Prevalence, longitudinal trajectory, and mortality of preserved ratio impaired spirometry (PRISm) in a Thai hospital-based cohort study

Introduction

Nowadays, abnormal pulmonary function tests are classified into obstructive, restrictive, and mixed patterns. However, some patterns are misunderstood as normal, despite exhibiting physiological abnormalities, which are referred to as non-specific patterns. The non-specific pattern spirometry has been recently described in the European Respiratory Society/American Thoracic Society (ERS/ATS) technical standard on interpretative strategies for routine lung function tests in 2021 as the pattern of reduced forced vital capacity (FVC) and/or forced expiratory volume in 1 sec (FEV1), normal FEV1/FVC, and normal total lung capacity (TLC) (1). Preserved ratio impaired spirometry (PRISm) was proposed as a proportional decrease between FEV1 and FVC, resulting in a normal FEV1/FVC despite impairment of pulmonary function (2,3). However, there is no consensus for the definition of PRISm.

In the ERS/ATS recommendation 2021, PRISm was described as a trend toward an obstructive pattern, where FEV1 is lower than the lower limit of normal (LLN) in the non-specific pattern. However, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2024, PRISm is now specifically defined as FEV1/FVC ≥0.7 after bronchodilator use, with FEV1 <80% of the reference in current or former smokers (4). The prevalence of PRISm ranges from 5–10% in different population-based studies, and up to 13% in current and former smokers, such as the COPDGene cohort (5-12). The prevalence of PRISm has been shown associated with both high and low body mass index (BMI), female gender, obesity, and smoking status (9,10). PRISm is an instability of lung function which can persist or transition to normal, obstructive or restrictive patterns (3). Relationship of PRISm with increasing risk of all-cause mortality, cardiovascular events (ischemic heart disease or heart failure), and respiratory events (pneumonia or COPD) have been mentioned (5,6,13,14).

Previous studies had a small Asian population because most were conducted in America and Europe. Some studies were conducted in Japan, South Korea, and China, which may have different racial background from Thai population. Our study aims to investigate the prevalence and trajectory of PRISm of a hospital-based setting in Thailand. We also explore the predictive factors and clinical outcomes of these subjects. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0808/rc).

Methods

Study design and study population

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective-cohort study was approved by Siriraj Institutional Review Board (No. Si374/2567). Informed consent was not taken according to the exemption protocol of the IRB. All patients who underwent spirometry at Siriraj Pulmonary Function Laboratory, Faculty of Medicine Siriraj Hospital with any indications between April 2017 to February 2018 were included and followed until March 2024.

A sample size estimation was performed to ensure adequacy for estimating the prevalence of PRISm. Based on previously reported prevalence of approximately 7%, assuming a 95% confidence level and precision of 1.5%, the minimum required sample size was calculated using the standard formula for single proportion, yielding 1,276 participants. The final sample size of 1,300 patients was considered sufficient for the study objectives.

Patients with incomplete medical records or those lost to follow up were excluded. A complete-case analysis was performed; therefore, no missing data remained for analysis and no imputation methods were applied. Demographic characteristics, smoking status, co-morbidity (including diabetes, hypertension, dyslipidemia, cardiovascular disease and lung disease), admission history, and mortality data were colloected. Laboratory results, including blood eosinophilic count (BEC) and serum creatinine for determining estimated glomerular filtration rate (eGFR) were also collected. Follow-up spirometry results in those with PRISm were also retrieved for its trajectory.

Data sources and measurement

Spirometry data were obtained from the Siriraj Pulmonary Function Laboratory, Faculty of Medicine Siriraj Hospital. All spirometric measurements were performed according to standardized protocols by trained technicians in accordance with international guidelines

Lung function parameters, including FEV1, FVC and FEV1/FVC ratio, were interpreted using reference equations from the Global Lung Function initiative (GLI) 2012 reference equations

Pre-Bronchodilator spirometry values were used for analysis. The classification of spirometric patterns, included PRISm, was based on defined criteria as described in the variable definition section.

Variable definition

Global Lung Function Initiative (GLI) 2012 references equations were used for calculating spirometry values and the PRISm was defined by either (I) lower limit of normal (LLN) criteria: FEV1 < LLN with FVC ≥ LLN and FEV1/FVC ≥ LLN or (II) fixed ratio criteria: FEV1 <80% predicted with FVC ≥80% predicted and FEV1/FVC ≥ 75% if age ≤45 years or ≥70% predicted if age >45 years. Pre-bronchodilator values were used in this study.

Statistical analysis

Prevalence was calculated by dividing the total number of PRISm cases by the total number of subjects. Continuous variables were described using medians and interquartile ranges (IQR), as variables were not normally distributed, while categorical variables were presented as frequencies and percentages. Continuous variables were primarily analyzed as continuous measures to preserve statistic power. Where appropriate, selected variables were categorized based on clinically relevant thresholds.

Comparisons between groups (normal vs. PRISm) were performed using the Chi-square test or Fisher’s exact test for categorial variables, and the Wilcoxon rank-sum tests for continuous variables.

