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WS07.1 Standardized treatment of pulmonary exacerbations (STOP) study: Treatment goals for pulmonary exacerbations
Oral Presentations
Workshop 7. Monitoring CF lung disease
WS07.1 Standardized treatment of pulmonary exacerbations (STOP) study: Treatment goals for pulmonary exacerbations
WS07.3 FEF25−75 does not contribute to the interpretation of spirometry in patients with cystic fibrosis
N.E. West1 , C.H. Goss2 , D.R. VanDevanter3 , S. Heltshe2 , V. Thompson4 , D.B. Sanders5 , P. Flume6 . 1 Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Baltimore, United States; 2 University of Washington, Seattle, United States; 3 Case Western Reserve University School of Medicine, Cleveland, United States; 4 Seattle Children’s Hospital, Seattle, United States; 5 University of Wisconsin, Madison, United States; 6 Medical University of South Carolina, Charleston, United States
F. Vermeulen1 , K. De Boeck1 . 1 University Hospital Leuven, Leuven, Belgium
Objectives: Pulmonary exacerbations (PEx) are common in individuals with CF, but there are no standard treatment recommendations. STOP collects information to define the primary endpoint for studies of treatment of PEx, and to access the feasibility for future trials to use the CF Foundation Patient Registry (CFFPR) for data capture. Methods: STOP is an observational pilot study using the CFFPR and projected to enroll over 200 patients (age >12 years) at 10 sites admitted to the hospital for PEx treatment. A survey of admitting physicians was performed to ascertain treatment goals and physician willingness to enroll the patient in hypothetical interventional trials. Results: After 12 months, 204 patients (56% female) have entered the study, with a mean age of 27.2±9.2 years and 53% homozygous F508del. The primary objective of treatment was recovery of lung function (53%) and improvement of symptoms (45%). The mean lung function recovery goal (target FEV1 − admission FEV1 ) was 13.7% predicted (range: 0–65.7%). For CF centers with a treatment protocol, the average planned treatment duration was 13.9±1.6 days. A majority of physicians were willing to enroll their patients in a trial of differing durations [10 days (71%) and 14 days (87%)], specified antibiotics (86%), and other treatments (83%), but less so for treatment of 7 days (30%). Conclusion: The primary goals for treatment of PEx are recovery of lung function, targeting almost 14% recovery, and symptom improvement. Most sites express willingness to enroll patients into interventional trials of treatments. Early experience suggests the CFFPR can be used successfully for clinical trials. Supported by CFFT.
S13
Objective: To explore the value of assessing the FEF25−75 , a measure of “small airway disease” in addition to the FEV1 , FVC and FEV1/FVC in patients with cystic fibrosis (CF) Methods: The spirometry of the patients followed between 1998 and 2013 at the CF Centre of Leuven, Belgium, were retrospectively reviewed. For each patient, the last measurement of each age year was included, resulting in 1793 measurements in 268 patients aged between 6 and 76 years. Z-scores were calculated with the equations from the Global Lung Initiative, with −1.645 as the lower limit of normal. Medians and interquartile ranges are reported. Results: Discordance between FEF25−75 and FEV1 /FVC was uncommon. In the 811 tests with normal FEV1 and FVC, the 95 tests with a low FEF25−75 but normal FEV1 /FVC were from younger patients [12.3 years (10.0; 21.9) vs 16.6 years (13.0; 27.9), p = 0.006] and had a lower FVC Z-score [−0.53 (−0.80; −0.21) vs +0.54 (−0.04; 1.17), p < 0.001] than the 126 tests with both low FEF25−75 and low FEV1 /FVC. In the 971 tests with a low FEV1 , FEF25−75 was also abnormal in 95.7% and FEV1 /FVC in 83.3%. The 122 tests with a low FEF25−75 but normal FEV1 /FVC were from younger patients [15.5 years (IQR 10.9; 24.9) vs 24.9 years (17.0; 31.5), p < 0.001] and had a lower FVC Z-score [−1.90 (−2.76; −1.41) vs −1.66 (−2.74; −0.71), p = 0.015] than the 807 tests with both low FEF25−75 and low FEV1 /FVC. Conclusion: A spirometry with only a low FEF25−75 was rare in patients with CF, and was seen more often at younger age and with FVC Z-scores at the lower end of the normal range. In this group of patients with CF assessment of FEF25−75 in addition to FEV1 , FVC and FEV1 /FVC added little information.
