A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis.
Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar proteinosis (PAP), a process in which accumulated surfactants are washed out of the lung with 0.5-2.0 l of saline aliquots for 10-30 wash cycles. The method has been established empirically. In contrast, the kinetics of protein transfer into the lavage fluid has not been fully evaluated either theoretically or practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We made accurate timetables for each stage of WLL, namely, instilling, retaining, draining, and preparing. Subsequently, we measured the volumes of both instilled saline and drained lavage fluid, as well as the concentrations of proteins in the drained lavage fluid. We also proposed a mathematical model of protein transfer into the lavage fluid in which time is a single variable as the protein moves in response to the simple diffusion. The measured concentrations of IgG, transferrin, albumin, and β2-microglobulin closely matched the corresponding theoretical values calculated through differential equations. Coefficients for transfer of β2-microglobulin from the blood to the lavage fluid were two orders of magnitude higher than those of IgG, transferrin, and albumin. Simulations using the mathematical model showed that the cumulative amount of eliminated protein was not affected by the duration of each cycle but dependent mostly on the total time of lavage and partially on the volume instilled. Although physicians have paid little attention to the transfer of substances from the lung to lavage fluid, WLL seems to be a procedure that follows a diffusion-based mathematical model.
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan;
Keiichi
K
Akasaka
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan;
Takahiro
T
Tanaka
Disaster Prevention Research Institute, Kyoto University, Kyoto, Japan;
Takashi
T
Maruyama
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan;
Nobutaka
N
Kitamura
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan;
Atsushi
A
Hashimoto
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan;
Yuko
Y
Ito
Department of Respiratory Medicine, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan;
Hiroyoshi
H
Watanabe
Department of Respiratory Medicine, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan;
Tomoshige
T
Wakayama
Department of Anesthesiology, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan;
Takero
T
Arai
Division of Respiratory Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan;
Masachika
M
Hayashi
Division of Respiratory Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan;
Hiroshi
H
Moriyama
Department of Anesthesiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;
Kanji
K
Uchida
Department of Respiratory Medicine, Tohoku University Graduate school of Medicine, Miyagi, Japan;
Shinya
S
Ohkouchi
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan;
Ryushi
R
Tazawa
Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan;
Toshinori
T
Takada
Department of Respiratory and Allergy Medicine, Aichi Medical University, Aichi, Japan;
Etsuro
E
Yamaguchi
Department of Pulmonary Medicine, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan;
Toshio
T
Ichiwata
Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, Osaka, Japan; and.
Masaki
M
Hirose
Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, Osaka, Japan; and.
Toru
T
Arai
Clinical Research Center, NHO Kinki-Chuo Chest Medical Center, Osaka, Japan; and.
Yoshikazu
Y
Inoue
Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan.
Hirosuke
H
Kobayashi
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan; radical@med.niigata-u.ac.jp.
Koh
K
Nakata
D000368:Aged; D000418:Albumins / Q000032:analysis / Q000378:metabolism; D000465:Algorithms; D001327:Autoimmune Diseases / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D005755:Gastrins / Q000032:analysis / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D021381:Protein Transport / Q000502:physiology; D011649:Pulmonary Alveolar Proteinosis / Q000628:therapy*; D037663:Pulmonary Surfactant-Associated Protein D / Q000032:analysis / Q000378:metabolism*; D012709:Serum Albumin / Q000032:analysis; D014168:Transferrin / Q000032:analysis / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000032:analysis / Q000097:blood
D000418:Albumins; D005755:Gastrins; D007074:Immunoglobulin G; D037663:Pulmonary Surfactant-Associated Protein D; D012709:Serum Albumin; D014168:Transferrin; D001613:beta 2-Microglobulin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
granulocyte/macrophage colony-stimulating factor autoantibody; protein transfer rate; pulmonary alveolar proteinosis; whole-lung lavage