The association between factors and each outcome were assessed by logistic regression analysis. Multivariable models were developed by adjusting for covariates with P<0.1 in univariate models.

Kaplan-Meier survival curves and the log-rank tests were used to estimate and compare survival rate among groups. Cox proportional hazards regression model was used to determine factors associated with all-cause mortality and multivariable models were adjusted for clinically relevant covariates.

Results were reported as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). All statistical analyses were performed using STATA version 18.5 (StataCorp LLC, College Station, Texas, USA).

Results

Prevalence of PRISm and its characteristics

Among 3,030 subjects during the study period, of whom 1,300 were included in this study. Patients were excluded primarily due to incomplete medical records or loss to follow-up. Normal spirometry was established in 523 subjects (40.2%), obstructive ventilatory impairment in 403 subjects (31%), and restrictive impairment in 177 subjects (13.6%). The crude prevalence of PRISm was 8.4% when defined by either LLN criteria or fixed ratio criteria. When analyzed separately, the prevalence was 3.5% and 6% using the LLN and fixed-ratio criteria, respectively. A flow diagram of patient’s selection and spirometric classification is shown in Figure 1.

Figure 1 Flow diagram of patient selection and spirometric classification. A total of 3,030 patients underwent spirometry during the study period. After excluding patients aged <18 years, those with incomplete data, and those loss to follow-up (n=1,730), 1,300 patients were included in the final analysis. These were classified into normal spirometry (n=523), obstructive ventilatory impairment (n=403), restrictive ventilatory impairment (n=117), mixed pattern (n=148), and preserved ratio impaired spirometry (PRISm; n=109). Among patients with PRISm, 52 underwent follow-up spirometry for trajectory analysis. PRISm, preserved ratio impaired spirometry.

Of the total cohort, 63.3% were women and 77.1% were non-smoker. When compared to those with normal spirometry (Table 1), the PRISm group trends to have more smoker (23% vs. 17.8%, P=0.36) with slightly higher median age (62 vs. 61 years, P=0.052). However, there were no significant statistical differences in term of sex, smoking intensity (pack-years), body weight, and BMI between both groups. Regarding co-morbidity, those with PRISm seem to have a higher prevalence of congestive heart failure (CHF), 7.3% vs. 4.2%, P=0.02.

Associated conditions and PRISm

In this study, only CHF was significantly associated with PRISm (OR 2.8, 95% CI: 1.09–7.18). Older age showed a trend toward association with PRISm, but there were no significant association with sex, smoking status, BMI, and other co-morbidities such as diabetes, hypertension, dyslipidemia, chronic kidney disease, ischemic heart disease, or stroke. Similarly, laboratory parameters including eGFR and BEC were not significantly associated with PRISm (Table 2).

Mortality and hospitalization

In unadjusted analysis, PRISm was associated with increased all-cause mortality (HR 2.37, 95% CI: 1.19–4.72, P=0.01) (Figure 2, Table 3). After adjustment for sex, age, smoking status, chronic kidney disease, CHF, and cancer, PRISm remained independently associated with mortality (aHR 2.08, 95% CI: 1.04–4.15, P=0.04). CHF and cancer were also independently associated with mortality (Figure 3).

Figure 2 Kaplan-Meier survival curves comparing all-cause mortality between patients with PRISm and normal spirometry. Patients with PRISm showed significantly lower survival rate compared with normal spirometry. HR and 95% CIs were estimated using Cox proportional hazards regression analysis, and group differences were assessed using the log-rank test. CI, confidence interval; HR, hazard ratio; PRISm, preserved ratio impaired spirometry.

Figure 3 Multivariable Cox proportional hazards regression analysis for predictors of all-cause mortality. Forest plot demonstrating aHRs with 95% CIs for variables associated with all-cause mortality. PRISm remained independently associated with increased mortality after adjustment for clinically relevant covariates. Other significant predictors included congestive heart failure and cancer. aHRs, adjusted hazard ratios; CHF, congestive heart failure; CI, confidence interval; CKD, chronic kidney disease; PRISm, preserved ratio impaired spirometry.

Trajectories in term of spirometry

Among the 109 subjects with PRISm, 52 had serial follow-up spirometry. The average duration of follow-up was approximately 7 years. Spirometric trajectory analysis revealed that 30.8% of subjects transitioned to normal, 28.8% developed an obstructive ventilatory impairment, 19.2% developed a restrictive ventilatory impairment, and 21.2% remained in the PRISm category (Figure 4). Among these subjects, 49 (94.2%) were treated with bronchodilator and 48 (92.3%) with inhaled corticosteroids.

Figure 4 Longitudinal spirometric trajectories of patients with PRISm. Fifty-two patients with follow-up spirometry, transitions were observed as follows: 30.8% to normal spirometry, 28.8% to obstructive ventilatory impairment, 19.2% to restrictive ventilatory impairment, and 21.2% remained PRISm. PRISm, preserved ratio impaired spirometry.

