- Email: [email protected]
297 Arab cystic fibrosis patients in Israel
S124
14. Epidemiology/Registry
Posters
295 CF patients diagnosed in adulthood: spectrum of referral source
297 Arab cystic fibrosis patients in Israel
N. Hunt1 , G.H. Jones1 , E. Phitidis1 , M. Murthy1 , J. Greenwood1 , M. Ledson1 , M. Walshaw1 . 1 Liverpool Heart and Chest Hospital, Respiratory Medicine, Liverpool, United Kingdom
M. Lavie1 , I. Lifshitz1 , D. Vilozni1 , I. Shapira1 , I. Sarouk1 , B.-E. Bar1 , A. Dagan1 , G. Livnat2 , M. Cohen-Cymberknoh3 , M. Mei-Zahav4 , J. Rivlin5 , O. Efrati1 . 1 Pediatric Pulmonary Unit and The National Center for Cystic Fibrosis, Edmond and Lili Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Affiliated to the Sackler Medical School, Tel Aviv University, Ramat Gan, Israel; 2 Pediatric Pulmonary Unit, Meyer Children’s Hospital, Rambam Health Care Campus, Affiliated to the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; 3 Pediatric Pulmonology and CF Center, Hadassah Mount Scopus Hospital, Affiliated to the Hebrew University, Jerusalem, Israel; 4 Pulmonary Unit and the Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel; 5 CF Center, Carmel Medical Center, Affiliated to the Technion Faculty of Medicine, Haifa, Israel
Objectives: Although the vast majority of individuals with CF are diagnosed under the age of 3 years, increased awareness of the condition amongst adult clinicians means that up to 12% of diagnoses are now made in adulthood (UK CF Registry 2012). As specific CF treatment is linked to improved outcomes, we looked at the characteristics of patients attending our centre who were diagnosed in adulthood. Methods: All 32 patients diagnosed in adulthood (defined as age >17 years, 11.2% of the total) were identified. The referral source and reason were studied: any radiological findings at referral were used to aid this. Results: The median diagnosis age was 30 years (range 19−60). Twenty-two patients (69%) were referred from general chest clinics and the remainder from surgical, fertility and genetics services. The commonest referral reason was recurrent lower respiratory infection (11, 34%), followed by a paediatric family history (5, 16%). 2 patients (6%) were referred from fertility services with azoospermia. 24 (75%) had undergone HRCT at referral (18 from chest clinics): 18 (82%) had bronchiectasis (7 severe widespread, 6 mild widespread, 3 lower lobe, 2 upper lobe) and 1 patient had bronchial wall thickening. Conclusion: CF can be diagnosed at any age and in a number of different specialties. Though the majority were referred by respiratory clinicians, some patients were diagnosed in surgery or fertility clinics illustrating the increasing awareness of adult CF as a clinical entity. As expected those referred from nonrespiratory sources were more likely to have a normal HRCT. Improving links between CF centres and other specialities may help the diagnosis rate in the adult population.
