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Microbiology of the respiratory tract in cystic fibrosis patients diagnosed by neonatal screening: differences with healthy patients
Posters / Paediatric Respiratory Reviews 11S1 (2010) S79–S115
sweat chloride were: ≤5 years – 18 mmol/L (6–36 mmol/L) ; >5 up to 10 years, 20 mmol/L (6–38 mmol/L); 11 to 15 years, 21 mmol/L (7–39 mmol/L); 16 years, 16 mmol/L (6–40 mmol/L); Sweat Chloride values increased with increasing age in study population. This is the first study done to determine age specific reference interval of sweat chloride values in paediatric population of India. The results of this study will create a data base which can be extrapolated to rest of paediatric population of India. P58F Improvement in ion transport biomarkers and spirometry with the investigational CFTR potentiator VX-770 in subjects with cystic fibrosis and the G551D-CFTR mutation S.M. Rowe1 , F.J. Accurso2 , J.P. Clancy1 , M.P. Boyle3 , J.M. Dunitz4 , P.R. Durie5 , S.D. Sagel2 , D.B. Hornick6 , M.W. Konstan7 , S.H. Donaldson8 , R.B. Moss9 , J.M. Pilewski10 , R. Rubenstein11 , D.B. Uluer12 , M.L. Aitken13 , Q. Dong14 , C.L. Ordonez14 , P.W. Campbell15 , M.A. Ashlock15 , B.W. Ramsey16 . 1 University of Alabama at Birmingham – Birmingham, USA; 2 University of Colorado Denver – Aurora, USA; 3 Johns Hopkins Medical Institutions – Baltimore, USA; 4 University of Minnesota – Minneapolis, USA; 5 The Hospital for Sick Children and the University of Toronto – Toronto, Canada; 6 University of Iowa Carver College of Medicine – Iowa City, USA; 7 Rainbow Babies and Children’s Hospital and Case Western Reserve University School of Medicine – Cleveland, USA; 8 University of North Carolina at Chapel Hill – Chapel Hill, USA; 9 Stanford University School of Medicine – Palo Alto, USA; 10 University of Pittsburgh – Pittsburgh, USA; 11 Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine – Philadelphia, USA; 12 Children’s Hospital of Boston – Boston, USA; 13 University of Washington – Seattle, USA; 14 Vertex Pharmaceuticals Incorporated – Cambridge, USA; 15 Cystic Fibrosis Foundation Therapeutics, Inc. – Bethesda, USA; 16 Seattle Children’s Hospital – Seattle, USA Purpose: Cystic fibrosis (CF) is an inherited chronic illness often diagnosed by 2 years of age. CF is characterized by progressive obstructive lung disease, which is the most common cause of mortality. CF is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), an epithelial ion channel involved in sodium and chloride transport in multiple organs, including the airway and sweat duct. One therapeutic approach being investigated in CF is restoring CFTR function through small molecule pharmaceuticals. Methods: This 2-part, randomized, double-blind, placebocontrolled Phase 2 trial evaluated the safety and tolerability of VX-770, an orally bioavailable investigational potentiator of CFTR function, in 39 adults with CF carrying a G551D-CFTR allele. VX770 at doses of 25, 75, 150, and 250 mg or placebo q12h was administered over 14 or 28 day treatment periods. Secondary outcomes included biomarkers of ion transport (nasal potential difference [NPD] and sweat chloride), spirometry, and quality of life (CFQ-R instrument). Results: VX-770 was well tolerated and no serious drug-related adverse events occurred. After 14 days of treatment (combined Parts 1 & 2), statistically significant (P < 0.05) within-subject improvements were observed in sweat chloride for all VX-770 dose groups but not for placebo. Sweat chloride concentrations fell below the 60 mmol/L diagnostic threshold for CF in at least 42% of subjects in the 75 mg or higher VX-770 dose groups. A significant improvement was also observed in NPD zero chloride plus isoproterenol response in the VX-770 75, 150, and 250 mg dose groups at Day 14. VX-770 significantly improved FEV1 and FEF25–75% at Day 14 at several dose levels. Mean relative change from baseline in the VX-770 150 mg group for FEV1 % and FEF25–75% % predicted was 10.8% and 9.4%, respectively (P < 0.05 within-subject). At 14 days, using a post-hoc significant response criterion of >10% in FEV1 % predicted, improvement was observed in 7/16 (43.8%) and 2/12 (16.7%) of patients in the VX-770 150 mg group and placebo group,
