Low Attenuation Area Research Articles

William M. Feinberg Award for Excellence in Clinical Stroke: Small Vessel Disease; a Big Problem, But Fixable.

Like much in stroke, this research journey started with a clot although this clot and this stroke were different.1 Small vessel disease (SVD) is now recognized to cause 20% to 25% of strokes, to be the second commonest cause of dementia, to cause cognitive decline, physical frailty, and late onset depression. In addition to acute small subcortical (lacunar) ischemic strokes, SVD includes lesions seen commonly on brain imaging: white matter hypertensities (WMH), lacunes, microbleeds, perivascular spaces (PVS), brain shrinkage,2 and biomarkers in apparently normal areas (eg, increased tissue fluid volume and mobility).3 However, when this research started, the strokes, cognitive presentations, and neuroimaging features of SVD were thought generally to be unrelated, silent, permanent, and lacunar stroke was a small version of large artery stroke. In 2000 AD, a 70-year-old man presented to our hospital with a recent lacunar stroke. His computed tomographic scan showed a small, low attenuation area, consistent with a recent small subcortical (lacunar) infarct. There were 3 odd features. 1. In the center was a small white dot, like a mini version of the hyperattenuated middle cerebral artery commonly seen in patients with hyperacute cardio- or athero-thromboembolic ischemic stroke, an appearance not described previously. 2. Brain magnetic resonance imaging (MRI) immediately after the computed tomographic scan confirmed the recent lacunar infarct, including the odd central line/dot, except that there also appeared to be some blood in the arteriole wall. Although a few small cardiac or carotid atheromatous emboli can enter the basal perforating arterioles, ≈6% in experimental models,4 and no more than 11% in patients,5 an embolus would not explain the blood in the arteriole wall. 3. The infarct was around the affected arteriolar segment, not at the end of it, as would be expected in, for example, an infarct occurring secondary to an …

Pruning of the Pulmonary Vasculature in Asthma. The Severe Asthma Research Program (SARP) Cohort.

Loss of the peripheral pulmonary vasculature, termed vascular pruning, is associated with disease severity in patients with chronic obstructive pulmonary disease. To determine if pulmonary vascular pruning is associated with asthma severity and exacerbations. We measured the total pulmonary blood vessel volume (TBV) and the blood vessel volume of vessels less than 5 mm2 in cross-sectional area (BV5) and of vessels less than 10 mm2 (BV10) in cross-sectional area on noncontrast computed tomographic scans of participants from the Severe Asthma Research Program. Lower values of the BV5 to TBV ratio (BV5/TBV) and the BV10 to TBV ratio (BV10/TBV) represented vascular pruning (loss of the peripheral pulmonary vasculature). Compared with healthy control subjects, patients with severe asthma had more pulmonary vascular pruning. Among those with asthma, those with poor asthma control had more pruning than those with well-controlled disease. Pruning of the pulmonary vasculature was also associated with lower percent predicted FEV1 and FVC, greater peripheral and sputum eosinophilia, and higher BAL serum amyloid A/lipoxin A4 ratio but not with low-attenuation area or with sputum neutrophilia. Compared with individuals with less pruning, individuals with the most vascular pruning had 150% greater odds of reporting an asthma exacerbation (odds ratio, 2.50; confidence interval, 1.05-5.98; P = 0.039 for BV10/TBV) and reported 45% more asthma exacerbations during follow-up (incidence rate ratio, 1.45; confidence interval, 1.02-2.06; P = 0.036 for BV10/TBV). Pruning of the peripheral pulmonary vasculature is associated with asthma severity, control, and exacerbations, and with lung function and eosinophilia.

Computed tomography quantification of emphysema in people living with HIV and uninfected controls.