296 Adult CF diagnosis − missed childhood opportunities or forme fruste disease?
298 Establishment of a Russian cystic fibrosis patient registry
N. Hunt1 , E. Phitidis1 , M. Murthy1 , G.H. Jones1 , J. Greenwood1 , M. Ledson1 , M. Walshaw1 . 1 Liverpool Heart & Chest Hospital, Respiratory Medicine, Liverpool, United Kingdom Objectives: Although the majority of the CF population is diagnosed in childhood, up to 12% only appear in adulthood (UK CF Registry 2012). To study the reasons for this we compared the characteristics of our patients diagnosed in adulthood (AD) with the general adult CF population (GP). Methods: We looked at all 32 patients diagnosed in adulthood (defined as >17 years of age) attending our large adult centre (11.2% of the total). We reviewed their phenotype and genotype and compared their cohort characteristics with those given in the UK CF Registry Report 2012 where possible. Results: Median age at diagnosis was 30 years (range 19−60 years) and 13 (41%) are male. Other results are given in the table. Parameter Genotype
CFRD CFRLD ABPA Employment
AD GP Parameter (%) (%) DF508/DF508 DF508/other Gene/− −/− or no DF508
12.5 62.5 43.7 25 32 3.1 18.8 75
51.7 Sputum culture 39 10.7 9.4 30 18.1 12.5 70 Pancreatic sufficient
AD GP (%) (%) Chronic Psa 28.1 S. aureus 28.1 MRSA 6.2 Burkholderia sp. 3.1 NTM 12.5 Unknown 6.2 Other 31 31
Objectives: Cystic Fibrosis (CF) population in Israel consists of 600 patients from whom 150 are Israeli Arabs (A-CF) who may differ from the Jewish population (J-CF) in genetics, demographics, economic status, cultural and religious aspects. The aim of our work was to characterize differences in CF between both populations. Methods: Data from medical records was retrospectively collected form 147 A-CF and compared to 64 age, sex and genetic mutation matched and 104 nonmatched J-CF. Results: Homozygotes or compound heterozygotes to 2 mild mutations were more common in A-CF (10.2% vs. 4.8%; p < 0.05), while 1 severe mutation was more common in J-CF (22.1% vs. 6.1%; p < 0.05). Airway colonization with Pseudomonas aeruginosa was similar between A-CF and J-CF but A-CF had less colonization with Methicillin-resistant Staphylococcus aureus and Mycobacterium abscessus (1.4% vs. 8.6% and 2.0% vs. 30.7%; p < 0.001). A-CF had less CF related conditions compared to J-CF (77.4% vs. 87.5; p < 0.05) however, failure to thrive was more prevalent in A-CF (26% vs. 10.6%; p < 0.05). In longitudinal follow up of pulmonary functions in the last 10 years A-CF showed a trend of higher FEV1 values. Conclusion: Israeli Arab patients seem to have a less severe course of disease compared to Jewish patients as reflected by less colonization of airways, less CFrelated conditions and better lung functions despite a worse nutritional state. This may be attributed to differences in genetics therefore a screening project is now being implemented.
54.3 24 4 5.1 7.3
20
Conclusion: Our CF patients diagnosed in adulthood tend to have a less severe disease phenotype compared to the general CF population. In keeping with this fewer were pancreatic insufficient or had liver disease. Nevertheless the lung pathogen load was similar although proportions of infecting organisms differed. These results suggest that most late diagnoses are a result of less severe disease: newborn screening programs may bring these forme fruste individuals to light earlier, possibly improving their prognosis.
S. Krasovskiy1 , N. Kashirskaya2 , N. Kapranov2 , A. Cherniak1 , E. Amelina1 , E. Kondrateva2 , I. Asherova3 , E. Boitsova4 , V. Brisin5 , V. Chikunov6 , O. Golubtsova7 , N. Ilenkova6 , M. Khachiyan5 , Y. Kondakova8 , L. Kozireva9 , V. Nikonova2 , T. Protasova10 , M. Rybalkina11 , T. Safonova12 , D. Sergienko13 , L. Shabalova2 , V. Shadrina14 , N. Shelepneva2 , V. Sherman2 , I. Smirnova15 , I. Uspenskaya16 , T. Vasileva17 , A. Voronkova2 , A. Chuchalin1 . 1 Institute of Pulmonology FMBA, Moscow, Russian Federation; 2 Research Centre for Medical Genetics, Department of Cystic Fibrosis, Moscow, Russian Federation; 3 Regional CF Center, Yaroslavl, Russian Federation; 4 Regional CF Center, St. Petersburg, Russian Federation; 5 Regional CF Center, Krasnodar, Russian Federation; 6 Regional CF Center, Krasnoyarsk, Russian Federation; 7 Regional CF Center, Cheboksary, Russian Federation; 8 Regional CF Center, Novosibirsk, Russian Federation; 9 Regional CF Center, Yfa, Russian Federation; 10 Regional CF Center, Kemerovo, Russian Federation; 11 Regional CF Center, Orenburg, Russian Federation; 12 Regional CF Center, Omsk, Russian Federation; 13 Regional CF Center, Astrakhan, Russian Federation; 14 Regional CF Center, Perm, Russian Federation; 15 Regional CF