UNLABELLED: The alpha1-protease inhibitor (alpha1-Pi) is separated from human serum and is therefore extremely expensive. Because only 2%-3% concentrates in the lung after intravenous administration, inhalational therapy for alpha1-Pi deficiency would seem likely to be better. The aims of this study were therefore to determine the pattern of deposition of inhaled alpha1-Pi labeled with 123I and measure the amount deposited in the lungs. METHODS: Eighteen patients with congenital severe alpha1-Pi deficiency were enrolled in the study. The low-specific-activity 123I-labeled alpha1-Pi aerosol (median particle size +/- SD, 3.9 +/- 2.5 microm) was generated by an air pressure-driven nebulizer. The patients inhaled for an average of 23.6 +/- 8.9 min. Static scintigrams in two projections were acquired immediately after (T1) and 1 (T2), 4 (T3), and 24 h (T4) after inhalation. The patients were divided into the following three groups according to their forced expiratory volume in 1 s (FEV1): group I, < or =40% of predicted normal (n = 8); group II, 40% < FEV1 < or = 60% of predicted normal (n = 4); group III, >60% of predicted normal (n = 6). RESULTS: The absolute percentage uptake values of alpha1-Pi in group I were 12.4 for T1, 7.3 for T2, 4.6 for T3, and 1.2 for T4; in group II the values were 13.0, 9.6, 6.2, and 2.0, respectively; and in group III, 14.6, 11.4, 6.5, and 3.6, respectively. Differences between the groups were generally statistically significant. Between T1 and T2, the probability value was <0.05 for group I versus group II, <0.006 for group I versus group III, and <0.39 for group II versus group III. Between T1 and T3, the probability value was <0.29 for group I versus group II, <0.22 for group I versus group III, and <0.94 for group II versus group III. Retention (between T1 and T4) was also dependent on the grade of the disease: P < 0.2 for group I versus group II, P < 0.001 for group I versus group III, and P < 0.02 for group II versus group III. Grading of the uptake pattern by three independent experienced investigators (87% agreement) revealed a peripheral deposition that was group dependent. We found that greater peripheral deposition corresponded with lower lung functional impairment: P < 0.5 for group I versus group II, P < 0.01 for group I versus group III, and P < 0.08 for group II versus group III. Degradation also corresponded with functional impairment: P < 0.05 for group I versus group II, P < 0.006 for group I versus group III, and P < 0.3 for group II versus group III. CONCLUSION: The results of this study show that sufficient amounts of alpha1-Pi can be deposited in the periphery of the lung by inhalation at least in patients with low-grade disease. Inhalation of alpha1-Pi may thus represent a new and more convenient route of drug administration.
UNLABELLED: The alpha1-protease inhibitor (alpha1-Pi) is separated from human serum and is therefore extremely expensive. Because only 2%-3% concentrates in the lung after intravenous administration, inhalational therapy for alpha1-Pi deficiency would seem likely to be better. The aims of this study were therefore to determine the pattern of deposition of inhaled alpha1-Pi labeled with 123I and measure the amount deposited in the lungs. METHODS: Eighteen patients with congenital severe alpha1-Pi deficiency were enrolled in the study. The low-specific-activity 123I-labeled alpha1-Pi aerosol (median particle size +/- SD, 3.9 +/- 2.5 microm) was generated by an air pressure-driven nebulizer. The patients inhaled for an average of 23.6 +/- 8.9 min. Static scintigrams in two projections were acquired immediately after (T1) and 1 (T2), 4 (T3), and 24 h (T4) after inhalation. The patients were divided into the following three groups according to their forced expiratory volume in 1 s (FEV1): group I, < or =40% of predicted normal (n = 8); group II, 40% < FEV1 < or = 60% of predicted normal (n = 4); group III, >60% of predicted normal (n = 6). RESULTS: The absolute percentage uptake values of alpha1-Pi in group I were 12.4 for T1, 7.3 for T2, 4.6 for T3, and 1.2 for T4; in group II the values were 13.0, 9.6, 6.2, and 2.0, respectively; and in group III, 14.6, 11.4, 6.5, and 3.6, respectively. Differences between the groups were generally statistically significant. Between T1 and T2, the probability value was <0.05 for group I versus group II, <0.006 for group I versus group III, and <0.39 for group II versus group III. Between T1 and T3, the probability value was <0.29 for group I versus group II, <0.22 for group I versus group III, and <0.94 for group II versus group III. Retention (between T1 and T4) was also dependent on the grade of the disease: P < 0.2 for group I versus group II, P < 0.001 for group I versus group III, and P < 0.02 for group II versus group III. Grading of the uptake pattern by three independent experienced investigators (87% agreement) revealed a peripheral deposition that was group dependent. We found that greater peripheral deposition corresponded with lower lung functional impairment: P < 0.5 for group I versus group II, P < 0.01 for group I versus group III, and P < 0.08 for group II versus group III. Degradation also corresponded with functional impairment: P < 0.05 for group I versus group II, P < 0.006 for group I versus group III, and P < 0.3 for group II versus group III. CONCLUSION: The results of this study show that sufficient amounts of alpha1-Pi can be deposited in the periphery of the lung by inhalation at least in patients with low-grade disease. Inhalation of alpha1-Pi may thus represent a new and more convenient route of drug administration.