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177 Strategies to improve influenza vaccination coverage in at-risk children: The experience of patients with cystic fibrosis
Posters
8. Immunology/Inflammation
174 Quantification of major urinary metabolite of PGE2 in cystic fibrosis (CF) patients: Correlation with parameters of disease severity S. Gartner1 , S. Jabr2 , J. Roca-Ferrer2 , G. Milne3 , A. Moreno1 , C. Picado2 . 1 Hosp`ıtal Universitario Vall d’Hebron. Cystic Fibrosis Unit and Pediatric Pulmonology, Barcelona, Spain; 2 Institut d’Investigacions Biom`ediques August Pi i Sunyer (IDIBAPS). Universitat de Barcelona., Barcelona, Spain; 3 Vanderbilt University, School of Medicine, Nashville, TN, United States Studies have demonstrated overproduction of prostaglandin E2 (PGE2 ) in CF. In vitro study show that alterations in CFTR are involved in overproduction of PGE2 . Findings that suggest that measurement of PGE2 production may help to assess the severity of the altered regulation of CFTR and intensity of inflammatory process in the airways of CF patients. Tetranor PGEM (PGE-M) is a metabolite present in urine that accurately reflects the biosynthesis of the PGE2 . In this study we assessed the relationship between levels of PGE-M with CF severity. Methods: 36 patients with stable CF and 24 healthy controls were recruited. All CF patients had undergone evaluation of pancreatic function, lung function by spirometry and genotype severity. PGE-M levels were measured by a liquid chromatographic/mass spectrometric assay. Results: PGE-M concentrations were markedly and significantly elevated (p < 0.0001) in the urine of CF patients (34.5±45 ng/mgCr) compared with healthy controls (7.4±4.25 ng/mgCr). There was no correlation between PGE-M urinary levels and spirometric values. In patients with pancreatic insufficiency there was a higher PGE-M urinary level (38±7 ng/mgCr) than in patients with conserved pancreatic function (10±4.6 ng/mgCr) (p = 0.05). There was an association of the severity of genotypes with levels of PGE-M: mild: 8.6±4.1 ng/mgCr; moderate: 19.7±11 ng/mgCr; severe: 48±53.3 ng/mgCr (p < 0.0027). Conclusions: Measurement of urinary PGE-M may be a useful tool to investigate severity of CF and to assess the efficacy of any therapy aimed to improve the function of a defective CFTR.
S93
176 Prevalence of autoimmune antibodies in patients with cystic fibrosis after lung transplantation K. Staufer1 , E. Halilbasic1 , S. Harm1 , A. Niculescu1 , P. Jaksch2 , G. Murak¨ozy2 , E. Hielle-Wittmann2 , C. Lichtenberger1 , H. Vogelsang1 , W. Klepetko2 , M. Trauner1 , L. Kazemi-Shirazi1 . 1 Medical University of Vienna, Internal Medicine III, Vienna, Austria; 2 Medical University of Vienna, Thoracic Surgery, Vienna, Austria Background: Autoimmune antibodies (Ab) can be found in up to 80% of CF patients prior to lung transplantation and anti-neutrophil cytoplasmic antibodies (ANCA) may be associated with severity of lung disease and disease prognosis [1]. In this pilot study, we investigated the prevalence of autoimmune antibodies in CF patients after lung transplantation (LuTx). Methods: Consecutive patients attending our outpatient clinic were screened for a wide range of autoantibodies in serum (ANA, AMA, SMA, EMA, TTG Ab, p-ANCA, c-ANCA, ASCA, SLA, LC-1 Ab), as well as immunoglobulins (IgG, IgA and IgM). Autoimmune diseases were excluded. Results: 36 patients (median age 30 y, IQR 25−38 y; 42% male) were included in the study. Median time since LuTx was 4.5 y (IQR: 2.3−8.3 y). IgG levels were elevated in 8% (3/36) of patients. Overall prevalence of autoantibodies was 83%. However, only 12% (4/34) of patients had elevated ANAs, only one patient tested positive for SMAs. Of note, 83% (24/29) of patients had elevated anti-saccharomyces cerevisiae antibodies (ASCA). Of these, 4 of 24 ASCA IgG only, in 8 of 24 ASCA IgA only, and in 12 of 24 both were positive. Yet, in none of the patients neither AMA, EMA, TTG Ab, SLA, LC-1 Ab, nor ANCA were detected. Conclusion: In contrast to published data in CF patients pre LuTx, ANCA were not found in patients post LuTx. ASCAs were the dominant fraction in our panel of autoantibodies. Association with clinical outcomes are part of this ongoing trial. Reference(s) [1] Lachenal et al, Prevalence and clinical significance of autoantibodies in adults with cystic fibrosis, Europ Resp J, 2009.