WS07.2 Bronchoalveolar lavage in children with cystic fibrosis and increasing Lung Clearance Index
WS07.4 MBW and MRI as sensitive markers of stable CF lung disease and at exacerbation in children and adolescents
M. Svedberg1 , K. K¨otz1 , P. Wilmar1 , P. Gustavsson2 , A. Lindblad1 . 1 Queen Siliva Children’s University Hospital, Department of Paediatrics, Gothenburg, Sweden; 2 Central Hospital, Dept of Pediatrics, Sk¨ ovde, Sweden
M. Stahl1,2 , M.O. Wielp¨utz2,3 , S.Y. Gr¨aber1,2 , S. H¨ammerling1 , O. Sommerburg1,2 , M. Eichinger3,4 , M.A. Mall1,2,5 . 1 University Children’s Hospital Heidelberg, Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Centre, Heidelberg, Germany; 2 German Centre for Lung Research (DZL), Translational Lung Research Center (TLRC), Heidelberg, Germany; 3 University of Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg, Germany; 4 Thoraxklinik at University of Heidelberg, Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg, Germany; 5 University of Heidelberg, Department of Translational Pulmonology, Heidelberg, Germany
Objectives: Lung Clearance Index (LCI) is a promising tool to identify early lung disease in children with cystic fibrosis (CF). This retrospective study presents the findings in bronchoalveolar lavage (BAL) in children with CF and an increasing LCI-value and the possibility to reverse the LCI-value with a BAL-directed therapy. Methods: 70 children with CF were monitored annually between October 2007 and April 2014 with Multiple Breath Washout (MBW) using SF6 as tracer gas. During this period 23 of 70 children (median 6.6 yrs, range 0.8–13.8 yrs) with an increasing LCI (not responding to treatment) or positive pseudomonas (PA) serum antibodies with negative PA sputum cultures underwent 31 BALs (minimum 1.9 yrs between BALs performed in the same child). Antibiotic treatment was ended 3 days prior to BAL. Results: LCI and BAL-neutrophils correlated significantly (r = 0.572, p = 0.001). In children with LCI 7.8, 18 of 21 BAL-cultures were positive (1000 cfu/ml or a positive fungus culture) and only 2 of 10 BAL-cultures were positive when LCI < 7.8 (p = 0.001). LCI was 7.8 in all 11 fungus positive BAL-cultures. In three of these, fungus was the only pathogen detected. LCI increased over time before BAL (mean increase 0.55, CI 0.0−1.11, p = 0.05). Mean LCI before BAL was 8.95 (median 68 days prior to BAL) and decreased with a BAL-directed therapy (mean decrease 0.59, CI 0.1−1.1, p = 0.02). Conclusion: An increasing LCI in CF patients correlates with neutrophil inflammation and infection in BAL. An increasing LCI might be an indication for BAL to achieve a more effective treatment. Fungus may play an active role in causing neutrophil inflammation and an increasing LCI.
Objectives: MBW and MRI have both been shown to be sensitive outcome measures for CF lung disease. Therefore, we wanted to determine the correlation of the LCI with alterations in the MRI chest score as markers of CF lung disease under stable conditions and at exacerbation. Methods: 57 stable children with CF (mean age, 9.5±6.2 years) had chest MRI scans performed. All children with CF and 106 healthy children (mean age, 8.9±4.8 years) underwent age-adapted MBW testing to assess LCI and to calculate LCI z-scores. 36 children (mean age, 13.9±4.4 years) were investigated at time of pulmonary exacerbation either via MRI (n = 10) or MBW (n = 26). Results: Mean LCI z-score in healthy children was 0.1±1.2). LCI z-score was significantly higher in stable children with CF (5.4±5.5, P < 0.001). Morphological, perfusion and global MRI chest score were elevated in stable children with CF and were positively correlated with a higher LCI z-score (R 0.682; 0.669; 0.711). Concordance between abnormal findings in MBW and MRI was above 70%. At exacerbation, LCI increased in children with CF from baseline (P < 0.001) and decreased after antibiotic therapy (P < 0.001). The MRI chest scores also decreased after iv antibiotic treatment (P < 0.05). Conclusion: LCI z-score and MRI chest score are elevated in CF and show a high correlation. Both methods are feasible and sensitive non-invasive markers of CF lung disease in children with CF under stable conditions and at time of exacerbation.
