Wall Area Percentage Research Articles

Radiological correlates and clinical implications of the paradoxical lung function response to β2 agonists: an observational study

Bronchodilator response has been noted in a significant proportion of patients with chronic obstructive pulmonary disease (COPD). However, there are also reports of a paradoxical response to β₂ agonists resulting in bronchoconstriction. Asymptomatic bronchoconstriction is likely to be far more common than is symptomatic bronchoconstriction with β₂ agonists, but no systematic studies have been done. We assessed the prevalence of paradoxical response in current and former smokers with and without COPD, and its radiological correlates and clinical implications. Non-Hispanic white and African-American patients (aged 45-80 years) from a large multicentre study COPDGene were classified into two groups on the basis of a paradoxical response, defined as at least a 12% and 200 mL reduction in forced expiratory volume in 1 sec (FEV₁) or forced vital capacity (FVC), or both, after administration of a shortacting β₂ agonist (180 μg salbutamol). Patients were recruited from January, 2008, to June, 2011. 9986 (96%) of 10,364 patients enrolled in the COPDGene study were included in the analysis population (mean age 59·6 years [SD 9·0]). Paradoxical response was noted in 453 (5%) of 9986 patients and the frequency was similar in patients with COPD (198 [4%] of 4439) and smokers without airflow obstruction (255 [5%] of 5547). Compared with white patients, a paradoxical response was twice as common in African-American patients (227 [7%] of 3282 vs 226 [3%] of 6704; p<0·0001). In the multivariate analyses, African-American ethnic origin (adjusted odds ratio 1·89, 95% CI 1·50-2·39; p<0·0001), less emphysema (0·96, 0·92-0·99; p=0·023), and increased wall-area percentage of the segmental airways (1·04, 1·01-1·08; p=0·023) were independently associated with a paradoxical response. A paradoxical response was independently associated with worse dyspnoea (adjusted β for Modified Medical Research Council Dyspnoea Scale 0·12 [95% CI 0·00 to 0·24]; p=0·05), lower 6 min walk distance (-45·8 [-78·5 to -13·2]; p=0·006), higher Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) index (0·31 [0·19 to 0·43]; p<0·0001), and a greater frequency of severe exacerbations (increased by a factor of 1·35, 1·00-1·81; p=0·048). Paradoxical response to β₂ agonists is associated with respiratory morbidity and is more common in African-Americans. These findings might have implications for the use of β2agonists in some patients. National Institutes of Health.

Comparison of airway dimensions with once daily tiotropium plus indacaterol versus twice daily Advair® in chronic obstructive pulmonary disease

Current guidelines recommend combining long-acting bronchodilators with different modes of action in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). We evaluated the effects of airway dimensions and pulmonary function with tiotropium plus indacaterol versus Advair(®). Subjects (n=46) were randomized to receive tiotropium (18μg once daily) plus indacaterol (150μg once daily) or Advair(®) (50/250μg twice daily) for 16 weeks. Airway geometry was determined by quantitative computed tomography (luminal area, Ai; total area of the airway, Ao; wall area, WA; and percentage wall area, WA/Ao and wall thickness, T). Spirometry (forced expiratory volume in 1s, FEV1; forced vital capacity, FVC and inspiratory capacity, IC) and St. George's Respiratory Questionnaire (SGRQ) were evaluated. Tiotropium plus indacaterol significantly increased CT-indices including Ai corrected for body surface area (Ai/BSA), and decreased WA/BSA, WA/Ao and T/√BSA compared with Advair(®) (p<0.05, respectively). In physiological parameters, mean difference in IC was significantly higher under treatment with tiotropium plus indacaterol than Advair(®) (p<0.05). The changes in Ai/BSA, WA/BSA, WA/Ao and T/√BSA were significantly correlated with changes in IC (r=0.535, p=0.011; r=-0.688, p<0.001; r=-0.555, p=0.002 and r=-0.542, p=0.007; respectively). There were more significant improvements in SGRQ scores after treatment with tiotropium plus indacaterol than Advair(®). These findings suggest that dual bronchodilation with tiotropium plus indacaterol is superior in airway geometry and lung function compared with Advair(®) in COPD.

Airway wall thickness is increased in COPD patients with bronchodilator responsiveness.

