Effects Of Scoliosis On Lung Function And Development During Growth And Animal Experimental Studies

Background:Scoliosis is a three-dimensional deformity,which leads to thoracic deformity and serious appearance problems.In severe cases,it will lead to cardiopulmonary insufficiency.During the growth period,thoracic scoliosis will affect the growth and development of the thorax and lungs,resulting in the distortion of the costal joints and ribs,which causes the torsion of the costal-vertebro-sternal complex,resulting in the"convex side"and"concave side"of the hemithorax.The change of thoracic volume and the damage of lung function have a great impact on the development of thorax and lung in children,often accompanied by thoracic insufficiency syndrome（TIS）,which will eventually lead to respiratory failure and increased early mortality.Moreover,in clinical practice,it is found that the earlier and more severe the onset of scoliosis,the greater the impact on lung function and lung development.Our study is based on the regularity and universality of adolescent idiopathic scoliosis（AIS）to study the relationship between the severity of scoliosis and lung function.We also studied the changes of thoracic spine and lung function scoliosis postoperative,and discussed the complex relationship between spine and thoracic deformity and the relationship with lung function,which is helpful to improve the level of clinical intervention in the treatment of scoliosis.The beginning time of alveolization in human and rabbit is similar,so rabbit is a useful model to understand the lung development after human birth.A design-based stereological method was used to study the lung development of rabbits with scoliosis,laying a foundation for evaluating the effect of spinal deformity on lung development and potential treatment methods.Purpose:1.This study evaluates the relationship between the radiological parameters of AIS and the parameters of pulmonary function test（PFT）,and infers the degree of lung function damage according to the characteristics of the different radiological parameters in scoliosis.Find out the most relevant radiological parameters of lung function injury.2.The patients with scoliosis treated by posterior spinal fusion（PSF）were followed up for 2 years to study the relationship between the correction of scoliosis postoperative and the spontaneous correction of thoracic spine,as well as the changes of lung function.3.Unilateral rib tethering was performed on 4-week-old female New Zealand white rabbits to simulate spinal and thoracic deformities.To establish a rabbit model with early onset scoliosis（EOS）.At maturity,the changes of lung volume in vivo and in vitro were evaluated.A design-based stereological method was used to evaluate the quantitative evaluation of lung structure at the age of 24 weeks.Methods:1.Seventy-two AIS patients with right main thoracic curvature received PFT and radiological evaluation of spinal and thoracic deformities.Among them,the radiologic parameters include the main thoracic curve Cobb（MT-Cobb）,main thoracic curve flexibility index（MT-FI）,main thoracic curve top vertebra to rib ratio（MT-ABV-R）,main thoracic curve top vertebra offset（MT-AVT）,main thoracic curve rib protrusion（MT-RH）,thoracic kyphosis（TK）and main thoracic curve chest depth（MT-TD）.PFT parameters were selected as forced vital capacity（FVC）%predictive value and forced expiratory volume（FEV₁）%predictive value.Use simple and multiple linear regression methods to explain the correlation between radiology parameters and PFT parameters.According to the PFTs interpretation strategy of the American Thoracic Society（ATS）/European Respiratory Society（ERS）in 2005,we divided the whole cohort into groups,and compared the mean by using two-sample t-test or single-factor analysis of variance and Tukey multiple comparison method.2.PSF was performed on 44 AIS patients with right main thoracic curvature,and the radiological parameters of spine and thoracic spine and PFT parameters at preoperative,postoperative and 2-year follow-up were evaluated respectively.Radiological parameters include:MT-Cobb,TK,Height of thoracic vertebrae 1 to 12（T1-T12 