Pseudomonas aeruginosa infection is a significant cause of morbidity and mortality in patients wi... more Pseudomonas aeruginosa infection is a significant cause of morbidity and mortality in patients with cystic fibrosis and is associated with a high economic burden. A recently published comparator trial demonstrated that outcomes in patients with cystic fibrosis with chronic P. aeruginosa infections switched from tobramycin solution for inhalation to aztreonam lysine for inhalation were better than those of patients who continued on tobramycin. To compare overall costs of treatment of chronic inhaled tobramycin and aztreonam lysine in patient with cystic fibrosis who have chronic Pseudomonas infection, taking differences in outcomes into account. A cost-effectiveness analysis with a 3-year time horizon was performed to simulate the economic consequences of either treatment from the perspective of a third party payer in the United States. We extrapolated results from the comparator trial and used data regarding clinical outcomes, quality of life, and costs from published literature and proprietary databases. A Markov structure was used to consider transitions between health states, defined principally by levels of percent predicted of FEV1. Extensive scenario and probabilistic sensitivity analyses were performed. Use of aztreonam lysine for inhalation was associated with an average cost saving of $41,947 per patient over 3 years, as well as greater quality-adjusted life-years and total life-years. Scenario analyses demonstrated that these findings were robust to changes in key assumptions. It appears, with high likelihood, that the use of aztreonam solution for inhalation is associated with cost savings, an increase in quality-adjusted life-years, and improved clinical outcomes among patients with extensive prior use of tobramycin solution for inhalation who are naive to inhaled aztreonam lysine.
Evidence-based treatments that achieve optimal energy intake and improve growth in preschool-aged... more Evidence-based treatments that achieve optimal energy intake and improve growth in preschool-aged children with cystic fibrosis (CF) are a critical need. To test whether behavioral and nutritional treatment (intervention) was superior to an education and attention control treatment in increasing energy intake, weight z (WAZ) score, and height z (HAZ) score. This randomized clinical trial included 78 children aged 2 to 6 years (mean age, 3.8 years) with CF and pancreatic insufficiency (intervention, n = 36 and control, n = 42). The study was conducted at 7 CF centers between January 2006 and November 2012; all 78 participants who met intent-to-treat criteria completed through follow-up. Behavioral intervention combined individualized nutritional counseling targeting increased energy intake and training in behavioral child management skills. The control arm provided education and served as a behavioral placebo controlling for attention and contact frequency. Both treatments were delivered in person or telehealth (via telephone). Sessions occurred weekly for 8 weeks then monthly for 4 months (6 months). Participants then returned to standard care for 1 year, with 12-month follow-up thereafter. Changes in energy intake and WAZ score were examined from pretreatment to posttreatment (6 months) and change in HAZ score was assessed pretreatment to follow-up (18 months). Covariates included sex, Pseudomonas aeruginosa status at baseline, and treatment modality (in person vs telehealth). At baseline, mean (SD) energy intake was 1462 (329) kcals/d, WAZ score was -0.44 (0.81), and HAZ score was -0.55 (0.84). From pretreatment to posttreatment, the intervention increased daily energy intake by 485 calories vs 58 calories for the control group (adjusted difference, 431 calories; 95% CI, 282 to 581; P < .001) and increased the WAZ score by 0.12 units vs 0.06 for the control (adjusted difference, 0.09; 95% CI, -0.06 to 0.24; P = .25). From pretreatment to follow-up, the intervention increased the HAZ score by 0.09 units vs -0.02 for the control (adjusted difference, 0.14 units; 95% CI, 0.001 to 0.27; P = .049). Measured treatment integrity and credibility were high for both groups. Behavioral and nutritional intervention improved energy intake and HAZ score outcomes but not WAZ score outcomes. Our results provide evidence that behavioral and nutritional treatment may be efficacious as a nutritional intervention for preschoolers aged 2 to 6 years with CF and pancreatic insufficiency. clinicaltrials.gov Identifier:NCT00241969.
