exposure, high protein and dietary salt intake, and Cystic Fibrosis Related Diabetes. Lung transplantation also entails a high renal burden in the long run because of calcineurin inhibitors exposure. We aimed at studying kidney function by gold standard glomerular filtration rate (mGFR) before and 1 year after lung transplantation, as well as identify risk factors for kidney function impairment. Method Patients from the Cystic Fibrosis reference center in Lyon, France were systematically referred to the nephrology department before lung transplantation. mGFR (iohexol or inulin clearance) was performed before and 12-18 months after lung transplantation. Risk factors for a worse nephrological outcome (i.e. post transplantation mGFR &amp;lt; 60mL/min/1.73m²) were searched for. Results 28 patients (10 males), mean age 32 yr, underwent pre transplantation mGFR. Three died following lung transplantation and two progressed to end stage renal disease rapidly thereafter. 23 patients benefited from both pre and post transplantation mGFR. Mean mGFR was 105±21mL/min/1.73m² and 67±19 mL/min/1.73m² before and after transplant respectively. Factors associated with a worse renal outcome in both univariate and multivariate analysis were age at transplantation (p=0.03) and the occurrence of acute kidney injury in the post-operative period (p=0.005). Cumulated aminoglycoside exposure and time spent under cardiopulmonary bypass were not associated with renal outcome. Conclusion Lung transplantation is associated with a high renal burden in adult Cystic Fibrosis patients. We advise a clinical referral to a nephrologist as part of the systematic evaluation in lung transplantation candidates even if GFR is in the normal range.

Determinants of Exercise Capacity Assessed With the Modified Shuttle Test in Individuals With Cystic Fibrosis.

Patients with cystic fibrosis develop decreased exercise capacity. However, the main factors responsible for this decline are still unclear. Thus, the objective of this study was to evaluate the factors influencing exercise capacity assessed with the modified shuttle test (MST) in individuals with cystic fibrosis. A cross-sectional study was carried out in subjects with a diagnosis of cystic fibrosis who were 6-26 y old and were regularly monitored at 2 cystic fibrosis reference centers in Brazil. Individuals who were unable to perform the tests or who exhibited hemodynamic instability and exacerbation of respiratory symptoms were excluded. Anthropometric, clinical, and genotype data were collected. In addition, lung function and exercise capacity were evaluated with the MST. 73 subjects (mean age 12.2 ± 4.9 y and FEV1 76.8 ± 23.3%) were included. The mean distance achieved in the MST was 765 ± 258 m (71.6% of predicted). The distance achieved on the MST correlated significantly with age (r = 0.49, P < .001), body mass index (r = 0.41, P < .001), resting heart rate (r = -0.51, P < .001), and FEV1 (r = 0.24, P = .042). Subjects with FEV1 > 67% of predicted (P = .02) and those with resting heart rate < 100 beats/min (P = .01) had a greater exercise capacity. Resting heart rate, age, and FEV1 (%) were found as significant variables to explain the distance achieved on the MST (R2 = 0.48, standard error = 191.0 m). The main determinants of exercise capacity assessed with the MST in individuals with cystic fibrosis were resting heart rate, age, and lung function.

Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis.

Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations.Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses.Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.

Review of the sweat test indications in a Brussels' cystic fibrosis reference center

We collected data of all sweat tests performed between 2008, 1th of March and 2015, 28th of February. They were analyzed following Rosenstein diagnosis criteria (1998): clinical manifestations suggesting CF, positive neonatal screening (≥ 1 positive assay of immunoreactive trypsin) or familial history of CF. We reviewed 1,208 sweat tests over this period. Patients were aged from 13 days to 79 years. Indications were: clinical events (94.0%), a positive neonatal screening (3.7%) and a family history (2.3%). Over the 20 newly diagnosed patients, a positive neonatal screening was the main indication for the sweat test (55%). A positive neonatal screening (p<0.0001), a family history (p<0.0001) and pulmonary signs associated with digestive signs (p=0.004) were more frequently found in these patients. Sweat test indications are mostly clinical and mainly pulmonary. This study confirms that a sweat test should be performed in case of pulmonary manifestations suggesting CF especially if these are associated with digestive manifestations.

One year prospective survey of azole resistance in Aspergillus fumigatus at a French cystic fibrosis reference centre: prevalence and mechanisms of resistance.

