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38 History of pulmonary exacerbations (PEx) as a predictor of response to nebulized levofloxacin compared with nebulized tobramycin
Posters / Journal of Cystic Fibrosis 15 (2016) S51–S120
demonstrated clinical non-inferiority to tobramycin inhalation solution (TIS). A concern with extended LIS use is a potential for reduction in levofloxacin-susceptible P. aeruginosa (Pa) isolate prevalence. We describe airway bacterial culture and Pa isolate antimicrobial susceptibilities at baseline and study end for LIS (N = 189) and TIS (N = 93) subjects. Methods: Sputum or throat swabs were cultured for Pa and other CF airway bacterial opportunists. Multiple Pa morphotypes were isolated when present and susceptibility was tested using microdilution with EUCAST breakpoints. Results: No statistically significant change in species prevalence from baseline or changes in prevalence of Pa isolates susceptible to levofloxacin (L) or tobramycin (T) were observed: 34% [95% CI 28–39%] of LIS isolates and 43[35–51]% of TIS isolates were L-susceptible at baseline; 64[59–70]% of LIS isolates and 66[58–73]% of TIS isolates were T-susceptible at baseline. At study end, 24[20–29]% of LIS isolates and 31[24–39]% of TIS isolates were L-susceptible; 63[57–68]% of LIS and 62[53–69]% of TIS isolates were T-susceptible. Prevalence of isolates not susceptible to any agent from ≥3 antipseudomonal classes did not differ from baseline (LIS 40[35–56]%, TIS 43[35–51]%) to study end (LIS 42[36–47]%, TIS 46[38–54]%). Conclusion: While the clinical utility of susceptibility testing in CF is uncertain, patients treated with LIS vs. TIS had no meaningful differences in microbial prevalence or Pa isolate antimicrobial susceptibilities at baseline or at treatment end. 38 History of pulmonary exacerbations (PEx) as a predictor of response to nebulized levofloxacin compared with nebulized tobramycin P. Flume1 , J.S. Elborn2 , K. Polu3 , L. Llorens3 , M.L. Pecoraro3 , N. Bhatt3 , D.R. VanDevanter4 . 1 Medical University of South Carolina, Charleston, United States; 2 Queen’s University, Belfast, United Kingdom; 3 Raptor Pharma, Novato, United States; 4 Case Western Reserve University School of Medicine, Cleveland, United States Objectives: PEx are important events among persons with CF and are a significant risk factor for future PEx and pulmonary deterioration. Levofloxacin inhalation solution (LIS; Quinsair® ) was evaluated in an open-label study (MPEX-209) with tobramycin inhalation solution (TIS) over three 28-day cycles, with intervals of 28-days off treatment. Here we describe the proportion of patients who experienced PEx and were treated with antibiotics stratified by the number of clinician-reported PEx patients had experienced in the prior year (prior-yr PEx). Methods: PEx were defined as patients meeting ≥4 of 12 Fuchs criteria and antibiotic treatment for the PEx Prior-yr PEx categories were defined as zero, 1 to 2, or ≥3 PEx. The incidence of PEx during the study was compared between LIS (N = 189) and TIS (N = 93) treatment groups both overall and among prior-yr PEx subgroups. Results: Baseline demographics, including mean FEV1 % predicted, were similar between treatment groups and across prior-yr PEx categories. The overall PEx incidence was not substantially different between LIS patients (53/189 = 28.0% [95% CI 21.8%, 35.0%]) and TIS patients (34/93 = 36.6% [26.8%, 47.2%]). Incidence of PEx increased with increasing prior-yr PEx, but did not differ between treatment groups with <3 prior-yr PEx. For those with ≥3 prior-yr PEx, 17/59 LIS patients (28.8% [17.8%, 42.1%]) had a PEx vs 14/25 TIS patients (56.0% [34.9%, 5.6%]). This 27.2% difference in PEx incidence was statistically significant (P = 0.03; two-tailed Fisher’s exact test). Conclusion: Patients with ≥3 PEx in the past year had the greatest PEx-reduction benefit from LIS treatment. 39 Results of a multicenter, open-label, phase IV study, to evaluate the early response to Bronchitol® in patients with cystic fibrosis A. Thronicke1 , C. Brandt1 , J. Roehmel1 , D. Staab1 , C. Schwarz1 , Bronchitol Study Group. 1 Charit´e-Universit¨ atsmedizin Berlin, Division of Cystic Fibrosis, Berlin, Germany Objectives: Cystic Fibrosis (CF) is a multiorgan disease. Malfunctional pulmonary secretion is a key characteristic of patients with CF. Therapy for better expectoration is one of the most wanted treatments.
