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BACKGROUND: A recent study demonstrated a significant correlation between bronchial biopsy airway remodeling and quantitative computed tomography looking at bronchial wall thickness. OBJECTIVE: To identify clinical associations with bronchial wall thickness in moderate to severe asthma. METHODS: Ninety-two respiratory physician-diagnosed Global Initiative for Asthma-defined patients with moderate to severe asthma were included in this retrospective cohort study. Blinded to all clinical data, 2 senior thoracic radiologists independently measured airway lumen and total airway area at 4 different bronchopulmonary segments using high-resolution computed tomography imaging. We calculated adjusted odds ratios with regard to the association of bronchial wall thickness with spirometry, oscillometry, exacerbations, and nasal polyps. RESULTS: The pooled analysis for all 4 bronchopulmonary segments showed that an area under reactance curve greater than or equal to 1.0 kPa/L, an R5-R20 ratio (resistance heterogeneity between 5 and 20 Hz divided by total resistance [R5]) of 25% or more, having 2 or more exacerbations per year, and presence of nasal polyposis exhibited adjusted odds ratios of 3.54 (95% CI, 1.22-10.32), 2.89 (95% CI, 1.03-8.05), 4.17 (95% CI, 1.25-13.90), and 9.85 (95% CI, 2.33-41.74), respectively, in their association with a wall area thickness of 50% or more. These translated into a respective 72%, 65%, 76%, and 90% increased likelihood for a wall area thickness of 50% or more. CONCLUSIONS: Bronchial wall thickness is associated with peripheral airways resistance and reactance, severe exacerbations, and nasal polyposis in persistent asthma.

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Background and Purpose: Considering the possible role of fungal sensitization in the treatment of resistant asthma, which may lead to the remodeling of bronchial structure, we theorized that itraconazole could result in better control of asthma. In this regard, this study aimed to compare the effects of itraconazole and prednisolone (routinely prescribed) on clinical, structural, and biomarker findings of the remodeling of asthma. Materials and Methods: This double-blind controlled randomized clinical trial was performed on 70 adult patients suffering from severe persistent asthma. The intervention group received 200 mg of itraconazole per day, and the control group received 10 mg of prednisolone per day, for 32 weeks, in addition to the classic treatment of asthma. The subjects were randomly divided into two groups, and assigned by sealed envelope. Blinding was performed by repacking the drug in a similar container. Primary outcomes were asthma control test score, fibroblast growth factor 2, and wall area percentage on RB1 bronchus measured by computed tomography. The outcomes were compared in subjects classified as allergic, eosinophilic, T2 low asthma, and four types of inflammatory cell classification in sputum. Results: Seventy subjects finished the 32-week trial (35 subjects in each group). Baseline data did not show significant differences between groups. A comparison of asthma variants showed significantly more severe cough and dyspnea in the allergic variant and higher spirometry results in T2-low asthma. Sputum cytology revealed a mixed pattern as the most frequent type (47%). After the trial, two groups improved in many parameters; however, FGF-2 improved more significantly by itraconazole (4.66±16.92 decreased to 1.14±2.98), and FEV1/FVC was significantly higher in the itraconazole group, compared to the control group. These results did not change in terms of asthma variants and sputum classification. Conclusion: Itraconazole was superior to prednisolone in the treatment of many clinical and spirometry aspects in severe persistent asthma.

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Primary pulmonary venous malformation is rare and usually presents as single or multiple round masses or nodules. Here, we present the first report of a case of venous malformation presenting as Mauritia arabica-like bronchial wall thickness that was initially misdiagnosed as bronchiectasis. A Chinese man in his late 20s presented complaining of hemoptysis for 10 days. Computed tomography demonstrated bronchiectasis and M. arabica-like bronchial wall thickening in the left lower lobe. He was unresponsive to medical treatment for bronchiectasis and underwent thoracoscopic left lower lobectomy. Histopathological examination revealed venous malformation around the bronchial walls with no bronchiectasis. Venous malformation should be considered in the differential diagnosis of bronchiectasis, especially in patients with the following triad of signs: no response to antibiotics, M. arabica-like bronchial wall thickness, and normal accompanying arteries.

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Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma.

