- Email: [email protected]
WS12.3 Vertebral fracture assessment (VFA): a useful additional assessment of bone health in CF patients?
Oral Presentations / Journal of Cystic Fibrosis 15 (2016) S1–S50
Methods: Skin wipe sampling was used to obtain sweat samples from 20 patients diagnosed with CF (10 adults, mean age 34 years; 10 children, mean age 8 years) and 10 control patients (10 children, mean age 7 years). The samples were analyzed by capillary electrophoresis with contactless conductometric detection. Cl− , potassium (K+ ) and sodium (Na+ ) ions were simultaneously determined in approximately 5 minutes in a background electrolyte containing 20 mM 2-(N-morpholino)ethanesulfonic acid, 20 mM L-histidine and 2 mM 18-crown-6. Results: Sweat sample is obtained by simple and fast wipe of the forearm (in <10 s) and is completely painless. Simultaneous analysis of Cl− , K+ and Na+ in sweat samples revealed that while Cl− alone can sometimes lead to false positive/negative result, the Cl− /K+ concentration ratio >4 (Cl− /K+ mean = 8.5, range 4.1–12.1 for children patients; Cl− /K+ mean = 7.5, range 5.2–12.6 for adult patients) correctly classified all CF patients and discriminated them from healthy controls (Cl− /K+ < 4, Cl− /K+ mean = 2.4, range 1.5–3.7). Conclusion: The newly developed skin wipe technique for sweat sampling is simple, fast and inexpensive and by using the Cl− /K+ ratio instead of Cl− concentration alone, the method can provide a better diagnostic tool with potential to reduce the false positive/negative values. WS11.6 Current status of early CF diagnosis in Latin America: results from the 1st LANES meeting N. Derichs1 , A. Kotnik Pirs2 , A. Jung3 , G.B. Aponte4 , M.L. Boza5 , C. Castanos6 , I. Chaustre7 , E. Chong8 , L. Cordero Onate9 , A. Hoepker10 , J.L. Lezana11 , M. Maestre12 , L. Rosal Palomo13 , C. Pinchak14 , L.V. Ferreira da Silva Filho15 , C. Vasquez-Mobile16 , P. Mastoridis17 , on behalf of the LANES Study Group and the ECFS Diagnostic Network Working atsmedizin Berlin, CFTR Biomarker Center, Berlin, Group. 1 Charit´e-Universit¨ Germany; 2 University Children’s Hospital Ljubljana, Ljubljana, Slovenia; 3 University Children’s Hospital Zurich, Zurich, Switzerland; 4 CF Centre, Lima, Peru; 5 Hospital Clinico San Borja Arriaran, Santiago de Chile, Chile; 6 Hospital de Pediatria, Buenos Aires, Argentina; 7 Children’s Hospital, Caracas, Venezuela; 8 Hospital Materno Infantil Jose Domingo de Obaldia, Panama, Panama; 9 Robert Reid Cabral Children Hospital, Dominican Republic, Dominican Republic; 10 National Children Hospital, San Jose, Costa Rica; 11 CF Centre, Mexico, Mexico; 12 Childrens Hospital, Cuenca, Ecuador; 13 CF Centre, Guatemala, Guatemala; 14 CF Centre, Montevideo, Uruguay; 15 CF Centre, Sao Paolo, Brazil; 16 CF Centre, Bogota, Colombia; 17 Novartis Pharma AG, East Hanover, United States Objectives: Establishing an early diagnosis of CF in Latin America is suspected to be challenging due to several reasons, including heterogeneity of the population, availability and costs of diagnostic tests and lack of public awareness for CF in some countries. Methods: An initiative by the ECFS Diagnostic Network Working Group aimed to better understand the current status of early CF diagnosis in Latin America. Expert representatives from 13 Latin American countries (Mexico, Guatemala, Costa Rica, Panama, Dominican Republic, Venezuela, Colombia, Ecuador, Uruguay, Brazil, Peru, Argentina, Chile) were invited to prepare a structured summary on the history and current situation of CF diagnosis in their country, and to share their experiences at the first Latin American Newborn and Early Screening of Cystic Fibrosis Patients (LANES) consensus meeting which was held in August 2015 in Sao Paolo, Brazil together with representatives from the ECFS DNWG and ECFS Patient Registry. Results: Important differences and challenges in diagnosing CF were discussed, including epidemiology, CF newborn screening, sweat test, CFTR genotyping and use of CF registries. Conclusion: The LANES project is the first joint initiative to summarise current practices and future perspectives for early CF diagnosis in Latin America. Increasing public awareness for early CF diagnosis was agreed to be of critical importance. Results from all attendees highlighted the significance and success of the LANES meeting, allowing for shared experiences to be discussed and future relationships and collaborations to achieve the best outcomes for CF patients in Latin America. Acknowledgement: Supported by Novartis
