Clinical Characteristics Of Preserved Ratio Impaired Spirometry:A Preliminary Study

BackgroundPreserved ratio impaired spirometry（PRISm）refers to decreased forced expiratory volume in 1 s（FEV₁）in the setting of preserved ratio.Previous studies have found that PRISm has a higher proportion,more chronic respiratory symptoms,a faster decline of lung function,a higher risk of COPD,all-cause mortality as well as cardiovascular mortality compared with healthy control.Some studies have indicated that PRISm may be one of the pre-COPD population in different categories.However,limited data regarding the clinical characteristics and longitudinal prognosis of PRISm in the Chinese population are available.Objective:1.To explore the clinical features of PRISm,such as the proportion,the chronic respiratory symptoms,the comorbidities,the spirometry,the small airway function,the chest imaging,the exercise physiology,and so on.2.To explore the rate of decline of lung function,the risk of airflow limitation and the risk of acute respiratory events in PRISm.3.To explore the clinical characteristics and the prognosis of subjects with persistent PRISm and those with reversible PRISm.Methods:1.This study is based on the ECOPD cohort study in Guangdong,China.The subjects were randomly invited into the group from July 2019 to December 2020from three regions（Guangzhou City;Shaoguan City and Heyuan City）.The data of standard respiratory epidemiology questionnaire,the symptom scores,the spirometry,the impulse oscillometry（IOS）,the chest inspiratory and expiratory high-resolution CT,and the cardiopulmonary exercise tests were collected.2.In this study,the subjects were regularly followed up once a year,and the follow-up data were collected,such as spirometry,bronchodilation test,quality of life assessment,and acute respiratory events or acute exacerbations risk assessment.3.The subjects were divided into three groups according to the FEV₁/FVC and FEV₁pred after inhalation of bronchodilators.PRISm was defined as post-bronchodilator FEV₁/FVC≥0.70 and FEV₁<80%predicted.Spirometry-defined COPD was defined as post-bronchodilator FEV₁/FVC<0.70.Healthy control was defined as post-bronchodilator FEV₁/FVC≥0.70 and FEV₁≥80%predicted.According to the longitudinal progress and outcome of PRISm,the subjects were divided into persistent PRISm group,the trajectory of the PRISm to healthy control group,the trajectory of the PRISm to COPD group,the trajectory of the healthy control to PRISm group and the trajectory of the COPD to PRISm group.4.As for the cross-sectional data,one-way ANOVA,Kruskal-Wallis test,Chi-square test or Fisher exact probability test was used to explore the differences in clinical characteristics between PRISm,healthy controls,and COPD.After the adjustment of the confounding factors,covariance analysis was used to explore the differences in spirometry,small airway function,chest imaging,and cardiopulmonary exercise function between PRISm,healthy controls,and COPD.As for the 1-year prognostic data,covariance analysis was used to explore the differences in lung function decline rate between different groups after confounding factors adjusted.The negative binomial distribution regression model was used to explore the risk difference of acute respiratory event or acute aggravation among different groups.The Cox proportional hazard regression model was used to explore the risk difference of acute respiratory events or acute exacerbations from different groups to the first acute respiratory event or acute aggravation.The multivariate logistics regression analysis was used to explore the risk of COPD in the PRISm.The confounding factors considered in the analysis were including age,sex,body mass index,smoking status,and smoking index.5.Another one diagnostic criteria of PRISm（post-bronchodilator FEV₁/FVC≥0.70 and FVC<80%predicted）was re-grouped for sensitivity analysis to evaluate the reliability and robustness of the above results.Results:1.The study finally analyzed 2055 subjects from July 2019 to August 2021, including 220 subjects with PRISm,920 subjects with healthy controls,and 915patients with COPD.PRISm accounted for 19.3%of subjects in the cohort with post-bronchodilator FEV₁/FVC≥0.70.All the subjects in the cohort have been followed up for one year,and a total of 1817 subjects have completed the standard respiratory epidemiology questionnaire follow-up.1738 subjects have completed the follow-up of spirometry.During the 1-year follow-up