RationaleBronchodilator responsiveness (BDR) is a common but variable phenomenon in COPD. The CT characteristics of airway dimensions that differentiate COPD subjects with BDR from those without BDR have not been well described. We aimed to assess airway dimensions in COPD subjects with and without BDR.MethodsWe analyzed subjects with GOLD 1–4 disease in the COPDGene® study who had CT airway analysis. We divided patients into two groups: BDR + (post bronchodilator ΔFEV1 ≥ 10%) and BDR-(post bronchodilator ΔFEV1 < 10%). The mean wall area percent (WA%) of six segmental bronchi in each subject was quantified using VIDA. Using 3D SLICER, airway wall thickness was also expressed as the square root wall area of an airway of 10 mm (Pi10) and 15 mm (Pi15) diameter. %Emphysema and %gas trapping were also calculated.Results2355 subjects in the BDR-group and 1306 in the BDR + group formed our analysis. The BDR + group had a greater Pi10, Pi15, and mean segmental WA% compared to the BDR-group. In multivariate logistic regression using gender, race, current smoking, history of asthma, %emphysema, %gas trapping, %predicted FEV1, and %predicted FVC, airway wall measures remained independent predictors of BDR. Using a threshold change in FEV1 ≥ 15% and FEV1 ≥ 12% and 200 mL to divide patients into groups, the results were similar.ConclusionBDR in COPD is independently associated with CT evidence of airway pathology. This study provides us with greater evidence of changes in lung structure that correlate with physiologic manifestations of airflow obstruction in COPD.

Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene.

BackgroundPreserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.MethodsData from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45–80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.ResultsThe prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter’s syndrome (47XXY) was observed (p-value < 0.001). Subgroups identified through k-means clustering include a putative “COPD-subtype”, “Restrictive-subtype”, and a highly symptomatic “Metabolic-subtype”.ConclusionsPRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.Trial registrationClinicaltrials.gov Identifier: NCT000608764.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0089-y) contains supplementary material, which is available to authorized users.

Longitudinal Changes in Airway Remodeling and Air Trapping in Severe Asthma

Previous cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aimed to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma. Phenotypic characterization and quantitative multidetector-row computed tomography (MDCT) of the chest were performed at baseline and ∼2.6years later in 38 participants with asthma (severe n=24 and mild-to-moderate n=14) and nine normal controls from the Severe Asthma Research Program. Subjects with severe asthma had a significant decline in postbronchodilator forced expiratory volume in 1 second percent (FEV1%) predicted over time (P < .001). Airway wall thickness measured by MDCT was increased at multiple airway generations in severe asthma compared to mild-to-moderate asthma (wall area percent [WA%]: P<.05) and normals (P<.05) at baseline and year 2. Over time, there was an increase in WA% and wall thickness percent (WT%) in all subjects (P=.030 and .009, respectively) with no change in emphysema-like lung or air trapping. Baseline prebronchodilator FEV1% inversely correlated with WA% and WT% (both P < .05). In a multivariable regression model, baseline WA%, race, and health care utilization were predictors of subsequent airway remodeling. Severe asthma subjects have a greater decline in lung function over time than normal subjects or those with mild-to-moderate asthma. MDCT provides a noninvasive measure of airway wall thickness that may predict subsequent airway remodeling.

Ratios of Peripheral-to-Central Airway Lumen Area and Percentage Wall Area as Predictors of Severity of Chronic Obstructive Pulmonary Disease

The purpose of this study was to assess the ability of the ratios of peripheral-to-central airway lumen area (hereafter referred to as LA) and percentage wall area (hereafter referred to as %WA) to predict the severity of chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. We examined 32 patients (27 men and five women; mean age ± SD, 70.0 ± 6.8 years; seven GOLD stage 0 [at risk for COPD], 19 GOLD stage 1-2 [mild to moderate airflow limitation], and six GOLD stage 3-4 [severe to very severe airflow limitation]) using inspiratory CT. Mean LA and %WA were measured for the first (main bronchi), third, and fifth generations of five bronchi in each lobe and the ratios of peripheral to central airways were calculated (third to first, fifth to first, and fifth to third) and statistically compared. The fifth-generation LA, LA fifth to first, and LA fifth to third significantly decreased and fifth %WA, %WA fifth to first, and %WA fifth to third also increased with progression of GOLD stage (p < 0.05), but central measurements, including first and third generations, did not. There were significant differences between GOLD 0 and GOLD 1-2 for %WA fifth to third and LA fifth to third and between GOLD 0 and GOLD 3-4 for all six parameters (p < 0.05); %WA fifth to third had the best cutoff value of 1.02 (sensitivity, 92%; specificity, 86%) for diagnosis of COPD (GOLD 1-4). The %WA fifth to first of 1.51 (sensitivity, 83%; specificity, 89%) was best for diagnosis of GOLD 3-4. Ratios of peripheral-to-central airway LA and %WA show improved correlation with COPD severity.