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respectively. A minimal clinically important difference (≥4 points) in the CFQ-R respiratory domain score was observed in 5/8 subjects in the VX-770 150 mg group at both Days 14 and 28 (Part 2 only). Improvements in CFTR biomarkers and lung function were sustained in subjects who completed 28 days. The VX-770 150 mg group had absolute changes from baseline in sweat chloride of −59.5 mmol/L (P < 0.01 within-subject) and −3.5 mV (P < 0.02) for NPD, and a median relative change from baseline in FEV1 % predicted of 8.7% (P < 0.01 within-subject). Conclusions: VX-770 was well tolerated and significantly improved CFTR-mediated chloride ion transport (NPD, sweat chloride) and lung function through 28 days of dosing. Further evaluation of VX-770 in large, long-term Phase 3 trials in CF subjects aged 6 years and above are in progress. Sponsored by Vertex Pharmaceuticals Incorporated with support from Cystic Fibrosis Foundation Therapeutics Inc. and a US FDA Office of Orphan Products Development Grant (# FD-R-003432– 01). P59F Interrelationships between lung clearance index and parameters of lung function and gas exchange in patients with cystic fibrosis J. Große-Onnebrink, F. Stehling, U. Mellies. University Hospital Essen Pediatric Pulmonology – Essen, Germany Background and Aim: Increased lung clearance index (LCI) measured by multiple breath wash-out (MBW) technique reflects ventilation inhomogeneity as a sign of early lung disease in patients with cystic fibrosis (CF). Aim of the study was to assess interrelationships between LCI and parameters of lung function that represent airflow limitation, pulmonary hyperinflation as well as impaired gas exchange in children, adolescents and adults with CF. Methods: In this retrospective study 33 patients with CF (age 5–44, mean 18 years) underwent as part of their routine annual review whole body plethysmography, MBW (with side stream ultrasonic flow sensor and sulfurhexafluorid (SF6) as tracer gas) and capillary blood gas analysis from arterialized earlobe blood. The correlation coefficients between LCI and FEV1 % predicted (pred), FEF25–75 % pred, specific airway resistance (sReff ), residual volume (RV) % pred, RV / total lung capacity (TLC) PL %, volume of trapped gas (VTG ), PaO2 , PaCO2 and alveolar arterial oxygen gradient (A-aO2 ) were calculated. Results: LCI correlated with FEV1 % pred (r = −0.791), FEF25–75 % pred (r = −0.674), sReff (r = 0.740), RV % pred (r = 0.658), RV/TLC PL% (r = 0.792), VTG (r = 0.575), PaO2 (r = −0.766), PaCO2 (r = 0.507) and A-aO2 (r = 0.619). Patients with normal FEV1 (FEV1 >80% pred) were divided in 2 subgroups with LCI <7 (n = 4) and LCI >7 (n = 8), resp. Mean PaO2 was 90.38 mmHg and 78.66 mmHg resp. and A-aO2 was 12.69 mmHg and 23.28 mmHg resp. (p < 0,05 for both). Conclusions: Lung clearance index correlates with parameters of airflow limitation, pulmonary hyperinflation and impaired gas exchange in patients with cystic fibrosis. Patients with normal FEV1 but abnormal LCI (>7) may already have small airway disease with impaired gas exchange. P60F Microbiology of the respiratory tract in cystic fibrosis patients diagnosed by neonatal screening: differences with healthy patients 1 L. Valdesoiro-Navarrete1 , M. Bosque1 , C. Rodrigo2 , N. Lopez ´ , 1 1 1 1 1 A. Valiente , O. Asensio , H. Larramona , Ch. Domingo . Corporacio Parc tauli – Sabadell, Spain; 2 Germans Trias i Pujol Pediatrics – Badalona, Spain
Introduction: The pathophysiology of lung disease at Cystic fibrosis (CF) is based in inflammation, infection and colonization of
S100
Posters / Paediatric Respiratory Reviews 11S1 (2010) S79–S115
respiratory tract. All of CF patients, still asymptomatics, could be positive specimens. Our aim was compared the microbiology of the respiratory tract of our patients with healthy controls of same ages. Method and Material: Observational prospective study. Patients: infants with newly diagnosed cystic fibrosis disease which were identified by neonatal screening, from October 1999 to February 2005. These patients will be followed since the age of four. Healthy controls: patients between 0 to 4 years old who needs surgery and without respiratory pathology. A collection of specimen is taken applying the oropharinx aspirate (AOF) technique. Patients: These specimens are taken monthly and should the infant develop respiratory infection symptoms, additional specimen was taken. Healthy controls: These specimens are taken during anaesthesia induction. A signed consent was obtained previously. Results: Patients: 21 (76.19% males) patients with cystic fibrosis diagnosis were recruited. All patients were followed four years. 