C. Shortt

Inhaled versus nebulised tobramycin: A real world comparison in adult cystic fibrosis (CF)

BACKGROUND There are no published data on real-life clinical experience comparing inhaled antibiotic therapy via new rapid delivery systems with nebulised antibiotic therapy in CF. This real world study compares safety, effectiveness and tolerability using tobramycin inhaled powder (TIP) versus tobramycin inhaled solution (TIS). METHODS Adult patients with CF commencing TIP (n=78) completed a questionnaire assessing safety, efficacy, tolerability, patient-satisfaction and self-reported adherence to TIS at baseline and during 12 months of TIP therapy. FEV1% predicted and exacerbation rate were recorded at each visit. RESULTS There was a significant improvement in adherence scores, with a significant decrease in the number of intravenous antibiotic courses received during 12 months of TIP compared with the preceding 12 months using TIS. 94% of patients who had previously used TIS preferred TIP therapy over TIS. CONCLUSIONS Inhaled powder tobramycin in CF is associated with improved adherence, tolerability and decreased exacerbation rates compared to nebulised treatment in real-life practice.

CORK Study in Cystic Fibrosis: Sustained Improvements in Ultra-Low-Dose Chest CT Scores After CFTR Modulation With Ivacaftor

Background Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment. Methods Thirty‐three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra‐low‐dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. Results Significant improvements in FEV1, BMI, and sweat chloride levels were observed post‐ivacaftor treatment. Improvement in ultra‐low‐dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)‐1&bgr;, IL‐6, and IL‐8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). Conclusions Early and sustained improvements on ultra‐low‐dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota.

74 Improved tolerability, adherence and reduced intravenous (IV) antibiotic usage in CF patients receiving inhaled versus nebulised antibiotic prophylaxis. A real world comparison of tobramycin inhaled powder (TIP) and tobramycin inhaled solution (TIS)

Objectives: Phosphodiesterase 5 inhibitors (IPDE5) are able to restore chloride transport in F508del cystic fibrosis (CF) airway epithelium. CF patients with severe lung disease are at risk of pulmonary hypertension and impaired exercise tolerance. Treatment with IPDE5 is a promising strategy in CF. Methods: We conducted a study in 12 stable F508del homozygous CF adults (5 males and 7 females) with median (IQR) age of 25.9 (22.8–27.6) years without Burkholderia cepacia complex airway colonization. We administered sildenafil for 30 days and evaluated pulmonary function, respiratory symptoms and exercise tolerance before and after treatment using spirometry (forced expiratory volume in 1 sec. [FEV1]), 6-minute walking test (6-minute walking distance [6-MWD]) and CFQ-R quality of life questionaire (physical and respiratory domain [PHYS and RESP, respectively]). 8 patients completed the study (2 dropped due to pulmonary exacerbation and further 2 due to headaches). Exercise tolerance changed significantly (median and IQR; Wilcoxon test): 6-MWD 618 (612–692) vs. 577 (562–633) m, p = 0.012, and PHYS 93.8 (68.8–100.0) vs. 89.6 (60.4–97.9), p = 0.043, whereas pulmonary function and respiratory symptoms did not. Transient headaches were common adverse events during the first 1−2 weeks of sildenafil treatment in 7 of the 12 patients. Conclusion: We conclude that short-term sildenafil treatment in CF adults led to an improvement of exercise tolerance without changing pulmonary function and respiratory symptoms. Supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00064203 (University Hospital Motol, Prague, Czech Republic).

37 Clinical outcomes of real world Kalydeco (CORK) study

36 The effect of ivacaftor therapy on clinical and PCR-identified microbial diversity of cystic fibrosis lung infection H. Green1,2, C. Paisey3, A. Smith3, P. Barry1, W. Flight1, A. Jones1,2, J. Marchesi3, A. Horsley1,2, E. Mahenthiralingam3. 1University Hospital of South Manchester NHS Foundation Trust, Manchester Adult Cystic Fibrosis Centre, Manchester, United Kingdom; 2University of Manchester, Institute of Inflammation and Repair, Manchester, United Kingdom; 3Cardiff University, Cardiff School of Biosciences, Cardiff, United Kingdom

A mHealth Patient Passport for Adult Cystic Fibrosis Patients

Life expectancy for some Cystic Fibrosis (CF) patients is rising and new complications and procedures are predicted. Subsequently there is need for education and management interventions that can benefit CF adults. This paper proposes a CF patient passport to record basic medical information through a smartphone application (app), giving the patient access to their own data. It is anticipated that such an app will be beneficial to patients when travelling abroad and between CF centres. This app is designed by a CF multidisciplinary team to be a lightweight reflection of a current patient file. The passport app is created using PhoneGap so that is can be deployed for both Android and iOS devices. The app is introduced to seven participants as part of a stress test. The app is found to be usable and accessible. The app is now being prepared for a pilot study with adult CF patients.

217 Medical outcomes post transition of clinical care from a paediatric cystic fibrosis care model to an adult cystic fibrosis care model – an Irish perspective

As life-expectancy increases in CF it is paralleled by an increasing number of patients transitioning from a paediatric care-model to an adult care-model. In chronic illnesses’ including CF the transition process is often complicated by concerns about the potential implications. Traditionally studies have evaluated subjective aspects of transition including patient satisfaction. There are limited objective studies in this area. Our study investigated the change in clinical status in the year pre & post transition.