People living with HIV (PLWH) may be more susceptible to the development of emphysema than uninfected individuals. We assessed prevalence and risk factors for emphysema in PLWH and uninfected controls. Spirometry and chest computed tomography scans were obtained in PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study and in uninfected controls from the Copenhagen General Population Study (CGPS) who were >40 years. Emphysema was quantified using a low attenuation area < -950 Hounsfield units (%LAA-950) and the 15th percentile density index (PD15) and assessed by semi-quantitative visual scales. Of 742 PLWH, 21.2% and 4.7% had emphysema according to the %LAA-950 threshold with cut-offs at 5% and 10%, respectively. Of 470 uninfected controls, these numbers were 24.3% (p=0.23) and 4.0% (p=0.68). HIV was not associated with emphysema (adjusted OR 1.25, 95% CI 0.68-2.36 for %LAA-950 >10%) by PD15 or by visually assessed emphysema. We found no interaction between HIV and cumulative smoking. Breathlessness and sputum production were more common in PLWH with emphysema, and emphysema seemed to be more prevalent in PLWH with airflow limitation. HIV was therefore not independently associated with emphysema, but the clinical impact of emphysema was greater in PLWH than in uninfected controls.

The pulmonary damage caused by smoking: A longitudinal study.

BACKGROUND:Smoking for a long period is known to cause several harms to the human body, chiefly associated with serious pulmonary damage.OBJECTIVE: The purpose of this study was to evaluate the difference in the pulmonary damage between current smokers and ex-smokers, through measuring the bronchial parameters and the extent of emphysema, in order to further illustrate the harm of smoking and the need to stop smoking.METHODS:Using the FACT-Digital lung TM software quantitatively analysis of CT images, including the WT, WA%, LD, LV, PD, and %LAA-950 was performed. The percentage of low attenuation areas less than -950 Hounsfield units (%LAA-950) was defined as the extent of emphysema. The longitudinal data in the two consecutive years of these current smoker group and ex-smoker group were compared by paired t-test.RESULTS:The LV, %LAA-950, WT and WA% of current smokers increased more rapidly each year than that of ex-smokers. The PD and LD of current smokers declined more rapidly each year than that of ex-smokers.CONCLUSIONS:This study shows that pulmonary damage caused by smoking related to the smoking status, can be measured. Smoking cessation has a positive role in alleviating the progress of pulmonary damage.

Assessment of the correlates of respiratory morbidity related quality of life, using St George Respiratory Questionnaire (SGRQ) among male COPD patients

Background: COPD is ranked eighth among the top 20 conditions causing disability globally. Assessment in subjective areas such as dyspnea and HRQL provides complementary information to physiologic measurements. Lower Health-Related Quality of Life has been associated with mortality and morbidity in COPD.Methods: The study was conducted at the Department of Respiratory Medicine and at Vallabhbhai Patel Chest Institute and the associated, Vishwanathan Chest Hospital, University of Delhi. Between September 2012 to August 2013. We conducted present study on 40 male COPD subjects aged more than 45 years, divided into 4 groups based on CT phenotype as normal, Airway Dominant (AD), Emphysema Dominant (ED) and mixed types. We compared the St. George Respiratory Questionnaire scores, 6 Minutes’ walk Distance scores, Clinical parameters, Spirometry indices across these phenotypes. Results: The mean SGRQ score in present study was 54.07 ± 17.24 (Range :17.3 to 84.57). The Mean 6MWD in present study was 434.58 ± 125.47 metres. The significant parameters which had correlation with SGRQ total score were Age (r=0.343, p = 0.03), 6MWD (-0.397, p = 0.011), FEV1 /FVC (0.499, p&lt; 0.001), DLCO (-0.601, p &lt;0.001), Low attenuation areas in CT (0.606, p&lt; 0.001). Conclusions: 6MWD, FEV1/FVC, age, Low attenuation areas in CT, DLCO had an influence on the quality of life as measured by SGRQ scores in present study. Therapeutic approaches to improve the quality of life in COPD should take these indices into consideration.

CT-based Visual Classification of Emphysema: Association with Mortality in the COPDGene Study.

