Lung clearance index for monitoring early lung disease in alpha-1-antitrypsin deficiency.
Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lung disease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lung disease even in genotypes other than PI-ZZ.
Department of Paediatrics and Research Institute, Marien Hospital Wesel, Germany. Electronic address: susanne.fuchs@prohomine.de.
Susanne I
SI
Fuchs
Paediatric Pulmonology, Allergology and Neonatology, Medical University Hannover, Germany.
Nicolaus
N
Schwerk
Marienklinik Bozen, Italy.
Klaus
K
Pittschieler
Children's Hospital Altona, Hamburg, Germany.
Frank
F
Ahrens
Children's University Hospital Tübingen, Germany.
Winfried
W
Baden
Department 5, University of Saarland, Homburg, Germany.
Robert
R
Bals
Department 5, University of Saarland, Homburg, Germany.
Sebastian
S
Fähndrich
Department 1, University Hospital Frankfurt a.M., Germany.
Wolfgang
W
Gleiber
Dr. von Haunersches Kinderspital, Medical University Munich, Germany.
Matthias
M
Griese
Department of Paediatrics, Clemenshospital Münster, Germany.
Georg
G
Hülskamp
Pulmonology, Medical University Hannover, Germany.
Thomas
T
Köhnlein
Department 1, University Hospital Frankfurt a.M., Germany.
Ludmilla
L
Reckling
Cystic Fibrosis Centre, University Hospital of Cologne, Germany.
Ernst
E
Rietschel
Paediatric Pulmonologie and Allergology, Charité Berlin, Germany.
Doris
D
Staab
Department of Paediatrics and Research Institute, Marien Hospital Wesel, Germany.
Monika
M
Gappa
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008171:Lung Diseases / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009584:Nitrogen / Q000378:metabolism*; D011446:Prospective Studies; D011656:Pulmonary Emphysema / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology; D012129:Respiratory Function Tests; D013147:Spirometry / Q000379:methods; D014797:Vital Capacity; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications* / Q000235:genetics / Q000503:physiopathology
D000515:alpha 1-Antitrypsin; D009584:Nitrogen