height）,Rib-vertebra angle difference（RVAD）,MT-AVB-R,MT-RH,MT-TD,Left and right thorax height,Space available for lungs（SAL）,Thoracic anteroposterior diameter and Thoracic sagittal longitudinal diameter.PFT parameter selects FVC%predicted value and FEV₁%predicted value.Paired t test and Wilcoxon signed rank test were used to evaluate the difference between preoperative,postoperative and 2-year follow-up,p<0.05 was significant.Pearson correlation coefficient was used to evaluate the correlation between correction rates.3.New Zealand white rabbits at the age of 4 weeks were randomly divided into 2groups:early-onset scoliosis group（EOS group）（8 rabbits）;In the control group（7rats）,the model of scoliosis was made by right rib tethering after anesthesia at the age of 4 weeks.At the age of 4,10,16 and 24 weeks,CT examination and weight measurement were performed.After 24 weeks of anesthesia,venous blood was collected to monitor blood routine,as well as CT and 3D reconstruction.Thoracic and lung reconstruction was performed through MINICS software,and in vivo lung volume was measured.After deep anesthesia,all lungs were perfused and stored in situ through the inferior vena cava under the fixed inflation pressure of 20cm H₂O and the hydrostatic pressure of 30cm H₂O.The volume of lung and lung lobe is estimated by Cavalieri principle.Samples were taken by systematic uniform random sampling（SURS）method,and then stained with toluidine blue and lichen red after paraffin embedding.Microscopic examination,image acquisition and analysis,measurement and calculation of lung structure and morphology,comparison of lung parenchyma,non-parenchyma,volume of alveolus,alveolar duct,alveolar septum,thickness and surface area of alveolar septum,number of alveoli and average alveolar volume.The volume changes of vascular lumen,blood vessels and perivascular volume,blood vessel diameter,blood vessel wall thickness,perivascular tissue thickness and surface area changes of vascular endothelium were also compared to evaluate the changes of lung structure and morphology in EOS group.Results:1.FVC%predicted value was significantly negatively correlated with MT-Cobb（R²=0.648,p<0.001）;significantly negatively correlated with MT-RH（R²=0.522,p<0.001）;and MT-ABV-R has a significant negative correlation（R²=0.536,p<0.001）;it has a significant negative correlation with MT-AVT（R²=0.383,p<0.001）.Multiple regression analysis was performed with FVC%predicted as the dependent variable and MT-Cobb,MT-RH,MT-AVB-R and MT-AVT as independent variables.MT-Cobb,MT-RH,MT-AVB-R,and MT-AVT had a significant effect on the FVC%predicted（p<0.001）.The mean MT-Cobb in the 45 patients in the preoperative FVC impaired group was 76.71°.The mean MT-Cobb in the 27 patients with normal preoperative FVC was smaller at 52.03°（p<0.001）.Among other radiological parameters,the MT-AVT of the FVC impaired group was 52.29 mm,while that of the FVC normal group was 38.06 mm（p<0.001）.The mean value of MT-AVB-R in FVC impaired group was 2.91,and the mean value of MT-AVB-R in FVC normal group was 1.78（p<0.001）.The average value of MT-RH in the FVC impaired group was28.79 mm,and the average value in the FVC normal group was 16.22 mm（p<0.001）.According to the measured value of FEV₁,the severity of abnormal FEV₁was classified,and FEV₁was divided into three groups:normal group,mild to moderate lung impaired group,and severe lung impaired group,and MT-Cobb,MT-RH,MT-AVB-R and MT-AVT were also significantly different（p<0.001）.2.For the correction of spine,the mean MT-Cobb values were 58.70±1.86°,21.76±1.74°（correction rate of 64%）and 20.56±1.62°（correction rate of 66%）at preoperative,immediate and 2-year follow-up.The average TK preoperative was32.72±2.66°,the immediate postoperative TK was 20.55±1.60°（correction rate of13%）and the 2-year follow-up was 19.77±1.36°（correction rate of 19%）.The average height of T1-T12 was 234.16±3.85mm preoperative,257.07±4.33mm immediately postoperative（correction rate of 10%）and 260.86±4.17mm（correction rate of 12%）at 2-year follow-up.For thoracic correction,RVAD decreased from33.70±2.76°preoperative to 14.61±1.95°immediately postoperative（correction rate59%）,and decreased