S19
Workshop 12. Bone health, glucose metabolism and CFRD WS12.2 Increased fracture rate in relation to macroscopic bone architecture in young patients with cystic fibrosis 3 M. Stahl1,2 , F.-M. Muller ¨ , C. Holfelder3 , C. Kneppo3 , M. Kieser4 , 4 5 3 1 C. Kasperk , E. Schonau ¨ , O. Sommerburg1 , B. Tonshoff ¨ . University Children’s Hospital Heidelberg, Pediatric Pulmonology, Allergy and CF-Centre, Heidelberg, Germany; 2 DZL, TLRC, Heidelberg, Germany; 3 ZKJM Heidelberg, Heidelberg, Germany; 4 University Heidelberg, Heidelberg, Germany; 5 University Cologne, Cologne, Germany Rationale: CF-related bone disease contributes significantly to patient morbidity. However, the relative risk for bone fractures is unknown and its relationship to parameters of macroscopic bone architecture is incompletely defined. Objectives: To evaluate the fracture rate in young CF patients and to analyze its relationship with parameters derived from DXA and pQCT measurements. Methods: This cross-sectional study investigated 43 CF patients (age, 17.8±6.2 years). The rate and location of radiographically confirmed fractures since birth was analyzed via a questionnaire. Bone mass, density, geometry, and strength of the radius as well as forearm muscle size were measured by pQCT, bone mineral density and content of the total skeleton and lumbar spine by DXA. Measurements and Main results: Eighteen of 43 patients (41.9%) had experienced fractures predominantly of the peripheral skeleton. Compared to an age-matched German control population, CF patients had a 9.2-fold higher fracture rate (P = 0.011). The probability of remaining free of any fracture in CF patients at 25 years was reduced to 39.8% compared to 84.6% in controls (P < 0.001). Combined assessment of macroscopic bone architecture by DXA and pQCT allowed the differentiation of patients with an increased fracture rate with a high sensitivity (100%) and specificity (94.3%). Conclusions: The fracture rate in young CF patients is markedly increased compared to controls and associated with alterations of macroscopic bone architecture. These results support the role of bone densitometry for noninvasive monitoring of bone quality in CF patients. WS12.3 Vertebral fracture assessment (VFA): a useful additional assessment of bone health in CF patients? A. Smith1 , S. Yoganathan1 , L. Speight1 , R. Petit2 , R.I. Ketchell1 , D. Lau1 , M. Stone3 , J. Duckers1 . 1 University Hospital Llandough, All Wales Adult Cystic Fibrosis Centre, Vale of Glamorgan, United Kingdom; 2 University Hospital of Wales, Cardiff, United Kingdom; 3 Cardiff University, Vale of Glamorgan, United Kingdom Objectives: To assess the utility of VFA in routine assessment of CF patient bone health. The presence of a vertebral fracture (VFr) significantly increases the risk of future fracture. Most VFr are silent and lateral X-rays are not routinely obtained in CF patients. VFA a technique of dual X-ray absorptiometry (DXA) based vertebral morphometry allows rapid assessment of VFr and is highly correlated with VFr as assessed on standard lateral spine X-rays. Methods: 138 patients attending their DXA also underwent VFA. Presence of VFr was determined using the McCloskey-Kanis method. Age, sex, FEV1 %, BMI, lumbar spine and total hip Z score, fracture history, whether they received oral or inhaled corticosteroids, bisphosphonate and calcium/vitamin D supplementation and the presence of common co-morbidities were recorded. Results: 138 patients (87 males) mean (SD) age 29.4(9.4)years, FEV1 % predicted 66.9(24.1)% and BMI of 22.8 (4.7)kg/m2 underwent VFA. Mean (SD) Z score at the lumbar spine −0.82 (1.12) and total hip −0.59 (1.01). Of 138 VFA performed 5 (3.6%) were abnormal 3 were suggestive of thoracic spine fractures which were not confirmed on subsequent lateral XR. A lumbar spine fracture and T11 fracture were detected on VFA in 2 (1.4%) patients that were retrospectively seen on CT images of the chest performed 2 years earlier.