Studies on Aspergillus fumigatus azole resistance in cystic fibrosis patients are scarce despite the fact that it is the most frequently isolated fungus from respiratory samples from these individuals. To evaluate resistance prevalence, investigate mechanisms of resistance and explore the relationship between resistant isolates by genotyping. We conducted a prospective 1 year study (from 1 January to 31 December 2015), based on the investigation of up to five colonies per sample from cystic fibrosis patients. Twenty-three (6.5%) isolates among the 355 tested were resistant to at least one triazole drug, using the EUCAST reference method, leading to a prevalence of 6.8% (6/88 patients). Analysis of resistance mechanisms highlighted TR34/L98H (n = 10), TR46/Y121F/T289A (n = 1), WT cyp51A (n = 11) and F46Y/M172V/N248T/D255E/E427K (n = 1). No genotype was shared between patients. This study showed a relatively stable resistance prevalence in comparison with the previous study conducted in 2010-11 (8%), although resistance mechanisms varied between the two studies.

Microbiological contamination of nebulizers used by cystic fibrosis patients: an underestimated problem.

ABSTRACTObjective:Home nebulizers are routinely used in the treatment of patients with cystic fibrosis (CF). This study aims to evaluate the contamination of nebulizers used for CF patients, that are chronically colonized by Pseudomonas aeruginosa, and the association of nebulizer contamination with cleaning, decontamination and drying practices. Methods:A cross-sectional, observational, multicenter study was conducted in seven CF reference centers in Brazil to obtain data from medical records, structured interviews with patients/caregivers were performed, and nebulizer’s parts (interface and cup) were collected for microbiological culture. Results:overall, 77 CF patients were included. The frequency of nebulizer contamination was 71.6%. Candida spp. (52.9%), Stenotrophomonas maltophilia (11.9%), non-mucoid P. aeruginosa (4.8%), Staphylococcus aureus (4.8%) and Burkholderia cepacia complex (2.4%) were the most common isolated pathogens. The frequency of nebulizers’ hygiene was 97.4%, and 70.3% of patients reported cleaning, disinfection and drying the nebulizers. The use of tap water in cleaning method and outdoor drying of the parts significantly increased (9.10 times) the chance of nebulizers’ contamination. Conclusion:Despite the high frequency hygiene of the nebulizers reported, the cleaning and disinfection methods used were often inadequate. A significant proportion of nebulizers was contaminated with potentially pathogenic microorganisms for CF patients. These findings support the need to include patients/caregivers in educational programs and / or new strategies for delivering inhaled antibiotics.

Adaptation of Pseudomonas aeruginosa to the chronic phenotype by mutations in the algTmucABD operon in isolates from Brazilian cystic fibrosis patients.

Chronic lung infection by Pseudomonas aeruginosa is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. This is associated with the conversion of the non-mucoid to the mucoid phenotype. However, there is little information about the occurrence of alginate-producing P. aeruginosa in CF patients outside Europe and North America. The aim of the present study was to investigate mutations in the algTmucABD operon in mucoid and non-mucoid isolates from Brazilian CF patients. Twenty-seven mucoid and 37 non-mucoid isolates from 40 CF patients chronically infected by P. aeruginosa attending a CF reference center in Brazil were evaluated by sequence analysis. Mutations in mucA were observed in 93% of the mucoid isolates and 54% of the non-mucoid isolates. Among these non-mucoid isolates, 55% were considered revertants, since they also had mutations in algT (algU). Most isolates associated with moderate alginate production presented point mutations in mucB and/or mucD. We identified 30 mutations not previously described in the operon. In conclusion, mutations in mucA were the main mechanism of conversion to mucoidy, and most of the non-mucoid isolates were revertants, but the mechanism of revertance is not fully explained by changes in algT.

Complications aiguës respiratoires et non respiratoires chez l’adulte mucoviscidosique

Cystic fibrosis (CF) is a genetic disease primarily affecting the lungs, which could lead to chronic respiratory failure and premature death. CF patients are usually followed in specialized centers, but may present outside of these centers when they seek care for acute pulmonary and/or non-pulmonary complications. The aim of this paper is to provide appropriate knowledge necessary for managing respiratory and non-respiratory emergencies in CF adults. The review is based on international guidelines, extensive search of the available literature using Pubmed, and experience of the CF reference center at Cochin hospital (Paris, France). Complications occurring after solid organ transplantation (e.g., lung and/or liver) are excluded from this review. Main acute respiratory complications are pulmonary exacerbations, hemoptysis, pneumothorax and allergic bronchopulmonary aspergillosis. Acute non-respiratory complications include hyponatremic dehydration, acute pancreatitis, acute complications of gallstones, distal intestinal obstruction syndrome, symptomatic nephrolithiasis, acute kidney injury, drug intolerances and catheter-related acute complications. This review summarizes acute pulmonary and non-pulmonary complications occurring in adults with CF, focusing on diagnosis and principles of treatment, with the aim of providing a reference that can be used in clinical practice.

