ArticleAmerican journal of respiratory and critical care medicine2014
Clarification of the risk of chronic obstructive pulmonary disease in α1-antitrypsin deficiency PiMZ heterozygotes.
Article in American journal of respiratory and critical care medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02810327 (Alpha-1 Carrier Genomics Study), which is not on this map. Cited by 97 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Alpha-1 Carrier Genomics Study
Who cites it
97 citing papers in PubMed, 3 syntheses or guidelines pooled it, 177 citations in OpenAlex.
- Diagnosis and treatment of lung disease associated with alpha one-antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand.Respirology (Carlton, Vic.) · 2020Guideline
- Alpha1-Antitrypsin Deficiency: Transition of Care for the Child With AAT Deficiency into Adulthood.Current pediatric reviews · 2019Pooled it
- A study of common Mendelian disease carriers across ageing British cohorts: meta-analyses reveal heterozygosity for alpha 1-antitrypsin deficiency increases respiratory capacity and height.Journal of medical genetics · 2016Pooled it
- Sequencing Alpha-1 MZ Individuals Shows Frequent Biallelic Mutations.Pulmonary medicine · 2018Trial
- The Association of Alpha-1 Antitrypsin Deficiency and Arterial Aneurysms: An Update and Review.Journal of clinical and translational hepatology · 2026Review
- Comment: Increased exacerbations and hospitalizations among Pi*MZ compared to Pi*MM individuals?Respiratory research · 2026Article
- Z variant heterozygosity in alpha-1 antitrypsin deficiency: disease risk and treatment implications.Orphanet journal of rare diseases · 2026Article
- Dual SORT LNPs for multi-organ base editing.Nature biotechnology · 2026Article
- Alpha-1 Antitrypsin Deficiency-Associated Chronic Obstructive Pulmonary Disease.Medicina (Kaunas, Lithuania) · 2026Review
- Alpha-1 Antitrypsin Levels and Phenotypes in Patients with Asthma and COPD in Appalachian East Tennessee.International journal of chronic obstructive pulmonary disease · 2026Article
- Mendelian causes of early-onset emphysema: a review of the current literature.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Phenotypic Expression of Respiratory Diseases and Tailored Treatment in Patients with Intermediate Alpha-1 Antitrypsin Deficiency: Evidence from a Retrospective Analysis of a Selected Cohort of Patients.Medicina (Kaunas, Lithuania) · 2025Article
- Pulmonary Emphysema: Current Understanding of Disease Pathogenesis and Therapeutic Approaches.Biomedicines · 2025Review
- αThe journal of allergy and clinical immunology. In practice · 2025Article
- Longitudinal Outcomes in Pi*MZ Alpha-1 Antitrypsin-Deficient Individuals with Tobacco Smoking History from the SPIROMICS Cohort.Annals of the American Thoracic Society · 2025Article
- Further Insights into Emphysema Progression and Lung Function Decline in MZ Alpha-1 Antitrypsin Deficiency.Annals of the American Thoracic Society · 2025Article
- Alpha-1 antitrypsin deficiency-associated liver disease: From understudied disorder to the poster child of genetic medicine.Hepatology communications · 2025Review
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- Mechanism underlying the therapeutic effects of effective component compatibility of Bufei Yishen formula III combined with exercise rehabilitation on chronic obstructive pulmonary disease.Annals of medicine · 2024Article
- A Multimodal Intervention to Improve Guideline-Based Screening for Alpha-1 Antitrypsin Deficiency in a Community Health Setting.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2024Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleSevere α1-antitrypsin deficiency (typically PiZZ homozygosity) is associated with a significantly increased risk of airflow obstruction and emphysema but the risk of chronic obstructive pulmonary disease (COPD) in PiMZ heterozygotes remains uncertain.
objectivesThis was a family-based study to determine the risk of COPD in PiMZ individuals.
methodsWe compared 99 PiMM and 89 PiMZ nonindex subjects recruited from 51 index probands who were confirmed PiMZ heterozygotes and also had a diagnosis of COPD Global Initiative for Chronic Obstructive Lung Disease stage II-IV. The primary outcome measures of interest were quantitative variables of pre- and post-bronchodilator FEV1/FVC ratio, FEV1 (liters), FEV1 (% predicted), forced expiratory flow midexpiratory phase (FEF25-75; liters per second), FEF25-75 (% predicted), and a categorical outcome of COPD. MEASUREMENTS AND MAIN
resultsPiMZ heterozygotes compared with PiMM individuals had a reduced median (interquartile range) post-bronchodilator FEV1 (% predicted) (92.0 [75.6-105.4] vs. 98.6 [85.5-109.7]; P = 0.04), FEV1/FVC ratio (0.75 [0.66-0.79] vs. 0.78 [0.73-0.83]; P = 0.004), and FEF25-75 (% predicted) (63.84 [38.45-84.35] vs. 72.8 [55.5-97.7]; P = 0.0013) compared with PiMM individuals. This effect was abrogated in never-smoking and accentuated in ever-smoking PiMZ individuals. PiMZ heterozygosity was associated with an adjusted odds ratio for COPD of 5.18 (95% confidence interval, 1.27-21.15; P = 0.02) and this was higher (odds ratio, 10.65; 95% confidence interval, 2.17-52.29; P = 0.004) in ever-smoking individuals.
conclusionsThese results indicate that PiMZ heterozygotes have significantly more airflow obstruction and COPD than PiMM individuals and cigarette smoke exposure exerts a significant modifier effect.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.