S20
Oral Presentations / Journal of Cystic Fibrosis 15 (2016) S1–S50
Conclusion: Two VFr were found on VFA scanning giving a prevalence of VFr of 1.4%. These VFr were present on review of previous radiology so VFA has not added any significant positive findings. The prevalence of VFr is surprisingly low compared to other chronic respiratory diseases (COPD prevalence 42% of patients sustaining VFr – Nuti R et al. Osteopor Int 2008). WS12.4 The predictive value of oral glucose tolerance for the development of CFRD in CF children: a longitudinal study M.M.M. van Oirschot-van de Ven1 , A.C. de Kiviet1 , G. Berkers1 , J.M. Witmond1 , H.G.M. Arets1 , C.K. van der Ent1 . 1 Wilhelmina Children’s Hospital – University Medical Center Utrecht, Utrecht, Netherlands Objectives: The oral glucose tolerance test (OGTT) is the current gold standard to screen for cystic fibrosis-related-diabetes (CFRD). Diagnostic protocols advocate performing annual OGTT in patients above the age of ten years. However, data on the long term repeatability of OGTT outcomes are scarce. Our objective was to evaluate the predictive value of the OGTT for the development of CFRD. Methods: We performed a longitudinal study from 2009 until 2014 in our CF centre, in which we included children (aged 10–18 years) with CF and exocrine pancreas insufficiency. We evaluated the OGTT results of each year, and scored these results in four diabetes mellitus grades; 1 = normal (post-challenge <7.0 mmol/L), 2 = INDET (post-challenge 7.0– 11.1 mmol/L), 3 = IFG (post-challenge >11.1 mmol/L), 4 = CFRD (fasting >7.0 mmol/L). We compared the OGTT result of each year with the OGTT result of the next year. Table 1. Change in OFTT score after 1 year OGTT grade
1 2 3
OGTT grade next year 1
2
3
4
55.5% 29.3% 13.9%
38.7% 54.3% 38.9%
5.8% 15.4% 38.8%
0.0% 1.0% 8.3%
Results: During the study period, 417 OGTT’s where carried out in 123 patients. We found the following OGTT results in patients without CFRD: 41% of OGTT’s scored grade 1, 50% grade 2 and 9% grade 3. The results of the next years’ OGTT in the different grades are shown in Table 1. Conclusion: Results of OGTT in children with CF vary widely during annual follow-up. None of the children with a grade 1 result developed CFRD within a year. The annual probability to develop CFRD in children with a grade 3 result was 8.3%. WS12.5 Continuous glucose monitoring is an essential tool, alongside the OGTT, in the diagnosis and treatment of CFRD R. Margetts1 , S. Drew1 , H. Gordon1 , C. Peters1 . 1 Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom Objectives: To demonstrate the use of OGTT and continuous glucose monitoring (CGM) in diagnosis and treatment of CFRD and whether OGTT at 3 hours demonstrates rebound hypoglycaemia (RH). Methods: Data from OGTT screening tests was collected from one paediatric centre over 12 months. 1.75 g/kg glucose (max 75 g) was administered and glucose concentrations measured at 0, 60, 120 and 180mins. Results were classified according to WHO diagnostic criteria. In addition, a blood glucose (BG) <4 mmol/l at 180mins was classified as RH. For abnormal results, CGM was used to confirm diagnosis and guide treatment. CGM was considered normal if glucose concentrations were 4–10 mmol/l over 5–7 days. Table: Summary of diagnoses from OGTT
OGTT (n = 25) RH (n = 13)
Normal
Indeterminate
IGT
CFRD
13 7
6 5
5 1
1 0
IGT, impaired glucose tolerance.