175 The onset of CFRD does not impact the association of IL-6 with worse clinical status
177 Strategies to improve influenza vaccination coverage in at-risk children: The experience of patients with cystic fibrosis
A. Coriati1,2 , S. Ziai1,2 , M.-S. Gauthier1,2 , Y. Berthiaume2,3,4 , R. RabasaLhoret1,2,4 . 1 Universit´e de Montr´eal, Nutrition, Montr´eal, Canada; 2 Institut de Recherches Cliniques de Montr´eal (IRCM), Montr´eal, Canada; 3 Universit´e de Montr´eal, Montr´eal, Canada; 4 Centre Hospitalier de l’Universit´e de Montr´eal, Montr´eal, Canada
M.G. Giagnorio1 , V. Minicucci1 , M. Mariano1 , R. Romano1 , C. Napolitano1 , M. Manchisi1 , A. Macchiaroli1 , A. Lo Vecchio2 , V. Raia2 , A. Giannattasio1 . 1 University of Molise, Medicine and Health Sciences Department, Campobasso, Italy; 2 University Federico II, Department of Translational Medical Sciences, Section of Pediatrics, Naples, Italy
Cystic Fibrosis (CF)-related diabetes (CFRD), the most common complication of CF, is preceded by a phase of low insulin secretion, glucose intolerance and accelerated decrease in weight and pulmonary function. However, no study has shown a direct link between systemic inflammation, clinical deterioration and the occurrence of CFRD in adult patients with CF. Objective: The aim of this study was to determine if interleukin (IL)-6, an important inflammatory mediator in CF as well as in diabetes, was associated to CFRD pathology. Methods: This cross-sectional study included 88 adult patients with CF (47 with normal glucose tolerance (NGT) and 41 with de novo CFRD, as determined by the oral glucose tolerance test) with a mean age of 29.7±8.4 years, an average body mass index (BMI) of 22.0±3.5 (kg/m2 ) and %FEV1 of 70.1±21.9, from the Montreal CF cohort (Hˆotel-Dieu CHUM, Montreal, Canada). Conclusions: There was no difference in plasma levels of IL-6, as measured by enzyme-linked immunosorbent assay, between patients with NGT and with CFRD. Also, plasma IL-6 was associated to neither insulin (secretion or sensitivity) nor glucose (glucose excursion during OGTT or glycated hemoglobin) indexes of homeostasis. However, high levels of IL-6 were independently associated to pulmonary function impairment (P < 0.01), low BMI (P < 0.05) and high levels of subclinical markers of inflammation, such as C-reactive protein (P < 0.01), fibrinogen (P < 0.01), white blood cells (P < 0.01) and neutrophils (P < 0.01). Although IL-6 appears to be an important biomarker in CF-related clinical degradation, the onset of CFRD does not seem to increase its level in stable patients with CF.
Objectives: Annual flu vaccination is strongly recommended to patients with cystic fibrosis (CF). In 2009, H1N1 vaccination was also recommended in atrisk categories. Several strategies to improve H1N1 vaccination were applied, with heterogeneous and often unsatisfactory results. Aim: To assess how the management of vaccination against pandemic and seasonal flu might have conditioned the adherence to the H1N1 immunization in at-risk children. Methods and Results: 161 children (CF, n = 35; HIV infection, HIV, n = 34; type I diabetes mellitus, DM, n = 34; neuromuscular disease, NNMD, n = 34; Down syndrome, DS, n = 24) were enrolled. 95 (59%) patients had received flu vaccination in 2008–2009 season and 120 (74%) in 2009–2010 (p < 0.05). CF was the category better vaccinated in both seasons. 48% of patients received H1N1 vaccine. The highest vaccination rate was registered in CF (83%) and HIV (82%), with a rate of 31% in the other categories (p < 0.05). The main reason to be vaccinated against H1N1 was recommendation by physicians of the Reference Center (RC) in case of CF and HIV. 14/35 (40%) CF and almost all (97%) HIV children received H1N1 vaccination at the RC, versus only 4% of the other categories. Conclusion: Developing specific communication strategies and enhancing compliance with the official recommendations is important to improve immunization in at-risk patients and identify barriers to local vaccine implementation. The H1N1 experience should be taken into account for planning future vaccination campaigns. Centralization of the immunization at the Reference Centers for chronic diseases, as in case of CF, may represent a key strategy to improve flu vaccination coverage.