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Structural changes to airway morphology, such as increased bronchial wall thickness (BWT) and airway wall area, are cardinal features of chronic obstructive pulmonary disease (COPD). Ferrets are a recently established animal model uniquely exhibiting similar clinical and pathological characteristics of COPD as humans, including chronic bronchitis. Our objective was to develop a microcomputed tomography (µCT) method for evaluating structural changes to the airways in ferrets and assess whether the effects of smoking induce changes consistent with chronic bronchitis in humans. Ferrets were exposed to mainstream cigarette smoke or air control twice daily for 6 mo. µCT was conducted in vivo at 6 mo; a longitudinal cohort was imaged monthly. Manual measurements of BWT, luminal diameter (LD), and BWT-to-LD ratio (BWT/LD) were conducted and confirmed by a semiautomated algorithm. The square root of bronchial wall area (√WA) versus luminal perimeter was determined on an individual ferret basis. Smoke-exposed ferrets reproducibly demonstrated 34% increased BWT (P < 0.001) along with increased LD and BWT/LD versus air controls. Regression indicated that the effect of smoking on BWT persisted despite controlling for covariates. Semiautomated measurements replicated findings. √WA for the theoretical median airway luminal perimeter of 4 mm (Pi4) was elevated 4.4% in smoke-exposed ferrets (P = 0.015). Increased BWT and Pi4 developed steadily over time. µCT-based airway measurements in ferrets are feasible and reproducible. Smoke-exposed ferrets develop increased BWT and Pi4, changes similar to humans with chronic bronchitis. µCT can be used as a significant translational platform to measure dynamic airway morphological changes.

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Objective: To explore the dynamic variation trend of bronchial wall thickness (BWT) in severely burned patients combined with inhalation injury, and to determine the value of BWT to prognosis of patients. Methods: Forty-three severely burned patients with inhalation injury hospitalized in Intensive Burn Department of the Affiliated Hospital of Nankai University (Tianjin No.4 Hospital) from July to November 2016, conforming to the study criteria, were divided into survival group (n=27) and death group (n=16) according to the prognosis of patients within 14 days after admission. All patients underwent fiberoptic bronchoscopy and inhalation injury rating based on abbreviated injury scale at admission. High resolution CT examination was performed in patients of two groups at admission and 24 h post admission, 3, 7, and 14 d post admission to measure the BWT of right superior lobar bronchus trunk opening. Receiver operating characteristic curves of rating of inhalation damage at admission and BWT at admission were drawn to evaluate the predictive value for death of 43 patients. Data were processed with chi-square test, independent sample t test, Wilcoxon rank sum test, analysis of variance for repeated measurement and least-significant difference-t test. Results: (1) The numbers of patients rated as 0, 1, 2, 3, and 4 grade for inhalation injury in survival group and death group were 0, 19, 6, 2, and 0, and 0, 2, 7, 7, and 0, respectively. There were statistically significant differences between the two groups (Z=-3.79, P<0.01). (2) BWT of patients in death group at admission and 24 h post admission, 3, 7, and 14 d post admission was respectively (2.72±0.26), (3.18±0.22), (2.98±0.18), (2.29±0.17), and (1.45±0.21) mm, which was significantly larger than (2.24±0.15), (2.49±0.15), (1.51±0.17), (1.04±0.16), and (1.01±0.13) mm in survival group (t=7.55, 12.14, 27.11, 19.99, 7.11, P<0.01). BWT of patients in survival group and death group at 24 h post admission, 3, 7, and 14 d post admission showed statistically significant difference when compared with that at admission within the corresponding group (t=5.97, 16.63, 28.21, 38.57, 5.34, 3.31, 4.39, 6.48, P<0.01). BWT of patients in survival group and death group on 3, 7, and 14 d post admission was significantly smaller than that at 24 h post admission within the corresponding group (t=22.27, 34.02, 45.03, 2.77, 10.53, 10.59, P<0.01). BWT of patients in survival group and death group on 7 and 14 d post admission was significantly smaller than that on 3 d post admission within the corresponding group (t=10.49, 18.26, 9.57, 11.44, P<0.01). BWT of patients in survival group and death group on 14 d post admission was significantly smaller than that on 7 d post admission within the corresponding group (t=6.97, 6.15, P<0.01). (3) The total areas under ROC curves of inhalation injury rating at admission and BWT at admission for predicting death of 43 patients were 0.880 and 0.956, respectively (with 95% confidence intervals 0.768-0.991, 0.882-1.000, P<0.05). Grade 1.5 and 2.75 mm were respectively chosen as the optimal threshold values of inhalation injury rating at admission and BWT at admission, with sensitivity of 87.50%, 83.33% and specificity of 77.78%, 96.00%, respectively. Conclusions: The BWT of survived and dead patients with severe burn and inhalation injury increases significantly post burn, while the BWT of survived patients restores to normal level faster. BWT can be used to assess the severity of inhalation injury and to predict death in severely burned patients combined with inhalation injury.

