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 ¼ 26) or placebo (n ¼ 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 FEV 1 , patients receiving ivacaftor had a significant increase in percent predicted FEV 1 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 253.5 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).

The panel formulated and provided a rationale for the direction as well as for the strength of each recommendation to establish the diagnosis of PCD.

Vertex Pharmaceuticals.

Background-The aim of this study was to determine the relationship of the power and recovery stroke of respiratory cilia using digital high speed video imaging. Beat frequency measurements made using digital high speed video were also compared with those obtained using the photomultiplier and modified photodiode techniques. Method-Ciliated epithelium was obtained by brushing the inferior nasal turbinate of 20 healthy subjects. Ciliated edges were observed by microscopy and the deviation of cilia during their recovery stroke relative to the path travelled during their power stroke was measured. Beat frequency measurements made by digital high speed video analysis were compared with those obtained using the photomultiplier and modified photodiode. Results-Cilia were found to beat with a forward power stroke and a backward recovery stroke within the same plane. The mean angular deviation of the cilia during the recovery stroke from the plane of the forward power stroke was only 3.6°(95% CI 3.1 to 4.1). There was a significant diVerence in beat frequency measurement between the digital high speed video (13.2 Hz (95% CI 11.8 to 14.6)) and both photomultiplier (12.0 Hz (95% CI 10.8 to 13.1), p = 0.01) and photodiode (11.2 Hz (95% CI 9.9 to 12.5), p<0.001) techniques. The Bland-Altman limits of agreement for the digital high speed video were -2.75 to 5.15 Hz with the photomultiplier and -2.30 to 6.06 Hz with the photodiode. Conclusion-Respiratory cilia beat forwards and backwards within the same plane without a classical sideways recovery sweep. Digital high speed video imaging allows both ciliary beat frequency and beat pattern to be evaluated.