Cystic fibrosis related diabetes before lung transplantation impacts survival but not long-term renal function

Introduction Lung transplantation (LT) is the final therapeutic option for cystic fibrosis (CF) patients with end stage lung disease. Lung transplanted CF patients differ from other LT patients because of their younger age, better survival after LT, but also specific associated comorbidities related to their underlying disease, particularly CF related diabetes (CFRD). The objective was to describe the prevalence of CFRD before and after LT; and to analyse survival and renal function after LT according to CFRD status before LT. Methods CF patients treated in the Lyon CF reference centre and transplanted at the Lyon University Hospital (France) between 2004 and 2014 were retrospectively included. Genotype (classified in delF508 homozygous, delF508 heterozygous or other), pancreatic status, age at LT and survival were recorded. The following criteria were recorded three months before LT, between three and six months after LT, and at each year of follow-up until December 2016: glucose tolerance status (CFRD or others), daily insulin dose requirement; renal function, defined by the estimated glomerular filtration rate (GFR, calculated with the Modification of Diet in Renal Disease formula); and daily glucocorticoid (GC) dose. Analysis for repeated measures data was conducted by using linear mixed-effect regression models that included fixed and random effects. Results Sixty-three adult CF patients were transplanted. Thirty-two (53.3%) patients were delF508 homozygous. All were pancreatic insufficient, and 42 (70%) had CFRD before LT. The mean ± SD calculated GFR before LT was 109 ± 47 mL/min/1.73 m2, and did not differ according to CFRD status (P = 0.68). The mean ± SD age at LT was 27.6 ± 8.4 year. The median (IQR) time of follow-up was 5.6 (3.8–8.2) years and 12 (20%) patients died in the follow-up: three patients died in the first three post-operative months, seven patients in the five years following LT and the last two respectively at 6 and 8 years after the LT. The prevalence of CFRD was 68% (41/60) and 54% (20/37) respectively at two and five years after LT. For the 27 patients who had persistent insulin-treated CFRD, insulin requirement decreased with an estimated slope of −2.1 ± 2.9 IU/day per year (P Conclusions CFRD before LT was associated with a poor survival after LT in CF patients, which should conduct to a better management of diabetes control in the peri- and post-operative period after LT. Some patients with pre-LT CFRD get free of diabetes after LT. CFRD is not associated with renal insufficiency after LT. Others factors might participate to renal insufficiency after LT such as perioperative hemodynamic conditions and immunosuppressive drugs.

Prevalence and clinical outcomes of nontuberculous mycobacteria in a Brazilian cystic fibrosis reference center.

Nontuberculous mycobacteria (NTM) have been well established as an opportunistic pathogenic bacterial group for cystic fibrosis (CF) patients, with a prevalence ranging from 3% to 23% worldwide. A myriad of factors can bias the prevalence rate in different CF centers, especially misdiagnosis as systematic screening for NTM are still lacking in a number of centers. Here, we evaluated the presence and clinical outcomes of NTM isolation in microbiological respiratory cultures from CF patients attending a Brazilian reference center after setting up a systematic diagnostic protocol. Of 117 patients with respiratory samples cultured for NTM research, we found seven patients (6%) with at least one positive result for NTM [four males (57.1%), median age=21 years (9-58)]. These cases are reported one-by-one. Median FEV1 was 40%, all patients showed signs of lung deterioration, with a median number of pulmonary exacerbations of three per patient/year. However, the impact of NTM isolation remains unclear in our center as all patients were coinfected with other CF respiratory pathogens. Our NTM prevalence assimilates to the lowest levels reported in literature, which is possibly influenced by the routinely applied Bacille Calmette-Guérin vaccine.