S61
Inhalation of hyperosmotic therapeutic Bronchitol® is licensed for the treatment of CF in adults aged 18 years and above in addition to standard care. It improves mucus clearance of retained secretions, hereby counteracting against pulmonary infections and inflammation. This study aimed to evaluate early response in lung function after 14 days of Bronchitol® to predict response after 12 weeks. Methods: A non-blinded, open-label, phase IV study at seven German Cystic Fibrosis centers was conducted between March 31, 2014 and April 15, 2015. The primary objective of the study was the investigation of the predictive value of inhaled dry powder Bronchitol® with respect to the success of treatment over 12 weeks. The primary endpoint was the determination of the prediction of the absolute change in FEV1 (ml) from baseline at week 2 relative to week 12. Results: Of 26 individuals enrolled between Mar 31, 2014 and Jan 15, 2015, all patients were assigned to Bronchitol® treatment (mean age 30.2 years, range 19–49 years). Eight from 26 patients (31%) were male and 18 (69%) were female. The probability that the respective change in lung function would predict positive lung function parameters at day 84 was 83% for FEV1 % predicted. Conclusion: The study showed that Bronchitol® is well tolerated and that the lung function test results after two weeks predicted for the response after 84 days. 40 Use of hypertonic saline solution + hyaluronic acid in patients with cystic fibrosis: a retrospective evaluation F. Majo1 , M. Di Carlo1 , S. Piga2 , M. Ciofi Degli Atti2 , V. Lucidi1 . 1 Bambino Ges` u Children’s Hospital, Cystic Fibrosis Unit, Rome, Italy; 2 Bambino Ges` u Children’s Hospital, Clinical Epidemiology Unit, Rome, Italy Objectives: 1. Evaluate whether the use of hypertonic saline solution with hyaluronic acid (HS+HA) is associated with a reduction in number of intraindividual pulmonary exacerbations (PE) and 2. changes in FEV1 in patients with cystic fibrosis (CF) after one and two years of treatment. 3. Evaluate the tolerability of HS+HA. Methods: Retrospective study on data from 2007 to 2012. Were enrolled in the study patients with CF, age ≥6 years, with FEV1 ≥40%, with at least three measurements of FEV1 per year. We analyzed data about the previous year and the two years following the start of treatment. Tolerability of HS+HA was intended as the need to discontinue therapy. The intra-individual variation for FEV1 and number of RR have been studied using the Student t test for paired data. Results: Of the 437 patients in the database, 127 patients meet the inclusion criteria. The average number of PE is significantly reduced after the second year of therapy (3.5 vs 2.7, SD 2.9 vs 2.2, p < 0.001). The mean FEV1 remains unchanged from the year before the start of HS+HA compared to the first year (80.9 vs. 80.4, SD 23.8 vs. 24.0, p = 0.42) and compared to the second year of treatment (80.9 vs. 79.9, SD 23.8 vs. 23.9, p = 0.17). Only two patients (1.5%) discontinued treatment with HS+HA, both for onset of cough in the first months of therapy. Conclusion: The results of our study show a significant reduction in the number of PE in the second year of treatment with HS+HA, coupled with a good tolerance to the drug. It is also noteworthy a stability of FEV1, as observed in other studies with HS. This is the first study that confirms the safety and efficacy in reducing PE in the long run of HS+HA. 41 Effects of combined exercise training during hospitalization in patients with cystic fibrosis 1 S. Stossel ¨ , O. Nitsche1 , S. Schlotter1 , J. Faber1 , K. Poplawska1 . 1 Universit¨ atsmedizin JGU, Mainz, Germany
Objectives: In patients with cystic fibrosis (CF) exercise can positively impact physical and mental wellbeing. However during hospitalization and need for intravenous antibiotics people with CF usually decrease their level of physical activity. Therefore we implemented combined exercise training for children and adolescents during hospitalization.