Results: 25 tests were performed. 18 females, age range 4–16 years (mean 11.3). 13/25 were referred for CGM, 2 refused but monitored BG at home. 4 cases with normal OGTT and RH received diet advice. In 8/11 cases, CGM showed normal BG needing no further intervention. 3 cases received diet advice. No insulin was required. Conclusion: Our data from CGM shows that not all children will require insulin despite abnormal OGTT. There was evidence of glucose dysregulation at 3 hours in those with normal OGTT. The OGTT is based on a glucose load whereas the CGM is based on lifestyle and diet. Some diet manipulation helps fluctuations in BG. We would recommend CGM surveillance for young people with abnormal OGTT in addition to an annual OGTT. Standardisation of CGM to provide diagnostic criteria for CFRD needs to be agreed before using it as a screening tool. WS12.6 How does transferral from CF doctors to endocrinologists affect blood glucose control in patients with CFRD R. a Rogvi1 , T.K. Hansen2 , H.V. Olesen3 . 1 Aarhus University, Aarhus, Denmark; 2 Aarhus University Hospital, Department of Endocrinology and Diabetes, Aarhus, Denmark; 3 Aarhus University Hospital, Department of Pediatrics, Aarhus, Denmark Background: CF Related Diabetes (CFRD) has a negative influence on the patients’ QoL, nutrition and lung function. The aim of this study was to investigate whether transferring from diabetes control by CF physicians to adult diabetologists has a positive effect on CF patients’ CFRD management. Methods: The study population was 17 patients with CFRD diagnosed before the transition registered in CF Registry Denmark. Mean HbA1c before (2010/2011) and after (2014/2015) the transfer was compared. Mean BMI and lung function (FEV1) in 2010 and 2014 were evaluated. Results: Mean HbA1c value before the transition was 66.9 mmol/mol (range 48.5–117.3). 11/17 patients had a lower mean HbA1c after transferring to diabetologists (Group 1); HbA1c was in average 7.6 mmol/mol lower in these patients [median 6.2 mmol/mol (range 0.25–29.2)]. 6/17 patients had a higher HbA1c level after the transition (Group 2) (mean change 20.1 mmol/mol; median 17.6; range 6.1–37.6). Both groups had a lower BMI after the transition. The mean difference in Group 1 was −0.5 vs −3.4 in Group 2, p = 0.09. FEV1 also declined in both groups (mean decline in Group 1 was 12.1% point compared to 18.7% in Group 2, p = 0.0002. Conclusion: Almost 2/3 of the patients had a lower HbA1c level after the transition. Group 1 also had a larger decline in both FEV1 and BMI compared to Group 2. 3 patients in Group 2 had a known history of poor compliance to other parts of CF treatment. We conclude that transferring to the diabetologists had a positive influence on most of the patients’ diabetes and indirectly affected their lung function and nutritional status in a positive way. Cooperation around patients with poor compliance is essential.
Workshop 13. Rescuing CFTR: new developments WS13.1 Ataluren significantly reduces exacerbations in nonsense mutation cystic fibrosis patients not receiving tobramycin K. De Boeck1 , H.G.M. Heijerman2 , J.C. Davies3 , I. Sermet-Gaudelus4 , L. Hjelte5 , E. Kerem6 , J. Sun7 , J. Mcintosh7 , A. Malfroot8 , H.A.W.M. Tiddens9 . 1 University Hospital Gasthuisberg, Leuven, Belgium; 2 HagaZiekenhuis, The Hague, Netherlands; 3 Royal Brompton and Harefield NHS Imperial College London, London, United Kingdom; 4 Hˆ opital Necker Enfants Malades, Paris, France; 5 Stockholm CF Center, Stockholm, Sweden; 6 Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 7 PTC Therapeutics, South Plainfield, United States; 8 Cystic Fibrosis Clinic, UZ Brussel, Brussel, Belgium; 9 ErasmusMC-Sophia Children’s Hospital, Rotterdam, Netherlands Introduction: Ataluren induces read-through of premature stop codons and can promote CFTR production in nonsense mutation CF (nmCF).