Workshop 7. Monitoring CF lung disease
WS07.1 Standardized treatment of pulmonary exacerbations (STOP) study: Treatment goals for pulmonary exacerbations
WS07.3 FEF25−75 does not contribute to the interpretation of spirometry in patients with cystic fibrosis
N.E. West1 , C.H. Goss2 , D.R. VanDevanter3 , S. Heltshe2 , V. Thompson4 , D.B. Sanders5 , P. Flume6 . 1 Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Baltimore, United States; 2 University of Washington, Seattle, United States; 3 Case Western Reserve University School of Medicine, Cleveland, United States; 4 Seattle Children’s Hospital, Seattle, United States; 5 University of Wisconsin, Madison, United States; 6 Medical University of South Carolina, Charleston, United States
F. Vermeulen1 , K. De Boeck1 . 1 University Hospital Leuven, Leuven, Belgium
Objectives: Pulmonary exacerbations (PEx) are common in individuals with CF, but there are no standard treatment recommendations. STOP collects information to define the primary endpoint for studies of treatment of PEx, and to access the feasibility for future trials to use the CF Foundation Patient Registry (CFFPR) for data capture. Methods: STOP is an observational pilot study using the CFFPR and projected to enroll over 200 patients (age >12 years) at 10 sites admitted to the hospital for PEx treatment. A survey of admitting physicians was performed to ascertain treatment goals and physician willingness to enroll the patient in hypothetical interventional trials. Results: After 12 months, 204 patients (56% female) have entered the study, with a mean age of 27.2±9.2 years and 53% homozygous F508del. The primary objective of treatment was recovery of lung function (53%) and improvement of symptoms (45%). The mean lung function recovery goal (target FEV1 − admission FEV1 ) was 13.7% predicted (range: 0–65.7%). For CF centers with a treatment protocol, the average planned treatment duration was 13.9±1.6 days. A majority of physicians were willing to enroll their patients in a trial of differing durations [10 days (71%) and 14 days (87%)], specified antibiotics (86%), and other treatments (83%), but less so for treatment of 7 days (30%). Conclusion: The primary goals for treatment of PEx are recovery of lung function, targeting almost 14% recovery, and symptom improvement. Most sites express willingness to enroll patients into interventional trials of treatments. Early experience suggests the CFFPR can be used successfully for clinical trials. Supported by CFFT.
S13
Objective: To explore the value of assessing the FEF25−75 , a measure of “small airway disease” in addition to the FEV1 , FVC and FEV1/FVC in patients with cystic fibrosis (CF) Methods: The spirometry of the patients followed between 1998 and 2013 at the CF Centre of Leuven, Belgium, were retrospectively reviewed. For each patient, the last measurement of each age year was included, resulting in 1793 measurements in 268 patients aged between 6 and 76 years. Z-scores were calculated with the equations from the Global Lung Initiative, with −1.645 as the lower limit of normal. Medians and interquartile ranges are reported. Results: Discordance between FEF25−75 and FEV1 /FVC was uncommon. In the 811 tests with normal FEV1 and FVC, the 95 tests with a low FEF25−75 but normal FEV1 /FVC were from younger patients [12.3 years (10.0; 21.9) vs 16.6 years (13.0; 27.9), p = 0.006] and had a lower FVC Z-score [−0.53 (−0.80; −0.21) vs +0.54 (−0.04; 1.17), p < 0.001] than the 126 tests with both low FEF25−75 and low FEV1 /FVC. In the 971 tests with a low FEV1 , FEF25−75 was also abnormal in 95.7% and FEV1 /FVC in 83.3%. The 122 tests with a low FEF25−75 but normal FEV1 /FVC were from younger patients [15.5 years (IQR 10.9; 24.9) vs 24.9 years (17.0; 31.5), p < 0.001] and had a lower FVC Z-score [−1.90 (−2.76; −1.41) vs −1.66 (−2.74; −0.71), p = 0.015] than the 807 tests with both low FEF25−75 and low FEV1 /FVC. Conclusion: A spirometry with only a low FEF25−75 was rare in patients with CF, and was seen more often at younger age and with FVC Z-scores at the lower end of the normal range. In this group of patients with CF assessment of FEF25−75 in addition to FEV1 , FVC and FEV1 /FVC added little information.