Patients with Coloboma, Heart defect, choanal Atresia, Retarded development, Genitorenal and Ear ... more Patients with Coloboma, Heart defect, choanal Atresia, Retarded development, Genitorenal and Ear abnormalities (CHARGE) syndrome have been reported to be at high risk for aspiration and swallowing difficulties. Aspiration has been implicated as the most common cause of mortality in these patients. To date, however, aspiration and swallowing disorders in CHARGE patients have not been independently studied. To determine the prevalence of aspiration and swallowing dysfunction in children with CHARGE syndrome. A retrospective chart review of 30 children with CHARGE syndrome was performed. Eighteen (60%) children had aspiration observed on video swallow study (VSS), flexible endoscopic evaluation of swallowing (FEES), and/or had otherwise unexplained bronchiectasis noted on CT scan of the chest. Twenty-four children (80%) had evidence of abnormal swallowing such as laryngeal penetration, dyscoordination, poor bolus mobility, or pooling of secretions. Aspiration and swallowing dysfunction are common in children with CHARGE syndrome. Formal evaluation of swallowing function should be part of the standard otolaryngologic examination for these patients.
A23. ADULT CYSTIC FIBROSIS: ADVANCES IN TREATMENT AND UNDERSTANDING OF MECHANISMS OF DISEASE, 2011
University of Arizona, Tucson, AZ, University of Arizona, Tucson, Arizona Health Sciences Center,... more University of Arizona, Tucson, AZ, University of Arizona, Tucson, Arizona Health Sciences Center, Tucson, AZ, Arizona Respiratory 1 2 3 4 ... Rationale: The amiloride-sensitive sodium channels (ENaC) are located on the apical membranes of epithelial cells including the ...
C109. REVISITING EXERCISE FOR CHILDREN AND ADULTS, 2010
University of Arizona, Tucson, AZ, United States of America, Arizona Health Science Center, Tucso... more University of Arizona, Tucson, AZ, United States of America, Arizona Health Science Center, Tucson, AZ, United States of America 1 ... Rationale: Previous studies have demonstrated desaturation during exercise in patients with cystic fibrosis (CF) when compared to healthy control ...
/ Thematic Poster Session / Sunday, May 16/8:15 AM-4:00 PM / Area A, A53 CYSTIC FIBROSIS: CLINICA... more / Thematic Poster Session / Sunday, May 16/8:15 AM-4:00 PM / Area A, A53 CYSTIC FIBROSIS: CLINICAL PEDIATRIC STUDIES ... Hall G (First Level), Morial Convention Center ... Influence Of An Inhaled B-agonist On Alveolar-Capillary Membrane Conductance And ...
Pseudomonas aeruginosa (Pa) serology could potentially be a useful adjunct to respiratory culture... more Pseudomonas aeruginosa (Pa) serology could potentially be a useful adjunct to respiratory culture methods for the detection of initial or early Pa infection in patients with cystic fibrosis (CF). To evaluate the utility of Pa serology to predict Pa isolation from respiratory (generally oropharyngeal) cultures in the subsequent 6 or 12 months among young children with CF from whom Pa had never been previously cultured. Pa serology was also evaluated in a group of healthy controls. Children ≤ 12 years of age without prior isolation of Pa from respiratory cultures participating in the Early Pseudomonal Infection Control EPIC Observational Study (EPIC OBS) had annual serum samples for measurement of antibodies against alkaline protease, elastase and exotoxin A using a commercial kit; controls had a single serum sample. Logistic regression with generalized estimating equations was used to characterize associations between log10 serum antibody titers and first isolation of Pa from a respiratory culture within the subsequent 6 or 12 months, with adjustment for sex and age. Receiver operating characteristic curves were used to optimize antibody titer cutpoints by age group. The diagnostic properties of each antibody were estimated using these optimized cutpoints. Pa serology was evaluated in 582 children with CF (2084 serum samples) and 94 healthy controls. There was substantial overlap between serum antibody titers among controls, CF patients who did not acquire Pa (N = 261) and CF patients who did acquire Pa (N = 321). The maximum positive predictive value for first Pa positive culture within the ensuing 6 months was 76.2% and maximum negative predictive value was 72.1% for any antigen or combination of antigens; values were similar for 12 months. Pa serology does not appear useful for predicting first Pa positive oropharyngeal culture among young CF patients.
Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lun... more Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the β(2)-adrenergic receptors mediates mucociliary clearance and bronchodilation. We sought to determine the influence of an inhaled β-agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-capillary membrane conductance (D(M)), pulmonary capillary blood volume (Vc), and peripheral oxygen saturation (SaO(2)) in subjects with CF, when compared to matched healthy subjects, according to genetic variation of the β(2)-adrenergic receptor (ADRB2). To determine this we recruited 18 subjects with CF and 20 healthy subjects (age = 23 ± 7 vs. 24±4years; ht = 168 ± 8 vs. 174 ± 12 cm; wt = 64 ± 16 vs. 70 ± 13 kg; BMI = 23 ± 4 vs. 23±3 kg/m(2); FEV(1) = 72 ± 27 vs. 92 ± 12%pred; VO(2peak) = 45 ± 25 vs. 99 ± 24%pred, p < 0.05 for FEV(1) and VO(2peak), mean ± SD, for CF and healthy, respectively). The study involved measurement of DLCO, D(M), V(C) and SaO(2) before and 30, 60, and 90 min following the administration of inhaled albuterol. Subjects were stratified according to genetic variation of ADRB2, Gln(27)Gln vs. Glu(27)Glu/Gln(27)Glu. Within the healthy group, there were no differences in DLCO, D(M), V(C), D(M)/V(C) at baseline or in response to albuterol according to genetic variation of the ADRB2 at amino acid 27. Within the CF group, the Glu(27)Glu/Gln(27)Glu group had higher D(M)/V(C) and SaO(2) when compared to the Gln(27)Gln group at baseline (p < 0.05). Both genotype groups demonstrated a significant decline in V(C) and an improvement in D(M)/V(C) and SaO(2) in response to albuterol. Subjects with the Glu(27) genotype experienced a greater improvement in D(M)/V(C) with albuterol when compared to subjects homozygous for Gln at amino acid 27. These results suggest that there are differences in lung diffusion and peripheral SaO(2) according to genetic variation of the ADRB2 at position 27 which could play a potential role in dosing options or adjustments that may be required according to genotype.
Aztreonam lysinate for inhalation (AI) is a novel monobactam formulation being investigated for p... more Aztreonam lysinate for inhalation (AI) is a novel monobactam formulation being investigated for pulmonary Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF). Pre-clinical studies investigated the pre- and post-nebulization activity of AI and its activity in the presence of CF sputum. A double-blind, placebo-controlled, dose-escalation trial determined pharmacokinetics and tolerability of AI in subjects with CF. Single daily escalating doses of AI 75, 150, or 225 mg, or placebo were self-administered using an eFlow Electronic Nebulizer. Sputum samples were collected up to 4 hr and blood samples up to 8 hr post-dose. AI activity against multiple CF isolates was retained after nebulization via eFlow, and activity was not inhibited by CF sputum. All 12 adult subjects and 11/12 adolescents tolerated all AI doses. One patient had an asymptomatic FEV1 decrease > 20% with the 150 mg dose. Median aztreonam sputum concentrations in adults 10 min after AI 75, 150, and 225 mg were 383, 879, and 985 microg/g, respectively. Median sputum concentrations in adolescents 10 min after AI 75, 150, and 225 mg were 324, 387, and 260 microg/g, respectively. Systemic exposure to AI was low. Plasma pharmacokinetics in adults receiving AI 75 mg were Cmax = 419 ng/g, Tmax = 0.99 hr, t1/2 = 2.1 hr. Aztreonam concentrations in sputum were at or above the MIC50 for at least 4 hr post-dose. These data support the continued development of AI for treatment of pulmonary infections in patients with CF.
