Clinical Phenotypes Of Asthma And Bronchiectasis Overlap Patients

Background:Asthma and bronchiectasis are common chronic inflammation airway diseases,which often co-exist,asthma-bronchiectasis overlap（ABO）.ABO patients are heterogeneous,but the clinical phenotypes of ABO patients have not been clearly defined.Aim:To explore and verify the clinical phenotypes of ABO patients,illustrate the important indicators affecting the classification and compare the prognostic differences of ABO patients with different phenotypes.Method:A retrospective and prospective cohort study was conducted.We collected clinical data of inpatients with ABO,pure asthma and pure bronchiectasis and their differences in clinical characteristics and hospitalization outcomes were compared.The inpatients with ABO were classified by variables screening and two-step unsupervised cluster analysis,and the differences in clinical characteristics and prognosis of different phenotypes of patients were compared.The outpatients with ABO were included and analyzed using the same variables and clustering method as inpatients,and outpatients were followed up for 1 year to record the pulmonary function and exacerbation of asthma or bronchiectasis patients with ABO.Result:A total of 322 inpatients with ABO,933 inpatients with pure asthma,and 1288inpatients with pure bronchiectasis were included from 2015 to 2020 in retrospective study.Compared with patients with pure asthma and pure bronchiectasis,ABO patients had more severe disease and worse hospitalization outcome.By cluster analysis,inpatients with ABO could be divided into three clinical phenotypes,including phenotype of ABO-A with asthma characteristics the main clinical manifestations,phenotype of ABO-B with bronchiectasis characteristics as the main clinical manifestations,and phenotype of severe ABO with obviously asthma and bronchiectasis characteristics and worse hospitalization outcome.In retrospective study,29 patients with repeated hospitalization while 4 of them change the cluster phenotypes.A confirmatory cluster analysis was performed on 98 ABO patients in the outpatient cohort,and two clusters of patients corresponding to ABO-A and ABO-B phenotypes in inpatient cohort were identified.In cluster analysis,the most important indicators affecting the classification were bronchiectasis severity（modified Reiff score）and asthma severity.During follow-up period,FVC%pred and FEV₁%pred of ABO-B patients improved compared with the lung function at baseline.The proportion of ABO-A patients with asthma exacerbation was significantly higher than ABO-B patients（28.1%vs.5.6%,P=0.012）,and the time to first asthma exacerbation was significantly shorter（HR:5.45,95%CI:1.66-17.87,P=0.015）.Compared with ABO-A patients,ABO-B patients had a significantly higher proportion of exacerbation（66.7%vs.37.5%,P=0.013）,and shorter time from the first bronchiectasis exacerbation（HR:0.43,95%CI:0.23-0.80,P=0.011）.Conclusion:There are different clinical phenotypes of ABO patients in clinical practice,and the bronchiectasis severity（modified Reiff score）and asthma severity are critical indicators in the classification of ABO patients,which provides a reference for clarifying the heterogeneity of clinical manifestations,improving management and prognosis of ABO patients.