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Objective@#To explore the dynamic variation trend of bronchial wall thickness (BWT) in severely burned patients combined with inhalation injury, and to determine the value of BWT to prognosis of patients.@*Methods@#Forty-three severely burned patients with inhalation injury hospitalized in Intensive Burn Department of the Affiliated Hospital of Nankai University (Tianjin No.4 Hospital) from July to November 2016, conforming to the study criteria, were divided into survival group (n=27) and death group (n=16) according to the prognosis of patients within 14 days after admission. All patients underwent fiberoptic bronchoscopy and inhalation injury rating based on abbreviated injury scale at admission. High resolution CT examination was performed in patients of two groups at admission and 24 h post admission, 3, 7, and 14 d post admission to measure the BWT of right superior lobar bronchus trunk opening. Receiver operating characteristic curves of rating of inhalation damage at admission and BWT at admission were drawn to evaluate the predictive value for death of 43 patients. Data were processed with chi-square test, independent sample t test, Wilcoxon rank sum test, analysis of variance for repeated measurement and least-significant difference-t test.@*Results@#(1) The numbers of patients rated as 0, 1, 2, 3, and 4 grade for inhalation injury in survival group and death group were 0, 19, 6, 2, and 0, and 0, 2, 7, 7, and 0, respectively. There were statistically significant differences between the two groups (Z=-3.79, P<0.01). (2) BWT of patients in death group at admission and 24 h post admission, 3, 7, and 14 d post admission was respectively (2.72±0.26), (3.18±0.22), (2.98±0.18), (2.29±0.17), and (1.45±0.21) mm, which was significantly larger than (2.24±0.15), (2.49±0.15), (1.51±0.17), (1.04±0.16), and (1.01±0.13) mm in survival group (t=7.55, 12.14, 27.11, 19.99, 7.11, P<0.01). BWT of patients in survival group and death group at 24 h post admission, 3, 7, and 14 d post admission showed statistically significant difference when compared with that at admission within the corresponding group (t=5.97, 16.63, 28.21, 38.57, 5.34, 3.31, 4.39, 6.48, P<0.01). BWT of patients in survival group and death group on 3, 7, and 14 d post admission was significantly smaller than that at 24 h post admission within the corresponding group (t=22.27, 34.02, 45.03, 2.77, 10.53, 10.59, P<0.01). BWT of patients in survival group and death group on 7 and 14 d post admission was significantly smaller than that on 3 d post admission within the corresponding group (t=10.49, 18.26, 9.57, 11.44, P<0.01). BWT of patients in survival group and death group on 14 d post admission was significantly smaller than that on 7 d post admission within the corresponding group (t=6.97, 6.15, P<0.01). (3) The total areas under ROC curves of inhalation injury rating at admission and BWT at admission for predicting death of 43 patients were 0.880 and 0.956, respectively (with 95% confidence intervals 0.768-0.991, 0.882-1.000, P<0.05). Grade 1.5 and 2.75 mm were respectively chosen as the optimal threshold values of inhalation injury rating at admission and BWT at admission, with sensitivity of 87.50%, 83.33% and specificity of 77.78%, 96.00%, respectively.@*Conclusions@#The BWT of survived and dead patients with severe burn and inhalation injury increases significantly post burn, while the BWT of survived patients restores to normal level faster. BWT can be used to assess the severity of inhalation injury and to predict death in severely burned patients combined with inhalation injury.

