Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial.

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence. OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence. METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial in children with CF, 6 months to 18 years of age, with early Pa. Azithromycin or placebo was given 3× weekly with standardized TIS. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the time to pulmonary exacerbation requiring antibiotics and the secondary endpoint was the time to Pa recurrence, in addition to other clinical and safety outcomes. A total of 221 participants (111 placebo, 110 azithromycin) out of a planned 274 were enrolled. Enrollment was stopped early by the NHLBI because the trial had reached the prespecified interim boundary for efficacy. The risk of pulmonary exacerbation was reduced by 44% in the azithromycin group as compared with the placebo group (hazard ratio, 0.56; 95% confidence interval, 0.37-0.83; P = 0.004). Weight increased by 1.27 kg in the azithromycin group compared with the placebo group (95% confidence interval, 0.01-2.52; P = 0.046). No significant differences were seen in microbiological or other clinical or safety endpoints. CONCLUSIONS: Azithromycin was associated with a significant reduction in the risk of pulmonary exacerbation and a sustained improvement in weight, but had no impact on microbiological outcomes in children with early Pa. Clinical trial registered with clinicaltrials.gov (NCT02054156).

Improvements in Cystic Fibrosis Quarterly Visits, Lung Function Tests, and Respiratory Cultures.

BACKGROUND: The Cystic Fibrosis (CF) Foundation recommends patients attend clinic ≥4 times per year with 4 respiratory cultures and 2 pulmonary function tests (PFTs). However, nationally only 57.4% of patients met these guidelines in 2012. We used a quality improvement program with a goal of 75% of our patients meeting this care guideline by 2012. METHODS: A 2-stage program was started in 2011. Stage 1: education of patients/caregivers on importance of quarterly visits. Stage 2: quarterly tracking system of patient appointments. Data on clinic visits, respiratory cultures, and PFTs were collected from the CF registry from January 2009 through December 2013. Statistical process control charts were used to track improvements. RESULTS: The average number of clinic visits increased significantly from 4.6 ± 2.3 in 2009 to 6.3 ± 4.6 in 2013 (P < .0001). The percentage of patients ages 6 through 18 completing a clinic visit, PFT, and respiratory culture per quarter increased significantly from 76.2% during 2009 to 86.4% in 2013. The percentage of patients completing ≥4 clinic visits with 4 respiratory cultures and 2 PFTs improved significantly from 47.5% in 2009 to 71.0% in 2013 (P < .0001). CONCLUSIONS: A tracking system of patient appointments significantly improved adherence to the care guidelines better than education alone. The multiple-stage quality improvement program we implemented may be modifiable and able to be integrated in other CF centers or other multiple disciplinary chronic illness care centers.

Severe bilateral panlobular emphysema and pulmonary arterial hypoplasia: unusual manifestations of Menkes disease.

Menkes disease is an X-linked recessive disorder of copper transport characterized by neurological deterioration, connective tissue, and vascular defects, abnormal hair, and death in early childhood. We report on a patient with Menkes disease in whom severe diffuse emphysema caused respiratory failure and death at 14 months of age. He had severe growth and developmental delays and other typical clinical manifestations of Menkes disease. He developed respiratory problems requiring continuous supplemental oxygen and a progressively enlarging soft tissue mass appeared on the neck. Imaging studies revealed cystic spaces in multiple lobes of the lung consistent with bullous emphysema. The neck mass was determined to be an internal jugular venous aneurysm. At autopsy, extensive emphysematous change was evident. Post-mortem barium injections of the pulmonary arterial system revealed marked dilatation and tortuosity of the preacinar pulmonary arteries and reduced numbers of intra-acinar arteries. Severe emphysema, presumably caused by abnormal elastin due to deficiency of the copper-dependent enzyme lysyl oxidase, may represent an underestimated clinical complication of Menkes disease and should be considered in the differential diagnosis of chronic respiratory disease in these patients.