Methods: Skin wipe sampling was used to obtain sweat samples from 20 patients diagnosed with CF (10 adults, mean age 34 years; 10 children, mean age 8 years) and 10 control patients (10 children, mean age 7 years). The samples were analyzed by capillary electrophoresis with contactless conductometric detection. Cl− , potassium (K+ ) and sodium (Na+ ) ions were simultaneously determined in approximately 5 minutes in a background electrolyte containing 20 mM 2-(N-morpholino)ethanesulfonic acid, 20 mM L-histidine and 2 mM 18-crown-6. Results: Sweat sample is obtained by simple and fast wipe of the forearm (in <10 s) and is completely painless. Simultaneous analysis of Cl− , K+ and Na+ in sweat samples revealed that while Cl− alone can sometimes lead to false positive/negative result, the Cl− /K+ concentration ratio >4 (Cl− /K+ mean = 8.5, range 4.1–12.1 for children patients; Cl− /K+ mean = 7.5, range 5.2–12.6 for adult patients) correctly classified all CF patients and discriminated them from healthy controls (Cl− /K+ < 4, Cl− /K+ mean = 2.4, range 1.5–3.7). Conclusion: The newly developed skin wipe technique for sweat sampling is simple, fast and inexpensive and by using the Cl− /K+ ratio instead of Cl− concentration alone, the method can provide a better diagnostic tool with potential to reduce the false positive/negative values. WS11.6 Current status of early CF diagnosis in Latin America: results from the 1st LANES meeting N. Derichs1 , A. Kotnik Pirs2 , A. Jung3 , G.B. Aponte4 , M.L. Boza5 , C. Castanos6 , I. Chaustre7 , E. Chong8 , L. Cordero Onate9 , A. Hoepker10 , J.L. Lezana11 , M. Maestre12 , L. Rosal Palomo13 , C. Pinchak14 , L.V. Ferreira da Silva Filho15 , C. Vasquez-Mobile16 , P. Mastoridis17 , on behalf of the LANES Study Group and the ECFS Diagnostic Network Working atsmedizin Berlin, CFTR Biomarker Center, Berlin, Group. 1 Charit´e-Universit¨ Germany; 2 University Children’s Hospital Ljubljana, Ljubljana, Slovenia; 3 University Children’s Hospital Zurich, Zurich, Switzerland; 4 CF Centre, Lima, Peru; 5 Hospital Clinico San Borja Arriaran, Santiago de Chile, Chile; 6 Hospital de Pediatria, Buenos Aires, Argentina; 7 Children’s Hospital, Caracas, Venezuela; 8 Hospital Materno Infantil Jose Domingo de Obaldia, Panama, Panama; 9 Robert Reid Cabral Children Hospital, Dominican Republic, Dominican Republic; 10 National Children Hospital, San Jose, Costa Rica; 11 CF Centre, Mexico, Mexico; 12 Childrens Hospital, Cuenca, Ecuador; 13 CF Centre, Guatemala, Guatemala; 14 CF Centre, Montevideo, Uruguay; 15 CF Centre, Sao Paolo, Brazil; 16 CF Centre, Bogota, Colombia; 17 Novartis Pharma AG, East Hanover, United States Objectives: Establishing an early diagnosis of CF in Latin America is suspected to be challenging due to several reasons, including heterogeneity of the population, availability and costs of diagnostic tests and lack of public awareness for CF in some countries. Methods: An initiative by the ECFS Diagnostic Network Working Group aimed to better understand the current status of early CF diagnosis in Latin America. Expert representatives from 13 Latin American countries (Mexico, Guatemala, Costa Rica, Panama, Dominican Republic, Venezuela, Colombia, Ecuador, Uruguay, Brazil, Peru, Argentina, Chile) were invited to prepare a structured summary on the history and current situation of CF diagnosis in their country, and to share their experiences at the first Latin American Newborn and Early Screening of Cystic Fibrosis Patients (LANES) consensus meeting which was held in August 2015 in Sao Paolo, Brazil together with representatives from the ECFS DNWG and ECFS Patient Registry. Results: Important differences and challenges in diagnosing CF were discussed, including epidemiology, CF newborn screening, sweat test, CFTR genotyping and use of CF registries. Conclusion: The LANES project is the first joint initiative to summarise current practices and future perspectives for early CF diagnosis in Latin America. Increasing public awareness for early CF diagnosis was agreed to be of critical importance. Results from all attendees highlighted the significance and success of the LANES meeting, allowing for shared experiences to be discussed and future relationships and collaborations to achieve the best outcomes for CF patients in Latin America. Acknowledgement: Supported by Novartis