960 AOF specimens were taken, 365 (38%) of which were positive and 447 microorganisms were isolated. Healthy controls: 106 (78.6% males) patients were recruited. 103 AOF specimens were taken, 30 (29%) of which were positive and 36 microorganisms were isolated. The more frequent microorganisms isolated at both groups (CF patients/ healthy controls) were: Staphylococcus aureus (33.3% vs 36.1%), Enterobacter cloacae (12% vs 16.7%), Escherichia coli (13.9% vs 11%), Klebsiella spp. (17.2% vs 16.6%), Pseudomonas aeruginosa (7.4% vs 8.3%). We did not find significant differences between both groups about the isolated microorganisms, but all the CF patients have positive cultures and only 29% of healthy patients have it. Conclusions: The microorganism isolated in our study show similarities between CF patients and healthy controls. Probably the differences are in the host. P61F The status of cystic fibrosis patients in 2009 in Albania E. Vevecka1 , S. Noka2 . 1 University Hospital Center of Tirana “Mother Teresa” Pediatrics – Tirana, Albania; 2 Faculty of Medicine, Tirana University – Tirana, Albania In Albania the care of children with CF consist of one Pediatric service in University Hospital Center of Tirana “Mother Teresa”, serving a whole population of about 3 million inhabitants. Aim: To evaluate the epidemiologic data on CF in Albania according to the European CF registry. Method: Demographic, genetic and clinical symptoms were collected in a database according to the European CF registry. Data collection was completed in a three months period (September– November 2009). All the information was obtained from patients’ clinical notes. Results: Totally 70 CF patients were identified with mean age 6.2±4.4 years. The older CF patient was 17 years old, while 7.2% were older than 14 years old. Mean age at diagnosis was 7.9±17.9 months. 65.7% of patients were identified with DF 508 mutation (Homozygous). 24.2% of patients were chronically colonized with Pseudomonas aeruginosa. Burkholderia cepacia was not isolated in any of our patients. 97% had pancreatic insufficiency, 85.5% were underweight (BMI < 18.5). 7% presented with meconeum ileus. 17% had CFRD. FEV1 among 6 yo patients was over 80% of predicted. One of our patients had undergone liver transplantation. Conclusions: The status of patients with CF in Albania is presented. The DF mutation is higher than other country of the region. The nutritional status of our patients is poor.
7. Respiratory manifestations of extra-pulmonary diseases (including AIDS) P62G Interstitial lung disease and gastroesophageal reflux M. Verini1 , D. Rapino2 , F. Matronola1 , N.P. Consilvio1 , C. Spagnuolo1 , A. Palazzo1 , A. Scaparrotta1 , A. Cingolani1 , S. Di Pillo1 , F. Chiarelli2 . 1 Allergological and Respiratory Unit, Paediatric Clinic, University of Chieti, Chieti, Italy; 2 Paediatric Clinic, University of Chieti, Chieti, Italy Interstitial lung diseases are an heterogeneus group of pathologies with etiology often unknown. These pathologies include alteration of peripheral airways related with alveolar wall thickness [1]. Some subgroups of these diseases are characterized by widespread pulmonary infiltrate, restrictive functional pattern, hypoxia, growth retardation, thorax abnormalities, digital clubbing and signs of cardiac involvement [2]. Many patients have a high mortality [3], some other have a good outcome [4]. We describe the case of a 22 month child with physiologic neonatal anamnesis, dystrophic appearance, digital clubbing and growth retardation, with a previous basal bilateral bronchopneumonia, who came to the admission for right basal bronchopneumonia with abnormal respiratory rate (RR = 70 b/m.). In the normal range were: serum electrolytes, lymphocytes subpopulations, EMA, TGA, thyroid function, serology for VRS, Adenovirus, Mycoplasma, Chlamydia, ECG, echocardiogram, echocolor-doppler of pulmonary circle, liver echography, EEG, total and specific IgE. Sweat test was normal and so also CFTR gene’s 57 mutations. The only abnormal parameters were high LDH serum value(1724 U/L) and the Tidal Flow/Volume curve that shows a restrictive pattern. Chest HRCT