8. Immunology/Inflammation
174 Quantification of major urinary metabolite of PGE2 in cystic fibrosis (CF) patients: Correlation with parameters of disease severity S. Gartner1 , S. Jabr2 , J. Roca-Ferrer2 , G. Milne3 , A. Moreno1 , C. Picado2 . 1 Hosp`ıtal Universitario Vall d’Hebron. Cystic Fibrosis Unit and Pediatric Pulmonology, Barcelona, Spain; 2 Institut d’Investigacions Biom`ediques August Pi i Sunyer (IDIBAPS). Universitat de Barcelona., Barcelona, Spain; 3 Vanderbilt University, School of Medicine, Nashville, TN, United States Studies have demonstrated overproduction of prostaglandin E2 (PGE2 ) in CF. In vitro study show that alterations in CFTR are involved in overproduction of PGE2 . Findings that suggest that measurement of PGE2 production may help to assess the severity of the altered regulation of CFTR and intensity of inflammatory process in the airways of CF patients. Tetranor PGEM (PGE-M) is a metabolite present in urine that accurately reflects the biosynthesis of the PGE2 . In this study we assessed the relationship between levels of PGE-M with CF severity. Methods: 36 patients with stable CF and 24 healthy controls were recruited. All CF patients had undergone evaluation of pancreatic function, lung function by spirometry and genotype severity. PGE-M levels were measured by a liquid chromatographic/mass spectrometric assay. Results: PGE-M concentrations were markedly and significantly elevated (p < 0.0001) in the urine of CF patients (34.5±45 ng/mgCr) compared with healthy controls (7.4±4.25 ng/mgCr). There was no correlation between PGE-M urinary levels and spirometric values. In patients with pancreatic insufficiency there was a higher PGE-M urinary level (38±7 ng/mgCr) than in patients with conserved pancreatic function (10±4.6 ng/mgCr) (p = 0.05). There was an association of the severity of genotypes with levels of PGE-M: mild: 8.6±4.1 ng/mgCr; moderate: 19.7±11 ng/mgCr; severe: 48±53.3 ng/mgCr (p < 0.0027). Conclusions: Measurement of urinary PGE-M may be a useful tool to investigate severity of CF and to assess the efficacy of any therapy aimed to improve the function of a defective CFTR.
S93
176 Prevalence of autoimmune antibodies in patients with cystic fibrosis after lung transplantation K. Staufer1 , E. Halilbasic1 , S. Harm1 , A. Niculescu1 , P. Jaksch2 , G. Murak¨ozy2 , E. Hielle-Wittmann2 , C. Lichtenberger1 , H. Vogelsang1 , W. Klepetko2 , M. Trauner1 , L. Kazemi-Shirazi1 . 1 Medical University of Vienna, Internal Medicine III, Vienna, Austria; 2 Medical University of Vienna, Thoracic Surgery, Vienna, Austria Background: Autoimmune antibodies (Ab) can be found in up to 80% of CF patients prior to lung transplantation and anti-neutrophil cytoplasmic antibodies (ANCA) may be associated with severity of lung disease and disease prognosis [1]. In this pilot study, we investigated the prevalence of autoimmune antibodies in CF patients after lung transplantation (LuTx). Methods: Consecutive patients attending our outpatient clinic were screened for a wide range of autoantibodies in serum (ANA, AMA, SMA, EMA, TTG Ab, p-ANCA, c-ANCA, ASCA, SLA, LC-1 Ab), as well as immunoglobulins (IgG, IgA and IgM). Autoimmune diseases were excluded. Results: 36 patients (median age 30 y, IQR 25−38 y; 42% male) were included in the study. Median time since LuTx was 4.5 y (IQR: 2.3−8.3 y). IgG levels were elevated in 8% (3/36) of patients. Overall prevalence of autoantibodies was 83%. However, only 12% (4/34) of patients had elevated ANAs, only one patient tested positive for SMAs. Of note, 83% (24/29) of patients had elevated anti-saccharomyces cerevisiae antibodies (ASCA). Of these, 4 of 24 ASCA IgG only, in 8 of 24 ASCA IgA only, and in 12 of 24 both were positive. Yet, in none of the patients neither AMA, EMA, TTG Ab, SLA, LC-1 Ab, nor ANCA were detected. Conclusion: In contrast to published data in CF patients pre LuTx, ANCA were not found in patients post LuTx. ASCAs were the dominant fraction in our panel of autoantibodies. Association with clinical outcomes are part of this ongoing trial. Reference(s) [1] Lachenal et al, Prevalence and clinical significance of autoantibodies in adults with cystic fibrosis, Europ Resp J, 2009.