PurposeTo determine whether visually assessed patterns of emphysema at CT might provide a simple assessment of mortality risk among cigarette smokers.Materials and MethodsOf the first 4000 cigarette smokers consecutively enrolled between 2007 and 2011 in this COPDGene study, 3171 had data available for both visual emphysema CT scores and survival. Each CT scan was retrospectively visually scored by two analysts using the Fleischner Society classification system. Severity of emphysema was also evaluated quantitatively by using percentage lung volume occupied by low-attenuation areas (voxels with attenuation of −950 HU or less) (LAA-950). Median duration of follow-up was 7.4 years. Regression analysis for the relationship between imaging patterns and survival was based on the Cox proportional hazards model, with adjustment for age, race, sex, height, weight, pack-years of cigarette smoking, current smoking status, educational level, LAA-950, and (in a second model) forced expiratory volume in 1 second (FEV1).ResultsObserver agreement in visual scoring was good (weighted κ values, 0.71–0.80). There were 519 deaths in the study cohort. Compared with subjects who did not have visible emphysema, mortality was greater in those with any grade of emphysema beyond trace (adjusted hazard ratios, 1.7, 2.5, 5.0, and 4.1, respectively, for mild centrilobular emphysema, moderate centrilobular emphysema, confluent emphysema, and advanced destructive emphysema, P < .001). This increased mortality generally persisted after adjusting for LAA-950.ConclusionThe visual presence and severity of emphysema is associated with significantly increased mortality risk, independent of the quantitative severity of emphysema.Online supplemental material is available for this article.

Is severe emphysema, as defined by quantitative CT measurement, a negative risk factor of radiation fibrosis?

To investigate whether patients with emphysema, as evaluated by quantitative CT image measurement, are at risk of developing radiation pneumonitis (RP) after radiotherapy (RT) for non-small cell lung cancer (NSCLC). Between March 2011 and June 2015, 68 consecutive patients with Stage I NSCLC treated with a RT dose of 75 Gy given in 30 fractions were enrolled. The median age was 79 years and there were 45 males and 23 females. The number of patients with T1 and T2 were 49 and 19, respectively. The severity of emphysema was evaluated by the percentages of the low attenuation area (LAA) of ≤-860 or -950 Hounsfield unit (HU) and average HU in the whole lung. The mean difference percentages of LAA of ≤-860 (p = 0.0004) or -950 HU (p = 0.005) and average HU (p = 0.001) in patients with RP were significantly lower than those in patients without RP. The area under curve (AUC) of average HU was significantly higher than AUC of LAA of ≤-860 (p < 0.0001) or -950 HU (p < 0.0001). The RP rate after RT was significantly lower when the average HU values were ≤-850 HU (p = 0.0003). Patients with emphysema evaluated by average HU (≤-850 HU) in the whole lung were found to be at low risk of RP after RT. Advances in Knowledge: Quantitative measurement of average HU from CT images was predicted of RP after RT.

Predicting the response to a bronchodilator in patients with airflow obstruction and lung cancer

BackgroundThe aim of the present study was to clarify the predictors of the response of patients with resectable lung cancer and untreated airflow obstruction to tiotropium, an antimuscarinic bronchodilator. MethodsTiotropium was administered to 29 preoperative patients with untreated airflow obstruction. The forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured before and after the introduction of tiotropium. The response to tiotropium was determined based on the percentage gain in the FEV1. The volume of the total lung area (TLV) and the low-attenuation area (LAA) was measured by deep inspiratory computed tomography based on the predefined thresholds for attenuation values. ResultsThe introduction of tiotropium resulted in a 15% gain in the FEV1 (P < 0.001). A univariate regression analysis revealed that the FVC/TLV was the best predictor of the gain in FEV1, followed by the FEV1/FVC. Based on the results of a multiple regression analysis, a regression equation to predict a gain in the FEV1 was generated using the FVC, TLV, and LAA. A receiver operating characteristic curve analysis revealed that this equation led to the highest area under the curve for predicting a major response to tiotropium, followed by the FVC/TLV and FEV1/FVC. Postoperatively, six of the 20 minor responders experienced a progression of dyspnea. In contrast, none of the major responders experienced a progression of dyspnea (P < 0.05). ConclusionsWe developed an equation for predicting the response to tiotropium using parameters obtained from spirometry and quantitative computed tomography. A large-scale study to validate the usefulness of this equation is warranted.

