Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation.

RATIONALE: Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has been shown to improve lung function, pulmonary exacerbation rate, respiratory symptoms, and weight gain compared with placebo in patients with cystic fibrosis aged 12 years or older with a G551D-CFTR mutation. OBJECTIVES: This randomized, double-blind, placebo-controlled trial evaluated ivacaftor in patients with cystic fibrosis aged 6-11 years with a G551D-CFTR mutation on at least one allele. METHODS: Patients were randomly assigned to receive ivacaftor administered orally at 150 mg (n = 26) or placebo (n = 26) every 12 hours for 48 weeks in addition to existing prescribed cystic fibrosis therapies. MEASUREMENTS AND MAIN RESULTS: Despite near-normal mean baseline values in FEV1, patients receiving ivacaftor had a significant increase in percent predicted FEV1 from baseline through Week 24 versus placebo group (treatment effect, 12.5 percentage points; P < 0.001). Effects on pulmonary function were evident by 2 weeks, and a significant treatment effect was maintained through Week 48. Patients treated with ivacaftor gained, on average, 2.8 kg more than those receiving placebo at Week 48 (P < 0.001). The change from baseline through Week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor was -53.5 mmol/L (P < 0.001) versus placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In patients who are younger and healthier than those in previously studied populations, ivacaftor demonstrated a significant improvement in pulmonary function, weight, and CFTR activity compared with placebo. Clinical trial registered with www.clinicaltrials.gov (NCT00909727).

Outcome in cystic fibrosis liver disease.

OBJECTIVES: Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD. METHODS: This is a 7-year follow-up of 42 children with CFLD and their age- and sex-matched controls. Participants were reviewed clinically, biochemically, and radiologically at follow-up. RESULTS: Overall, 85% (72 of 84) of the original cohort were included, 36 CFLD participants and 36 CF controls. There was no significant difference in the number of deaths/transplants between groups (7 of 36 (19.4%) CFLD participants, 3 of 36 (8.3%) CF controls). There was a tendency for participants with CFLD to die younger than their respective CF controls. There was no difference in height, weight, body mass index, or pulmonary function between the groups. Nutritional parameters (sum skinfold thickness 31.6 vs. 42.3, P=0.03; mean upper arm fat area 15.08 vs. 10.59, P=0.001; Shwachman score 43.7 vs. 32.1, P=0.001) were worse among CFLD participants than among CF controls. Cystic fibrosis-related diabetes was more common in CFLD participants (11 of 27 (40.7%) vs. 5 of 33 (15.2%), P=0.02). Eight children (22.2%) with evidence of CFLD at baseline had no clinical evidence of liver disease as adults. CONCLUSIONS: Patients with CFLD have a more severe CF phenotype than do CF patients without liver disease. However, a subgroup of children with CFLD will not manifest clinically significant liver disease as adults.

Congenital broncho-esophageal fistula: A case report.

Bronchopulmonary foregut malformations are a group of rare congenital anomalies affecting the respiratory and upper gastrointestinal tract. The rarity of these cases means their embryological origin continues to be a source of controversy. We present the case of a female infant, born at term with a malformed right arm, an absent right kidney and aplasia of the right lung. Although initially asymptomatic she presented at 5 months of age in severe respiratory distress. An upper gastro-intestinal contrast study demonstrated a right broncho-esophageal fistula. At surgical resection it was discovered that the right main bronchus ended abruptly just beyond the carina, with total aplasia of the right lung. A bronchoesophageal fistula originating from the lower third of the esophagus communicated with a sequestered right lobe. The lobe was removed and the fistula ligated. The infant remains well 13 months post surgery. This represents only the twelfth case of this rare form of bronchopulmonary foregut malformation. The associated renal and limb malformations make this case unique and may add weight to the theory that the underlying insult to the developing lung is vascular in origin.

Outcome in patients with cystic fibrosis liver disease.