TU‐A‐12A‐11: Improved Airway Measurement Accuracy for Low Dose Quantitative CT (qCT) Using Statistical (ASIR), at Reduced DFOV, and High Resolution Kernels in a Phantom and Swine Model

Purpose:To improve the accuracy of airway measures and reduce x‐ray dose in quantitative CT (qCT) of the lung.Methods:qCT was performed on an airway phantom (COPD gene) and a swine model. The airway phantom was used to identify expected improvements in spatial resolution and noise tradeoffs for choice of CT reconstruction kernel and display FOV (DFOV).Results in the phantom were then applied to the swine model. Images were obtained via helical scans that were performed using a GE Discovery CT750 HD with the COPD Gene/SARP protocols except tube current was varied from 790 to 50 mA, and lung inflation was fixed via mechanical ventilator. CT data were reconstructed using STANDARD (Std) and Bone reconstruction kernels for FBP and 100% ASIR at half and full DFOV. Inner Diameter(ID) and wall area percent (WA%) of selected airway sizes were matched across the swine lung and phantom and performed using Airway Inspector (Surgical Planning Laboratory, Brigham and Women's Hospital, Boston, MA). For the swine lung the CT acquisition at 790 mA with ASIR and Bone kernel at half DFOV parameters was the reference standard for comparison to the lower dose scans. Results:The accuracy of the ID and WA% improved by ∼24% and ∼23% for half DFOV with the Bone kernel and ASIR reconstruction for both phantom and swine models for all airways investigated. For low dose qCT, the difference between the reference standard measures and the measures obtained with half DFOV with Bone+ASIR remained much lower than those using current clinical parameters (FBP at full DFOV) even at one fourth the dose for all airways investigated as is shown in Table 1.Conclusion:The combination of ASIR with higher spatial resolution reconstruction shows promise to reduce x‐ray dose and improve qCT of lung airways.NIBIB PB EB 1010 159 JKS Recovery Quantitative Imaging Biomarker Alliance (QIBA) U10 HL109168 SARP

Iterative reconstruction technique vs filter back projection: utility for quantitative bronchial assessment on low-dose thin-section MDCT in patients with/without chronic obstructive pulmonary disease.

The aim of this study was to evaluate the utility of the iterative reconstruction (IR) technique for quantitative bronchial assessment during low-dose computed tomography (CT) as a substitute for standard-dose CT in patients with/without chronic obstructive pulmonary disease. Fifty patients (mean age, 69.2; mean % predicted FEV1, 79.4) underwent standard-dose CT (150mAs) and low-dose CT (25mAs). Except for tube current, the imaging parameters were identical for both protocols. Standard-dose CT was reconstructed using filtered back-projection (FBP), and low-dose CT was reconstructed using IR and FBP. For quantitative bronchial assessment, the wall area percentage (WA%) of the sub-segmental bronchi and the airway luminal volume percentage (LV%) from the main bronchus to the peripheral bronchi were acquired in each dataset. The correlation and agreement of WA% and LV% between standard-dose CT and both low-dose CTs were statistically evaluated. WA% and LV% between standard-dose CT and both low-dose CTs were significant correlated (r > 0.77, p < 0.00001); however, only the LV% agreement between SD-CT and low-dose CT reconstructed with IR was moderate (concordance correlation coefficient = 0.93); the other agreement was poor (concordance correlation coefficient <0.90). Quantitative bronchial assessment via low-dose CT has potential as a substitute for standard-dose CT by using IR and airway luminal volumetry techniques. • Quantitative bronchial assessment of COPD using low-dose CT is possible. • Airway luminal volumetry with iterative reconstruction is insusceptible to dose reduction. • Filtered back-projection is susceptible to the effect of dose reduction. • Wall area percentage assessment is easily influenced by dose reduction.

Clinical and computed tomographic predictors of chronic bronchitis in COPD: a cross sectional analysis of the COPDGene study.

BackgroundChronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB.MethodsWe divided 2703 GOLD 1–4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%). Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com). Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org).ResultsThere were no differences in % emphysema (11.4 ± 12.0 vs. 12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs. 36.3 ± 20.6%, p = 0.272) between groups. Mean segmental WA% (63.0 ± 3.2 vs. 62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs. 3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs. 5.17 ± 0.20, p < 0.0001) were greater in the CB + group. Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group. In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV1%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB.ConclusionsHistories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV1%, Caucasian race, male gender, and increased airway wall thickness are associated with CB. These data provide clinical and radiologic correlations to the clinical phenotype of CB.

Bronchial Wall Measurements in Patients after Lung Transplantation: Evaluation of the Diagnostic Value for the Diagnosis of Bronchiolitis Obliterans Syndrome

ObjectivesTo prospectively evaluate quantitative airway wall measurements of thin-section CT for the diagnosis of Bronchiolitis Obliterans Syndrome (BOS) following lung transplantation.Materials and MethodsIn 141 CT examinations, bronchial wall thickness (WT), the wall area percentage (WA%) calculated as the ratio of the bronchial wall area and the total area (sum of bronchial wall area and bronchial lumen area) and the difference of the WT on inspiration and expiration (WTdiff) were automatically measured in different bronchial generations. The measurements were correlated with the lung function parameters. WT and WA% in CT examinations of patients with (n = 25) and without (n = 116) BOS, were compared using the unpaired t-test and univariate analysis of variance, while also considering the differing lung volumes.ResultsMeasurements could be performed in 2,978 bronchial generations. WT, WA%, and WTdiff did not correlate with the lung function parameters (r<0.5). The WA% on inspiration was significantly greater in patients with BOS than in patients without BOS, even when considering the dependency of the lung volume on the measurements. WT on inspiration and expiration and WA% on expiration did not show significant differences between the groups.ConclusionWA% on inspiration was significantly greater in patients with than in those without BOS. However, WA% measurements were significantly dependent on lung volume and showed a high variability, thus not allowing the sole use of bronchial wall measurements to differentiate patients with from those without BOS.

The Use of Volumetric Chest Computed Tomography in Determination of Chronic Obstructive Pulmonary Disease Phenotypes

Background: Chronic Obstructive Pulmonary Disease (COPD) represents one of the major causes of chronic morbidity where, airflow limitation is caused by a mixture of small airways disease and parenchyma destruction.Objective: to correlate the clinical characteristics of patients with COPD with imaging classification into phenotypes.Patients and Methods: Thirty patients with stable COPD were examined by chest CT. Bronchial wall thickness is evaluated by measuring the wall area percentage by identifying the trunk of the apical bronchus of the right upper lobe, while the extent of emphysema was assessed using the percentage of lung voxels with X-ray attenuation values less than -950 HU {automatically calculated by special software}.Results: Three phenotypes were found: A phenotype (airway-predominant) , 66.6% of total, E phenotype (emphysema predominant), 20% of total and M phenotype (mixed), 13.3% of total.Conclusions: Using volumetric chest CT in patients with chronic obstructive pulmonary diseases determine three disease patterns. Airway predominant disease which correlate to patients who have clinical &amp; spirometric pattern of chronic bronchitis rather than emphysema. Emphysema predominant on CT correlated with patients with clinical findings of lung hyperinflation rather than bronchial inflammation. Patients with mixed CT findings combined of both previously mentioned types found to be correlated with those with overlapped clinical patterns of both chronic bronchitis &amp; emphysema.

The effects of emphysema on airway disease: Correlations between multi-detector CT and pulmonary function tests in smokers

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and small airway narrowing. Quantitative evaluation of airway dimensions by multi-detector computed tomography (MDCT) has revealed a correlation between airway dimension and airflow limitation. However, the effect of emphysema on this correlation is unclear. ObjectiveThe goal of this study was to determine whether emphysematous changes alter the relationships between airflow limitation and airway dimensions as measured by inspiratory and expiratory MDCT. MethodsNinety-one subjects underwent inspiratory and expiratory MDCT. Images were evaluated for mean airway luminal area (Ai), wall area percentage (WA%) from the third to the fifth generation of three bronchi (B1, B5, B8) in the right lung, and low attenuation volume percent (LAV%). Correlations between each airway index and airflow limitation were determined for each patient and compared between patients with and without evidence of emphysema. ResultsIn patients without emphysema, Ai and WA% from both the inspiratory and expiratory scans were significantly correlated with FEV1. No correlation was detected in patients with emphysema. In addition, emphysematous COPD patients with GOLD stage 1 or 2 disease had significantly lower changes in B8 Ai than non-emphysematous patients. ConclusionsA significant correlation exists between airway parameters and FEV1 in patients without emphysema. Emphysema may influence airway dimensions even in patients with mild to moderate COPD.