Assessment of emphysema severity as measured on three-dimensional computed tomography images for predicting respiratory complications after lung surgery.

Emphysema is one of the main causes of respiratory complications in patients operated on for lung cancer. We have used three-dimensional computed tomography (3D CT) for surgical simulations, as well as for depicting emphysematous areas as low attenuation areas (LAAs) and visual scores based on the Goddard classification (Goddard score), which is a visual scale of the area of vascular disruption and LAA for each lung field. This study aimed to investigate the effectiveness of the 3D CT function for assessing emphysema severity and its association with respiratory complications. The study included 504 lung cancer patients who had preoperative 3D CT from October 2010 to March 2015. Goddard score and LAA% (LAA/total lung volume) were measured using 3D CT data. The relationship between respiratory complications and independent variables was investigated. Postoperative respiratory complications were observed in 69 (13.6%) patients. The receiver operating characteristic curves for respiratory complications determined using the Goddard score and LAA% dichotomized at each cut-off level (1 and 0.7%, respectively) showed that the events were observed in 32% of the patients with a Goddard score ≥1 and in 25% of the patients with an LAA% ≥0.7. On multivariable analyses, the Goddard score was significantly correlated with postoperative respiratory complications (P < 0.001). Preoperative measurement of the Goddard score and LAA% using 3D CT in patients with lung cancer, particularly with the coexistence of emphysema, was beneficial for predicting postoperative respiratory complications.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

Solid Small Renal Mass Without Gross Fat: CT Criteria for Achieving Excellent Positive Predictive Value for Renal Cell Carcinoma.

The purpose of this study was to evaluate CT criteria for achieving high positive predictive value (PPV) for renal cell carcinoma (RCC) in patients with solid small renal masses (SRMs) less than 4 cm without macroscopic fat. One hundred fifty consecutive patients with a solid SRM without macroscopic fat (mean size ± SD, 2.5 ± 0.8 cm) who underwent CT including unenhanced, corticomedullary (CMP), and nephrographic phases (NP) were evaluated. Pathologically proven solid SRMs without macroscopic fat were classified into RCC (n = 131) and not RCC (n = 19). A "persistent low" sign was defined as a focal area or areas of low attenuation seen at the same location within the lesion on both CMP and NP imaging. Calcification, shape, and lesion attenuation on unenhanced CT were analyzed by two independent readers. PPV of CT criteria (calcification [criterion 1] or spherical shape, lower or equal attenuation, and persistent low sign [criterion 2]) for RCC was 98.3% (58/59) for reader 1 and 100% (53/53) for reader 2. Weighted kappa of interreader agreement was 1.000 for calcification, 0.966 of lower or equal attenuation, 0.834 for spherical shape, 0.823 for persistent low sign, and 0.829 for CT criteria. Interpretation of CT allowed reproducible and excellent PPV for RCC. Current CT criteria may effectively shorten the management process for solid SRMs without macroscopic fat by reducing unnecessary biopsy for a substantial number of RCCs showing typical CT findings.

Lumen area change (Delta Lumen) between inspiratory and expiratory multidetector computed tomography as a measure of severe outcomes in asthmatic patients

