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RESEARCH PAPER
Causal association between cigarette smoking and the prevalence of preserved ratio impaired spirometry (PRISm), and the progression risk factors of PRISm: A study based on Mendelian randomization and meta-analysis
1
Department of Respiratory
Medicine, The Second
Affiliated Hospital of
Chongqing Medical University,
Chongqing, People’s Republic
of China
2
Department of Radiology,
The Second Affiliated Hospital
of Chongqing Medical
University, Chongqing,
People’s Republic of China
Submission date: 2025-06-11
Final revision date: 2025-08-17
Acceptance date: 2025-08-20
Publication date: 2025-11-21
Corresponding author
Rui Xu*
Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China
Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China
Tob. Induc. Dis. 2025;23(November):179
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Preserved ratio impaired spirometry (PRISm) is a new and variable phenotype of spirometry impairment that was first defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2023. The identification of high-risk factors for the progression from PRISm to COPD remains insufficient at present.
Methods:
Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) summary statistics. Genetic instruments for smoking behavior were derived from the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (n=607291), while PRISm case-control data were sourced from the UK Biobank (n=296282). The inverse-variance weighted (IVW) method served as the primary analytical approach, supplemented by heterogeneity assessment, pleiotropy evaluation, and sensitivity analyses. For the meta-analysis, PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from inception to 31 December 2024, to identify relevant studies that followed up on the changes in spirometry among individuals with PRISm or studies that reported the possible factors related to the changes in spirometry among individuals with PRISm. The risk of bias and the quality of the included studies were assessed using the Newcastle–Ottawa Scale (NOS).
Results:
The MR analysis identified 85 SNPs as genetic instruments, revealing a modest causal link between cigarette smoking and PRISm prevalence (IVW: OR=1.01–1.02, p=0.048). The meta-analysis of 14 studies (n=7336 PRISm cases) shows 20.8% (95% CI: 15.6–25.9) progress to COPD at follow-up, with no significant difference by follow-up duration (<5 vs ≥5 years). Persistent PRISm occurs in 41.5% (95% CI: 35.8–47.2), more frequently in long-term follow-up subgroups. Baseline ‘chest distress/dyspnea’ (OR=3.81; 95% CI: 1.47–9.84) and ‘current smoking’ (OR=2.18; 95% CI: 1.14–4.15) significantly predict progression, while respiratory symptoms, FEV1/FVC ratio, TLC%, and FVC% show no association.
Conclusions:
Our findings suggest a modest causal link between cigarette smoking and PRISm prevalence. The progression of PRISm to COPD within 5 years is approximately 20.8%. Among individuals with PRISm at the first visit, ‘chest distress or dyspnea’ and ‘current smoking’ are potential clinical risk factors for the progression of PRISm to COPD.
Preserved ratio impaired spirometry (PRISm) is a new and variable phenotype of spirometry impairment that was first defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2023. The identification of high-risk factors for the progression from PRISm to COPD remains insufficient at present.
Methods:
Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) summary statistics. Genetic instruments for smoking behavior were derived from the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (n=607291), while PRISm case-control data were sourced from the UK Biobank (n=296282). The inverse-variance weighted (IVW) method served as the primary analytical approach, supplemented by heterogeneity assessment, pleiotropy evaluation, and sensitivity analyses. For the meta-analysis, PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from inception to 31 December 2024, to identify relevant studies that followed up on the changes in spirometry among individuals with PRISm or studies that reported the possible factors related to the changes in spirometry among individuals with PRISm. The risk of bias and the quality of the included studies were assessed using the Newcastle–Ottawa Scale (NOS).
Results:
The MR analysis identified 85 SNPs as genetic instruments, revealing a modest causal link between cigarette smoking and PRISm prevalence (IVW: OR=1.01–1.02, p=0.048). The meta-analysis of 14 studies (n=7336 PRISm cases) shows 20.8% (95% CI: 15.6–25.9) progress to COPD at follow-up, with no significant difference by follow-up duration (<5 vs ≥5 years). Persistent PRISm occurs in 41.5% (95% CI: 35.8–47.2), more frequently in long-term follow-up subgroups. Baseline ‘chest distress/dyspnea’ (OR=3.81; 95% CI: 1.47–9.84) and ‘current smoking’ (OR=2.18; 95% CI: 1.14–4.15) significantly predict progression, while respiratory symptoms, FEV1/FVC ratio, TLC%, and FVC% show no association.
Conclusions:
Our findings suggest a modest causal link between cigarette smoking and PRISm prevalence. The progression of PRISm to COPD within 5 years is approximately 20.8%. Among individuals with PRISm at the first visit, ‘chest distress or dyspnea’ and ‘current smoking’ are potential clinical risk factors for the progression of PRISm to COPD.
CONFLICTS OF INTEREST
The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. T. Chen and X. Rui report that since the initial planning of the work, this research was funded from the Chongqing Natural Science Foundation (CSTB2024NSCQ-KJFZZDX0014), Chongqing Health Commission and Science and Technology Bureau (2022MSXM144 and 2024MSXM044), and Chongqing Medical University (W0118).
FUNDING
This study was funded by the Chongqing Natural Science Foundation
(Chongqing Science and Technology Development Foundation; Project
CSTB2024NSCQ-KJFZZDX0014), Chongqing Medical Scientific Research
Project (Joint project of Chongqing Health Commission and Science and
Technology Bureau; 2022MSXM144), Program for Youth Innovation in
Future Medicine, (Chongqing Medical University; W0118), Chongqing
Medical Scientific Research Project (Joint Project of Chongqing Health
Commission and Science and Technology Bureau; 2024MSXM044).
ETHICAL APPROVAL AND INFORMED CONSENT
Ethical approval and informed consent were not required for this study.
DATA AVAILABILITY
The data supporting this research can be found in the published articles
and in the Supplementary file.
AUTHORS' CONTRIBUTIONS
TC and RX: research concept and design. GZ: collection and/or assembly
of data. XZ, RX and GZ: data analysis and interpretation. XZ and GZ:
writing of the manuscript. TC, RX and XD: critical revision of the
manuscript. All authors read and approved the final version of the
manuscript.
PROVENANCE AND PEER REVIEW
Not commissioned; externally peer reviewed.
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