Computed tomography assessment of airway dimensions with combined tiotropium and indacaterol therapy in COPD patients

Combining a long-acting muscarinic antagonist with a long-acting β₂-agonist has been shown to be pharmacologically useful in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to evaluate the effectiveness of the dual bronchodilator therapy on airway dimensions in COPD. Patients (n = 54) were randomly assigned to receive tiotropium (18 μg once daily), indacaterol (150 μg once daily) or tiotropium plus indacaterol for 16 weeks. Quantitative computed tomography (CT), pulmonary function and health status (St. George's Respiratory Questionnaire) were measured. Compared with tiotropium or indacaterol alone, combination therapy resulted in a significant decrease in percentage wall area (WA%) and wall thickness, corrected for body surface area, and an increase in luminal area (Ai/BSA). Concurrent treatment was superior to monotherapy in physiological indices, including forced vital capacity, forced expiratory volume in 1 s (FEV₁) and inspiratory capacity. The changes in WA% and Ai/BSA were significantly correlated with changes in FEV₁ (r = -0.44, P < 0.01 and r = 0.37, P < 0.01). There were more significant improvements in SGRQ scores after treatment with combined therapy than with either treatment alone. Concurrent therapy with tiotropium and indacaterol is effective for COPD patients to promote reduction in airway wall thickness, bronchodilation, and improvements in lung function compared with a single inhaler.

Optimal surface segmentation using flow lines to quantify airway abnormalities in chronic obstructive pulmonary disease

This paper introduces a graph construction method for multi-dimensional and multi-surface segmentation problems. Such problems can be solved by searching for the optimal separating surfaces given the space of graph columns defined by an initial coarse surface. Conventional straight graph columns are not well suited for surfaces with high curvature, we therefore propose to derive columns from properly generated, non-intersecting flow lines. This guarantees solutions that do not self-intersect. The method is applied to segment human airway walls in computed tomography images in three-dimensions. Phantom measurements show that the inner and outer radii are estimated with sub-voxel accuracy. Two-dimensional manually annotated cross-sectional images were used to compare the results with those of another recently published graph based method. The proposed approach had an average overlap of 89.3±5.8%, and was on average within 0.096±0.097mm of the manually annotated surfaces, which is significantly better than what the previously published approach achieved. A medical expert visually evaluated 499 randomly extracted cross-sectional images from 499 scans and preferred the proposed approach in 68.5%, the alternative approach in 11.2%, and in 20.3% no method was favoured. Airway abnormality measurements obtained with the method on 490 scan pairs from a lung cancer screening trial correlate significantly with lung function and are reproducible; repeat scan R(2) of measures of the airway lumen diameter and wall area percentage in the airways from generation 0 (trachea) to 5 range from 0.96 to 0.73.

Computed tomographic measures of airway morphology in smokers and never-smoking normals

Bronchial wall area percent (WA% = 100 × wall area/total bronchial cross sectional area) is a standard computed tomographic (CT) measure of central airway morphology utilized in smokers with chronic obstructive pulmonary disease (COPD). Although it provides significant clinical correlations, the range of reported WA% is narrow. This suggests limited macroscopic change in response to smoking or that remodeling proportionally affects the airway wall and lumen dimensions such that their ratio is preserved. The objective of this study is to assess central airway wall area (WA), lumen area (Ai), and total bronchial area (Ao) from CT scans of 5,179 smokers and 92 never smoking normal subjects. In smokers, WA, Ai, and Ao were positively correlated with forced expiratory volume in 1 s (FEV1) expressed as a percent of predicted (FEV1%), and the WA% was negatively correlated with FEV1% (P < 0.0001 for all comparisons). Importantly, smokers with lower FEV1% tended to have airways of smaller cross-sectional area with lower WA. The increases in the WA% across GOLD stages of chronic obstructive pulmonary disease (COPD) can therefore not be due to increases in WA. The data suggest two possible origins for the WA% increases: 1) central airway remodeling resulting in overall reductions in airway caliber in excess of the decreased WA or 2) those with COPD had smaller native airways before they began smoking. In both cases, these observations provide an explanation for the limited range of values of WA% across stages of COPD.