showed bronchial walls thickening and parailar air trapping, after two month of oral steroid (prednisone) and inhalatory therapy (beclometasone dipropionate and salbutamol) she had a clinical improvement with a lower respiratory rate (RR = 52 b./m.), in contrast to the following chest HRCT that didn’t show any improvement. A subsequent 24 hs pH measuring showed an high pathological acid gastro esophageal reflux that recommended an anti acid therapy with protonic pump inhibitors (ppi). After 3 months of ppi therapy a second 24 hs pH measuring showed a disappearance of acid reflux. When the girl reached a good clinical and functional control prednisone therapy was stopped whit a clinical worsening: RR = 72 acts/minute. In order to investigate the cause of Chronic Interstitial pneumonia a Broncho Alveolar Lavage (BAL) was done. BAL showed the typical cellural and cytokines pattern of “Inhalation Syndrome”: presence of macrophages, lymphocytes, granulocytes with high intracytoplasmic lipids levels, and associated cytokines levels of IL-8 = 213 ng/L (n.v. <62 ng/L), of TNF = 7.7 ng/L (n.v. <8.1 ng/L), and of ECP = 2.3 ng/L. (n.v. 0–16). BAL culture was negative for bacteria, micetes and viruses. Clinical Radiographic, pH monitoring and BAL data are suggestive for an Intersititial Lung Disease (ILD) caused by gastric asymptomatic micro inhalations. Growth retardation and low weight could be related more to chronic respiratory failure than to the primitive gastro-esophageal pathology [5]. Biopsy remain the gold standard of IDL diagnosis for children and adults because it can identify the typical histological features [6]. Gastro Esophageal Reflux is a common problem in childhood but it may cause an important pulmonary interstitial disease that is a diagnostic challenge for pediatricians radiologists and lung specialist. Reference(s) [1] Fauroux B et al. Pediatr Respir Rev. 2004. [2] Barbato A, Panizzolo C. Paediatr Respir Rev. 2000. [3] Osika E, et al Pediatr Pulmonol 1997.
sweat chloride were: ≤5 years – 18 mmol/L (6–36 mmol/L) ; >5 up to 10 years, 20 mmol/L (6–38 mmol/L); 11 to 15 years, 21 mmol/L (7–39 mmol/L); 16 years, 16 mmol/L (6–40 mmol/L); Sweat Chloride values increased with increasing age in study population. This is the first study done to determine age specific reference interval of sweat chloride values in paediatric population of India. The results of this study will create a data base which can be extrapolated to rest of paediatric population of India. P58F Improvement in ion transport biomarkers and spirometry with the investigational CFTR potentiator VX-770 in subjects with cystic fibrosis and the G551D-CFTR mutation S.M. Rowe1 , F.J. Accurso2 , J.P. Clancy1 , M.P. Boyle3 , J.M. Dunitz4 , P.R. Durie5 , S.D. Sagel2 , D.B. Hornick6 , M.W. Konstan7 , S.H. Donaldson8 , R.B. Moss9 , J.M. Pilewski10 , R. Rubenstein11 , D.B. Uluer12 , M.L. Aitken13 , Q. Dong14 , C.L. Ordonez14 , P.W. Campbell15 , M.A. Ashlock15 , B.W. Ramsey16 . 1 University of Alabama at Birmingham – Birmingham, USA; 2 University of Colorado Denver – Aurora, USA; 3 Johns Hopkins Medical Institutions – Baltimore, USA; 4 University of Minnesota – Minneapolis, USA; 5 The Hospital for Sick Children and the University of Toronto – Toronto, Canada; 6 University of Iowa Carver College of Medicine – Iowa City, USA; 7 Rainbow Babies and Children’s Hospital and Case Western Reserve University School of Medicine – Cleveland, USA; 8 University of North Carolina at Chapel Hill – Chapel Hill, USA; 9 Stanford University School of Medicine – Palo Alto, USA; 10 University of Pittsburgh – Pittsburgh, USA; 11 Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine – Philadelphia, USA; 12 Children’s Hospital of Boston – Boston, USA; 13 University of Washington – Seattle, USA; 14 Vertex Pharmaceuticals Incorporated – Cambridge, USA; 15 Cystic Fibrosis Foundation Therapeutics, Inc. – Bethesda, USA; 16 Seattle Children’s Hospital – Seattle, USA Purpose: Cystic fibrosis (CF) is an inherited chronic illness often diagnosed by 2 years of age. CF is characterized by progressive obstructive lung disease, which is the most common cause of mortality. CF is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), an epithelial ion channel involved in sodium and chloride transport in multiple organs, including the airway and sweat duct. One therapeutic approach being