period,41.8%of PRISm transitioned to healthy controls and 13.2%progressed to COPD.It is suggested that PRISm may be unstable.2.In terms of demographic characteristics,compared with healthy controls,PRISm were older,had a higher proportion of wheezing symptoms,and had a larger proportion of acute respiratory events/exacerbations during preceding year.There was no significant difference in risk factors exposure,including smoking status,biofuel exposure,occupational history to dusts/gases/fumes exposure between the two groups.The family history of respiratory diseases,complications,and respiratory symptoms such as cough,phlegm,and dyspnea between these two groups.Compared with COPD,PRISm were younger,had higher incidence of diabetes,lower incidence of respiratory symptoms,lower proportion of past and current smoking,lower proportion of occupational history to dusts/gases/fumes exposure,and lower proportion of acute respiratory events/exacerbations during preceding year.3.In terms of spirometry,the FEV₁%of predicted in PRISm（pre-bronchodilator: 75.6±9.5%vs.97.3±11.9%,P<0.001;post-bronchodilator:74.9±8.0%vs.97.1±11.2%,P<0.001）was lower than that in healthy controls.The FVC%of predicted in PRISm was lower than that of healthy controls（pre-bronchodilator:75.6±9.5%vs.97.3±11.9%,P<0.001;post-bronchodilator:74.9±8.0%vs.97.1±11.2%,P<0.001）and COPD（pre-bronchodilator:75.6±9.5%vs.92.5±18.9%,P<0.001;post-bronchodilator:74.9±8.0%vs.96.4±17.7%,P<0.001）.The post-bronchodilator FEV₁/FVC of PRISm lower than that of healthy subjects（75.6±9.5%vs.97.3±11.9%;P<0.05）and higher than COPD（75.6±9.5%vs.58.0±10.1%;P<0.05）.The results of small airway function in PRISm showed that after adjustment for confounding factors,compared with healthy controls,MMEF,FEF50 and FEF75 related to spirometry in PRISm pre-bronchodilator and post-bronchodilator were significantly lower（all P<0.001）,and the risk of small airway disease in PRISm pre-bronchodilator（OR=6.11,95%CI:4.35-8.57,P<0.001）and post-bronchodilator（OR=10.33,95%CI:7.29-14.64,P<0.001）is higher.4.In terms of chest imaging,high-resolution CT showed the TLC_CT%of predicted in PRISm was significantly lower than that of healthy controls（79.1±13.0%vs.90.3±13.2%;P<0.001）and COPD（79.1±13.0%vs.94.3±15.4%;P<0.001）.The ratio of the mean lung density of expiration to inspiration and the ratio of residual volume to total lung volume of CT-measured small airway indexes in PRISm were significantly higher（all P<0.001）and the risk of air trapping in PRISm（OR=1.63,95%CI:1.01-2.65,P=0.048）was significantly higher than that in healthy controls.There was no significant difference between the two groups after confounding factor correction.5.In terms of small airway function and exercise physiological characteristics,R5,R20,A_X,X5 and Fres related to impulse oscillometry in PRISm were significantly higher than those in healthy subjects（all P<0.001）,and the risk of small airway disease was higher（OR=3.08,95%CI:2.14-4.42,P<0.001）than that in healthy controls.In terms of exercise physiological,the peak power（115±25 Watt vs.126±28 Watt,P=0.004）and peak tidal volume（1.40[1.22-1.66]L[btps]vs.1.62[1.36-1.91]L[btps]）in PRISm were lower than those in healthy controls,but there was no significant difference between PRISm and COPD.6.During the 1-year follow-up period,the risk of airflow limitation,the risk of acute respiratory events and the annual decline rate of lung function in PRISm showed that in terms of the risk of airflow limitation,the risk of airflow limitation in PRISm（OR=1.65,95%CI:1.01-2.69,P=0.045 after correction）was significantly higher than that in healthy controls.In terms of the risk of acute respiratory events,the incidence and risk of moderate and severe acute respiratory events in PRISm were significantly higher than those in healthy subjects（RR=1.47,95%CI:1.02-2.12,P=0.039 after correction）after adjusting for confounding factors.In terms of the annual decline rate of lung function,before and after adjusting for confounding factors,the annual decline rates of FEV₁and FVC in PRISm pre-bronchodilator and post-bronchodilator were slower than those in healthy controls and COPD.And the annual decline rate of FEV₁/FVC in PRISm was faster than that in COPD,and there was no significant difference between PRISm and healthy subjects.7.The clinical characteristics,the risk of acute respiratory events and the rate of decline of lung function in subjects with the PRISm to other pulmonary function states were compared with persistent