Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis
Abstract Background The best described endotype of COPD is alpha-1 antitrypsin (AAT) deficiency, due to a genetic abnormality in the SERPINA1 gene. Common deficient PI variants are the Z and S variants. Homozygotes for the Z allele (PI*ZZ individuals) carry the genotype most commonly associated with...
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| Language: | English |
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BMC
2025-07-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-025-03322-6 |
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| author | Vickram Tejwani Yifan Wang Lauren Munoz Tremblay Elizabeth Azzato Arianne K. Baldomero Christine Wendt Amy Attaway Russell Bowler Umur Hatipoglu Rebecca Hutton Charlie Strange Xiaofeng Wang Victor E. Ortega Joe Zein James K. Stoller |
| author_facet | Vickram Tejwani Yifan Wang Lauren Munoz Tremblay Elizabeth Azzato Arianne K. Baldomero Christine Wendt Amy Attaway Russell Bowler Umur Hatipoglu Rebecca Hutton Charlie Strange Xiaofeng Wang Victor E. Ortega Joe Zein James K. Stoller |
| author_sort | Vickram Tejwani |
| collection | DOAJ |
| description | Abstract Background The best described endotype of COPD is alpha-1 antitrypsin (AAT) deficiency, due to a genetic abnormality in the SERPINA1 gene. Common deficient PI variants are the Z and S variants. Homozygotes for the Z allele (PI*ZZ individuals) carry the genotype most commonly associated with severe AAT deficiency (AATD), but a highly prevalent endotype is the heterozygous state (PI*MZ individuals). The effect of PI*MZ status on exacerbations and health care utilization is unknown. Study design and methods Cleveland electronic health record data was examined to compare healthcare utilization between PI*MZ and PI*MM individuals. Three outcomes were assessed: moderate COPD exacerbation (defined as short-term steroid prescription), any emergent care (defined as an express care, urgent care, or emergency department visit), and any hospitalization. Models were adjusted for age, sex, race, BMI, smoking status, comorbidity count, liver disease, zip code median income. Results 4,148 individuals had the PI*MM genotype and 308 PI*MZ. PI*MZ was associated with increased risk for moderate COPD exacerbations (HR [95% CI]: 1.66 [1.27, 2.17]) and hospitalizations (HR [95% CI]: 1.44 [1.19, 1.75]) compared to PI*MM. The risk of hospitalization was higher among PI*MZ individuals with AAT levels < 90 mg/dL (HR [95% CI]: 1.59 [1.14, 2.23]) but not in those with AAT levels > 90 mg/dL, as compared to PI*MM. Interpretation Given the high prevalence, PI*MZ represents a COPD phenotype that is associated with worse outcomes, inviting additional investigation to identify predictive biomarkers of worse disease and treatable traits. Future prospective studies to better characterize the longitudinal course and healthcare utilization among individuals with a PI*MZ genotype. |
| format | Article |
| id | doaj-art-6c87d21119c640e9b4e34a1a304e9d52 |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj-art-6c87d21119c640e9b4e34a1a304e9d522025-08-20T03:46:27ZengBMCRespiratory Research1465-993X2025-07-012611710.1186/s12931-025-03322-6Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysisVickram Tejwani0Yifan Wang1Lauren Munoz Tremblay2Elizabeth Azzato3Arianne K. Baldomero4Christine Wendt5Amy Attaway6Russell Bowler7Umur Hatipoglu8Rebecca Hutton9Charlie Strange10Xiaofeng Wang11Victor E. Ortega12Joe Zein13James K. Stoller14Department of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland ClinicDepartment of Quantitative Health Sciences, Cleveland ClinicDivision of Pulmonary and Critical Care Medicine, University of WashingtonPathology and Laboratory Medicine Institute, Cleveland ClinicPulmonary, Allergy, Critical Care, and Sleep Medicine, Minneapolis VA Health Care SystemPulmonary, Allergy, Critical Care, and Sleep Medicine, Minneapolis VA Health Care SystemDepartment of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland ClinicDepartment of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland ClinicDepartment of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland ClinicPathology and Laboratory Medicine Institute, Cleveland ClinicDepartment of Internal Medicine, Division of Pulmonary Medicine, Medical University of South CarolinaDepartment of Quantitative Health Sciences, Cleveland ClinicDepartment of Internal Medicine, Division of Respiratory Medicine, Mayo ClinicDepartment of Internal Medicine, Division of Respiratory Medicine, Mayo ClinicDepartment of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland ClinicAbstract Background The best described endotype of COPD is alpha-1 antitrypsin (AAT) deficiency, due to a genetic abnormality in the SERPINA1 gene. Common deficient PI variants are the Z and S variants. Homozygotes for the Z allele (PI*ZZ individuals) carry the genotype most commonly associated with severe AAT deficiency (AATD), but a highly prevalent endotype is the heterozygous state (PI*MZ individuals). The effect of PI*MZ status on exacerbations and health care utilization is unknown. Study design and methods Cleveland electronic health record data was examined to compare healthcare utilization between PI*MZ and PI*MM individuals. Three outcomes were assessed: moderate COPD exacerbation (defined as short-term steroid prescription), any emergent care (defined as an express care, urgent care, or emergency department visit), and any hospitalization. Models were adjusted for age, sex, race, BMI, smoking status, comorbidity count, liver disease, zip code median income. Results 4,148 individuals had the PI*MM genotype and 308 PI*MZ. PI*MZ was associated with increased risk for moderate COPD exacerbations (HR [95% CI]: 1.66 [1.27, 2.17]) and hospitalizations (HR [95% CI]: 1.44 [1.19, 1.75]) compared to PI*MM. The risk of hospitalization was higher among PI*MZ individuals with AAT levels < 90 mg/dL (HR [95% CI]: 1.59 [1.14, 2.23]) but not in those with AAT levels > 90 mg/dL, as compared to PI*MM. Interpretation Given the high prevalence, PI*MZ represents a COPD phenotype that is associated with worse outcomes, inviting additional investigation to identify predictive biomarkers of worse disease and treatable traits. Future prospective studies to better characterize the longitudinal course and healthcare utilization among individuals with a PI*MZ genotype.https://doi.org/10.1186/s12931-025-03322-6Alpha-1 antitrypsinCOPDExacerbationsHealthcare utilizations |
| spellingShingle | Vickram Tejwani Yifan Wang Lauren Munoz Tremblay Elizabeth Azzato Arianne K. Baldomero Christine Wendt Amy Attaway Russell Bowler Umur Hatipoglu Rebecca Hutton Charlie Strange Xiaofeng Wang Victor E. Ortega Joe Zein James K. Stoller Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis Respiratory Research Alpha-1 antitrypsin COPD Exacerbations Healthcare utilizations |
| title | Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis |
| title_full | Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis |
| title_fullStr | Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis |
| title_full_unstemmed | Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis |
| title_short | Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis |
| title_sort | increased exacerbations and hospitalizations among pi mz compared to pi mm individuals an electronic health record analysis |
| topic | Alpha-1 antitrypsin COPD Exacerbations Healthcare utilizations |
| url | https://doi.org/10.1186/s12931-025-03322-6 |
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