175 The onset of CFRD does not impact the association of IL-6 with worse clinical status
177 Strategies to improve influenza vaccination coverage in at-risk children: The experience of patients with cystic fibrosis
A. Coriati1,2 , S. Ziai1,2 , M.-S. Gauthier1,2 , Y. Berthiaume2,3,4 , R. RabasaLhoret1,2,4 . 1 Universit´e de Montr´eal, Nutrition, Montr´eal, Canada; 2 Institut de Recherches Cliniques de Montr´eal (IRCM), Montr´eal, Canada; 3 Universit´e de Montr´eal, Montr´eal, Canada; 4 Centre Hospitalier de l’Universit´e de Montr´eal, Montr´eal, Canada
M.G. Giagnorio1 , V. Minicucci1 , M. Mariano1 , R. Romano1 , C. Napolitano1 , M. Manchisi1 , A. Macchiaroli1 , A. Lo Vecchio2 , V. Raia2 , A. Giannattasio1 . 1 University of Molise, Medicine and Health Sciences Department, Campobasso, Italy; 2 University Federico II, Department of Translational Medical Sciences, Section of Pediatrics, Naples, Italy
Cystic Fibrosis (CF)-related diabetes (CFRD), the most common complication of CF, is preceded by a phase of low insulin secretion, glucose intolerance and accelerated decrease in weight and pulmonary function. However, no study has shown a direct link between systemic inflammation, clinical deterioration and the occurrence of CFRD in adult patients with CF. Objective: The aim of this study was to determine if interleukin (IL)-6, an important inflammatory mediator in CF as well as in diabetes, was associated to CFRD pathology. Methods: This cross-sectional study included 88 adult patients with CF (47 with normal glucose tolerance (NGT) and 41 with de novo CFRD, as determined by the oral glucose tolerance test) with a mean age of 29.7±8.4 years, an average body mass index (BMI) of 22.0±3.5 (kg/m2 ) and %FEV1 of 70.1±21.9, from the Montreal CF cohort (Hˆotel-Dieu CHUM, Montreal, Canada). Conclusions: There was no difference in plasma levels of IL-6, as measured by enzyme-linked immunosorbent assay, between patients with NGT and with CFRD. Also, plasma IL-6 was associated to neither insulin (secretion or sensitivity) nor glucose (glucose excursion during OGTT or glycated hemoglobin) indexes of homeostasis. However, high levels of IL-6 were independently associated to pulmonary function impairment (P < 0.01), low BMI (P < 0.05) and high levels of subclinical markers of inflammation, such as C-reactive protein (P < 0.01), fibrinogen (P < 0.01), white blood cells (P < 0.01) and neutrophils (P < 0.01). Although IL-6 appears to be an important biomarker in CF-related clinical degradation, the onset of CFRD does not seem to increase its level in stable patients with CF.
Objectives: Annual flu vaccination is strongly recommended to patients with cystic fibrosis (CF). In 2009, H1N1 vaccination was also recommended in atrisk categories. Several strategies to improve H1N1 vaccination were applied, with heterogeneous and often unsatisfactory results. Aim: To assess how the management of vaccination against pandemic and seasonal flu might have conditioned the adherence to the H1N1 immunization in at-risk children. Methods and Results: 161 children (CF, n = 35; HIV infection, HIV, n = 34; type I diabetes mellitus, DM, n = 34; neuromuscular disease, NNMD, n = 34; Down syndrome, DS, n = 24) were enrolled. 95 (59%) patients had received flu vaccination in 2008–2009 season and 120 (74%) in 2009–2010 (p < 0.05). CF was the category better vaccinated in both seasons. 48% of patients received H1N1 vaccine. The highest vaccination rate was registered in CF (83%) and HIV (82%), with a rate of 31% in the other categories (p < 0.05). The main reason to be vaccinated against H1N1 was recommendation by physicians of the Reference Center (RC) in case of CF and HIV. 14/35 (40%) CF and almost all (97%) HIV children received H1N1 vaccination at the RC, versus only 4% of the other categories. Conclusion: Developing specific communication strategies and enhancing compliance with the official recommendations is important to improve immunization in at-risk patients and identify barriers to local vaccine implementation. The H1N1 experience should be taken into account for planning future vaccination campaigns. Centralization of the immunization at the Reference Centers for chronic diseases, as in case of CF, may represent a key strategy to improve flu vaccination coverage.