investigated in CF is restoring CFTR function through small molecule pharmaceuticals. Methods: This 2-part, randomized, double-blind, placebocontrolled Phase 2 trial evaluated the safety and tolerability of VX-770, an orally bioavailable investigational potentiator of CFTR function, in 39 adults with CF carrying a G551D-CFTR allele. VX770 at doses of 25, 75, 150, and 250 mg or placebo q12h was administered over 14 or 28 day treatment periods. Secondary outcomes included biomarkers of ion transport (nasal potential difference [NPD] and sweat chloride), spirometry, and quality of life (CFQ-R instrument). Results: VX-770 was well tolerated and no serious drug-related adverse events occurred. After 14 days of treatment (combined Parts 1 & 2), statistically significant (P < 0.05) within-subject improvements were observed in sweat chloride for all VX-770 dose groups but not for placebo. Sweat chloride concentrations fell below the 60 mmol/L diagnostic threshold for CF in at least 42% of subjects in the 75 mg or higher VX-770 dose groups. A significant improvement was also observed in NPD zero chloride plus isoproterenol response in the VX-770 75, 150, and 250 mg dose groups at Day 14. VX-770 significantly improved FEV1 and FEF25–75% at Day 14 at several dose levels. Mean relative change from baseline in the VX-770 150 mg group for FEV1 % and FEF25–75% % predicted was 10.8% and 9.4%, respectively (P < 0.05 within-subject). At 14 days, using a post-hoc significant response criterion of >10% in FEV1 % predicted, improvement was observed in 7/16 (43.8%) and 2/12 (16.7%) of patients in the VX-770 150 mg group and placebo group,
S99
respectively. A minimal clinically important difference (≥4 points) in the CFQ-R respiratory domain score was observed in 5/8 subjects in the VX-770 150 mg group at both Days 14 and 28 (Part 2 only). Improvements in CFTR biomarkers and lung function were sustained in subjects who completed 28 days. The VX-770 150 mg group had absolute changes from baseline in sweat chloride of −59.5 mmol/L (P < 0.01 within-subject) and −3.5 mV (P < 0.02) for NPD, and a median relative change from baseline in FEV1 % predicted of 8.7% (P < 0.01 within-subject). Conclusions: VX-770 was well tolerated and significantly improved CFTR-mediated chloride ion transport (NPD, sweat chloride) and lung function through 28 days of dosing. Further evaluation of VX-770 in large, long-term Phase 3 trials in CF subjects aged 6 years and above are in progress. Sponsored by Vertex Pharmaceuticals Incorporated with support from Cystic Fibrosis Foundation Therapeutics Inc. and a US FDA Office of Orphan Products Development Grant (# FD-R-003432– 01). P59F Interrelationships between lung clearance index and parameters of lung function and gas exchange in patients with cystic fibrosis J. Große-Onnebrink, F. Stehling, U. Mellies. University Hospital Essen Pediatric Pulmonology – Essen, Germany Background and Aim: Increased lung clearance index (LCI) measured by multiple breath wash-out (MBW) technique reflects ventilation inhomogeneity as a sign of early lung disease in patients with cystic fibrosis (CF). Aim of the study was to assess interrelationships between LCI and parameters of lung function that represent airflow limitation, pulmonary hyperinflation as well as impaired gas exchange in children, adolescents and adults with CF. Methods: In this retrospective study 33 patients with CF (age 5–44, mean 18 years) underwent as part of their routine annual review whole body plethysmography, MBW (with side stream ultrasonic flow sensor and sulfurhexafluorid (SF6) as tracer gas) and capillary blood gas analysis from arterialized earlobe blood. The correlation coefficients between LCI and FEV1 % predicted (pred), FEF25–75 % pred, specific airway resistance (sReff ), residual volume (RV) % pred, RV / total lung capacity (TLC) PL %, volume of trapped gas (VTG ), PaO2 , PaCO2 and alveolar arterial oxygen gradient (A-aO2 ) were calculated. Results: LCI correlated with FEV1 % pred (r = −0.791), FEF25–75 % pred (r = −0.674), sReff (r = 0.740), RV % pred (r = 0.658), RV/TLC PL% (r = 0.792), VTG (r = 0.575), PaO2 (r = −0.766), PaCO2 (r = 0.507) and A-aO2 (r = 0.619). Patients with normal FEV1 (FEV1 >80% pred) were divided in 2 subgroups with LCI <7 (n = 4) and LCI >7 (n = 8), resp. Mean PaO2 was 90.38 mmHg and 78.66 mmHg resp. and A-aO2 was 12.69 mmHg