demonstrated clinical non-inferiority to tobramycin inhalation solution (TIS). A concern with extended LIS use is a potential for reduction in levofloxacin-susceptible P. aeruginosa (Pa) isolate prevalence. We describe airway bacterial culture and Pa isolate antimicrobial susceptibilities at baseline and study end for LIS (N = 189) and TIS (N = 93) subjects. Methods: Sputum or throat swabs were cultured for Pa and other CF airway bacterial opportunists. Multiple Pa morphotypes were isolated when present and susceptibility was tested using microdilution with EUCAST breakpoints. Results: No statistically significant change in species prevalence from baseline or changes in prevalence of Pa isolates susceptible to levofloxacin (L) or tobramycin (T) were observed: 34% [95% CI 28–39%] of LIS isolates and 43[35–51]% of TIS isolates were L-susceptible at baseline; 64[59–70]% of LIS isolates and 66[58–73]% of TIS isolates were T-susceptible at baseline. At study end, 24[20–29]% of LIS isolates and 31[24–39]% of TIS isolates were L-susceptible; 63[57–68]% of LIS and 62[53–69]% of TIS isolates were T-susceptible. Prevalence of isolates not susceptible to any agent from ≥3 antipseudomonal classes did not differ from baseline (LIS 40[35–56]%, TIS 43[35–51]%) to study end (LIS 42[36–47]%, TIS 46[38–54]%). Conclusion: While the clinical utility of susceptibility testing in CF is uncertain, patients treated with LIS vs. TIS had no meaningful differences in microbial prevalence or Pa isolate antimicrobial susceptibilities at baseline or at treatment end. 38 History of pulmonary exacerbations (PEx) as a predictor of response to nebulized levofloxacin compared with nebulized tobramycin P. Flume1 , J.S. Elborn2 , K. Polu3 , L. Llorens3 , M.L. Pecoraro3 , N. Bhatt3 , D.R. VanDevanter4 . 1 Medical University of South Carolina, Charleston, United States; 2 Queen’s University, Belfast, United Kingdom; 3 Raptor Pharma, Novato, United States; 4 Case Western Reserve University School of Medicine, Cleveland, United States Objectives: PEx are important events among persons with CF and are a significant risk factor for future PEx and pulmonary deterioration. Levofloxacin inhalation solution (LIS; Quinsair® ) was evaluated in an open-label study (MPEX-209) with tobramycin inhalation solution (TIS) over three 28-day cycles, with intervals of 28-days off treatment. Here we describe the proportion of patients who experienced PEx and were treated with antibiotics stratified by the number of clinician-reported PEx patients had experienced in the prior year (prior-yr PEx). Methods: PEx were defined as patients meeting ≥4 of 12 Fuchs criteria and antibiotic treatment for the PEx Prior-yr PEx categories were defined as zero, 1 to 2, or ≥3 PEx. The incidence of PEx during the study was compared between LIS (N = 189) and TIS (N = 93) treatment groups both overall and among prior-yr PEx subgroups. Results: Baseline demographics, including mean FEV1 % predicted, were similar between treatment groups and across prior-yr PEx categories. The overall PEx incidence was not substantially different between LIS patients (53/189 = 28.0% [95% CI 21.8%, 35.0%]) and TIS patients (34/93 = 36.6% [26.8%, 47.2%]). Incidence of PEx increased with increasing prior-yr PEx, but did not differ between treatment groups with <3 prior-yr PEx. For those with ≥3 prior-yr PEx, 17/59 LIS patients (28.8% [17.8%, 42.1%]) had a PEx vs 14/25 TIS patients (56.0% [34.9%, 5.6%]). This 27.2% difference in PEx incidence was statistically significant (P = 0.03; two-tailed Fisher’s exact test). Conclusion: Patients with ≥3 PEx in the past year had the greatest PEx-reduction benefit from LIS treatment. 39 Results of a multicenter, open-label, phase IV study, to evaluate the early response to Bronchitol® in patients with cystic fibrosis A. Thronicke1 , C. Brandt1 , J. Roehmel1 , D. Staab1 , C. Schwarz1 , Bronchitol Study Group. 1 Charit´e-Universit¨ atsmedizin Berlin, Division of Cystic Fibrosis, Berlin, Germany Objectives: Cystic Fibrosis (CF) is a multiorgan disease. Malfunctional pulmonary secretion is a key characteristic of patients with CF. Therapy for better expectoration is one of the most wanted treatments.