Pseudomonas aeruginosa infection is a significant cause of morbidity and mortality in patients wi... more Pseudomonas aeruginosa infection is a significant cause of morbidity and mortality in patients with cystic fibrosis and is associated with a high economic burden. A recently published comparator trial demonstrated that outcomes in patients with cystic fibrosis with chronic P. aeruginosa infections switched from tobramycin solution for inhalation to aztreonam lysine for inhalation were better than those of patients who continued on tobramycin. To compare overall costs of treatment of chronic inhaled tobramycin and aztreonam lysine in patient with cystic fibrosis who have chronic Pseudomonas infection, taking differences in outcomes into account. A cost-effectiveness analysis with a 3-year time horizon was performed to simulate the economic consequences of either treatment from the perspective of a third party payer in the United States. We extrapolated results from the comparator trial and used data regarding clinical outcomes, quality of life, and costs from published literature and proprietary databases. A Markov structure was used to consider transitions between health states, defined principally by levels of percent predicted of FEV1. Extensive scenario and probabilistic sensitivity analyses were performed. Use of aztreonam lysine for inhalation was associated with an average cost saving of $41,947 per patient over 3 years, as well as greater quality-adjusted life-years and total life-years. Scenario analyses demonstrated that these findings were robust to changes in key assumptions. It appears, with high likelihood, that the use of aztreonam solution for inhalation is associated with cost savings, an increase in quality-adjusted life-years, and improved clinical outcomes among patients with extensive prior use of tobramycin solution for inhalation who are naive to inhaled aztreonam lysine.
Evidence-based treatments that achieve optimal energy intake and improve growth in preschool-aged... more Evidence-based treatments that achieve optimal energy intake and improve growth in preschool-aged children with cystic fibrosis (CF) are a critical need. To test whether behavioral and nutritional treatment (intervention) was superior to an education and attention control treatment in increasing energy intake, weight z (WAZ) score, and height z (HAZ) score. This randomized clinical trial included 78 children aged 2 to 6 years (mean age, 3.8 years) with CF and pancreatic insufficiency (intervention, n = 36 and control, n = 42). The study was conducted at 7 CF centers between January 2006 and November 2012; all 78 participants who met intent-to-treat criteria completed through follow-up. Behavioral intervention combined individualized nutritional counseling targeting increased energy intake and training in behavioral child management skills. The control arm provided education and served as a behavioral placebo controlling for attention and contact frequency. Both treatments were delivered in person or telehealth (via telephone). Sessions occurred weekly for 8 weeks then monthly for 4 months (6 months). Participants then returned to standard care for 1 year, with 12-month follow-up thereafter. Changes in energy intake and WAZ score were examined from pretreatment to posttreatment (6 months) and change in HAZ score was assessed pretreatment to follow-up (18 months). Covariates included sex, Pseudomonas aeruginosa status at baseline, and treatment modality (in person vs telehealth). At baseline, mean (SD) energy intake was 1462 (329) kcals/d, WAZ score was -0.44 (0.81), and HAZ score was -0.55 (0.84). From pretreatment to posttreatment, the intervention increased daily energy intake by 485 calories vs 58 calories for the control group (adjusted difference, 431 calories; 95% CI, 282 to 581; P < .001) and increased the WAZ score by 0.12 units vs 0.06 for the control (adjusted difference, 0.09; 95% CI, -0.06 to 0.24; P = .25). From pretreatment to follow-up, the intervention increased the HAZ score by 0.09 units vs -0.02 for the control (adjusted difference, 0.14 units; 95% CI, 0.001 to 0.27; P = .049). Measured treatment integrity and credibility were high for both groups. Behavioral and nutritional intervention improved energy intake and HAZ score outcomes but not WAZ score outcomes. Our results provide evidence that behavioral and nutritional treatment may be efficacious as a nutritional intervention for preschoolers aged 2 to 6 years with CF and pancreatic insufficiency. clinicaltrials.gov Identifier:NCT00241969.