Quantitative computed tomographic (QCT) biomarkers of airway morphology hold potential for understanding and monitoring regional airway remodeling in asthmatic patients. We sought to determine whether the change in airway lumen area between total lung capacity (TLC) and functional residual capacity (FRC) lung volumes measured from CT imaging data was correlated with severe outcomes in asthmatic patients. We studied 152 asthmatic patients (90 female and 62 male patients) and 33 healthy subjects (12 female and 21 male subjects) using QCT. Postprocessing of airways at generations 1 to 5 (1=trachea) was performed for wall area percentage, wall thickness percentage (WT%), lumen area at baseline total lung capacity (LATLC), lumen area at baseline functional residual capacity (LAFRC), and low attenuation area at FRC. Anew metric (reflecting remodeling, distal air trapping, or both), Delta Lumen, was determined as follows: Percentage difference in lumen area (LATLC-LAFRC)/LATLC×100. Postprocessing of 4501 airway segments was performed (3681 segments in the 152 patients with asthma and 820 segments in the 33 healthy subjects; range, 17-28 segments per subject). Delta Lumen values were negatively correlated with WT% and low attenuation area (P<.01) in asthmatic patients. Delta Lumen values were significantly lower for airway generations 3 to 5 (segmental airways) in subjects undergoing hospitalization because of exacerbation and in patients with refractory asthma requiring treatment with systemic corticosteroids. WT% and low attenuation area were positively and Delta Lumen values were negatively associated with systemic corticosteroid treatment (P<.05), suggesting that a reduced Delta Lumen value is a potential outcome biomarker in patients with severe asthma. Reduced Delta Lumen value in the central airways measured by using QCT is a promising exploratory biomarker of unstable refractory asthma that warrants further study.

Emphysema and extrapulmonary tissue loss in COPD: a multi-organ loss of tissue phenotype.

We tested whether emphysema progression accompanies enhanced tissue loss in other body compartments in 1817 patients from the ECLIPSE chronic obstructive pulmonary disease (COPD) cohort.Clinical and selected systemic biomarker measurements were compared in subjects grouped by quantitative tomography scan emphysema quartiles using the percentage of low attenuation area (LAA%). Lowest and highest quartile patients had amino-acid metabolomic profiles. We related LAA% to 3 years decline in lung function (forced expiratory volume in 1 s (FEV1)), body mass index (BMI), fat-free mass index (FFMI) and exacerbations, hospitalisations and mortality rates.Participants with more baseline emphysema had lower FEV1, BMI and FFMI, worse functional capacity, and less cardiovascular disease but more osteoporosis. Systemic C-reactive protein and interleukin-6 levels were similar among groups, but club cell protein 16 was higher and interleukin-8, surfactant protein D and soluble receptor for advanced glycation end product were lower with more emphysema. Metabolomics differed between extreme emphysema quartiles. Patients with more emphysema had accelerated FEV1, BMI and FFMI decline and more exacerbations, hospitalisations and mortality.COPD patients with more emphysema undergo excessive loss of pulmonary and extrapulmonary tissue, which is probably related to abnormal tissue maintenance. Because of worse clinical outcomes, we propose this subgroup be named the multi-organ loss of tissue (MOLT) COPD phenotype.

Emphysematous change with scleroderma-associated interstitial lung disease: the potential contribution of vasculopathy?

BackgroundPulmonary emphysema combined with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) occurs more often in smokers but also in never-smokers. This study aimed to describe a new finding characterized by peculiar emphysematous change with SSc-associated ILD (SSc-ILD).MethodsWe conducted a retrospective review of 21 consecutive patients with SSc-ILD diagnosed by surgical lung biopsy and focused on the radio-pathological correlation of the emphysematous change.ResultsPathological pulmonary emphysema (p-PE) with SSc-ILD was the predominant complication in 16 patients (76.2%) with/without a smoking history, of whom 62.5% were never-smokers. A low attenuation area (LAA) within interstitial abnormality on high-resolution computed tomography (HRCT) was present in 31.3%. Diffusing capacity of the lung for carbon monoxide (DLCO) was lower, disease extent on HRCT higher, and intimal/medial thickening in muscular pulmonary arteries more common in the patients with p-PE with SSc-ILD. However, forced vital capacity (FVC) was well preserved regardless of whether p-PE was observed. Most SSc-ILD patients had pulmonary microvasculature changes in arterioles (90.5%), venules (85.7%), and interlobular veins (81.0%).ConclusionsPulmonary emphysematous changes (LAA within interstitial abnormalities on HRCT and destruction of fibrously thickened alveolar walls) are specific and novel radio-pathological features of SSc-ILD. Peripheral vasculopathy may help to destroy the fibrously thickened alveolar walls, resulting in emphysematous change in SSc-ILD.