S19
Workshop 12. Bone health, glucose metabolism and CFRD WS12.2 Increased fracture rate in relation to macroscopic bone architecture in young patients with cystic fibrosis 3 M. Stahl1,2 , F.-M. Muller ¨ , C. Holfelder3 , C. Kneppo3 , M. Kieser4 , 4 5 3 1 C. Kasperk , E. Schonau ¨ , O. Sommerburg1 , B. Tonshoff ¨ . University Children’s Hospital Heidelberg, Pediatric Pulmonology, Allergy and CF-Centre, Heidelberg, Germany; 2 DZL, TLRC, Heidelberg, Germany; 3 ZKJM Heidelberg, Heidelberg, Germany; 4 University Heidelberg, Heidelberg, Germany; 5 University Cologne, Cologne, Germany Rationale: CF-related bone disease contributes significantly to patient morbidity. However, the relative risk for bone fractures is unknown and its relationship to parameters of macroscopic bone architecture is incompletely defined. Objectives: To evaluate the fracture rate in young CF patients and to analyze its relationship with parameters derived from DXA and pQCT measurements. Methods: This cross-sectional study investigated 43 CF patients (age, 17.8±6.2 years). The rate and location of radiographically confirmed fractures since birth was analyzed via a questionnaire. Bone mass, density, geometry, and strength of the radius as well as forearm muscle size were measured by pQCT, bone mineral density and content of the total skeleton and lumbar spine by DXA. Measurements and Main results: Eighteen of 43 patients (41.9%) had experienced fractures predominantly of the peripheral skeleton. Compared to an age-matched German control population, CF patients had a 9.2-fold higher fracture rate (P = 0.011). The probability of remaining free of any fracture in CF patients at 25 years was reduced to 39.8% compared to 84.6% in controls (P < 0.001). Combined assessment of macroscopic bone architecture by DXA and pQCT allowed the differentiation of patients with an increased fracture rate with a high sensitivity (100%) and specificity (94.3%). Conclusions: The fracture rate in young CF patients is markedly increased compared to controls and associated with alterations of macroscopic bone architecture. These results support the role of bone densitometry for noninvasive monitoring of bone quality in CF patients. WS12.3 Vertebral fracture assessment (VFA): a useful additional assessment of bone health in CF patients? A. Smith1 , S. Yoganathan1 , L. Speight1 , R. Petit2 , R.I. Ketchell1 , D. Lau1 , M. Stone3 , J. Duckers1 . 1 University Hospital Llandough, All Wales Adult Cystic Fibrosis Centre, Vale of Glamorgan, United Kingdom; 2 University Hospital of Wales, Cardiff, United Kingdom; 3 Cardiff University, Vale of Glamorgan, United Kingdom Objectives: To assess the utility of VFA in routine assessment of CF patient bone health. The presence of a vertebral fracture (VFr) significantly increases the risk of future fracture. Most VFr are silent and lateral X-rays are not routinely obtained in CF patients. VFA a technique of dual X-ray absorptiometry (DXA) based vertebral morphometry allows rapid assessment of VFr and is highly correlated with VFr as assessed on standard lateral spine X-rays. Methods: 138 patients attending their DXA also underwent VFA. Presence of VFr was determined using the McCloskey-Kanis method. Age, sex, FEV1 %, BMI, lumbar spine and total hip Z score, fracture history, whether they received oral or inhaled corticosteroids, bisphosphonate and calcium/vitamin D supplementation and the presence of common co-morbidities were recorded. Results: 138 patients (87 males) mean (SD) age 29.4(9.4)years, FEV1 % predicted 66.9(24.1)% and BMI of 22.8 (4.7)kg/m2 underwent VFA. Mean (SD) Z score at the lumbar spine −0.82 (1.12) and total hip −0.59 (1.01). Of 138 VFA performed 5 (3.6%) were abnormal 3 were suggestive of thoracic spine fractures which were not confirmed on subsequent lateral XR. A lumbar spine fracture and T11 fracture were detected on VFA in 2 (1.4%) patients that were retrospectively seen on CT images of the chest performed 2 years earlier.