Patients with Coloboma, Heart defect, choanal Atresia, Retarded development, Genitorenal and Ear ... more Patients with Coloboma, Heart defect, choanal Atresia, Retarded development, Genitorenal and Ear abnormalities (CHARGE) syndrome have been reported to be at high risk for aspiration and swallowing difficulties. Aspiration has been implicated as the most common cause of mortality in these patients. To date, however, aspiration and swallowing disorders in CHARGE patients have not been independently studied. To determine the prevalence of aspiration and swallowing dysfunction in children with CHARGE syndrome. A retrospective chart review of 30 children with CHARGE syndrome was performed. Eighteen (60%) children had aspiration observed on video swallow study (VSS), flexible endoscopic evaluation of swallowing (FEES), and/or had otherwise unexplained bronchiectasis noted on CT scan of the chest. Twenty-four children (80%) had evidence of abnormal swallowing such as laryngeal penetration, dyscoordination, poor bolus mobility, or pooling of secretions. Aspiration and swallowing dysfunction are common in children with CHARGE syndrome. Formal evaluation of swallowing function should be part of the standard otolaryngologic examination for these patients.
A23. ADULT CYSTIC FIBROSIS: ADVANCES IN TREATMENT AND UNDERSTANDING OF MECHANISMS OF DISEASE, 2011
University of Arizona, Tucson, AZ, University of Arizona, Tucson, Arizona Health Sciences Center,... more University of Arizona, Tucson, AZ, University of Arizona, Tucson, Arizona Health Sciences Center, Tucson, AZ, Arizona Respiratory 1 2 3 4 ... Rationale: The amiloride-sensitive sodium channels (ENaC) are located on the apical membranes of epithelial cells including the ...
C109. REVISITING EXERCISE FOR CHILDREN AND ADULTS, 2010
University of Arizona, Tucson, AZ, United States of America, Arizona Health Science Center, Tucso... more University of Arizona, Tucson, AZ, United States of America, Arizona Health Science Center, Tucson, AZ, United States of America 1 ... Rationale: Previous studies have demonstrated desaturation during exercise in patients with cystic fibrosis (CF) when compared to healthy control ...
/ Thematic Poster Session / Sunday, May 16/8:15 AM-4:00 PM / Area A, A53 CYSTIC FIBROSIS: CLINICA... more / Thematic Poster Session / Sunday, May 16/8:15 AM-4:00 PM / Area A, A53 CYSTIC FIBROSIS: CLINICAL PEDIATRIC STUDIES ... Hall G (First Level), Morial Convention Center ... Influence Of An Inhaled B-agonist On Alveolar-Capillary Membrane Conductance And ...
Pseudomonas aeruginosa (Pa) serology could potentially be a useful adjunct to respiratory culture... more Pseudomonas aeruginosa (Pa) serology could potentially be a useful adjunct to respiratory culture methods for the detection of initial or early Pa infection in patients with cystic fibrosis (CF). To evaluate the utility of Pa serology to predict Pa isolation from respiratory (generally oropharyngeal) cultures in the subsequent 6 or 12 months among young children with CF from whom Pa had never been previously cultured. Pa serology was also evaluated in a group of healthy controls. Children ≤ 12 years of age without prior isolation of Pa from respiratory cultures participating in the Early Pseudomonal Infection Control EPIC Observational Study (EPIC OBS) had annual serum samples for measurement of antibodies against alkaline protease, elastase and exotoxin A using a commercial kit; controls had a single serum sample. Logistic regression with generalized estimating equations was used to characterize associations between log10 serum antibody titers and first isolation of Pa from a respiratory culture within the subsequent 6 or 12 months, with adjustment for sex and age. Receiver operating characteristic curves were used to optimize antibody titer cutpoints by age group. The diagnostic properties of each antibody were estimated using these optimized cutpoints. Pa serology was evaluated in 582 children with CF (2084 serum samples) and 94 healthy controls. There was substantial overlap between serum antibody titers among controls, CF patients who did not acquire Pa (N = 261) and CF patients who did acquire Pa (N = 321). The maximum positive predictive value for first Pa positive culture within the ensuing 6 months was 76.2% and maximum negative predictive value was 72.1% for any antigen or combination of antigens; values were similar for 12 months. Pa serology does not appear useful for predicting first Pa positive oropharyngeal culture among young CF patients.
Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lun... more Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the β(2)-adrenergic receptors mediates mucociliary clearance and bronchodilation. We sought to determine the influence of an inhaled β-agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-capillary membrane conductance (D(M)), pulmonary capillary blood volume (Vc), and peripheral oxygen saturation (SaO(2)) in subjects with CF, when compared to matched healthy subjects, according to genetic variation of the β(2)-adrenergic receptor (ADRB2). To determine this we recruited 18 subjects with CF and 20 healthy subjects (age = 23 ± 7 vs. 24±4years; ht = 168 ± 8 vs. 174 ± 12 cm; wt = 64 ± 16 vs. 70 ± 13 kg; BMI = 23 ± 4 vs. 23±3 kg/m(2); FEV(1) = 72 ± 27 vs. 92 ± 12%pred; VO(2peak) = 45 ± 25 vs. 99 ± 24%pred, p < 0.05 for FEV(1) and VO(2peak), mean ± SD, for CF and healthy, respectively). The study involved measurement of DLCO, D(M), V(C) and SaO(2) before and 30, 60, and 90 min following the administration of inhaled albuterol. Subjects were stratified according to genetic variation of ADRB2, Gln(27)Gln vs. Glu(27)Glu/Gln(27)Glu. Within the healthy group, there were no differences in DLCO, D(M), V(C), D(M)/V(C) at baseline or in response to albuterol according to genetic variation of the ADRB2 at amino acid 27. Within the CF group, the Glu(27)Glu/Gln(27)Glu group had higher D(M)/V(C) and SaO(2) when compared to the Gln(27)Gln group at baseline (p < 0.05). Both genotype groups demonstrated a significant decline in V(C) and an improvement in D(M)/V(C) and SaO(2) in response to albuterol. Subjects with the Glu(27) genotype experienced a greater improvement in D(M)/V(C) with albuterol when compared to subjects homozygous for Gln at amino acid 27. These results suggest that there are differences in lung diffusion and peripheral SaO(2) according to genetic variation of the ADRB2 at position 27 which could play a potential role in dosing options or adjustments that may be required according to genotype.
Aztreonam lysinate for inhalation (AI) is a novel monobactam formulation being investigated for p... more Aztreonam lysinate for inhalation (AI) is a novel monobactam formulation being investigated for pulmonary Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF). Pre-clinical studies investigated the pre- and post-nebulization activity of AI and its activity in the presence of CF sputum. A double-blind, placebo-controlled, dose-escalation trial determined pharmacokinetics and tolerability of AI in subjects with CF. Single daily escalating doses of AI 75, 150, or 225 mg, or placebo were self-administered using an eFlow Electronic Nebulizer. Sputum samples were collected up to 4 hr and blood samples up to 8 hr post-dose. AI activity against multiple CF isolates was retained after nebulization via eFlow, and activity was not inhibited by CF sputum. All 12 adult subjects and 11/12 adolescents tolerated all AI doses. One patient had an asymptomatic FEV1 decrease > 20% with the 150 mg dose. Median aztreonam sputum concentrations in adults 10 min after AI 75, 150, and 225 mg were 383, 879, and 985 microg/g, respectively. Median sputum concentrations in adolescents 10 min after AI 75, 150, and 225 mg were 324, 387, and 260 microg/g, respectively. Systemic exposure to AI was low. Plasma pharmacokinetics in adults receiving AI 75 mg were Cmax = 419 ng/g, Tmax = 0.99 hr, t1/2 = 2.1 hr. Aztreonam concentrations in sputum were at or above the MIC50 for at least 4 hr post-dose. These data support the continued development of AI for treatment of pulmonary infections in patients with CF.
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