Inherited deficiency of surfactant protein-B (SP-B) is a fatal autosomal recessive disorder of lung cell metabolism that is characterized by rapidly progressive repiratory failure. The 121ins2 mutation of the SP-B gene is the most common mutation associated with SP-B deficiency. Murine lineages with targeted disruption of the SP-B gene exhibit a phenotype which is similar to infants homozygous for 121ins2. Heterozygous mice exhibit mild air trapping but are otherwise normal (Am Rev Resp Crit Care Med 1996; 153:A765). Historically, heterozygous family members of homozygous 121ins2 infants have been free from respiratory illness. To evaluate whether subtle abnormalities in lung mechanics may exist in these related individuals, we measured forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), residual volume (RV), total lung capacity (TLC), diffusing capacity (DLCO), airway resistance (Raw) and oxygen saturation (SaO2) in 5 heterozygotes from 3 families (121/+, 3 males and 2 females, ages 23-41 years, mean 32±8 years) and 2 unaffected females from 2 families (+/+, ages 7 and 35 years). Results are reported as mean (±SD) percent of predicted value normalized for age, sex, and height. No overt obstructive or restrictive changes were evident in either the carriers or unaffected family members, with the exception of a 34 year old 121/+ male with a 40 pack-year history of smoking who exhibited mildly diminished FEV1, FVC, and DLCO.Table

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Maximum transpulmonary pressure was normal in the 4 subjects who were studied.We conclude that, unlike the SP-B deficient mice, humans heterozygous for the 121ins2 mutation 1) do not exhibit air trapping, and 2) have normal lung volumes, air flow, and gas exchange. Thus, expression of one intact SP-B gene permits normal pulmonary function for the first four decades of life.The impact of advancing age and environmental exposures on heterozygotes' lung function remains to be determined.