Limitations of Airway Dimension Measurement on Images Obtained Using Multi-Detector Row Computed Tomography

Objectives(a) To assess the effects of computed tomography (CT) scanners, scanning conditions, airway size, and phantom composition on airway dimension measurement and (b) to investigate the limitations of accurate quantitative assessment of small airways using CT images.MethodsAn airway phantom, which was constructed using various types of material and with various tube sizes, was scanned using four CT scanner types under different conditions to calculate airway dimensions, luminal area (Ai), and the wall area percentage (WA%). To investigate the limitations of accurate airway dimension measurement, we then developed a second airway phantom with a thinner tube wall, and compared the clinical CT images of healthy subjects with the phantom images scanned using the same CT scanner. The study using clinical CT images was approved by the local ethics committee, and written informed consent was obtained from all subjects. Data were statistically analyzed using one-way ANOVA.ResultsErrors noted in airway dimension measurement were greater in the tube of small inner radius made of material with a high CT density and on images reconstructed by body algorithm (p<0.001), and there was some variation in error among CT scanners under different fields of view. Airway wall thickness had the maximum effect on the accuracy of measurements with all CT scanners under all scanning conditions, and the magnitude of errors for WA% and Ai varied depending on wall thickness when airways of <1.0-mm wall thickness were measured.ConclusionsThe parameters of airway dimensions measured were affected by airway size, reconstruction algorithm, composition of the airway phantom, and CT scanner types. In dimension measurement of small airways with wall thickness of <1.0 mm, the accuracy of measurement according to quantitative CT parameters can decrease as the walls become thinner.

Evaluation of Airway Wall Thickness Via High-Resolution Computed Tomography in Mild Intermittent Asthma

This study aims to evaluate bronchial thickness via thorax high-resolution computed tomography (HRCT) in subjects with mild intermittent asthma in comparison with healthy control subjects. A total of 37 out-patients (mean ± SD age = 36.7 years (9.7 years); 54.8% males) with mild intermittent asthma and 13 healthy control subjects (mean ± SD age = 25.0 years (2.9 years); 61.5% males) were included in this case control study. Data on demographics, pulmonary function test results, and segmental and subsegmental thorax HRCT results were recorded. The ratio of bronchial wall thickness to bronchial lumen diameter (T/D) and bronchial wall area percentage (WA%) were calculated for all cases. Subject and control groups were similar in terms of pulmonary function test results, and total and subsegmental T/D values. Mean ± SD subsegmental WA% values at the level of inferior pulmonary vein (55.6% [16.8%] vs. 41.7% [7.4%], P = .047) and 2 cm above the diaphragm (49.8% [15.8%] vs. 38.6% [10.4%], P = .046) were significantly higher in subjects than control subjects. No significant correlation of overall and subsegmental T/D and WA% values to age in both groups, and to asthma duration in subjects. Our findings revealed an increase in bronchial wall thickness in peripheral airways in subjects with mild intermittent asthma regardless of the duration of asthma. This may indicate a need to also administer anti-inflammatory or bronchodilator therapy, which is effective in peripheral airways during the early period of the disease.

Effects of Tiotropium and Salmeterol/Fluticasone Propionate on Airway Wall Thickness in Chronic Obstructive Pulmonary Disease

Background: Triple inhalation therapy with tiotropium (Tio) and salmeterol/fluticasone propionate combination (SFC) is widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, the effects of triple therapy on airway structural changes remain unknown. Objective: The aim of the study was to assess the effects of Tio, salmeterol (SM), SFC and Tio plus SFC on airway dimensions in COPD. Methods: A randomized, open-label, 4-way study (n = 60) was conducted comparing 16-week treatment periods of Tio (18 μg once daily), SM (50 μg twice daily), SFC (50/250 μg twice daily) and Tio (18 μg once daily) plus SFC (50/250 μg twice daily). Airway dimensions were assessed by a validated CT technique, and airway wall area (WA) corrected for body surface area (BSA), percentage WA (WA%), wall thickness/√BSA and luminal area (Ai)/BSA at the right apical segmental bronchus were measured. Pulmonary function and the St. George's Respiratory Questionnaire (SGRQ) were evaluated. Results: Tio plus SFC resulted in a significant decrease in WA corrected for BSA and WA% compared with Tio, SM and SFC (p < 0.05 for all). The changes in WA% and Ai/BSA were significantly correlated with changes in forced expiratory volume in 1 s (r = -0.86, p < 0.001, and r = 0.48, p < 0.05, respectively). There were more significant improvements in SGRQ scores after treatment with triple therapy than after the 3 other treatments. Conclusions: Tio plus SFC therapy is more effective than Tio, SM and SFC for reducing airway wall thickness in COPD.

