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. 2023 Sep 18;9(5):00302-2023.
doi: 10.1183/23120541.00302-2023. eCollection 2023 Sep.

Development of a risk score to increase detection of severe alpha-1 antitrypsin deficiency

E Leonard Riley  1 , J Cory Brunson  2 , Soroush Eydgahi  3 , Mark L Brantly  3 , Jorge E Lascano  3
Affiliations

Development of a risk score to increase detection of severe alpha-1 antitrypsin deficiency

E Leonard Riley et al. ERJ Open Res. .

Abstract

Background: Alpha-1 antitrypsin deficiency (AATD) is an under-recognised genetic cause of chronic obstructive lung disease, and many fewer cases than estimated have been identified. Can a reported respiratory and hepatic disease history from a large AATD testing database be used to stratify a person's risk of severe AATD?

Methods: We analysed data extracted from the AATD National Detection Program. Demographics and medical history were evaluated to predict AATD PI*ZZ genotype. Logistic regression and integer programming models identified predictors and obtained risk scores. These were internally validated on a subset of the data.

Results: Out of 301 343 subjects, 1529 (0.5%) had PI*ZZ genotype. Predictors of severe AATD were asthma, bronchitis, emphysema, allergies, bronchiectasis, family history of AATD, cirrhosis, hepatitis and history of abnormal liver function tests. The derived model establishes a subject's risk of severe AATD, and scores ≥0 had an estimated risk of 0.41%, sensitivity 84.62% and specificity 24.32%. A model simulating guideline recommendations had an estimated risk of 0.51% with a sensitivity of 37.98% and specificity 46.60%. By recommending screening for scores ≥0, we estimate that more subjects would be screened (75.7% versus 53.4%) and detected (84.6% versus 58.2%) compared to a guideline-simulated model.

Conclusion: This medical history risk model is a useful predictive tool to detect subjects at greater risk of having severe AATD and improves sensitivity of detection. Scores <0 are at lower risk and may need not be screened; testing is recommended for scores ≥0 and consistent with current guidelines.

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Conflict of interest statement

Conflict of interest: None declared.

Figures

FIGURE 1
FIGURE 1
Flowchart showing participant disposition through the study.
FIGURE 2
FIGURE 2
Receiver operating characteristic curves (ROC) of the model for a) current screening recommendations and the two final models b) medical history only and c) medical history plus smoking history. Suggested screening threshold values are outlined.
FIGURE 3
FIGURE 3
Alluvial plot of how all PI*ZZ cases were treated by a model simulating current guidelines and medical history model (scores ≥0 and ≥1).
See this image and copyright information in PMC

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