S20
Oral Presentations / Journal of Cystic Fibrosis 15 (2016) S1–S50
Conclusion: Two VFr were found on VFA scanning giving a prevalence of VFr of 1.4%. These VFr were present on review of previous radiology so VFA has not added any significant positive findings. The prevalence of VFr is surprisingly low compared to other chronic respiratory diseases (COPD prevalence 42% of patients sustaining VFr – Nuti R et al. Osteopor Int 2008). WS12.4 The predictive value of oral glucose tolerance for the development of CFRD in CF children: a longitudinal study M.M.M. van Oirschot-van de Ven1 , A.C. de Kiviet1 , G. Berkers1 , J.M. Witmond1 , H.G.M. Arets1 , C.K. van der Ent1 . 1 Wilhelmina Children’s Hospital – University Medical Center Utrecht, Utrecht, Netherlands Objectives: The oral glucose tolerance test (OGTT) is the current gold standard to screen for cystic fibrosis-related-diabetes (CFRD). Diagnostic protocols advocate performing annual OGTT in patients above the age of ten years. However, data on the long term repeatability of OGTT outcomes are scarce. Our objective was to evaluate the predictive value of the OGTT for the development of CFRD. Methods: We performed a longitudinal study from 2009 until 2014 in our CF centre, in which we included children (aged 10–18 years) with CF and exocrine pancreas insufficiency. We evaluated the OGTT results of each year, and scored these results in four diabetes mellitus grades; 1 = normal (post-challenge <7.0 mmol/L), 2 = INDET (post-challenge 7.0– 11.1 mmol/L), 3 = IFG (post-challenge >11.1 mmol/L), 4 = CFRD (fasting >7.0 mmol/L). We compared the OGTT result of each year with the OGTT result of the next year. Table 1. Change in OFTT score after 1 year OGTT grade
1 2 3
OGTT grade next year 1
2
3
4
55.5% 29.3% 13.9%
38.7% 54.3% 38.9%
5.8% 15.4% 38.8%
0.0% 1.0% 8.3%
Results: During the study period, 417 OGTT’s where carried out in 123 patients. We found the following OGTT results in patients without CFRD: 41% of OGTT’s scored grade 1, 50% grade 2 and 9% grade 3. The results of the next years’ OGTT in the different grades are shown in Table 1. Conclusion: Results of OGTT in children with CF vary widely during annual follow-up. None of the children with a grade 1 result developed CFRD within a year. The annual probability to develop CFRD in children with a grade 3 result was 8.3%. WS12.5 Continuous glucose monitoring is an essential tool, alongside the OGTT, in the diagnosis and treatment of CFRD R. Margetts1 , S. Drew1 , H. Gordon1 , C. Peters1 . 1 Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom Objectives: To demonstrate the use of OGTT and continuous glucose monitoring (CGM) in diagnosis and treatment of CFRD and whether OGTT at 3 hours demonstrates rebound hypoglycaemia (RH). Methods: Data from OGTT screening tests was collected from one paediatric centre over 12 months. 1.75 g/kg glucose (max 75 g) was administered and glucose concentrations measured at 0, 60, 120 and 180mins. Results were classified according to WHO diagnostic criteria. In addition, a blood glucose (BG) <4 mmol/l at 180mins was classified as RH. For abnormal results, CGM was used to confirm diagnosis and guide treatment. CGM was considered normal if glucose concentrations were 4–10 mmol/l over 5–7 days. Table: Summary of diagnoses from OGTT
OGTT (n = 25) RH (n = 13)
Normal
Indeterminate
IGT
CFRD
13 7
6 5
5 1
1 0
IGT, impaired glucose tolerance.