Center, Tomsk, Russian Federation; 16 Regional CF Center, Nizhniy Novgorod, Russian Federation; 17 Regional CF Center, Vladivostok, Russian Federation Objectives: To identify clinical and genetic features of CF in Russia by establishing the CF patients Registry (RCFpR). Methods: In 2011 there was initiated a project to establish and maintain the new version of RCFpR with the inclusion of detailed data on the genetic, diagnostic, clinical and therapeutic information comparable with the ECFS Patient Registry. RCFpR included data from 17 regions, representing a total of almost 54 million of the Russian population (37.4% of the total population). RCFpR included 1015 (544 male) CF patients. Results: The main data: average age of CF patients was 11.5±8.8 (min 0.03, max 44.2), the proportion of patients older 18 years was 24.0%, median age at diagnosis 1 year (min 0, max 41.0). Frequency of F508del was 52.2%, CFTR dele2,3 6.3%, E92K 2.5%. FEV1 64.3±23.5%, FVC 72.1±24.3%. 91.9% of patients were treated with dornase alpha, 60% with bronchodilators, 18.4% inhaled steroids, 8.2% hypertonic saline, 48.5% intravenous antibiotics, 46.3% oral antibiotics, 39.6% inhaled antibiotics, 92.6% pancreatic enzymes, 91.5% UDCA, 5.8% systemic steroids, 62.0% fat-soluble vitamins. Only 55.8% did physiotherapy, 5.8% were on oxygen therapy. Chronic infection with P. aeruginosa was present in 30.4% (intermittent 9.3%) of patients, with S. aureus in 55.3%, B. cepacia in 6.5% and S. maltophilia in 3.1%. CF complications: diabetes 3.1%, liver disease 28.5%, electrolyte disorders 2.8%, pneumothorax 1.5%. During this period 15 patients died, mean age at death 16.0±12.8 years (min 0.3, max 36.8). Conclusion: The establishing of the RCFpR will facilitate a long-term planning of CF service including financial costs in Russia.
14. Epidemiology/Registry
Posters
295 CF patients diagnosed in adulthood: spectrum of referral source
297 Arab cystic fibrosis patients in Israel
N. Hunt1 , G.H. Jones1 , E. Phitidis1 , M. Murthy1 , J. Greenwood1 , M. Ledson1 , M. Walshaw1 . 1 Liverpool Heart and Chest Hospital, Respiratory Medicine, Liverpool, United Kingdom
M. Lavie1 , I. Lifshitz1 , D. Vilozni1 , I. Shapira1 , I. Sarouk1 , B.-E. Bar1 , A. Dagan1 , G. Livnat2 , M. Cohen-Cymberknoh3 , M. Mei-Zahav4 , J. Rivlin5 , O. Efrati1 . 1 Pediatric Pulmonary Unit and The National Center for Cystic Fibrosis, Edmond and Lili Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Affiliated to the Sackler Medical School, Tel Aviv University, Ramat Gan, Israel; 2 Pediatric Pulmonary Unit, Meyer Children’s Hospital, Rambam Health Care Campus, Affiliated to the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; 3 Pediatric Pulmonology and CF Center, Hadassah Mount Scopus Hospital, Affiliated to the Hebrew University, Jerusalem, Israel; 4 Pulmonary Unit and the Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel; 5 CF Center, Carmel Medical Center, Affiliated to the Technion Faculty of Medicine, Haifa, Israel
Objectives: Although the vast majority of individuals with CF are diagnosed under the age of 3 years, increased awareness of the condition amongst adult clinicians means that up to 12% of diagnoses are now made in adulthood (UK CF Registry 2012). As specific CF treatment is linked to improved outcomes, we looked at the characteristics of patients attending our centre who were diagnosed in adulthood. Methods: All 32 patients diagnosed in adulthood (defined as age >17 years, 11.2% of the total) were identified. The referral source and reason were studied: any radiological findings at referral were used to aid this. Results: The median diagnosis age was 30 years (range 19−60). Twenty-two patients (69%) were referred from general chest clinics and the remainder from surgical, fertility and genetics services. The commonest referral reason was recurrent lower respiratory infection (11, 34%), followed by a paediatric family history (5, 16%). 2 patients (6%) were referred from fertility services with azoospermia. 24 (75%) had undergone HRCT at referral (18 from chest clinics): 18 (82%) had bronchiectasis (7 severe widespread, 6 mild widespread, 3 lower lobe, 2 upper lobe) and 1 patient had bronchial wall thickening. Conclusion: CF can be diagnosed at any age and in a number of different specialties. Though the majority were referred by respiratory clinicians, some patients were diagnosed in surgery or fertility clinics illustrating the increasing awareness of adult CF as a clinical entity. As expected those referred from nonrespiratory sources were more likely to have a normal HRCT. Improving links between CF centres and other specialities may help the diagnosis rate in the adult population.
