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ABSTRACT: We evaluated safety and efficacy of recombinant human growth hormone (rhGH) for improving growth, lean body mass (LBM), pulmonary function, and exercise tolerance in children with cystic fibrosis (CF) and growth restriction.
Multicenter, open-label, controlled clinical trial comparing outcomes in prepubertal children <14 years with CF, randomized in a 1:1 ratio to receive daily rhGH (Nutropin AQ) or no treatment (control) for 12 months, followed by a 6-month observation (month 18). Safety was monitored at each visit, including assessments of glucose tolerance.
Sixty-eight subjects were randomized (control n = 32; rhGH n = 36). Mean height standard deviation score (SDS) in the rhGH group increased by 0.5 ± 0.4 at 12 months (mean ± SD, P < 0.001); the control group height SDS remained unchanged. Weight increased by 3.8 ± 1.8 versus 2.8 ± 1.5 kg, (mean ± SD, P = 0.0356) and LBM increased by 3.8 ± 1.8 versus 2.1 ± 1.4 kg (P = 0.0002) in the rhGH group versus controls, respectively. Forced vital capacity increased by 325 ± 319 in the rhGH group compared with 178 ± 152 ml in controls (mean ± SD, P = 0.032). Forced expiratory volume in 1 sec improved in both groups with a significant difference between groups after adjustment for baseline severity (LS mean ± SE: rhGH, 224 ± 37, vs. controls, 108 ± 40 ml; P = 0.04). There was no difference between groups in exercise tolerance (6-min walk distance) at 1 year. Changes in glucose tolerance for the two groups were similar over the 12-month study period, with three subjects developing IGT and one CFRD in each group. One rhGH-treated patient developed increased intracranial pressure.
Treatment with rhGH in prepubertal children with CF was effective in promoting growth, weight, LBM, lung volume, and lung flows, and had an acceptable safety profile.
Pediatric Pulmonology 09/2011; 47(3):252-63. · 2.53 Impact Factor
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ABSTRACT: Randomized controlled trials of dornase alpha have shown forced expiratory volume in 1 sec (FEV(1) ) to improve in patients with cystic fibrosis (CF) but have not assessed change in the rate of lung function decline. We assessed the relationship of dornase alpha use and FEV(1) decline using the Epidemiologic Study of Cystic Fibrosis (ESCF).
Patients aged 8-38 years who had been enrolled in ESCF for 2 years when initially treated with dornase alpha were selected if they remained on treatment during the following 2 years. A comparator group included patients aged 8-38 who were not yet reported to have received dornase alpha. For each patient we estimated the annual rate of decline in FEV(1) % predicted before and after the index using a mixed-effects model adjusted for age, gender, pulmonary exacerbations, respiratory therapies, and nutritional supplements.
The dornase alpha group (n = 2,230) had a lower FEV(1) % predicted at index and a more rapid decline during the pre-index period. The mean rate of FEV(1) decline improved for the dornase alpha group; the improvement was similar in adults and children 8-17 years old but was not statistically significant in adults. The comparator group (n = 5,970) showed no change among adults and an increased rate of decline among children 8-17 years old.
The use of dornase alpha for a 2-year period is associated with a reduction in the rate of FEV(1) decline. These results also demonstrate the value of using an observational study to assess the association of instituting new therapies in the clinical setting with changes in the rate of FEV(1) decline in patients with CF.
Pediatric Pulmonology 03/2011; 46(6):545-53. · 2.53 Impact Factor
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ABSTRACT: Loss of lung function in patients with cystic fibrosis (CF) is associated with increased mortality and varies between individuals and over time. Predicting this decline could improve patient management.
To develop simple pulmonary outcome prediction (POP) tools to estimate lung function at age 6 in patients aged 2-5 years (POP(2-5)) and lung function change over a 4-year period in patients aged 6-17 years (POP(6-17)).
Analyses were conducted using patients from the Epidemiologic Study of CF (ESCF). To be included in any analysis, patients had to have 1 year of clinical history recorded in ESCF prior to a clinically stable routine Index Clinic Visit (ICV). In addition to this criterion, for the POP(2-5) tool patients had to be between 2 and 5 years old at ICV and have a second clinically stable visit with spirometric measures at age 6. For the POP(6-17) tool, patients had to be between the ages of 6 and 17 years old at an ICV that included spirometric measures and had to have a second clinically stable visit with spirometric measures from 3 to 5 years after ICV. All patients enrolled in ESCF who met these inclusion criteria were studied. POP(2-5) and POP(6-17) populations were further divided into development groups (with ICV before January 1, 1998) and validation groups (with ICV after that date). Development groups were used to model forced expiratory volume in 1 sec (FEV(1)) percent predicted at age 6 years (for POP(2-5)) and annualized FEV(1) % predicted change from ICV to the second visit (for POP(6-17)) by multivariable linear regression using age, sex, weight-for-age percentile, cough, sputum production, clubbing, crackles, wheeze, sinusitis, number of exacerbations requiring intravenous antibiotics in the past year, elevated liver enzymes, pancreatic enzyme use, and respiratory tract culture status, plus height-for-age percentile (POP(2-5)) and index FEV(1) (POP(6-17)). Integer-based POP(2-5) and POP(6-17) tools created from selected variables were evaluated by Pearson correlation and then prospectively validated with separate data collected later from ESCF patients with ICV after January 1, 1998.
POP(2-5) and POP(6-17) development groups included 2,709 and 6,113 patients and validation groups included 3,458 and 7,086 patients, respectively. Variables retained were weight-for-age percentile, clubbing, crackles, wheeze, number of exacerbations, and Pseudomonas aeruginosa culture status (both tools), daily cough (POP(2-5)), and age, sex, and index FEV(1) % predicted (POP(6-17)). Correlation coefficients for POP(2-5) and POP(6-17) tools prospectively applied to validation groups were +0.32 and +0.37, respectively.
These simple integer-based POP algorithms employ variables available at clinic visits and can be used to predict the probability of different future pulmonary outcomes for individual patients and patient populations.
Pediatric Pulmonology 12/2010; 45(12):1156-66. · 2.53 Impact Factor
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ABSTRACT: We examined the year-to-year change in FEV(1) for individuals and the overall cystic fibrosis population to better understand how individual trends may differ from population trends.
We calculated individual yearly changes using the largest annual FEV(1) percent predicted (FEV(1)%) measurement in 20,644 patients (6-45years old) included in the Epidemiologic Study of Cystic Fibrosis. We calculated yearly population changes using age-specific medians.
FEV(1)% predicted decreased 1-3 points per year for individuals, with maximal decreases in 14-15year olds. Population changes agreed with individual changes up to age 15; however after age 30, yearly population change approximated zero while individual FEV(1)% predicted decreases were 1-2 points per year.
Adolescents have the greatest FEV(1)% predicted decreases; however, loss of FEV(1) is a persistent risk in 6-45year old CF patients. Recognizing individual year-to-year changes may improve patient-specific care and may suggest new methods for measuring program quality.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 07/2010; 9(4):250-6. · 3.19 Impact Factor