128 The metabolic consequences of CFTR modulation with ivacaftor in a single adult cystic fibrosis centre cohort

Objectives Ivacaftor produces significant benefit in patients with cystic fibrosis (CF) with the G551D mutation. Recent data have supported improved insulin secretion profile and reversal of CF related diabetes (CFRD) in patients treated with ivacaftor. Significant weight gain has been demonstrated with ivacaftor, thus raising the potential for development of dyslipidaemia in a cohort traditionally treated with a high fat diet. Methods 24 Adult patients with the G551D mutation had Oral Glucose Tolerance Test (OGTT), Fasting lipid profile and HbA1C measured before and after commencing ivacaftor therapy. 6 patients had pre-existing CFRD and Insulin requirements were analysed in this cohort before and after ivacaftor. Data was analysed using Wilcoxon signed-rank test. Results No significant change was observed in fasting glucose, 2 hour post prandial glucose, or HbA1C after commencement of ivacaftor. Significant median increase in total fasting cholesterol (0.2 mmol/L, P=0.025) and HDL (0.16 mmol/L, P=0.03) were observed after commencement of treatment. There was no significant change in LDL or Triglycerides. In the 6 patients with CFRD no significant change in either total insulin requirements or units of insulin per kilogram of weight were observed. Conclusion In a large single centre cohort with the G551D mutation we report no significant change in OGTT, HbA1c or insulin requirements after ivacaftor. While a significant increase in Fasting cholesterol was observed, median values were within normal limits. Changes in lipid profile may reflect the impact of adhering to a high fat diet as a consequence of therapy and will required long-term follow up.

WS20.4 Clinical outcomes of Real-World Kalydeco (CORK) study – a prospective 12 month analysis addressing the impact of CFTR modulation on the cystic fibrosis lung

Objectives Ivacaftor produces significant benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at Cork University Hospital (CUH) is 23% making it uniquely placed to provide single centre insight into CFTR modulation. Methods 33 Ivacaftor-naive Patients with CF (age ≥6) consented to routine quarterly clinical follow up (median 1 year follow up) where clinical changes pre and post ivacaftor were recorded. 3 monthly sputum, blood and low dose CT Thoraces were performed at baseline and post-ivacaftor. Sputum bacteria were detected by plating on selective agars, quantified by total viable count and identified by PCR and sequencing of 16S rRNA genes. Circulating cytokines were measured in blood samples using an MSD platform. CT Thoraces were Bhalla scored. Results Significant mean improvements in FEV1 (10.26%), BMI (1.2 kg/m2), Sweat test (–57.65 mmol/l), Respiratory Domain of CFQ-R (17.51 point), exacerbation rate requiring IV antibiotics were observed, with a significant increase in Sputum diversity (P Conclusion In a large single centre cohort CFTR modulation is associated with a sustained improvement in clinical phenotype, decrease in inflammatory markers, change in lung microbiome and reduction in intraluminal bronchiectatic radiological complications.

48 Altered gut microbiota in stable patients with cystic fibrosis (CF) compared to controls and its relationship with intravenous (IV) antibiotic usage and lung function

Objective CF is associated with altered digestive function and thus nutrient availability for gut microbes in addition to altered gut microbiota, compared with healthy controls. Equally intensive antibiotic and nutritional therapy may further compound this. We present results from the largest CF gut microbiota study to date. Methods The gut microbiota of 43 stable adults with CF was compared to 69 age-matched controls. DNA was extracted from faecal samples and the V4 region of the 16S rRNA gene was sequenced using 454-pyrosequencing. Results were correlated with baseline %FEV 1 results and to total courses of IVs in the previous 12 months. Results The gut microbiota diversity of patients with CF was significantly reduced compared to controls (p Faecalibacterium, Roseburia and Bifidobacterium (p 1 and gut diversity (Simpsons diversity index: r=0.47, p=0.0015) was found in those with CF. Conclusion This study highlights that patients with CF have an altered gut microbiota which correlates with clinical outcomes. Further longitudinal studies will enable us to interrogate the causality of such microbiota alterations and determine the potential role of probiotics in CF therapy.

200 Prevalence of dyslipidaemia in an Irish adult cystic fibrosis cohort

Patients with cystic fibrosis (PWCF) are typically prescribed high calorie, high fat diets. With improved survival, there is emerging data that suggests an increased risk of cardiovascular disease. This study examines the prevalence of dyslipidaemia and its associated clinical phenotype in an Irish adult CF population. Biometric data and fasting lipid profiles were collected from patients attending annual assessment at the CF day unit between August 2012 and August 2013. Phenotypic information was collected from patient charts. 98 participants (mean age 28±10) were included in the study. Of this sample, 31% had CF-related diabetes and 83% were pancreatic insufficient. Across the population, mean and median lipid profiles were normal. However, 25% had lower HDL, 17% had elevated triglycerides, 17% elevated LDL, and 8% elevated total cholesterol. Total cholesterol and LDL were found to increase with increasing age and BMI. Increased total cholesterol was strongly correlated with increased LDL. On subgroup analysis, pancreatic sufficient subjects were more likely to have higher LDL (p< 0.001) and 63% of these had higher than optimal LDL. Diabetics were more likely to have higher triglycerides (p< 0.05) and 29% had higher than optimal levels. Men were found to have lower total cholesterol (p = 0.007) and lower HDL (p = 0.001). With increasing age, dyslipidaemia is an important emerging cardiovascular risk factor for PWCF. This is the first study to show this in a European population and is in keeping with previous studies.