296 Adult CF diagnosis − missed childhood opportunities or forme fruste disease?
298 Establishment of a Russian cystic fibrosis patient registry
N. Hunt1 , E. Phitidis1 , M. Murthy1 , G.H. Jones1 , J. Greenwood1 , M. Ledson1 , M. Walshaw1 . 1 Liverpool Heart & Chest Hospital, Respiratory Medicine, Liverpool, United Kingdom Objectives: Although the majority of the CF population is diagnosed in childhood, up to 12% only appear in adulthood (UK CF Registry 2012). To study the reasons for this we compared the characteristics of our patients diagnosed in adulthood (AD) with the general adult CF population (GP). Methods: We looked at all 32 patients diagnosed in adulthood (defined as >17 years of age) attending our large adult centre (11.2% of the total). We reviewed their phenotype and genotype and compared their cohort characteristics with those given in the UK CF Registry Report 2012 where possible. Results: Median age at diagnosis was 30 years (range 19−60 years) and 13 (41%) are male. Other results are given in the table. Parameter Genotype
CFRD CFRLD ABPA Employment
AD GP Parameter (%) (%) DF508/DF508 DF508/other Gene/− −/− or no DF508
12.5 62.5 43.7 25 32 3.1 18.8 75
51.7 Sputum culture 39 10.7 9.4 30 18.1 12.5 70 Pancreatic sufficient
AD GP (%) (%) Chronic Psa 28.1 S. aureus 28.1 MRSA 6.2 Burkholderia sp. 3.1 NTM 12.5 Unknown 6.2 Other 31 31
Objectives: Cystic Fibrosis (CF) population in Israel consists of 600 patients from whom 150 are Israeli Arabs (A-CF) who may differ from the Jewish population (J-CF) in genetics, demographics, economic status, cultural and religious aspects. The aim of our work was to characterize differences in CF between both populations. Methods: Data from medical records was retrospectively collected form 147 A-CF and compared to 64 age, sex and genetic mutation matched and 104 nonmatched J-CF. Results: Homozygotes or compound heterozygotes to 2 mild mutations were more common in A-CF (10.2% vs. 4.8%; p < 0.05), while 1 severe mutation was more common in J-CF (22.1% vs. 6.1%; p < 0.05). Airway colonization with Pseudomonas aeruginosa was similar between A-CF and J-CF but A-CF had less colonization with Methicillin-resistant Staphylococcus aureus and Mycobacterium abscessus (1.4% vs. 8.6% and 2.0% vs. 30.7%; p < 0.001). A-CF had less CF related conditions compared to J-CF (77.4% vs. 87.5; p < 0.05) however, failure to thrive was more prevalent in A-CF (26% vs. 10.6%; p < 0.05). In longitudinal follow up of pulmonary functions in the last 10 years A-CF showed a trend of higher FEV1 values. Conclusion: Israeli Arab patients seem to have a less severe course of disease compared to Jewish patients as reflected by less colonization of airways, less CFrelated conditions and better lung functions despite a worse nutritional state. This may be attributed to differences in genetics therefore a screening project is now being implemented.
