Results from a large targeted screening program for alpha-1-antitrypsin deficiency: 2003 - 2015.
Alpha-1-antitrypsin deficiency (AATD) is an autosomal codominant inherited disease that is significantly underdiagnosed. We have previously shown that the combination of an awareness campaign with the offer of free diagnostic testing results in the detection of a relevant number of severely deficient AATD patients. The present study provides an update on the results of our targeted screening program (German AAT laboratory, University of Marburg) covering a period from August 2003 to May 2015.



Diagnostic AATD detection test kits were offered free of charge. Dried blood samples were sent to our laboratory and used for the semiquantitative measurement of the AAT-level (nephelometry) and the detection of the S- or Z-allele (PCR). Isoelectric focusing was performed when either of the initial tests was indicative for at least one mutation. Besides, we evaluated the impact of additional screening efforts and the changes of the detection rate over time, and analysed the relevance of clinical parameters in the prediction of severe AATD.



Between 2003 and 2015, 18,638 testing kits were analysed. 6919 (37.12 %) carried at least one mutation. Of those, we identified 1835 patients with severe AATD (9.82 % of the total test population) including 194 individuals with rare genotypes. Test initiatives offered to an unselected population resulted in a dramatically decreased detection rate. Among clinical characteristics, a history of COPD, emphysema, and bronchiectasis were significant predictors for Pi*ZZ, whereas a history of asthma, cough and phlegm were predictors of not carrying the genotype Pi*ZZ.



A targeted screening program, combining measures to increase awareness with cost-free diagnostic testing, resulted in a high rate of AATD detection. The clinical data suggest that testing should be primarily offered to patients with COPD, emphysema, and/or bronchiectasis.
Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Marburg, Germany. greulich@med.uni-marburg.de.|Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Baldingerstraße, 35043, Marburg, Germany. greulich@med.uni-marburg.de.
Timm
T
Greulich
Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Marburg, Germany.|Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Baldingerstraße, 35043, Marburg, Germany.
Christoph
C
Nell
Department of Internal Medicine V, Pulmonology, Allergology, Respiratory and Environmental Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
Christian
C
Herr
Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Marburg, Germany.|Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Baldingerstraße, 35043, Marburg, Germany.
Claus
C
Vogelmeier
Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Marburg, Germany.|Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Baldingerstraße, 35043, Marburg, Germany.
Viktor
V
Kotke
Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Marburg, Germany.|Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Baldingerstraße, 35043, Marburg, Germany.
Stefan
S
Wiedmann
Department of Pneumology, University Hospital Essen, Ruhrlandklinik, 45239, Essen, Germany.
Marion
M
Wencker
Department of Internal Medicine V, Pulmonology, Allergology, Respiratory and Environmental Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
Robert
R
Bals
Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Marburg, Germany.|Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Baldingerstraße, 35043, Marburg, Germany.
Andreas Rembert
AR
Koczulla
D001987:Bronchiectasis / Q000175:diagnosis / Q000235:genetics; D004646:Emphysema / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000235:genetics; D011656:Pulmonary Emphysema / Q000175:diagnosis / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis* / Q000235:genetics
Alpha 1-antitrypsin deficiency; Asthma; Bronchiectasis; Chronic obstructive pulmonary disease; Targeted screening