Abstract
Clinical consequences and longitudinal outcomes in PiMZ heterozygous a1-antitrypsin deficiency smokers from SPIROMICS
European respiratory journal, Vol.58(Suppl. 65), p.OA2834
09/05/2021
DOI: 10.1183/13993003.congress-2021.oa2834
Abstract
Background: The consequence of PiZ allele presence on lung function and emphysema in smokers from the SPIROMICS cohort were previously reported. The risk for accelerated lung function decline in heterozygous α-1 antitrypsin deficient smokers remains unclear. Focused on PiMZ heterozygosity as the most prevalent Z allele-containing genotype, we investigated its effects on baseline and longitudinal disease severity and progression.
Methods: We identified 82 PiMZ and 2454 PiMM smokers without additional pathogenic SERPINA1 variation based on DNA sequencing. Baseline and longitudinal regression-based models included age, race, sex, smoking status and smoking history.
Results: Compared to PiMM, PiMZ cohort was similar in age, sex, BMI, history of asthma and smoking, predominantly non-Hispanic white. PiMZ smokers had lower mean %predicted FEV1 (74.1±1.4 vs 65.9±3.1, p = 0.004) and were more likely to have emphysema based on normative equations for -950HU cutoff (OR 1.75, p=0.018). PiMZ smokers had a greater extent of parametric response mapping (PRM) emphysema (+3.4%, CI 0.4-6.3, p=0.027) but no significant difference in PRM functional small airway disease (+2.5%, CI -1.0-6.0, p=0.16) . In longitudinal models, there was a non-significant trend toward higher rate of severe exacerbations (SE) (RR=1.6, p=0.1), but no difference in mortality, the slope of FEV1 decline or SGRQ change over three years.
Conclusion: Compared with PiMM genotype, smokers with PiMZ are more likely to have emphysema and with a trend towards more SE. Longer observational cohorts of PiMZ smokers are needed to characterize the natural history of lung disease in PiMZ heterozygotes.
Details
- Title: Subtitle
- Clinical consequences and longitudinal outcomes in PiMZ heterozygous a1-antitrypsin deficiency smokers from SPIROMICS
- Creators
- Igor Barjaktarevic - University of California, Los AngelesAni Manichaikul - University of VirginiaDaniela Markovic - University of California, Los AngelesRoxana Hixson - University of California, Los AngelesChristopher J. Cooper - University of California, Los AngelesRussell G. Buhr - University of California, Los AngelesR G Barr - Columbia UniversityJeffrey R. Curtis - University of Michigan–Ann ArborM. Bradley Drummond - University of North Carolina at Chapel HillSpyridon Fortis - University of IowaGregory A. HawkinsMeiLan K. HanEric A. Hoffman - University of IowaVictor Kim - Temple UniversityXingnan Li - University of ArizonaFernando J. Martinez - Cornell UniversityRobert Paine - University of UtahCheryl S. Pirozzi - University of UtahDonald P. Tashkin - University of California, Los AngelesJames A. Wells - University of Alabama at BirminghamPrescott G. Woodruff - University of California, San FranciscoDeborah A. Meyers - University of ArizonaEugene R. Bleecker - University of ArizonaVictor E. Ortega - Wake Forest University
- Resource Type
- Abstract
- Publication Details
- European respiratory journal, Vol.58(Suppl. 65), p.OA2834
- Publisher
- European Respiratory Society
- DOI
- 10.1183/13993003.congress-2021.oa2834
- ISSN
- 0903-1936
- eISSN
- 1399-3003
- Language
- English
- Date published
- 09/05/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Internal Medicine; Radiology; Pulmonary, Critical Care, and Occupational Medicine
- Record Identifier
- 9984528108302771
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