The Evaluation And Clinical Research Of The Frequent Exacerbator Phenotype In Patients With Chronic Obstructive Pulmonary Disease

Objective:1. To compare clinical differences between the frequent exacerbator phenotype and non-frequent exacerbator phenotype in patients with chronic obstructive pulmonary disease(COPD), and discuss clinical characteristics of different phenotypes in general clinical data,pulmonary function, inflammation, oxidative stress and immunological function.2. To discuss the correlation of the number of hospitalized exacerbation in previous year with general clinical data,pulmonary function,inflammation,oxidative stress and immunological function.Methods:1. This is a clinical prospective case and control study. We designed two different groups:COPD group, normal group, and formulate the standards of enrollment and elimination. The diagnosis of COPD refers to the diagnostic and treatment guide in GLOD (Revised 2011). The normal group comes from helathy people. All inpatients and outpatients meetting standard from December 2013 to March 2015 are included in the study.We collected general clinical data(gender, age, smoking index, body mass index),pulmonary function (FEV1/FVC, FEV1%Pre, RV/TLC), airway inflammation and oxidative stress cytokines (IL-6、8-iso-PG) of all objects,additional medical history and symptom information(hospitalized exacerbation rate in previous year,cough and sputum years,symptom score and MMRC),system inflammation (ESR、CRP、PCT、Fib) and immunological index(IgG、 IgM、IgA、CD3、CD4+、CD8+、CD4+/CD8+、NK、CIK、B cell).2. We divided the objects of COPD into two phenotypes depending on the rate of hospitalized exacerbation in previous year(exclude current event):frequent exacerbator phenotype(2 or more hospitalized exacerbation in previous year) and non-frequent exacerbator phenotype(0 or 1 hospitalized exacerbation in previous year).We compared general clinical data,pulmonary function,inflammationl,oxidative stress and immunological function of the two phenotypes and discuss the correlation of hospitalized exacerbation times in previous year with above indexes. Results:1. The comparison of general clinical data,pulmonary function,airwa y inflammation and oxidative stress bettween COPD and normal group(1) General clinical data:62 COPD sbjects were enrolled in this study,49 cases are male(79.03%),13 cases are female(20.97%). Age of COPD group is 68.26±9.33 (rang from 45 to 80), There are 45 smokers in COPD group (72.58%), smoking index is 528.31±433.2 piece-years; In COPD group,31 cares are pulmonary function 2 grade(50.00%),23 cases are pulmonary function 3 grade(37.10%),8 cases are pulmonary function 4 grade(12.9%).12 normal sbjects were enrolled in normal group,12 cases are male(80%), 3 cases are female(20%). Age of normal group is 65.93±9.15 (rang from 51 to 84), There are 11 smokers in normal group (73.33%), smoking index is 528. 31±433.2 piece-years; 11 smokers in normal group (91.67%), smoking index is 3 40.00±273.99 piece-years.The age of COPD group and normal group is 68.26±9.33,65.93±9.15 res pectively, and has no statistical difference (t=0.869, P=0.388). The smoking ind ex of COPD group and normal group is 528.31±433.2,340.00±273.99 respectiv ely, and has statistical difference (t=2.101, P=0.043). BMI of COPD group and normal group is 22.38±2.71,24.51±1.7 respectively, and has significant statist ical difference (t=-2.898, P=0.005).(2) pulmonary function:The FEV1/FVC of COPD group and normal group is 52.78±12.57%,86.07±5.39% respectively, and has significant statistical diffe rence (t=-15.726,P=0.000). The FEV1%Pre of COPD group and normal group i s 49.89±15.87%,105.29±20.45% respectively, and has significant statistical differ ence (t=-11.446,P=0.000). The RV/TLC of COPD group and normal group is 4 8.69±8.6%,40.9±7.45% respectively, and has significant statistical difference (t=3. 