S61
Inhalation of hyperosmotic therapeutic Bronchitol® is licensed for the treatment of CF in adults aged 18 years and above in addition to standard care. It improves mucus clearance of retained secretions, hereby counteracting against pulmonary infections and inflammation. This study aimed to evaluate early response in lung function after 14 days of Bronchitol® to predict response after 12 weeks. Methods: A non-blinded, open-label, phase IV study at seven German Cystic Fibrosis centers was conducted between March 31, 2014 and April 15, 2015. The primary objective of the study was the investigation of the predictive value of inhaled dry powder Bronchitol® with respect to the success of treatment over 12 weeks. The primary endpoint was the determination of the prediction of the absolute change in FEV1 (ml) from baseline at week 2 relative to week 12. Results: Of 26 individuals enrolled between Mar 31, 2014 and Jan 15, 2015, all patients were assigned to Bronchitol® treatment (mean age 30.2 years, range 19–49 years). Eight from 26 patients (31%) were male and 18 (69%) were female. The probability that the respective change in lung function would predict positive lung function parameters at day 84 was 83% for FEV1 % predicted. Conclusion: The study showed that Bronchitol® is well tolerated and that the lung function test results after two weeks predicted for the response after 84 days. 40 Use of hypertonic saline solution + hyaluronic acid in patients with cystic fibrosis: a retrospective evaluation F. Majo1 , M. Di Carlo1 , S. Piga2 , M. Ciofi Degli Atti2 , V. Lucidi1 . 1 Bambino Ges` u Children’s Hospital, Cystic Fibrosis Unit, Rome, Italy; 2 Bambino Ges` u Children’s Hospital, Clinical Epidemiology Unit, Rome, Italy Objectives: 1. Evaluate whether the use of hypertonic saline solution with hyaluronic acid (HS+HA) is associated with a reduction in number of intraindividual pulmonary exacerbations (PE) and 2. changes in FEV1 in patients with cystic fibrosis (CF) after one and two years of treatment. 3. Evaluate the tolerability of HS+HA. Methods: Retrospective study on data from 2007 to 2012. Were enrolled in the study patients with CF, age ≥6 years, with FEV1 ≥40%, with at least three measurements of FEV1 per year. We analyzed data about the previous year and the two years following the start of treatment. Tolerability of HS+HA was intended as the need to discontinue therapy. The intra-individual variation for FEV1 and number of RR have been studied using the Student t test for paired data. Results: Of the 437 patients in the database, 127 patients meet the inclusion criteria. The average number of PE is significantly reduced after the second year of therapy (3.5 vs 2.7, SD 2.9 vs 2.2, p < 0.001). The mean FEV1 remains unchanged from the year before the start of HS+HA compared to the first year (80.9 vs. 80.4, SD 23.8 vs. 24.0, p = 0.42) and compared to the second year of treatment (80.9 vs. 79.9, SD 23.8 vs. 23.9, p = 0.17). Only two patients (1.5%) discontinued treatment with HS+HA, both for onset of cough in the first months of therapy. Conclusion: The results of our study show a significant reduction in the number of PE in the second year of treatment with HS+HA, coupled with a good tolerance to the drug. It is also noteworthy a stability of FEV1, as observed in other studies with HS. This is the first study that confirms the safety and efficacy in reducing PE in the long run of HS+HA. 41 Effects of combined exercise training during hospitalization in patients with cystic fibrosis 1 S. Stossel ¨ , O. Nitsche1 , S. Schlotter1 , J. Faber1 , K. Poplawska1 . 1 Universit¨ atsmedizin JGU, Mainz, Germany
Objectives: In patients with cystic fibrosis (CF) exercise can positively impact physical and mental wellbeing. However during hospitalization and need for intravenous antibiotics people with CF usually decrease their level of physical activity. Therefore we implemented combined exercise training for children and adolescents during hospitalization.