Normal lung function in subjects heterozygous for surfactant protein-B deficiency

Inherited deficiency of surfactant protein-B (SP-B) is a fatal autosomal re cessive disorder of lung cell metabolism caused most frequently by a frames hift mutation in codon 121 of the SP-B gene (121ins2) and is characterized by rapidly progressive respiratory failure immediately after birth. Lungs f rom genetically engineered heterozygous SP-B-deficient mice exhibit decreas ed compliance and mild air trapping. To determine whether pulmonary functio n of heterozygous SP-B-deficient humans is similarly affected, we studied n ine heterozygous subjects 16 to 44 yr of age and two unaffected subjects 7 and 23 yr of age from five families of 121ins2 SP-B-deficient infants. An i ncrease in residual volume was noted in one heterozygous family member and one unaffected family member. Compliance, maximal transpulmonary pressure, air flow, and gas exchange were normal in all heterozygous subjects tested. These data suggest that humans heterozygous for the 121ins2 mutation have normal pulmonary function through the first four decades of life. The impac t of advancing age and environmental exposures on the lung function of hete rozygotes remains to be determined.