225,P=0.002).(3) airway inflammation and oxidative stress:The EBC IL-6 concentration of COPD group and normal group is 7.57±2.24,4.13±1.44 respectively, and has significant statistical difference (t=7.332,P=0.000).The EBC 8-iso-PG concen tration of COPD group and normal group is 15.73±7.77,7.61±6.31 respectively, and also has significant statistical difference (t=3.75,P=0.000).2. The comparison of general clinical data,pulmonary function,inflammati on,oxidative stress and immunological function bettween frequent exacerbator p henotype and non-frequent exacerbator phenotype in COPD(1) General clinical data:62 COPD objects had been divided into two phenotypes:frequent exacerbator phenotype(32 cases,the number of hospitalized exacerbation in previous year is 2-8) and non-frequent exacerbator phenotype(30 cases,the number of hospitalized exacerbation in previous yea is 0-1).the number of hospitalized exacerbation in previous year is 3.47±1.61,0. 63±0.49 respectively, and has significant statistical difference (t= 9.525,P=0.00 0),the age is 70.84±7.94,65.5±10.03 respectively, and has statistical differenc e (t=2.334,P=0.023),the BMI is 21.53±2.46,23.29±2.71 respectively, and has significant statistical difference (t=-2.681, P=0.009),the smoking index is 618. 44±421.76,432.17±431.34 respectively, and has no statistical difference (t=1. 719, P=0.091),time of cough and sputum is 9.66±4.94,5.23±2.92 respectively, and has significant statistical difference (t=4.253,P=0.000),the symptom score i s 5.63±1.31,3.87±1.07 respectively, and has significant statistical difference (t =5.747, P=0.000),the MMRC is 2.38±0.71,1.37±0.61 respectively, and has si gnificant statistical difference (t=5.974, P=0.000).(2) Pulmonary function:FEV1/FVC is 47.27±13.69,58.65±7.93 respectivel y, and has significant statistical difference (t=-4.036,P=0.000),the FEV1%Pre is 43.53±16.41%,56.67±12.24% respectively, and has significant statistical differe nce (t=-3.557,P=0.001),the RV/TLC is 50.44±9.79,46.82±6.79 respectively, an d has no statistical difference (t=1.684,P=0.097).(3) Inflammation and oxidative stress:CRP has statistical difference (z=-2. 226,P=0.026),the Fib is 3.58±0.97,3.15±0.59 respectively, and has statistical difference (t=2.116,P=0.039),the PCT has no statistical difference(z=-0.543,P =0.587),the ESR is 9.16±6.73,6.87±6.09 respectively, and has no statistical di fference(t= 1.401,P=0.166),the EBC IL-6 concentration is 8.55±1.92,6.51±2.10 respectively, and has significant statistical difference (P=0.000),the EBC 8-iso-PG concentration is 19.11±6.73,12.13±7.25 respectively, and has significant st atistical difference(P=0.000).(4) Immunological function:IgG is 9.48±2.49,10.43±2,56 respectively, and has no statistical difference(t=-1.481,P=0.144),the IgM is 1.06+0.57,1.34±0.75 respectively, and has no statistical difference(t=-1.64,P=0.107),the IgA is 1.15± 0.72,1.43±0.55 respectively, and has no statistical difference(t=-1.77,P=0.082),the CD3±is 69.42±10.25,65.51±8.42 respectively, and has no statistical difference (t=1.632,P=0.108),the CD4±is 33.48±10.02,37.86±5.84 respectively, and has statistical difference (t=-2.116,P=0.039),the CD8±is 35.58±11.64,30.27±9.37 respectively, and has no statistical difference (t=1.97,P=0.053),the CD4+/CD8+has significant statistical difference(Z=-2.726,p=0.006),the NK is 17.83+9.68, 18.59±7.19 respectively, and has no statistical difference (t=-1.652,P=0.104),the CIK is 5.41±4.16,5.82±3.88 respectively, and has no statistical difference (t=-0.402,P=0.689),the B cell is 6.77±3.32,8.90±3.60 respectively, and has statistical