54.3 24 4 5.1 7.3
20
Conclusion: Our CF patients diagnosed in adulthood tend to have a less severe disease phenotype compared to the general CF population. In keeping with this fewer were pancreatic insufficient or had liver disease. Nevertheless the lung pathogen load was similar although proportions of infecting organisms differed. These results suggest that most late diagnoses are a result of less severe disease: newborn screening programs may bring these forme fruste individuals to light earlier, possibly improving their prognosis.
S. Krasovskiy1 , N. Kashirskaya2 , N. Kapranov2 , A. Cherniak1 , E. Amelina1 , E. Kondrateva2 , I. Asherova3 , E. Boitsova4 , V. Brisin5 , V. Chikunov6 , O. Golubtsova7 , N. Ilenkova6 , M. Khachiyan5 , Y. Kondakova8 , L. Kozireva9 , V. Nikonova2 , T. Protasova10 , M. Rybalkina11 , T. Safonova12 , D. Sergienko13 , L. Shabalova2 , V. Shadrina14 , N. Shelepneva2 , V. Sherman2 , I. Smirnova15 , I. Uspenskaya16 , T. Vasileva17 , A. Voronkova2 , A. Chuchalin1 . 1 Institute of Pulmonology FMBA, Moscow, Russian Federation; 2 Research Centre for Medical Genetics, Department of Cystic Fibrosis, Moscow, Russian Federation; 3 Regional CF Center, Yaroslavl, Russian Federation; 4 Regional CF Center, St. Petersburg, Russian Federation; 5 Regional CF Center, Krasnodar, Russian Federation; 6 Regional CF Center, Krasnoyarsk, Russian Federation; 7 Regional CF Center, Cheboksary, Russian Federation; 8 Regional CF Center, Novosibirsk, Russian Federation; 9 Regional CF Center, Yfa, Russian Federation; 10 Regional CF Center, Kemerovo, Russian Federation; 11 Regional CF Center, Orenburg, Russian Federation; 12 Regional CF Center, Omsk, Russian Federation; 13 Regional CF Center, Astrakhan, Russian Federation; 14 Regional CF Center, Perm, Russian Federation; 15 Regional CF Center, Tomsk, Russian Federation; 16 Regional CF Center, Nizhniy Novgorod, Russian Federation; 17 Regional CF Center, Vladivostok, Russian Federation Objectives: To identify clinical and genetic features of CF in Russia by establishing the CF patients Registry (RCFpR). Methods: In 2011 there was initiated a project to establish and maintain the new version of RCFpR with the inclusion of detailed data on the genetic, diagnostic, clinical and therapeutic information comparable with the ECFS Patient Registry. RCFpR included data from 17 regions, representing a total of almost 54 million of the Russian population (37.4% of the total population). RCFpR included 1015 (544 male) CF patients. Results: The main data: average age of CF patients was 11.5±8.8 (min 0.03, max 44.2), the proportion of patients older 18 years was 24.0%, median age at diagnosis 1 year (min 0, max 41.0). Frequency of F508del was 52.2%, CFTR dele2,3 6.3%, E92K 2.5%. FEV1 64.3±23.5%, FVC 72.1±24.3%. 91.9% of patients were treated with dornase alpha, 60% with bronchodilators, 18.4% inhaled steroids, 8.2% hypertonic saline, 48.5% intravenous antibiotics, 46.3% oral antibiotics, 39.6% inhaled antibiotics, 92.6% pancreatic enzymes, 91.5% UDCA, 5.8% systemic steroids, 62.0% fat-soluble vitamins. Only 55.8% did physiotherapy, 5.8% were on oxygen therapy. Chronic infection with P. aeruginosa was present in 30.4% (intermittent 9.3%) of patients, with S. aureus in 55.3%, B. cepacia in 6.5% and S. maltophilia in 3.1%. CF complications: diabetes 3.1%, liver disease 28.5%, electrolyte disorders 2.8%, pneumothorax 1.5%. During this period 15 patients died, mean age at death 16.0±12.8 years (min 0.3, max 36.8). Conclusion: The establishing of the RCFpR will facilitate a long-term planning of CF service including financial costs in Russia.