319 Nutritional intervention at the cystic fibrosis reference center of children and adults in Uruguay

319 Nutritional intervention at the cystic fibrosis reference center of children and adults in Uruguay

The diagnosis of cystic fibrosis

Establishing the diagnosis of cystic fibrosis (CF) is straight forward in the majority of patients: they present with a clear clinical picture (most frequently chronic respiratory symptoms plus malabsorption), the sweat chloride value is>60mmol/L and two known disease causing CFTR mutations are identified. In less than 5% of subjects, mainly those with a milder or limited phenotype, the diagnostic process is more complex, because initial diagnostic test results are inconclusive: sweat chloride concentration in the intermediate range, less than 2 CF causing mutations identified or both. These patients should be referred to expert centers where bioassays of CFTR function like nasal potential difference measurement or intestinal current measurement can be done. Still, in some patients, despite symptoms compatible with CF and some indication of CFTR dysfunction (e.g. only intermediate sweat chloride value), diagnostic criteria are not met (e.g. only 1 CFTR mutation identified). For these subjects, the term CFTR related disorder (CFTR-RD) is used. Patients with disseminated bronchiectasis, congenital bilateral absence of the vas deferens and acute or recurrent pancreatitis may fall in this category. CF has a very wide disease spectrum and increasingly the diagnosis is being made during adult life, mainly in subjects with milder phenotypes. In many countries, nationwide CF newborn screening (NBS) has been introduced. In screen positive babies, the diagnosis of CF must be confirmed by a sweat test demonstrating a sweat chloride concentration above 60mmol/L. To achieve the benefit of NBS, every baby in whom the diagnosis of CF is confirmed must receive immediate follow-up and treatment in a CF reference center. CF NBS is not full proof: some diagnoses will be missed and in some babies the diagnosis cannot be confirmed nor ruled out with certainty. Screening algorithms that include gene sequencing will detect a high number of such babies that are screen positive with an inconclusive diagnosis (CFSPID). Even in 2016, the most reliable and widely available diagnostic test for CF is the measurement of chloride concentration in sweat. The method of choice is sweat induction by pilocarpine iontophoresis, followed by sweat collection on a gauze or filter paper or in a Macroduct coil. Since mutation specific therapies have become available, it is important to identify the mutations responsible for CF in each individual patient.

EPS06.2 Cysteamine as a strategy against Burkholderia cepacia complex

ePS06.1 Interference of b-lactamases with the determination of antibiotic concentrations in sputum by liquid chromatography–tandem mass spectrometry (LC-MS/MS) K. Forier, V. Van Heck, E. Van Braeckel, S. Van Daele, F. De Baets, P. Schelstraete, F. Haerynck, M. Vaneechoutte, V. Stove, A. Verstraete. Ghent University, Dept. Clinical Chemistry, Microbiology and Immunology, Ghent, Belgium; Ghent University Hospital, Dept. of Respiratory Medicine, Ghent, Belgium; Ghent University Hospital, Cystic Fibrosis Reference Center, Ghent, Belgium; Ghent University Hospital, Laboratory Medicine, Ghent, Belgium

Pseudomonas aeruginosa and Periodontal Pathogens in the Oral Cavity and Lungs of Cystic Fibrosis Patients: a Case-Control Study.

Cystic fibrosis (CF) is the most frequent lethal genetic disease in the Caucasian population. Lung destruction is the principal cause of death by chronic Pseudomonas aeruginosa colonization. There is a high prevalence of oropharyngeal anaerobic bacteria in sputum of CF patients. This study was carried out due to the lack of results comparing subgingival periodontal pathogenic bacteria between the oral cavity and lungs in patients with CF in relation with P. aeruginosa presence. Our first goal was to detect P. aeruginosa in oral and sputum samples by culture and molecular methods and to determine clonality of isolates. In addition, subgingival periodontal anaerobic bacteria were searched for in sputum. A cross-sectional pilot case-control study was conducted in the CF Reference Center in Roscoff, France. Ten CF patients with a ΔF508 homozygous mutation (5 chronically colonized [CC] and 5 not colonized [NC]) were enrolled. P. aeruginosa was detected in saliva, sputum, and subgingival plaque samples by real-time quantitative PCR (qPCR). Subsequently, periodontal bacteria were also detected and quantified in subgingival plaque and sputum samples by qPCR. In CC patients, P. aeruginosa was recovered in saliva and subgingival plaque samples. Sixteen P. aeruginosa strains were isolated in saliva and sputum from this group and compared by pulsed-field gel electrophoresis (PFGE). Subgingival periodontal anaerobic bacteria were found in sputum samples. A lower diversity of these species was recovered in the CC patients than in the NC patients. The presence of the same P. aeruginosa clonal types in saliva and sputum samples underlines that the oral cavity is a possible reservoir for lung infection.