difference (t=-2.425,P=0.018).3. The correlation of the number of hospitalized exacerbation in previous year with general clinical data,pulmonary function,inflammationl,Oxidative stress and immunological function(1) general clinical data:The number of hospitalized exacerbation in previous year is positively correlated with age(r=0.342, p=0.007),time of cough and sputum (r=0.58, p=0.000),MMRC(r=0.628, p=0.000), symptom score (r=0.718, p =0.000),and negatively co-rrelated with BMI(r=-0.425, p=0.001).There is no correlation between the number of hospitalized exacerbation in previous year and smoking index(r=0.179, p=0.163).(2) Pulmonary function:The number of hospitalized exacerbation in previous year is negatively co-rrelated with FEV1/FVC(r=-0.477, p=0.000)、 FEV1%Pre(r=-0.476,p=0.000).There is no correlation between the number of hospitalized exacerbation in previous year and RV/TLC(r=0.085, p=0.513).(3) Inflammationl and oxidative stress:The number of hospitalized exacerbation in previous year is positively correlated with CRP(r=0.397, P=0.001),Fib(r=0.445, P=0.000),IL-6(r=0.529, P=0.000),8-iso-PG(r=0.611, P=0.000),There is no correlation between the number of hospitalized exacerbation in previous year and ESR(r=.163, P=0.205)、PCT(r=0.062, P=0.633).(4) Immunological function:The number of hospitalized exacerbation in previous year is negatively correlated with IgA(r=-0.56, P=0.000), CD4+(r=-0.265, P=0.038)、 B(r=-0.334, P=0.008), There is no correlation between the number of hospitalized exacerbation in previous year and IgG(r=-0.165, P=0.201)、IgM(r=-0.255, P=0.055)、 CD3+(r=0.112, P=0.388)、CD8+(r=0.153,P=0.234)、CD4+/CD8+(r=-0.242, P=0.058)、NK(r=-0.029, P=0.824)、CIK(r=-0.083, P=0.522). Conclusions:1. Smoking index in COPD patients are higher than in normal gr oup.Body mass index and pulmonary function in COPD patients are significan tly lowwer than in normal group.Airway inflammation and oxidative stress in COPD patients may be higher than in normal group.2. There is differences between the frequent exacerbator phenotype and non-frequent exacerbator phenotype in general clinical data,pulmonary function,inflammation,oxidative stress and immunological function in COPD. Compared with non-frequent exacerbator phenotype,frequent exacerbator phenotype has higher age,time of cough and sputum,symptom score,MMRC, system inflammation,airway inflammation and oxidative stress,lower BMI, more severe airway limitation and poorer immunological function.3. The patients of frequent exacerbator phenotype in COPD is a group of special patients worthy of clinical research and particular attention.Seeking effectively individualized treatment and improve the prognosis of such patients is needed.4. The number of hospitalized exacerbation in previous year is positively correlated with age,time of cough and sputum,MMRC,symptom score,CRP, Fib,IL-6, 8-iso-PG,and negatively correlated with BMI,FEV1/FVC,FEV1%Pre, IgA, CD4+,B cell.There is no correlation between the number of hospitalized exacerbation in previous year and smoking index,RV/TLC,ESR,PCT,IgG, IgM,CD3+, CD8+, CD4+/CD8+,NK and CIK.5. There is better correlation between the number of hospitalized exacerbation in previous year and multiple clinical indexes (age, BMI,time of cough and sputum,symptom core,MMRC,pulmonary function,inflammation and oxidative stress and immunological function) in COPD patients,illuminating that the number of hospitalized exacerbation in previous year has important guiding significance in reflecting whole condition and disease severity.6. Primitively diagnosis clinical phenotypes of COPD according to the number of hospitalized exacerbation in previous year is simple and feasible,and is worthy of clinical application.