Quantitative Computed Tomography Measurements Of Emphysema And Computer Quantification Of "Angle Of Collapse" On MEFV Curve For Diagnosing Asthma-chronic Obstructive Pulmonary Disease Overlap Syndrome

BackgroundA considerable proportion of patients with chronic airway disease share the clinical features of both asthma and chronic obstructive pulmonary disease. In 2014, GOLD and GINA science committees jointly issued the chapter of "Diagnosis Of Diseases Of Chronic Airflow Limitation:Asthma, COPD and Asthma-COPD Overlap Syndrome" the concept of ACOS was formally proposed in GINA/GOLD guidelines. However, GINA and GOLD guidelines did not make a precise definition of ACOS, the diagnostic criteria of ACOS remained unclear. In clinical practice, based on detailed history and physical examination, it would be very helpful to establish the diagnosis of ACOS if an objective indicator could contribute to the differential diagnosis of asthma and COPD.The pathology of asthma differs from COPD. The pathology of COPD includs airway disease and emphysema, whereas typical asthma is considered to be predominantly an airway disease, generally without emphysema. The pathophysiological mechanism of expiratory airflow limitation is also different in asthma and COPD patients. In asthma patients, expiratory airflow limitation is mainly due to airway obstruction, whereas in COPD patients, it is due to both airway obstruction and airway collapse. For those who have been definitely diagnosed with asthma, if there are objective evidences of the presence of emphysema, the diagnosis of ACOS might be established.Quantitative computed tomography has made repeated and non-invasive measurements of emphysema in the lungs possible. The decrease of elastic support of small airway lead to airway collapse in emphysema during forced expiration. In maximal expiratory flow-volume curve, emphysema often showed a sharp angulation, which was called " angle of collapse, AC". Ths sharp AC was considered to be an indicator of emphysema.In this study, we tried to use relatively large sample size case-control study to investigate the value of quantitative CT emphysema index and AC in the diagnosis of ACOS. This study was divided into two parts.Part One:Quantitative computed tomography measurements of emphysema for diagnosing asthma-chronic obstructive pulmonary disease overlap syndromeObjectiveThe aim of this part was to compare the emphysema index (EI) between normal, asthmatic and COPD patients, and investigate the value of quantitative CT measurements of emphysema in the diagnosis of ACOSMethodsThis study was a cross-sectional case-control study. We recruited 404 participants: 156 with stable asthma; 125 with stable COPD; and 128 normal control participants. All participants completed standardized questionnaires and underwent pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT). The% LAA-950 (emphysema index) was measured with the airway inspector software using the DICOM data of chest CT (1 mm slice thickness). The emphysema measurements was compared in asthmatic patients, COPD patients and controls. The cut-off point of high-EI was determined as 3 standard deviations above the mean in controls. The asthmatic patients were divided into high-and low-EI groups based on the cut-off point of high EL The characteristics of asthmatic patients with high- and low-EI was investigated.Results1. The mean El of asthmatic patients was 6.19±6.79%, which was significantly higher than normal (2.79±2.37%,p< 0.01) and lower than COPD patients (15.84±11.90%, P< 0.01).2. The mean plus 3 standard deviation of EI,9.9%, was used as the cut-off point of high EI. In asthmatic patients,21.2%(31/151) of patients had high EI.3. In comparison with asthmatic patients with low EI, those with high EI were significantly older, more likely to be male, had higher pack-years of smoking, had more upper-zone-predominant emphysema, and had greater airflow limitation (P<0.05). There was no significant difference in sex ratios, pack-years smoking, extent of airflow limitation, El, or emphysema distribution between asthmatic patients with high EI and COPD patients (P>0.05).Conclusions1. Those asthmatic patients with high-EI, who were determined by cut-off point of EI=9.9%, shared similar clinical characteristics with COPD patients, and fulfilled the diagnosis of ACOS.2. Emphysema index of quantitative CT could become a part of diagnostic criteria of ACOS.Part Two:Computer quantification of "angle of collapse" on maximum expiratory flow volume (MEFV) curve for diagnosing ACOSObjectiveThe aim of this part was to investigate the relationship between "angle of collapse, AC" on maximum expiratory flow volume (MEFV) curve and emphysema, and investigate the diagnostic value of AC in ACOS.MethodsThis study was a cross-sectional case-control study. We recruited 404 participants: 156 with stable asthma; 125 with stable COPD; and 392 normal control participants. Patients with asthma or COPD underwent chest high-resolution CT scan and pulmonary function tests, normal controls underwent pulmonary function tests. The computer quantification of AC was measured with Curvesnap and Matlab software. The %LAA-950 (emphysema index) was measured with the airway inspector software. We investigated the correlation between AC and age in normal controls, and the difference of AC between high-EI and low-EI patients with airflow limitation. Receiver-operating characteristic (ROC) analyses were conducted to investigate capacity of AC for diagnosing high-EI among chronic airway disease patients. The diagnostic value of AC for ACOS patients among asthma patients was verified.Results1. The AC of asthmatic patients was 145.45±13.23, which was significantly higher than COPD patients (130.67±14.01, P<0.01) and lower than normal controls (161.1±9.2°,P<0.01).2. The AC was significantly negative correlated with emphysema index (R=-0.67, P＜0.001) in patients with chronic airway inflammatory disease. In patients with aiflow limitation, the AC of those who had high El was significantly lower than those who had low EI.3. The analysis of area under the curve of ROC curve showed that diagnostic value of AC for high EI was superior to other lung function parameters, including FEV1.0%, FVC% and VC%. The best cut-off of AC for diagnosing high EI was 129.19°, when AC<129.19° was used as criteria of high EI, a sensitivity of 65.63% and a specificity of 96.64% was found in asthmatic patients.Conclusions1. The computer quantification of airway collapse on MEFV correlate well with quantitative CT measurements of emphysema. Using AC<129.19° as cut-off point, a sensitivity of 65.63% and a specificity of 96.64% was found in asthmatic patients.2. Computer quantification of "angle of collapse" on MEFV curve may become a surrogate indicator for the diagnosis of emphysema, which may help to the diagnosis of ACOS.