Respiratory mechanics in an infant with perinatal lethal hypophosphatasia treated with human recombinant enzyme replacement therapy.
Hypophosphatasia is a rare autosomal recessive disorder caused by deficient activity of tissue nonspecific alkaline phosphatase (TNSALP) and characterized by defective bone mineralization. In the perinatal lethal form, respiratory complications due to rachitic deformities of the thoracic cage and associated hypoplastic lungs are present. ENB-0040 is a bone-targeted human recombinant TNSALP fusion protein that aims to restore skeletal mineralization. The goal of this study was to characterize pulmonary and thoracic cage mechanics in an infant with the perinatal lethal form of hypophosphatasia under enzyme replacement therapy. Pulmonary function testing was performed on a preterm, 8-week-old patient with hypophosphatasia who was mechanically ventilated since birth because of severe chest wall insufficiency. The measurements consisted of respiratory impulse oscillation measurements (resistance and reactance), ventilatory mechanics (compliance and resistance), and thoracoabdominal motion (TAM) analysis. At baseline, chest wall compliance was 50% of normal, and the TAM indicated predominantly abdominal displacement. After 12 weeks of treatment, a consistent decrease in ventilator requirements and improvement in lung function and chest wall mechanics were observed and correlated with thoracic cage radiologic findings. Measurable changes in chest wall dynamics and respiratory mechanics using noninvasive technology were useful for respiratory management and therapeutic guidance of ENB-0040 treatment in this patient.
Nemours Research Lung Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA. merodrig@nemours.org
Elena
E
Rodriguez
Michael B
MB
Bober
Lauren
L
Davey
Arlene
A
Zamora
Annelise B
AB
Li Puma
Aaron
A
Chidekel
Thomas H
TH
Shaffer
D000403:Airway Resistance; D000469:Alkaline Phosphatase / Q000627:therapeutic use*; D056947:Enzyme Replacement Therapy; D006801:Humans; D007014:Hypophosphatasia / Q000188:drug therapy*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000187:drug effects*; D035441:Thoracic Wall / Q000187:drug effects / Q000503:physiopathology*; D013990:Tidal Volume
D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D000469:Alkaline Phosphatase; C570710:asfotase alfa