Montelukast improves air trapping, not airway remodeling, in patients with moderate-to-severe asthma: a pilot study

Background Evidence has demonstrated that the distal lung, which includes airways of &lt;2 mm in diameter and lung parenchyma, constitutes an important component of asthma pathology. Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and bronchoconstrictors involved in the asthmatic process. Guidelines recommend the leukotriene-modifying agents for asthma treatment. We hypothesized that a leukotriene receptor antagonist with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combination would improve small airways function in moderate-to-severe asthmatics evaluated by physiological tests and high-resolution computed tomography (HRCT) analysis. This study was performed at a tertiary university hospital in Beijing. Methods This was a randomized, double-blind, parallel study performed in 38 patients with moderate-to-severe asthma treated with salmeterol/fluticasone (SFC) plus montelukast (SFC+M) or SFC plus placebo over 24 weeks. Small airway function was assessed by physiological studies and HRCT image analysis. Results Montelukast significantly improved air trapping as expressed by the residual volume (RV)/total lung capacity (TLC). Over 24 weeks of treatment, RV/TLC was improved by (15.41±6.67)% in patients receiving SFC+M while RV/TLC was decreased by (8.57±10.26)% in patients receiving SFC alone, the difference between the two groups was significant (P=0.02). There was a trend towards a significant difference in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) in the SFC+M group compared to that in the SFC group ((17.87±8.17)% vs. (12.28±9.20)%, P=0.056). There was no significant change in percentage wall area (WA%) after 24 weeks of add-on treatment with montelukast. Patients receiving SFC+M showed significant improvement in the ratio of CT-determined values at full expiration to those at full inspiration (E/I ratio) (0.894±0.005 vs. 0.871±0.003, P=0.002). Conclusion We have shown, using lung function tests and HRCT image technique, that add-on therapy with montelukast improves distal lung function reflected by air trapping, but not airway wall thickness in moderate-to-severe asthma. (ClinicalTrials.gov number, NCT00699062)

Hyperpolarized 3He and 129Xe MRI: Differences in asthma before bronchodilation

To compare hyperpolarized helium-3 ((3) He) and xenon-129 ((129) Xe) MRI in asthmatics before and after salbutamol inhalation. Seven asthmatics provided written informed consent and underwent spirometry, plethysmography, and MRI before and after salbutamol inhalation. (3) He and (129) Xe ventilation defect percent (VDP) and ventilation coefficient of variation (COV) were measured. To characterize the airways spatially related to ventilation defects, wall area percent (WA%) and lumen area (LA) were evaluated for two subjects who had thoracic x-ray computed tomography (CT) acquired 1 year before MRI. Before salbutamol inhalation, (129) Xe VDP (8 ± 5%) was significantly greater than (3) He VDP (6 ± 5%, P = 0.003). Post-salbutamol, there was a significant improvement in both (129) Xe (5 ± 4%, P < 0.0001) and (3) He (4 ± 3%, P = 0.001) VDP, and the improvement in (129) Xe VDP was significantly greater (P = 0.008). (129) Xe MRI COV (Pre: 0.309 ± 0.028, Post: 0.296 ± 0.036) was significantly greater than (3) He MRI COV (Pre: 0.282 ± 0.018, Post: 0.269 ± 0.024), pre- (P < 0.0001) and post-salbutamol (P < 0.0001) and the decrease in COV post-salbutamol was significant ((129) Xe, P = 0.002; (3) He, P < 0.0001). For a single asthmatic, a sub-segmental (129) Xe MRI ventilation defect that was visible only before salbutamol inhalation but not visible using (3) He MRI was spatially related to a remodeled fourth generation sub-segmental airway (WA% = 78%, LA = 2.9 mm(2) ). In asthma, hyperpolarized (129) Xe MRI may help reveal ventilation abnormalities before bronchodilation that are not observed using hyperpolarized (3) He MRI.