The Influence Of Inhaled Corticosteroids On Airway Inflammation And Remodeling Of Different Types And Stages In Patients With Chronic Obstructive Pulmonary Disease

[ Objective] To observe the influence of inhaled fluticasone propionate (FP) on clinic symptom, quality of life, pulmonary function test, airway inflammation and remodeling of different types and stages patients with chronic obstructive pulmonary disease (COPD). At the same time, we can evaluate the role of induced sputum analysis on predicting therapeutic effect of inhaled cortico steroids (ICS) in patients with COPD in order to find the theoretical basement for the ICS treatment in patients with COPD.[ Methods]1. 66 acute COPD patients in exacerbation and 15 healthy control subjects were enrolled in this study. All the subjects accepted the test of pulmonary function and bronchodilatation. Record clinic symptom scores, quality of life scores, FEV₁ and FEV₁ percent predicted.2. Sputum induction and analysisAll the subjects were premedicated with 200 μg of inhaled salbutamol. Induction was performed using hypertonic saline (3%) aerosolised by compressed nebuliser for 15 20min. Entire sputum was collected in a plastic container. Select sputum and weigh sputum, then incubate with 4 × volume 0.1 % dithiothreitol (DTT) for 15min. Rock on bench rocker for 15 minutes, then mix with equal volume (to DTT) of phosphatebuffered saline (PBS) and rock for 5 minutes. Filter through 48|im nylon gauze. Centrifuge at 2000r/min for 10 minutes. The supernatant was separated and stored at -70°C for future measurements the concentrations of.JL-8 and MMP-9.The cell pellet re- suspended in lml PBS. Samples were discarded if squamous epithelial cells contamination was 20% or more. Total cell counts was determined in a haemocytometer . Make cell slides and Wright's staining. An overall differential cell counts on 400 nucleated non-squamous cells was performed by a examiner. 3. AH the patients were classified into two groups according to eosinophilic cell counts. Group A: bronchodilatation test was negative and sputum eosinophilic cell counts -^ 3%;Group B: neutrophil counts significant increasing, and sputum eosinophilic cell counts < 3%. According to FEV] percent predicted, divided into I , II ,111 stages. The patients were treated with FP 500jag twice a day, recording clinic symptom scores, quality of life scores, and redetecting pulmonary function. After the treatment induced sputum was analysed and measured the concentrations of IL-8, MMP-9. [Results)1. There were no significant differences in common data including sex, age, smoking history and pulmonary function test in A and B groups at baseline (P > 0.05 ) .2. The comparison of every maker between A and B groups in patients with COPD(1) Clinic symptom scores:There were no differences in clinic symptom scores in A and B groups before treatment(5.4±1.6 vs 5.3 + 1.8) (P>0.05) .But compared with healthy control group, the patient groups showed significant difference (P < 0.0] ) . After treatment, the patient groups in clinic symptom scores decreased (4.4 ± 1.3, 4.5 ± 1.5. respectively). There were significant difference between before treatment and after treatment (P < 0.05) .(2) Quality of life scores:There were no differences in clinic symptom scores in A and B groups before treatment(7.8±1.3 vs 8.0±l.l) (P>0.05) .But compared with healthycontrol group, the patient groups showed significant difference (P < 0.05) . After treatment, the patient groups on clinic symptom scores decreased (6.9 + ].2, 7.0± 1.1, respectively). There were significant difference between before treatment and after treatment (P<0.05) .(3) FEV,:After treatment FEV]increased from 1.28±0.12Lto 1.49±0.14L in the group A. There were significant difference in FEVj between before treatment and after treatment (P < 0.01) . However FEV] were unchanged after FP in the group B.(4) Sputum total and differential cell counts :The percentage of eosinophils were declined from 1 % to 3.5 % after treatment in the group A, there were significant difference between before treatment and after treatment (P<0.01) . But total cell counts and the percentage of neutrophils were unchanged after treatment. However cell counts, the percentage of neutrophils and eosinophils did not differ between the treatment period in the group B.(5) IL-8:The sputum concentration of IL-8 was significantly higher in the group B than in the group A and health control group(956±138 pg/ml, 596 ±115 pg/ml, 160±35 pg/ml, respectively). There were no significant difference between before treatment and after treatment in group A(P > 0.05). And There were no significant difference between before treatment and after treatment in group B (P>0.05) .(6) MMP-9:There were no differences in MMP-9 in A and B groups at base]ine(P > 0.05). There were no significant difference between before treatment and after treatment in group A (P > 0.05 ) . And There were no significant difference between before treatment and after treatment in group B (P > 0.05) . 3. Relationship between FEV]> the percentage of neutrophils and inflammatory mediatorThe sputum concentration of I.L-8 was negatively correlated with FEV] percent â– predicted (r = -0.72, P<0.01).The percentage of neutrophils was positively correlated with the sputum concentrationofJL-8(;-= 0.43,P< 0.01).4. The comparison of every maker among stages in patients with COPD(1) No significant differences was observed in clinic symptom scores ,quality of life scores, FEVj, sputum cell counts, the percentage of neutrophils and eosinophils, IL-8 and MMP-9 in the patients with COPD stage I (P > 0.05) .(2) Clinic symptom scores , quality of life scores and the percentage of eosinophils were decrease significantly and FEV] was increased after treatment in the stages II and III patients . There were significant difference between before treatment and after treatment (P < 0.05 ). However there were no difference in sputum cell counts, the percentage of neutrophils, IL-8 and MMP-9 between before treatment and after treatment (P > 0.05 ) .[Conclusion)l.One subdivision in the patients with COPD manifested neutrophilic airway inflammation, however the other subdivision showed eosinophilic inflammation. 2. IL-8 and MMP-9 played important roles in airway inflammation and airway remodeling.3.Short-time inhaled corticosteroids could improve pulmonary function and reduce eosinophilic inflammation in the eosinophilic infiltation in patients with COPD. But there were no significant role to neutrophilic airway inflammation, airway remodeling and clinical effect.4. Inhaled corticosteroids could produce a part of clinical effect in moderate and severe patients with COPD, however there was no significant role in mild patients with COPD.5.The eosinophil counts in induced sputum could become a predict maker to detect whether inhaled corticosteroids treat acute COPD patients in exacerbation effectively or not.