A genetically determined deficiency of α1-antitrypsin in 15 members of one family appeared with wheezing and progressive dyspnea in six. Because of the early age of onset of wheezing and dyspnea, it may be confused with bronchial asthma. Five of the 15 were found to have severe obstructive emphysema; one brother died at age 43 years of the disease, two have had severe hypoxia with oxygen tensions under 50 mm Hg and respiratory failure, and all five had a one-second-timed vital capacity of under 30% of predicted, residual volumes greater than 54% of total lung capacity, and marked uneveness of ventilation. Quantitation of α1-antitrypsin by radial immunoassay showed four of 13 studied to be homozygous and nine heterozygous. Total serum enzyme antitrypsin activity correlated highly with radial gel immunoassay. A hypothetical pathogenic mechanism is described.
Townley RG, Ryning F, Lynch H, Brody AW. Obstructive Lung Disease in Hereditary α1-Antitrypsin Deficiency. JAMA. 1970;214(2):325–331. doi:10.1001/jama.1970.03180020045008