Research On The Relationship Between Age And Small Airway Dysfunction

BackgroundSmall airway dysfunction（SAD）,a key feature of chronic obstructive pulmonary disease（COPD）and a major cause of airway limitation,has been regarded as a precursor for the development of COPD in recent years,so it is highly valued.There are many factors affecting SAD.Age is one of the important factors in lung growth,development and aging,and its role in SAD remains to be further explored.ObjectiveWe aimed to explore the relationship between age and SAD.Methods1.The participants were continuously recruited from communities in Wengyuan County,Shaoguan City and Lianping County,Heyuan City,Guangdong Province from July 2019 to August 2021.All participants completed demographic data collection,COPD epidemiology questionnaire information collection,biphasic high resolution chest CT,impulse oscillometry（IOS）,and pre-bronchodilator and post-bronchodilator spirometry according to relevant guidelines.2.The total population was divided into four age groups including aged 40-49 group,aged 50-59 group、aged 60-69 group,and aged>=70 group.Chest CT,IOS,and spirometry methods were used to define SAD,respectively.Among them,CT-defined SAD（CT-SAD）was defined as LAA_-856>20%from CT.IOS-defined SAD（IOS-SAD）was defined as R5-R20>0.07 k Pa/L/s from IOS.And spirometry-defined SAD（Spirometry-SAD）will be determined if post-bronchodilator MMEF%predicted,FEF₅₀%predicted or FEF₇₅%predicted（any two of the three values）are<65%.3.Analysis of variance,Kruskal-Wallis test,Chi-square test or Fisher accuracy test were used to compare the differences in clinical characteristics among the four age groups.Analysis of covariance was used to compare small airway function indexes among four age groups.The linear-by-linear association test in Chi-square test was used to evaluate the linear trend of SAD frequency in different age groups.Binary logistic regression model was used to assess the relationship between age and the risk of SAD,and multiple linear regression model was used to analyze the effect of age on the severity of small airway function.Covariates adjusted included sex,body mass index（BMI）,smoking status,smoking index,passive smoking,family history of respiratory disease,biofuel exposure,and occupational exposure.In addition to the analysis in the general population,the main analyses were repeated in the group without airflow limitation,the airflow limitation group,the male group,the female group,the never smoking group,and ever smoking group to assess the robustness of the results.4.The multiplication of age and airflow limitation,the multiplication of age and gender,and the multiplication of age and smoking status were included as interaction terms in the repeated primary analysis of each binary logistic regression model and multiple linear regression model,respectively,to evaluate whether the relationships between age and SAD risk and the severity of small airway function were affected by airflow limitation,gender,and smoking status.Results1.A total of 1859 people were included in the final analysis in our study,including157 participants（8.4%）in the aged 40-49 group,592 participants（31.8%）in the aged50-59 group,831participants（44.7%）in the aged 60-69 group,and 279 participants（15.0%）in the aged>=70 group.Participants in the older group had lower BMI（P<0.001）,higher proportion of males（P<0.001）,higher proportion of smokers（P<0.001）,higher smoking index（P<0.001）,and lower pre-bronchodilator and post-bronchodilator lung function than those in younger group（all P<0.001）.2.After adjusting for confounding factors,compared with the participants in the aged 40-49 group,participants in older age groups had lower post-bronchodilator MMEF%predicted（aged 50-59 group vs.aged 40-49 group:60.5±27.2%vs.71.4±27.3%,mean difference:7.9%,95%CI:2.1 to 13.6,P=0.002;aged 60-69 group vs.aged 40-49 group:44.5±25.4%vs.71.4±27.3%,mean difference:20.9%,95%CI:15.1 to 26.6,P<0.001;aged>=70 group vs.aged 40-49 group:34.7±19.8%vs.71.4±27.3%,mean difference:30.3%,95%CI:23.6 to 36.9,P<0.001）,lower post-bronchodilator FEF₅₀%predicted（aged 50-59 group vs.aged 40-49 group:68.1±29.5%vs.78.8±27.8%,mean difference:7.2%,95%CI:0.9 to 13.5,P=0.015;aged 