and 23.28 mmHg resp. (p < 0,05 for both). Conclusions: Lung clearance index correlates with parameters of airflow limitation, pulmonary hyperinflation and impaired gas exchange in patients with cystic fibrosis. Patients with normal FEV1 but abnormal LCI (>7) may already have small airway disease with impaired gas exchange. P60F Microbiology of the respiratory tract in cystic fibrosis patients diagnosed by neonatal screening: differences with healthy patients 1 L. Valdesoiro-Navarrete1 , M. Bosque1 , C. Rodrigo2 , N. Lopez ´ , 1 1 1 1 1 A. Valiente , O. Asensio , H. Larramona , Ch. Domingo . Corporacio Parc tauli – Sabadell, Spain; 2 Germans Trias i Pujol Pediatrics – Badalona, Spain
Introduction: The pathophysiology of lung disease at Cystic fibrosis (CF) is based in inflammation, infection and colonization of
S100
Posters / Paediatric Respiratory Reviews 11S1 (2010) S79–S115
respiratory tract. All of CF patients, still asymptomatics, could be positive specimens. Our aim was compared the microbiology of the respiratory tract of our patients with healthy controls of same ages. Method and Material: Observational prospective study. Patients: infants with newly diagnosed cystic fibrosis disease which were identified by neonatal screening, from October 1999 to February 2005. These patients will be followed since the age of four. Healthy controls: patients between 0 to 4 years old who needs surgery and without respiratory pathology. A collection of specimen is taken applying the oropharinx aspirate (AOF) technique. Patients: These specimens are taken monthly and should the infant develop respiratory infection symptoms, additional specimen was taken. Healthy controls: These specimens are taken during anaesthesia induction. A signed consent was obtained previously. Results: Patients: 21 (76.19% males) patients with cystic fibrosis diagnosis were recruited. All patients were followed four years. 960 AOF specimens were taken, 365 (38%) of which were positive and 447 microorganisms were isolated. Healthy controls: 106 (78.6% males) patients were recruited. 103 AOF specimens were taken, 30 (29%) of which were positive and 36 microorganisms were isolated. The more frequent microorganisms isolated at both groups (CF patients/ healthy controls) were: Staphylococcus aureus (33.3% vs 36.1%), Enterobacter cloacae (12% vs 16.7%), Escherichia coli (13.9% vs 11%), Klebsiella spp. (17.2% vs 16.6%), Pseudomonas aeruginosa (7.4% vs 8.3%). We did not find significant differences between both groups about the isolated microorganisms, but all the CF patients have positive cultures and only 29% of healthy patients have it. Conclusions: The microorganism isolated in our study show similarities between CF patients and healthy controls. Probably the differences are in the host. P61F The status of cystic fibrosis patients in 2009 in Albania E. Vevecka1 , S. Noka2 . 1 University Hospital Center of Tirana “Mother Teresa” Pediatrics – Tirana, Albania; 2 Faculty of Medicine, Tirana University – Tirana, Albania In Albania the care of children with CF consist of one Pediatric service in University Hospital Center of Tirana “Mother Teresa”, serving a whole population of about 3 million inhabitants. Aim: To evaluate the epidemiologic data on CF in Albania according to the European CF registry. Method: Demographic, genetic and clinical symptoms were collected in a database according to the European CF registry. Data collection was completed in a three months period (September– November 2009). All the information was obtained from patients’ clinical notes. Results: Totally 70 CF patients were identified with mean age 6.2±4.4 years. The older CF patient was 17 years old, while 7.2% were older than 14 years old. Mean age at diagnosis was 7.9±17.9 months. 65.7% of patients were identified with DF 508 mutation (Homozygous). 24.2% of patients were chronically colonized with Pseudomonas aeruginosa. Burkholderia cepacia was not isolated in any of our patients. 97% had pancreatic insufficiency, 85.5% were underweight (BMI < 18.5). 7% presented with meconeum ileus. 17% had CFRD. FEV1 among 6 yo patients was over 80% of predicted. One of our patients had undergone liver transplantation. Conclusions: The status of patients with CF in Albania is presented. The DF mutation is higher than other country of the region. The nutritional status of our patients is poor.