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INTRODUCTION: Airway remodeling in asthma and chronic obstructive pulmonary disease (COPD) results in bronchial wall thickening. Bronchial wall thickness (BWT) can be assessed in high-resolution computed tomography (HRCT) and endobronchial ultrasound (EBUS). AIMS: To compare BWT measured by EBUS and HRCT in patients with mild-to-moderate asthma and COPD, and to evaluate the relationship between the BWT and pulmonary function. METHODS: The study included patients with mild-to-moderate asthma (n = 24), COPD (n = 36) and controls (n = 12). Bronchoscopy with EBUS (radial probe) and HRCT were performed to measure the BWT in the segmental bronchus. RESULTS: Good overall agreement between EBUS and HRCT measurements of BWT was demonstrated. Median HRCT-BWT did not reveal any significant differences between individuals with asthma and COPD, and control subjects: 1.56 (1.27-1.70) mm, 1.62 (1.45-1.90) mm, and 1.63 (1.41-1.77) mm, respectively (p = 0.315). In contrast, median BWT measured by EBUS was significantly higher in asthma and COPD groups when compared to controls: 1.20 (1.02-1.41) mm, 1.19 (1.10-1.48) mm, and 0.99 (0.90-1.08) mm, respectively (p = 0.006). There were no differences in BWT in mild-to-moderate asthma and COPD or significant correlations between BWT and the results of pulmonary function tests. CONCLUSIONS: The use of EBUS to assess BWT in asthma and COPD is feasible and it shows good compatibility with HRCT. A tendency towards lower BWT values in EBUS when compared to HRCT was observed. The finding that EBUS measurements demonstrated the differences between BWT in patients with obstructive lung diseases and controls, may suggest that EBUS is a more sensitive method to study the BWT than HRCT.

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OBJECTIVES: To semi-quantitatively assess expiratory air trapping (AT(exp)) and structural changes in the proximal airways in asthma during asthma exacerbation (AE) and to explore the relationships among AT(exp), clinical indices, and proximal airway changes. METHODS: Paired inspiratory-dynamic forced expiratory CT scans of 36 asthmatics (30 women, 6 men; mean age, 49.2±18.9 years) performed during AE were retrospectively reviewed for the total AT(exp) score (summed scores [extent grading (0-4)×pattern grading (1-4)] of the twelve lung zones), morphologic parameters and expiratory bronchial collapse (BC(exp)) of the proximal airways. The relationships of the score with clinical indices and proximal airway morphology (normalized by body surface area [BSA]) were analyzed. A p value of <0.05 was considered statistically significant. RESULTS: The mean total AT(exp) score was 110.1±43.4 (range, 8-166). It was higher in the lower zones and in patients older than 60 years, having BMI of <27.5 kg/m(2), and peak expiratory flow rate (PEFR) of <60% predicted. Correlation existed between the score and age (r=0.331), BMI (r=-0.375), BSA (r=-0.442), % predicted PEFR (r=-0.332), right upper lobe apical segmental bronchus (RB1)-wall area (WA)/BSA (r=0.467), %RB1-WA (r=0.395), and RB1-bronchial wall thickness (BWT)/BSA (r=0.378). The score showed no correlation with BC(exp) and other morphologic bronchial parameters. Area under receiver-operating-characteristic curve 0.724 (95% CI) showed that the score of 110 could discriminate patients with PEFR of <60% predicted from those with PEFR of ≥60% predicted. CONCLUSION: During AE, there was a high prevalence of extensive AT(exp) which was correlated with patient's age, BMI, BSA, AE severity and RB1 morphology but not correlated with BC(exp).

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PURPOSE: The prediction of pulmonary deterioration in patients with smoke inhalation injury is important because this influences the strategy for patient management. We hypothesized that narrowing of the luminal bronchus due to bronchial wall thickening correlates to respiratory deterioration in smoke inhalation injury patients. METHODS: In a prospective observational study, all patients were enrolled at a single tertiary trauma and critical care center. In 40 patients, chest computed tomographic images were obtained within a few hours after smoke inhalation injury. We assessed bronchial wall thickness and luminal area % on chest computed tomographic images. Airway wall thickness to total bronchial diameter (T/D) ratio, percentage of luminal area, and clinical indices were compared between patients with smoke inhalation injury and control patients. RESULTS: The T/D ratio of patients with smoke inhalation was significantly higher than that of control patients (p<0.001), and the luminal area of these patients was significantly smaller than that of control patients (p<0.001). The number of mechanical ventilation days correlated with the initial infusion volume, T/D ratio, and luminal area %. ROC analysis showed a cut-off value of 0.26 for the T/D ratio, with a sensitivity of 79.0% and specificity of 73.7%, and a value of 23.4% for luminal area %, with a sensitivity of 68.4% and specificity of 84.2%. CONCLUSIONS: These data revealed the utility of computed tomography scanning on admission to show that the patients with smoke inhalation injury had airway wall thickening compared to control patients without smoke inhalation injury. Airflow narrowing due to airway wall thickening was related to the development of pneumonia and the number of mechanical ventilation days in patients with smoke inhalation injury. Airflow narrowing is one important factor of respiratory deterioration in smoke inhalation injury.

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