to 18.43%±2.17°at 2-year follow-up（correction rate 52%）.The average MT-RH was 22.04±1.34mm preoperative,decreased to 9.66±1.02mm immediately postoperative（correction rate of 58%）,and decreased to 6.09±1.14mm at2-year follow-up（correction rate of 76%）.MT-AVB-R decreased from 2.09±0.11preoperative to 1.61±0.09 immediately postoperative（correction rate 23%）and 1.52±0.55 at 2-year follow-up（correction rate 25%）.The above results showed that there was significant difference between the radiological parameters of the immediate postoperative and 2-year follow-up and the preoperative（p<0.001）.There is significant correlation between these radiological parameters.MT-Cobb and T1-T12are highly correlated（R²=0.524,p<0.001）,MT-Cobb and RVAD（R²=0.320,p<0.001）,MT-Cobb and MT-RH（R²=0.497,p<0.001）,MT-Cobb and MT-AVB-R（R²=0.356,p<0.001）.The lung function of 20 patients in the lung injury group（FVC%predictive<80%）was significantly improved after 2 years of follow-up compared with preoperative lung function.The average FVC%predictive was 61.32±17.42preoperative and 77.87±9.93 2-year follow-up（the correction rate was 40%）,p<0.001.The FEV₁%predictive was 65.22±20.53 pretoperative,and 78.68±10.32 after 2 years of follow-up（the correction rate was 34%）,p<0.05.3.After the New Zealand white rabbit model was established,the average Cobb angle gradually increased with the growth.The half chest symmetry ratio,torso rotation angle and spine rotation angle are positively correlated with Cobb’s.There was a negative correlation between body weight normalized total lung volume（TLV）and Cobb.The total lung volume and right lung volume（RLV）were significantly decreased in EOS group.In EOS group,the volume of right upper lobe（RUL）,right middle lobe（RML）and right lower lobe（RLL）decreased significantly.In the quantitative analysis of lung stereology,the volume of lung parenchyma and non-parenchyma in each lung lobe of EOS group decreased significantly;For alveolar volume,each lung lobe decreased significantly;For alveolar duct volume,the left lower lobe（LLL）,RUL,RML and RLL were significantly decreased;For alveolar septal volume,RUL,RML and RLL decreased significantly.For the area of alveolar septa,the lung lobes were significantly smaller;For the average alveolar septal thickness,the lung lobes were significantly thickened;For the number of alveoli,LLL,RUL,RML and RLL decreased significantly;For the mean alveolar volume,LLL and RML increased significantly,while the left upper lobe（LUL）decreased significantly;The average linear intercept length（Lm）in each lung lobe has no significant difference;In non-pulmonary parenchyma,only RML and RLL significantly decreased the volume of vascular lumen.The volume of blood vessels and perivascular tissues decreased significantly in the right lung lobes.For mean vessel diameter,RML and RLL decreased significantly,while LUL and LLL increased;For vascular endothelial surface area,LLL,RML and RLL were significantly reduced;For mean vessel thickness and mean perivascular tissue thickness,LUL and LLL were significantly thicker,while RUL,RLL and RML were significantly thinner.Conclusion:1.The progress of AIS can increase the degree of thoracic deformity,thus increasing the risk of lung function injury.In addition,the changes of lung function can be well predicted according to the radiological parameters of scoliosis.2.PSF can correct scoliosis and thoracic deformity to a certain extent.The higher the correction rate of Cobb angle,the higher the correction rate of MT-RH,T11-T12height,MT-AVB-R and RVAD,and there is a positive correlation between the two.For changes in lung function,correction of spinal deformities can improve lung function,but some patients cannot return to normal lung function（FVC%predictive value≤80%）.3.The lung characteristics of the EOS rabbit model in adulthood are that the lung volume is significantly reduced,the process of alveolization is weakened,the alveolar septa are thickened,and the blood vessels are further reconstructed,and scoliosis has an impact on the development of the whole thorax and lung,but the impact on the concave（right）lung is significantly greater than that on the convex（left）lung.