Effects Of Bronchial Thermoplasty On Airway Responsiveness And Airway Remodeling In Patients With Severe Asthma And Its Correlation With Clinical Effectiveness

BackgroundThe incidence rate of asthma has been increasing in recent years.Severe asthma is the main cause of disability and death of asthma,which is often accompanied by severe respiratory symptoms,persistent airway hyperresponsiveness,irreversible airflow restriction and severe airway remodeling.Bronchial thermoplasty(BT)is a non-pharmacological therapy technology applied in the field of asthma.It can ablate airway tissue to achieve the purpose of treatment using radio-frequency energy.BT has shown good safety and effectiveness in clinical application,but the potential mechanism is not clear at present.ObjectiveTo investigate the effect of BT on airway responsiveness and airway remodeling in patients with severe asthma,and to study the correlation between airway responsiveness and airway remodeling and the clinical efficacy of BT.MethodsFrom January to September 2019,the adult severe asthma patients were recruited who were treated in the Department of respiratory and critical care medicine of China Japan Friendship Hospital to receive BT treatment.The treatment was performed over three sessions separated by at least 3 weeks interval.The right lower lobe,the left lower lobe and the bilateral upper lobes were treated respectively.In this study,patients' self-control method was used.The timepoint before the first BT treatment was defined as pre-treatment group,and the timepoint before the third treatment was defined as post-treatment group.Local airway provocation test was used to detect the airway responsiveness of the lateral basal segment of the left lower lobe of the lung before and after treatment,and to compare the changes of airway contraction rate and degree after acetylcholine provocation.Histological staining was used to detect the airway structure of the posterior basal segment of the left lower lobe of the lung before and after treatment,and to compare the mass ratio of airway smooth muscle(ASM),the mass ratio of collagen,the thickness of basement membrane and the thickness of epithelial cell layer in the biopsy tissue of airway wall.Transmission electron microscopy(TEM)was used to detect the changes of ASM subcellular structure in the posterior basal segment of the left lower lobe of the lung before and after treatment.Contraction related structures include dense body,dense spot and thick and thin muscle filaments,synthesis related structures include endoplasmic reticulum and vesicular system,and cell metabolism structure is represented by mitochondrion.The airway and systemic inflammation levels before and after treatment were analysis by detecting cell classification of bronchoalveolar lavage fluid(HALF)from the left lower lobe and peripheral blood,and total serum IgE.The clinical effectiveness of the patients before and after treatment were evaluating by analyzing the changes of asthma control test(ACT),mini asthma quality of life questionnaire(miniAQLQ)and the forced expiratory volume in 1 second expressed as percent predicted(FEV1%pred).ResultsIn this study,11 patients with severe asthma who met the inclusion criteria were enrolled for BT treatment,including 3 males and 8 females.Effects of-BT compared with pre-treatment group:airway contraction rate and maximal airway contraction rate decreased significantly[(0.019±0.008)%/s vs(0.035±0.008)%/s,(0.449± 0.183)%vs(0.687±0.109)%,both P<0.05];the mass of ASM and collagen in airway wall was significantly decreased[(9.8±2.5)%vs(25.8±7.7)%,(12.9±4.0)%vs(17.4±5.6)%,both P<0.05],while basement membrane thickness had no significant difference(P>0.05);the proportion of contractile structure area was decreased significantly,the proportion of vesicle area and synthetic structure area were increased significantly,and the contractile/synthetic ratio was decreased significantly[(85.9±3.4)%vs(89.0±2.5)%,(4.1±1.7)%vs(2.5±1.1)%,(11.3±3.0)%vs(7.9±1.6)%,(8.2±2.8)%vs(11.7±2.5)%,all P<0.05],while the density of dense body,proportion of circumference of dense spot,proportion of endoplasmic reticulum area,mitochondrial area,mitochondrial density and proportion of mitochondrial area had no significant differences(all P>0.05);the percentage of eosinophils in BALF and peripheral blood,and total serum IgE had no significant differences(all P>0.05);ACT score and miniAQLQ score were significantly increased[(23.1±1.8)vs(13.8±6.2)polints,(5.3±13)vs(3.6±1.5)points,both P<0.05],while FEV1%pred had no statistical difference(P>0.05).The proportion of ASM was positively correlated with the rate of airway contraction and the maximum rate of airway contraction(r=0.666,r=0.482,both P<0.05),while ASM systolic/synthetic ratio was positively correlated with airway systolic rate(r=0.510,P<0.05).The airway contraction rate was negatively correlated with ACT score(r=-0.558,P<0.05),the mass of ASM was negatively correlated with ACT score and miniAQLQ score(r=-0.712,r=-0.557,both P<0.05),while the mass of collagen was negatively correlated with ACT score and miniAQLQ score(r=-0.549,r=-0.639,both P<0.05),while ASM systolic/synthetic ratio was negatively correlated with ACT score(r=-0.490,P<0.05).ConclusionsBT treatment can reduce airway responsiveness and improve airway remodeling in patients with severe asthma,and the decrease of airway responsiveness and the improvement of airway remodeling are related to the clinical efficacy of BT.