Patients with cystic fibrosis should be considered candidates for lung transplantation when the FEV1 falls below 30 percent of the predicted value. Female patients and younger patients may need to be considered for transplantation at an earlier stage.

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).

Epithelial cells which line mucosal surfaces are the first line of defense against bacterial invasion and infection. Recent studies have also indicated that epithelial cells contribute significantly to the orchestration of ongoing inflammatory processes. Here, we demonstrate that human epithelial cells express bactericidal͞permeability-increasing protein (BPI), an antibacterial and endotoxin-neutralizing molecule previously associated with neutrophils. Moreover, we demonstrate that such BPI expression is transcriptionally regulated by analogs of endogenously occurring anti-inflammatory eicosanoids (aspirin-triggered lipoxins, ATLa). Initial studies to verify microarray analysis revealed that epithelial cells of wide origin (oral, pulmonary, and gastrointestinal mucosa) express BPI and each is similarly regulated by aspirin-triggered lipoxins. Studies aimed at localization of BPI revealed that such expression occurs on the cell surface of cultured epithelial cell lines and dominantly localizes to epithelia in human mucosal tissue. Functional studies employing a BPI-neutralizing antiserum revealed that surface BPI blocks endotoxin-mediated signaling in epithelia and kills Salmonella typhimurium. These studies identify a previously unappreciated ''molecular shield'' for protection of mucosal surfaces against Gram-negative bacteria and their endotoxin.mucosa ͉ infection ͉ inflammation ͉ eicosanoid

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