Results: 25 tests were performed. 18 females, age range 4–16 years (mean 11.3). 13/25 were referred for CGM, 2 refused but monitored BG at home. 4 cases with normal OGTT and RH received diet advice. In 8/11 cases, CGM showed normal BG needing no further intervention. 3 cases received diet advice. No insulin was required. Conclusion: Our data from CGM shows that not all children will require insulin despite abnormal OGTT. There was evidence of glucose dysregulation at 3 hours in those with normal OGTT. The OGTT is based on a glucose load whereas the CGM is based on lifestyle and diet. Some diet manipulation helps fluctuations in BG. We would recommend CGM surveillance for young people with abnormal OGTT in addition to an annual OGTT. Standardisation of CGM to provide diagnostic criteria for CFRD needs to be agreed before using it as a screening tool. WS12.6 How does transferral from CF doctors to endocrinologists affect blood glucose control in patients with CFRD R. a Rogvi1 , T.K. Hansen2 , H.V. Olesen3 . 1 Aarhus University, Aarhus, Denmark; 2 Aarhus University Hospital, Department of Endocrinology and Diabetes, Aarhus, Denmark; 3 Aarhus University Hospital, Department of Pediatrics, Aarhus, Denmark Background: CF Related Diabetes (CFRD) has a negative influence on the patients’ QoL, nutrition and lung function. The aim of this study was to investigate whether transferring from diabetes control by CF physicians to adult diabetologists has a positive effect on CF patients’ CFRD management. Methods: The study population was 17 patients with CFRD diagnosed before the transition registered in CF Registry Denmark. Mean HbA1c before (2010/2011) and after (2014/2015) the transfer was compared. Mean BMI and lung function (FEV1) in 2010 and 2014 were evaluated. Results: Mean HbA1c value before the transition was 66.9 mmol/mol (range 48.5–117.3). 11/17 patients had a lower mean HbA1c after transferring to diabetologists (Group 1); HbA1c was in average 7.6 mmol/mol lower in these patients [median 6.2 mmol/mol (range 0.25–29.2)]. 6/17 patients had a higher HbA1c level after the transition (Group 2) (mean change 20.1 mmol/mol; median 17.6; range 6.1–37.6). Both groups had a lower BMI after the transition. The mean difference in Group 1 was −0.5 vs −3.4 in Group 2, p = 0.09. FEV1 also declined in both groups (mean decline in Group 1 was 12.1% point compared to 18.7% in Group 2, p = 0.0002. Conclusion: Almost 2/3 of the patients had a lower HbA1c level after the transition. Group 1 also had a larger decline in both FEV1 and BMI compared to Group 2. 3 patients in Group 2 had a known history of poor compliance to other parts of CF treatment. We conclude that transferring to the diabetologists had a positive influence on most of the patients’ diabetes and indirectly affected their lung function and nutritional status in a positive way. Cooperation around patients with poor compliance is essential.
Workshop 13. Rescuing CFTR: new developments WS13.1 Ataluren significantly reduces exacerbations in nonsense mutation cystic fibrosis patients not receiving tobramycin K. De Boeck1 , H.G.M. Heijerman2 , J.C. Davies3 , I. Sermet-Gaudelus4 , L. Hjelte5 , E. Kerem6 , J. Sun7 , J. Mcintosh7 , A. Malfroot8 , H.A.W.M. Tiddens9 . 1 University Hospital Gasthuisberg, Leuven, Belgium; 2 HagaZiekenhuis, The Hague, Netherlands; 3 Royal Brompton and Harefield NHS Imperial College London, London, United Kingdom; 4 Hˆ opital Necker Enfants Malades, Paris, France; 5 Stockholm CF Center, Stockholm, Sweden; 6 Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 7 PTC Therapeutics, South Plainfield, United States; 8 Cystic Fibrosis Clinic, UZ Brussel, Brussel, Belgium; 9 ErasmusMC-Sophia Children’s Hospital, Rotterdam, Netherlands Introduction: Ataluren induces read-through of premature stop codons and can promote CFTR production in nonsense mutation CF (nmCF).