60-69group vs.aged 40-49 group:49.8±28.1%vs.78.8±27.8%,mean difference:22.1%,95%CI:15.9 to 28.4,P<0.001;aged>=70 group vs.aged 40-49group:38.1±23.4%vs.78.8±27.8%,mean difference:33.1%,95%CI:25.9 to 40.3,P<0.001）,lower post-bronchodilator FEF₇₅%predicted（aged 50-59 group vs.aged 40-49 group:47.0±26.4%vs.58.5±31.7%,mean difference:9.4%,95%CI:3.5 to 15.3,P<0.001;aged 60-69group vs.aged 40-49 group:36.1±25.4%vs.58.5±31.7%,mean difference:18.2%,95%CI:12.4 to 24.1,P<0.001;aged>=70 group vs.aged 40-49 group:30.7±17.8%vs.58.5±31.7%,mean difference:23.9%,95%CI:17.1 to 30.7,P<0.001）,greater degree of gas trapping（aged 60-69 group vs.aged 40-49 group:20.4±20.3%vs.3.8±7.6%,mean difference:-10.7%,95%CI:-14.5 to-6.8,P<0.001;aged>=70 group vs.aged40-49 group:30.0±21.3%vs.3.8±7.6%,mean difference:-18.2%,95%CI:-22.7 to-13.8,P<0.001）,greater peripheral airway viscous resistance（aged 60-69 group vs.aged40-49 group:0.08±0.07 k Pa/L/s vs.0.06±0.00 k Pa/L/s,mean difference:-0.02k Pa/L/s,95%CI:-0.03 to-0.00,P value=0.018;aged>=70 group vs.aged 40-49 group:0.09±0.09 k Pa/L/s vs.0.06±0.00 k Pa/L/s,mean difference:-0.02 k Pa/L/s,95%CI:-0.03to-0.00,P<0.001）.3.Using any one of the three methods of chest CT,IOS and spirometry to define SAD,it was found that SAD frequency showed a gradually increasing trend in all age groups（P for trend<0.001）.After adjusting for confounding factors,each increase in age of 10 years was significantly associated with higher risk of CT-SAD（OR:2.80,95%CI:2.34 to 3.36,P<0.001）,IOS-SAD（OR:1.88,95%CI:1.62 to 2.16,P<0.001）and Spirometry-SAD risk（OR:2.45,95%CI:2.09 to 2.88,P<0.001）.In addition,each increase in age of 10 years was significantly associated with higher degree of gas trapping（adjustedβ:7.38,95%CI:6.42 to 8.34,P<0.001）,greater the ratio of residual volume to total lung capacity（adjustedβ:0.06,95%CI:0.06 to 0.07,P<0.001）,greater peripheral airway viscous resistance（adjustedβ:0.02,95%CI:0.02 to 0.02,P<0.001）,greater peripheral airway elastic resistance（adjustedβ:-0.02,95%CI:-0.03 to-0.02,P<0.001）,larger airway reactance area（adjustedβ:0.24,95%CI:0.19 to 0.29,P<0.001）,larger resonance frequency（adjustedβ:1.99,95%CI:1.67 to 2.31,P<0.001）,lower MMEF%predicted（adjustedβ:-11.99,95%CI:-13.42 to-7.19,P<0.001）,lower FEF₅₀%predicted（adjustedβ:-11.99,95%CI:-13.42 to-7.19,P<0.001）-13.37,95%CI:-14.93 to 11.81,P<0.001)and lower FEF₇₅%predicted（adjustedβ:-8.86,95%CI:-10.32 to 7.39,P<0.001）.These findings were still consistent in the group without airflow limitation,airflow limitation group,male group,female group,never smoking group,and ever smoking group.4.After adjusting for confounding factors,each increase in age of 10 years was significantly associated with higher risk of CT-SAD,higher risk of IOS-SAD,higher risk of Spirometry-SAD,greater peripheral airway viscous resistance and lower forced mid-end expiratory flow,which were more significant in the population without airflow limitation（all P for interaction<0.001）.Each increase in age of 10 years was associated with higher risk of IOS-SAD（P for interaction=0.008）,greater gas trapping（P for interaction<0.001）,and greater peripheral airway viscous resistance（P for interaction=0.002）,which were more significant in the male population.Each increase in age of10 years was associated with higher risk of IOS-SAD（P for interaction=0.03）,greater gas trapping（P for interaction<0.001）,and higher peripheral airway viscous resistance（P for interaction=0.001）,which were more significant among smokers.Conclusions1.Using any one of the three methods including chest CT,IOS and spirometry to define SAD,after adjusting for confounding factors in the total population and each subgroup analysis,we found that increasing age was significantly associated with higher proportion of SAD,higher risk of SAD and greater severity of small airway function,suggesting that age may be an independent risk factor for SAD.2.The association between increasing age and higher risk of SAD and greater severity of small airway function was more significant in the population without airflow limitation,males and smokers,suggesting that aging in some target populations,such as males and smokers,may be at greater risk of SAD progression,which should be paid more attention.