Outcomes of children treated with tracheostomy and positive-pressure ventilation at home.

BACKGROUND: Long-term outcomes for children who survive on tracheostomy and positive-pressure ventilation (TPPV) at home are not well known. METHODS: A retrospective review of 20 years of clinical data at a single institution was performed. Outcome measures included 5-year survival, decannulation rate, and neurocognition. RESULTS: A total of 91 children were categorized under neuromotor dysfunction (52%), chronic lung disease (29%), and congenital anomalies (20%). The 5-year survival rates for these categories were 89% (95% confidence interval [CI] = 80%-99%), 76% (95% CI = 57%-100%), and 94% (95% CI = 83%-100%), respectively. Overall, the 5-year decannulation rate was 25% (95% CI = 14%-35%), with children with chronic lung disease having the highest rate (51%). It was found that 14% were extremely delayed in neurocognition. CONCLUSION: Most children on TPPV at home survive beyond 5 years, and a significant number are decannulated. Primary care physicians and communities should be prepared to accommodate the increasing number of children on TPPV at home.

Enzyme-replacement therapy in life-threatening hypophosphatasia.

BACKGROUND: Hypophosphatasia results from mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate accumulates extracellularly, leading to rickets or osteomalacia. Severely affected babies often die from respiratory insufficiency due to progressive chest deformity or have persistent bone disease. There is no approved medical therapy. ENB-0040 is a bone-targeted, recombinant human TNSALP that prevents the manifestations of hypophosphatasia in Tnsalp knockout mice. METHODS: We enrolled infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of treatment with ENB-0040. The primary objective was the healing of rickets, as assessed by means of radiographic scales. Motor and cognitive development, respiratory function, and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics of ENB-0040. RESULTS: Of the 11 patients recruited, 10 completed 6 months of therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was accompanied by improvement in developmental milestones and pulmonary function. Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone accompanied skeletal healing, often necessitating dietary calcium supplementation. There was no evidence of hypocalcemia, ectopic calcification, or definite drug-related serious adverse events. Low titers of anti-ENB-0040 antibodies developed in four patients, with no evident clinical, biochemical, or autoimmune abnormalities at 48 weeks of treatment. CONCLUSIONS: ENB-0040, an enzyme-replacement therapy, was associated with improved findings on skeletal radiographs and improved pulmonary and physical function in infants and young children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.).