BACKGROUND: Liver disease is an important complication in CF. AIMS: To determine if CFLD is a risk factor for mortality in CF, and which baseline characteristics predict all-cause mortality. METHODS: Irish children with CFLD, and their age and gender matched controls were enrolled at baseline and reviewed after 10years to determine which characteristics predict mortality. RESULTS: 72/84 (85.71%) participants were followed, (mean age Cases 21.71yrs SD 6.5, CF controls 23.62 SD 5.6, 22 (61%) males), with no difference in duration of follow-up. Nineteen participants (26.4%) died, 38.9% (14/36) with CFLD and 13.89% (5/36) CF controls (Odds Ratio (OR) 3.94 95% CI:1.23-12.56 p=0.005). In logistic regression, liver disease (OR 4.28 95% CI 1.07-17.16) female gender (OR 12.25 95% CI 2.37-63.24), reduced pulmonary function, (OR 5.11 95% CI 1.09-23.81) were each independent risk factors for mortality in CF. CONCLUSIONS: Liver disease is an independent risk factor for mortality in CF.

Active video games as an exercise tool for children with cystic fibrosis.

BACKGROUND: Active video games are used in many hospitals as exercise tools for children with cystic fibrosis. However, the exercise intensity associated with playing these games has not been examined in this population. METHODS: Children with cystic fibrosis [n=30, aged 12.3 (2.6) years, 17 boys, BMI 17.7 (2.8) kg/m(2)] were recruited from outpatient clinics in Dublin hospitals. Age and gender matched control children were recruited from local schools. Oxygen consumption, metabolic equivalents (METs) calculated from resting V˙O2, and heart rate were measured while playing Nintendo Wii™ (Nintendo Co. Ltd., Tokyo, Japan) Sports Boxing and Nintendo Wii Fit Free Jogging using a portable indirect calorimeter (Oxycon Mobile). RESULTS: Playing Wii Boxing resulted in light intensity activity (2.46METs) while playing Wii Fit Free Jogging resulted in moderate intensity physical activity (4.44METs). No significant difference was seen between groups in the energy cost of playing active video games. CONCLUSION: Active video games are a useful source of light to moderate intensity physical activity in children with cystic fibrosis.

Validation of continuous glucose monitoring in children and adolescents with cystic fibrosis: a prospective cohort study.

OBJECTIVE: To validate continuous glucose monitoring (CGM) in children and adolescents with cystic fibrosis. RESEARCH DESIGN AND METHODS: Paired oral glucose tolerance tests (OGTTs) and CGM monitoring was undertaken in 102 children and adolescents with cystic fibrosis (age 9.5-19.0 years) at baseline (CGM1) and after 12 months (CGM2). CGM validity was assessed by reliability, reproducibility, and repeatability. RESULTS: CGM was reliable with a Bland-Altman agreement between CGM and OGTT of 0.81 mmol/l (95% CI for bias +/- 2.90 mmol/l) and good correlation between the two (r = 0.74-0.9; P < 0.01). CGM was reproducible with no significant differences in the coefficient of variation of the CGM assessment between visits and repeatable with a mean difference between CGM1 and CGM2 of 0.09 mmol/l (95% CI for difference +/- 0.46 mmol/l) and a discriminant ratio of 13.0 and 15.1, respectively. CONCLUSIONS: In this cohort of children and adolescents with cystic fibrosis, CGM performed on two occasions over a 12-month period was reliable, reproducible, and repeatable.

Cystic fibrosis-associated liver disease: a population-based study.

OBJECTIVES: The aim of this study was to explore the clinical factors associated with the development of cystic fibrosis-associated liver disease (CFALD). STUDY DESIGN: This was a case-control study of all children (age 5-18 years) with established CFALD in the Republic of Ireland between January 1999 and June 2000. Each child was pair matched for age and sex with a patient with cystic fibrosis (CF) without evidence of liver disease. Only children with clinically overt liver disease were enrolled in the disease group. RESULTS: Patients with established CFALD (n = 42; 26 boys) were enrolled. Children with CFALD had worse forced expiratory volume in 1 second values than those without CFALD. However, chest radiography and clinical scores did not differ between groups. Height (mean difference, -4.2 cm [95% confidence interval [CI], -7.41 to -0.90], P =.014), weight (mean difference, -3.21 kg [95% CI, -6.03 to -0.40], P =.026), and mid-upper arm circumference (mean difference, -1.23 cm [95% CI, -2.35 to -0.12], P =.031) were significantly lower among children with CFALD. Children with CFALD were given diagnoses of CF later than children without liver disease. There were more children with meconium ileus in the control group (14 vs 4) than among those with CFALD. CONCLUSIONS: Children with established CFALD have impaired growth and nutrition, altered body composition, and worse forced expiratory volume in 1 second values. CFALD is associated with later age of diagnosis of CF.