WS07.2 Bronchoalveolar lavage in children with cystic fibrosis and increasing Lung Clearance Index
WS07.4 MBW and MRI as sensitive markers of stable CF lung disease and at exacerbation in children and adolescents
M. Svedberg1 , K. K¨otz1 , P. Wilmar1 , P. Gustavsson2 , A. Lindblad1 . 1 Queen Siliva Children’s University Hospital, Department of Paediatrics, Gothenburg, Sweden; 2 Central Hospital, Dept of Pediatrics, Sk¨ ovde, Sweden
M. Stahl1,2 , M.O. Wielp¨utz2,3 , S.Y. Gr¨aber1,2 , S. H¨ammerling1 , O. Sommerburg1,2 , M. Eichinger3,4 , M.A. Mall1,2,5 . 1 University Children’s Hospital Heidelberg, Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Centre, Heidelberg, Germany; 2 German Centre for Lung Research (DZL), Translational Lung Research Center (TLRC), Heidelberg, Germany; 3 University of Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg, Germany; 4 Thoraxklinik at University of Heidelberg, Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg, Germany; 5 University of Heidelberg, Department of Translational Pulmonology, Heidelberg, Germany
Objectives: Lung Clearance Index (LCI) is a promising tool to identify early lung disease in children with cystic fibrosis (CF). This retrospective study presents the findings in bronchoalveolar lavage (BAL) in children with CF and an increasing LCI-value and the possibility to reverse the LCI-value with a BAL-directed therapy. Methods: 70 children with CF were monitored annually between October 2007 and April 2014 with Multiple Breath Washout (MBW) using SF6 as tracer gas. During this period 23 of 70 children (median 6.6 yrs, range 0.8–13.8 yrs) with an increasing LCI (not responding to treatment) or positive pseudomonas (PA) serum antibodies with negative PA sputum cultures underwent 31 BALs (minimum 1.9 yrs between BALs performed in the same child). Antibiotic treatment was ended 3 days prior to BAL. Results: LCI and BAL-neutrophils correlated significantly (r = 0.572, p = 0.001). In children with LCI 7.8, 18 of 21 BAL-cultures were positive (1000 cfu/ml or a positive fungus culture) and only 2 of 10 BAL-cultures were positive when LCI < 7.8 (p = 0.001). LCI was 7.8 in all 11 fungus positive BAL-cultures. In three of these, fungus was the only pathogen detected. LCI increased over time before BAL (mean increase 0.55, CI 0.0−1.11, p = 0.05). Mean LCI before BAL was 8.95 (median 68 days prior to BAL) and decreased with a BAL-directed therapy (mean decrease 0.59, CI 0.1−1.1, p = 0.02). Conclusion: An increasing LCI in CF patients correlates with neutrophil inflammation and infection in BAL. An increasing LCI might be an indication for BAL to achieve a more effective treatment. Fungus may play an active role in causing neutrophil inflammation and an increasing LCI.
Objectives: MBW and MRI have both been shown to be sensitive outcome measures for CF lung disease. Therefore, we wanted to determine the correlation of the LCI with alterations in the MRI chest score as markers of CF lung disease under stable conditions and at exacerbation. Methods: 57 stable children with CF (mean age, 9.5±6.2 years) had chest MRI scans performed. All children with CF and 106 healthy children (mean age, 8.9±4.8 years) underwent age-adapted MBW testing to assess LCI and to calculate LCI z-scores. 36 children (mean age, 13.9±4.4 years) were investigated at time of pulmonary exacerbation either via MRI (n = 10) or MBW (n = 26). Results: Mean LCI z-score in healthy children was 0.1±1.2). LCI z-score was significantly higher in stable children with CF (5.4±5.5, P < 0.001). Morphological, perfusion and global MRI chest score were elevated in stable children with CF and were positively correlated with a higher LCI z-score (R 0.682; 0.669; 0.711). Concordance between abnormal findings in MBW and MRI was above 70%. At exacerbation, LCI increased in children with CF from baseline (P < 0.001) and decreased after antibiotic therapy (P < 0.001). The MRI chest scores also decreased after iv antibiotic treatment (P < 0.05). Conclusion: LCI z-score and MRI chest score are elevated in CF and show a high correlation. Both methods are feasible and sensitive non-invasive markers of CF lung disease in children with CF under stable conditions and at time of exacerbation.