PRISm.The results showed that compared with the PRISm to healthy controls trajectory,persistent PRISm subjects had a higher proportion of males（66.1%vs.42.4%,P=0.004）in terms of demographic characteristics,higher rates of past and current smoking（53.2%vs.34.8%,P=0.023）,and higher occupational history to dust/gas/fume exposures（25.8%vs.9.8%,P=0.008）in terms of exposure to risk factors.There was no significant difference in smoking index,biofuel exposure,second-hand smoke exposure and other risk factors between the two groups.In terms of symptoms,persistent PRISm had a higher CAT score（4.6±5.9 vs.2.2±3.3,P=0.010）than the PRISm to healthy controls trajectory subjects.There was no significant difference in chronic respiratory symptoms between the two groups.In terms of complications,persistent PRISm had a larger proportion of cerebral infarction（11.3%vs.0%,P=0.004）than the PRISm to healthy controls trajectory subjects.There was no significant difference in the family history of respiratory diseases and the proportion of acute respiratory events/exacerbations during the preceding year between the two groups.It is suggested that former and current smoking and occupational history of dust/gas/fume exposures may be related to the maintenance of PRISm.There was no significant difference in the risk of acute respiratory events among the three groups.In terms of the annual decline rate of lung function,before and after correcting confounding factors,compared with the subjects with persistent PRISm,the annual decline rate of FEV₁and FVC was lower in the subjects with the PRISm to healthy control trajectory pre-bronchodilator and post-bronchodilator,and there was no significant difference in the annual decline rate of FEV₁/FVC between the two groups.The annual decline rate of FVC was lower and the annual decline rate of FEV₁/FVC was higher in patients with the PRISm to COPD trajectory,and there was no significant difference in the annual decline rate of FEV₁between the subjects with the PRISm to COPD trajectory and persistent PRISm.It is suggested that the transition from PRISm to healthy control population has a better prognosis.8.The clinical characteristics,the risk of acute respiratory events and the rate of decline of lung function in patients with other pulmonary function to PRISm trajectory were compared with those in subjects with persistent PRISm.The results showed that subjects with persistent PRISm had a higher proportion of women than those with the COPD to PRISm trajectory（33.9%vs.0%,P=0.002）,and a higher proportion of dyspnea（29.0%vs.4.5%,P=0.39）.There was no significant difference in the exposure of risk factors and the ratio of acute respiratory events/acute exacerbation in the previous year between the subjects with persistent PRISm and the other two groups.In terms of the risk of acute respiratory events,the total risk of acute respiratory events（RR=3.74,95%CI:1.33-10.54,P=0.013 after correction）and the risk of moderate and severe acute respiratory events（RR=3.50,95%CI:1.15-10.68,p=0.028 after correction）in the healthy control to PRISm trajectory were also higher than those with persistent PRISm after adjusting for age and gender confounding factors.In terms of annual decline rate of lung function,before and after correcting confounding factors,the annual decline rate of FEV₁and FVC was faster in the healthy control to PRISm trajectory compared with persistent PRISm post-bronchodilator.But there was no significant difference in FEV₁/FVC annual decline rate between the two groups.The annual decline rate of FVC was faster in patients with the COPD to PRISm trajectory,and the annual decline rate of FEV₁/FVC was slower post-bronchodilator.There was no significant difference in the one-year decline rate of FEV₁between the two groups.Pre-bronchodilator there was no significant difference in the annual decline rate of FEV₁and FVC between the subjects with persistent PRISm and the other two groups.9.The above results are still robust in the sensitivity analysis of PRISm（post-bronchodilator FEV₁/FVC≥0.70 and FVC<80%predicted）defined by FVC.Conclusions:1.PRISm is a common mode of spirometry measurement,which has a higher proportion and more severe small airway dysfunction,and is more likely to progress to COPD,which may be one of the pre-COPD population.2.PRISm is unstable and its diagnosis is prone to fluctuation.At the same time,it is heterogeneous.There are significant differences in prognosis among different PRISm groups.