7. Respiratory manifestations of extra-pulmonary diseases (including AIDS) P62G Interstitial lung disease and gastroesophageal reflux M. Verini1 , D. Rapino2 , F. Matronola1 , N.P. Consilvio1 , C. Spagnuolo1 , A. Palazzo1 , A. Scaparrotta1 , A. Cingolani1 , S. Di Pillo1 , F. Chiarelli2 . 1 Allergological and Respiratory Unit, Paediatric Clinic, University of Chieti, Chieti, Italy; 2 Paediatric Clinic, University of Chieti, Chieti, Italy Interstitial lung diseases are an heterogeneus group of pathologies with etiology often unknown. These pathologies include alteration of peripheral airways related with alveolar wall thickness [1]. Some subgroups of these diseases are characterized by widespread pulmonary infiltrate, restrictive functional pattern, hypoxia, growth retardation, thorax abnormalities, digital clubbing and signs of cardiac involvement [2]. Many patients have a high mortality [3], some other have a good outcome [4]. We describe the case of a 22 month child with physiologic neonatal anamnesis, dystrophic appearance, digital clubbing and growth retardation, with a previous basal bilateral bronchopneumonia, who came to the admission for right basal bronchopneumonia with abnormal respiratory rate (RR = 70 b/m.). In the normal range were: serum electrolytes, lymphocytes subpopulations, EMA, TGA, thyroid function, serology for VRS, Adenovirus, Mycoplasma, Chlamydia, ECG, echocardiogram, echocolor-doppler of pulmonary circle, liver echography, EEG, total and specific IgE. Sweat test was normal and so also CFTR gene’s 57 mutations. The only abnormal parameters were high LDH serum value(1724 U/L) and the Tidal Flow/Volume curve that shows a restrictive pattern. Chest HRCT showed bronchial walls thickening and parailar air trapping, after two month of oral steroid (prednisone) and inhalatory therapy (beclometasone dipropionate and salbutamol) she had a clinical improvement with a lower respiratory rate (RR = 52 b./m.), in contrast to the following chest HRCT that didn’t show any improvement. A subsequent 24 hs pH measuring showed an high pathological acid gastro esophageal reflux that recommended an anti acid therapy with protonic pump inhibitors (ppi). After 3 months of ppi therapy a second 24 hs pH measuring showed a disappearance of acid reflux. When the girl reached a good clinical and functional control prednisone therapy was stopped whit a clinical worsening: RR = 72 acts/minute. In order to investigate the cause of Chronic Interstitial pneumonia a Broncho Alveolar Lavage (BAL) was done. BAL showed the typical cellural and cytokines pattern of “Inhalation Syndrome”: presence of macrophages, lymphocytes, granulocytes with high intracytoplasmic lipids levels, and associated cytokines levels of IL-8 = 213 ng/L (n.v. <62 ng/L), of TNF = 7.7 ng/L (n.v. <8.1 ng/L), and of ECP = 2.3 ng/L. (n.v. 0–16). BAL culture was negative for bacteria, micetes and viruses. Clinical Radiographic, pH monitoring and BAL data are suggestive for an Intersititial Lung Disease (ILD) caused by gastric asymptomatic micro inhalations. Growth retardation and low weight could be related more to chronic respiratory failure than to the primitive gastro-esophageal pathology [5]. Biopsy remain the gold standard of IDL diagnosis for children and adults because it can identify the typical histological features [6]. Gastro Esophageal Reflux is a common problem in childhood but it may cause an important pulmonary interstitial disease that is a diagnostic challenge for pediatricians radiologists and lung specialist. Reference(s) [1] Fauroux B et al. Pediatr Respir Rev. 2004. [2] Barbato A, Panizzolo C. Paediatr Respir Rev. 2000. [3] Osika E, et al Pediatr Pulmonol 1997.