Discussion

This study supports the clinical importance of PRISm as a distinct spirometric pattern in the Thai population. The overall prevalence of PRISm in our cohort was 8.4% using both criteria. When using the fixed-ratio criteria, the prevalence was approximately 6% and comparable to the 7.1% observed in the Rotterdam study (older population, >45 years) and 8.5% in the general population (5,6). In contrast, prevalence decreased to 3.5% using LLN criteria, consistent with prior studies (5,6,10). This lower prevalence may reflect reduced false-positive diagnoses in the elderly individuals, as this population naturally experiences a decline in lung function with time.

The association between PRISm and smoking remains inconclusive. While some studies have reported a link between PRISm and smoking but some were not (3,5-7,9,10). In our study, smoking was not significantly associated with PRISm, although a trend toward a higher proportion of smokers was observed. Previous studies have identified associations between PRISm and some factors such as older age, higher BMI, and co-morbidities including diabetes, hypertension, stroke, ischemic heart disease, and CHF (5,6,9,10). Only the CHF was significantly associated with PRISm in our cohort. The effects of pulmonary venous hypertension from impaired ventricular function, has been shown to result in both obstructive and restrictive ventilatory impairments (15). Although the majority of subjects with PRISm in our study were female (63.3%), but no significant association with female gender was verified, supporting the inconsistency results in this aspect from previous studies (7,15).

PRISm was associated with significantly increased all-cause mortality, consistent with previous studies (5-9,12,14,16-19). Our study similarly demonstrated a significantly higher mortality risk among individuals with PRISm compared with those with normal spirometry. Although cardiovascular events or hospitalizations were not significantly increased, a trend toward higher respiratory events was observed. Reduced FEV1 may contribute to adverse outcomes through impaired cardiopulmonary reserve (16,18,19).

Interestingly, despite the higher prevalence of CHF among patients with PRISm, no cardiovascular-related deaths were observed during follow-up. This finding may be explained by the relatively small number of deaths, the predominance of cancer-related mortality in our tertiary-care cohort, and the low absolute prevalence of CHF despite its significant association with PRISm. In addition, differences in demographic and clinical characteristics between our predominantly female, never-smoker Thai cohort and previously reported Western cohorts may contribute to differing mortality patterns. Therefore, the absence of cardiovascular mortality should be interpreted cautiously and does not necessarily contradict previous evidence linking PRISm with adverse cardiovascular outcomes.

Among patients with follow-up spirometry, Prism demonstrated a dynamic trajectory, transitioning to normal, obstructive, or restrictive patterns or persistent as PRISm patterns, consistent with previous reports (5,7,8,11,13). However, only a subset of patients underwent repeat spirometry, and most received respiratory therapies during follow-up. Consequently, the observed transitions likely reflect the clinical course of treated patients rather than the natural history of PRISm. Nevertheless, these findings further support PRISm as a clicically relevant spirometric phenotype requiring longitudinal assessment.

Strengths of this study include, this study provided novel data on PRISm in Thai population that might be underrepresentation of Southeast Asian cohort previous literature. We applied both LLN- and fixed- ration definitions, allowing comparison across commonly nature of PRISm. We evaluated clinically meaningful outcomes including mortality, strengthening the clinical relevance of PRISm moreover spirometric classification.

Several limitations should be acknowledged. First, this was retrospective, single-center study, which may limit external validity. Second, the use of pre-bronchodilator spirometry may have led to misclassification between PRISm and obstructive impairment. Third, only 52 of the 109 patients with PRISm underwent repeat spirometry, which may have introduced attrition bias and limited the reliability of the trajectory analysis. Furthermore, nearly all patients with follow-up spirometry were receiving bronchodilators and inhaled corticosteroids, which may have influenced longitudinal lung function changes. Therefore, the observed trajectories likely represent treated symptomatic patients rather than true natural history of PRISm.

Fourth, complete-case-analysis resulted in a high exclusion rate from the initially screened population, primarily due to missing clinical information or inadequate follow-up. As baseline data for excluded subjects were unavailable, the extent of potential selection bias could not be formally assessed. Consequently, the representativeness of the final cohort and the observed associations should be interpreted with caution.

The generalizability of these findings is limited, as this was a hospital-based cohort from a tertiary care center. Furthermore, our predominantly Southeast Asian, female, and never smoker population differs from many Western cohorts. Therefore, extrapolation of these findings to other populations should be undertaken with caution. Nevertheless, standardized measurements and long-term follow up support the relevance of findings to similar clinical settings. Future multicenter studies are needed to confirm these findings.

Conclusions

In our study, PRISm may represent an important spirometric abnormality that warrants clinical attention. Given its association with cardiovascular co-morbidities and significantly increased all-cause mortality. However, it is retrospective single-center study, potential selection bias, and the use of prebronchodilator spirometry, these finding should be interpreted with caution. Further prospective multicenter studies using standardized post-bronchodilator measurements are needed to confirm the prognostic significance and natural history of PRISm.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0808/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0808/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0808/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0808/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective-cohort study was approved by Siriraj Institutional Review Board (No. Si374/2567). Informed consent was not taken according to the exemption protocol of the IRB.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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