Clinical Characteristics And Features Of Airway Inflammation Of Difficult-to-treat-asthma In Adult

[Background]Clinically,there are approximately 5%-10%asthma patients whose asthma still may not be effectively controlled after receiving treatment regimens recommended for gradeâ…£patients by the Global Initiative for Asthma(GINA).This type of asthma is called difficult-to-treat-asthma(DTA).Although the number of patients with DTA is low,they consume about 80%of medical resources related to asthma.DTA is a type of asthma that is persistent and associated with a high risk of death.Therefore,DTA is a huge challenge for clinicians.[Objective]Patients with either DTA or Well-controlled asthma were included in this study.Clinical data concerning these two groups of patients was collected.Serum inflammatory markers and fractional exhaled nitric oxide(F_ENO) levels were measured.Differences in family history,allergen skin test and concurrent allergic disease were analyzed between patients with DTA and those with Well-controlled asthma. Differences and correlation in inflammatory markers were analyzed between the two groups.Clinical characteristics and features of airway inflammation of DTA were investigated.In addition,effects of inhaled corticosteroids(ICS) on the levels of total serum IgE(TsIgE),TNF-αand F_ENO in asthma patients were examined.[Methods]Fifty-eight sporadic cases of asthma(n=30 for DAT,n = 28 for Well-controlled asthma) from asthma specialty clinics in Zhongshan Hospital included in this study.Clinical data of patients were recorded for classification of the level of asthma control.ICS-based treatment regimens were administered according to the GINA 2006.During the 12-month follow-up,lung function was detected and the level of asthma control was evaluated.The levels of TsIgE and TNF-αwere detected at both the starting point and end point of follow-up.F_ENO was measured at end point.Differences in clinical data,treatment regimens,response to treatment(evaluated by FEV₁ and ACT scores) between patients with DAT and those with Well-controlled asthma were analyzed.Investigations on correlation among the levels of TsIgE,TNF-αand F_ENO were performed.Differences in the levels of TsIgE,TNF-αand F_ENO between DTA patients and those with Well-controlled asthma were analyzed.A P value of less than 0.05 was defined as statistically significant for differences or correlation. [Results]A total of 58 patients completed follow-up:30 patients(n = 15 for male and female,respectively) in the DTA group and 28 patients (15 men and 13 women) in the Well-controlled asthma group.Compared with the Well-controlled asthma group,the DTA group had a longer course of asthma,a greater mean age(56.4±8.9 years vs.45.6±14.3),and a higher BMI and proportion of smokers.There were no differences in onset age,family history and biparental history of asthma between the two groups.Although the total positive rate of allergen skin prick test was higher in the DTA group than in the Well-controlled asthma group,there were no significant differences in concurrent allergic disease between these two groups.Patients with DTA received treatment regimens for gradeâ…£andâ…¤,and all failed to response to degraded treatment regimens. In this group,during the twelve-month follow-up,14 patients suffered from more than 2 times(mean:1.33 times/person) of aggravation of asthma.In the Well-controlled asthma group,pharmaceutical treatments were completely discontinued in 3 patients among 14 patients whose treatment regimens were degraded,and during the twelve-month follow-up,3 patients suffered from aggravation of asthma.FEV₁ and ACT scores at starting point and end point were significantly lower in the DTA group than in the Well-controlled asthma group.In the DTA group, the mean daily dose of ICS at end point was comparable to that at starting point;no significant improvements in FEV₁ were seen;inconsistent with improvements of FEV₁,ACT scores at end point were significantly increased(3.53±4.82 points,P=0.000) when compared with those at starting point.TNF-αlevels at both starting point and end point were higher in the DTA group than in the Well-controlled asthma group(P＜0.05).In both groups,TNF-αlevels at end point were significantly decreased as compared with respective levels at starting point.At starting point,the DTA group had lower TsIgE levels with the differences reaching statistical significance(P＜0.05)and lower blood EOS count but without the differences reaching statistical significance(P＜0.05),as compared with the Well-controlled asthma group.TsIgE levels at end point did not differ significantly between the two groups but were substantially decreased as compared with respective levels at starting point.FeNO levels were lower in the DTA group than in the Well-controlled asthma group,with the differences reaching statistical significance(P＜0.05).In the DTA group,there was a linear correlation between FeNO and TsIgE(r=0.711,P=0.000) but no correlation between TNF-αand TsIgE;total FeNO was linearly correlated with TsIgE(r=0.597,P=0.000).[Conclusion]Compared with those with Well-controlled asthma, patients with DTA had a longer course of asthma,a greater mean age and a higher BMI.In the DTA group,ACT scores improved better than FEV₁ after treatment.Compared with those with Well-controlled asthma, patients with DTA showed higher serum TNF-αlevels but lower TsIgE levels.ICS-based treatment regimens led to significantly decreased serum levels of TNF-αand TsIgE.F_ENO levels were lower in patients with DTA than in those with Well-controlled asthma.F_ENO was positively correlated with TsIgE.