Study On The Relationship Between Small Airway Dysfunction And Future Incidence Of COPD

BackgroundSmall airways are airways less than 2 mm in diameter.Because of their large surface area,large number,and strong reserve capacity,pathological changes in small airways,such as stenosis,obstruction,and loss,can progress undetected for years without symptoms or changes in lung functions and are therefore also referred to as"silent areas" of the lung,Small airway dysfunction(SAD)is the earliest abnormality in the COPD disease process and can be assessed by forced lung function,volumetric tracing,pulsed oscillatory lung function,inert gas flushing,imaging,etc.Current studies have shown that small airway dysfunction as defined by parametric response mapping(PRM)is significantly correlated with future decline in FEV1.In clinical practice,only inspiratory chest CT is commonly performed,but the prerequisite for the application of PRM is the need for biphasic chest CT for inhalation and exhalation and professional analysis software and measurement knowledge are also required for the evaluation of small airway dysfunction on CT,which has certain complexity and difficulty in clinical application.In addition,CT examination is radiative and expensive,which is unfavorable for patients who need long-term follow-up.However,technologies such as pulse oscillation lung function and inert gas flushing require expensive equipment and are difficult to popularize.The application technology of forced lung function in clinical practice is mature and the required equipment is simple.In addition,the forced lung function is cost-effective,radiation free and has good repeatability-It has been included in routine physical examinations and widely used in grassroots medical institutions.There are multiple indicators for diagnosing small airway dysfunction using forced lung function.Currently,studies have shown that low MMEF and FEV3/FEV6 below the lower limit of normal values are associated with an increased risk of COPD in patients.However,using only one indicator to diagnose small airway dysfunction may have significant variability.At present,the diagnostic criteria for small airway dysfunction in lung function reports are mainly based on at least two indicators,FEF50%,FEF75%,and MMEF,which are less than 65%of the expected value.Some scholars believe that,this standard can better reflect small airway dysfunction,and there is currently no research on the relationship between small airway dysfunction diagnosed by this standard and the risk of obstructive ventilation dysfunction and COPD.Therefore,this study uses at least two indicators of FEF50%,FEF75%,and MMEF that are less than 65%of the expected value to diagnose small airway dysfunction,and explores its relationship with obstructive ventilation dysfunction and COPD incidence,providing a basis for early diagnosis and prevention of COPD.PurposeTo explore the relationship between small airway dysfunction and obstructive ventilation dysfunction and incidence of COPD in patients and to evaluate whether at least two indicators of FEF50%,FEF75%,and MMEF with predicted values less than 65%can be used as indicators for screening high-risk populations for obstructive ventilation dysfunction and COPD.Research MethodsThis is a retrospective study that included 546 study subjects aged 40 years or older with two or more pulmonary function results from 01/01/2009 to 28/02/2023.All participants had a baseline FEV1/FVC≥0.7 and FEV1/FVCpred≥92%,Patients were divided into SAD and NSAD groups according to their first pulmonary function results.General information(including gender,age,BMI,smoking history,the time between pulmonary functions,etc.),two pulmonary function parameters(FEV1,FEV1%pred,FVC,FVC%pred,FEV1/FVC,FEV1/FVC%pred,FEF50%pred,FE F75%pred,MMEF%pred)and the above parameters after inhaling bronchodilators.The above data were analyzed to observe the ratio of patients who progressed to obstructive ventilation dysfunction(defined as FEV1/FVCpred<92%before inhaling bronchodilators)and COPD(FEV/FVC<0.7 after inhaled bronchodilator)in both groups,respectively,and thus to explore the relationship between SAD and incidence of obstructive ventilation dysfunction and COPD.Results1.Both the NSAD and SAD groups were predominantly female and nonsmokers;the number of smokers in the SAD group was more than that in the NSAD group(P=0.043);there were no statistical differences between the NSAD and SAD groups in terms of gender,age,BMI,and time between pulmonary functions;The median time between two pulmonary functions in the NSAD group was 26 months and in the SAD group was 30 months.2.FEV1%pred,FVC%pred,FEV1/FVC%pred,DLCO%pred,and TLC%pred were significantly lower in the SAD group than in the NSAD group(P<0.05);RV was not statistically different(P=0.839);RV/TLC was significantly higher in the SAD group than in the NSAD group(P<0.001).3.The SAD group showed better responsiveness to salbutamol and more significant improvement in FEV1(P=0.026)and FEV1/FVC%(P=0.011).4.6.0%of the NSAD group developed obstructive ventilation dysfunction,while 17.7%of the SAD group developed obstructive ventilation dysfunction,with significant differences between the two groups(P<0.001).5.3.0%of the NSAD group progressed to COPD and 9.3%of the SAD group progressed to COPD,with a significant difference between the two groups(P=0.002),but there was no significant difference in the severity of patients progressing to obstructive ventilation dysfunction and COPD between the two groups(P>0.05).6.Single factor COX regression analysis showed that gender(HR 0.456,95%CI 0.273-0.759,P=0.003),smoking history(HR 2.600,95%CI 1.576-4.291,P<0.001),and SAD(HR 3.029,95%CI 1.738-5.279,P<0.001)were risk factors for obstructive ventilation dysfunction in patients;In multivariate COX regression analysis,gender,age,BMI,smoking history,and SAD were included as covariates in the model,and it was found that patients in the SAD group had a higher risk of developing obstractive ventilation dysfunction in the future than those in the NSAD group(HR 3.009,95%CI 1.695-5.341,P<0.001).7.Single factor COX regression analysis showed that SAD(HR 3.154,95%CI 1.441-6.901,P-0.004)and age(HR 1.038,95%CI 1.006-1.071,P=0.018)were risk factors for future incidence of COPD;In multivariate COX regression analysis,gender,age,BMI,smoking history,and SAD were included as covariates in the model,and it was found that SAD and age are still risk factors for future incidence of COPD.The SAD group has a higher risk of developing COPD in the future compared to the NSAD group(HR 3.312,95%CI 1.461-7.509,P=0.004);the older the age,the higher the risk of incidence of COPD(HR 1.036,95%CI 1.003-1.069,P=0.031).8.Among patients with small airway dysfunction,there were statistical differences in gender(P=0.015)and smoking history(P=0.002)between patients who advanced to obstructive ventilation dysfunction and those who did not.However,there were no statistical differences in gender,age,BMI,and smoking history between patients who advanced to COPD and those who did not.Conclusion1.In the NSAD group,6.0%of patients progressed to obstructive ventilation dysfunction,and 3.0%of patients progressed to COPD;In the SAD group,17.7%of patients progress to obstructive ventilation dysfunction,and 9.3%of patients progress to COPD.2.Patients with small airway dysfunction have a higher risk of developing obstructive ventilation dysfunction and COPD in the future compared to those without small airway dysfunction.3.Among patients with small airway dysfunction,male and smoking patients with small airway dysfunction are more likely to develop obstructive ventilation dysfunction.