Systemic vascular dysfunction is associated with emphysema burden in mild COPD.

Cardiovascular diseases play a major role in morbidity and mortality in the earlier stages of COPD. We hypothesized that systemic vascular dysfunction would be present even in patients who are currently considered at "low-risk" for negative cardiovascular outcomes, i.e., those with largely preserved FEV1, few exacerbations and only mild burden of respiratory symptoms (GOLD spirometric grade 1, clinical group A). 16 patients (FEV1 = 86 ± 13%) and 16 age- and gender-matched controls underwent measurements of: a) central arterial stiffness by pulse wave velocity, b) brachial flow-mediated dilation and c) forearm muscle oxygenation by near-infrared spectroscopy. Computed tomography quantified emphysema (% of low attenuation areas (LAA)) and airway disease. Patients and controls were well matched for key clinical variables including co-morbidities burden. Thirteen patients presented with more than 5% LAA: emphysema extension was negatively related to transfer factor for carbon monoxide (TLCO) (r = -0.63; p = .01). Compared to controls, patients had higher central arterial stiffness, lower normalized (to shear stress) flow-mediated dilation, delayed time to peak flow-mediated dilation and poorer muscle oxygenation (p < .05). TLCO and emphysema, but not airway disease, were significantly related to each of these functional abnormalities (r values ranging from 0.51 to 0.66; p < .05). Systemic vascular dysfunction is present in the earlier stages of COPD, particularly in patients with greater emphysema burden and low TLCO. Regardless FEV1, patients showing those structural and functional abnormalities might be at higher risk of negative events thereby deserving closer follow-up for early detection of cardiovascular disease.

Impact of Model-Based Iterative Reconstruction on the Correlation between Computed Tomography Quantification of a Low Lung Attenuation Area and Airway Measurements and Pulmonary Function Test Results in Normal Subjects.

ObjectiveTo compare correlations between pulmonary function test (PFT) results and different reconstruction algorithms and to suggest the optimal reconstruction protocol for computed tomography (CT) quantification of low lung attenuation areas and airways in healthy individuals.Materials and MethodsA total of 259 subjects with normal PFT and chest CT results were included. CT scans were reconstructed using filtered back projection, hybrid-iterative reconstruction, and model–based IR (MIR). For quantitative analysis, the emphysema index (EI) and wall area percentage (WA%) were determined. Subgroup analysis according to smoking history was also performed.ResultsThe EIs of all the reconstruction algorithms correlated significantly with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (all p < 0.001). The EI of MIR showed the strongest correlation with FEV1/FVC (r = −0.437). WA% showed a significant correlation with FEV1 in all the reconstruction algorithms (all p < 0.05) correlated significantly with FEV1/FVC for MIR only (p < 0.001). The WA% of MIR showed the strongest correlations with FEV1 (r = −0.205) and FEV1/FVC (r = −0.250). In subgroup analysis, the EI of MIR had the strongest correlation with PFT in both ever-smoker and never-smoker subgroups, although there was no significant difference in the EI between the reconstruction algorithms. WA% of MIR showed a significantly thinner airway thickness than the other algorithms (49.7 ± 7.6 in ever-smokers and 49.5 ± 7.5 in never-smokers, all p < 0.001), and also showed the strongest correlation with PFT in both ever-smoker and never-smoker subgroups.ConclusionCT quantification of low lung attenuation areas and airways by means of MIR showed the strongest correlation with PFT results among the algorithms used, in normal subjects.

Lung, Fat and Bone: Increased Adiponectin Associates with the Combination of Smoking-Related Lung Disease and Osteoporosis

Background: Adiponectin has been proposed as a biomarker of disease severity and progression in chronic obstructive pulmonary disease (COPD) and associated with spirometry-defined COPD and with computed tomography (CT)-measured emphysema. Increased adiponectin plays a role in other diseases including diabetes/metabolic syndrome, cardiovascular disease and osteoporosis. Previous studies of adiponectin and COPD have not assessed the relationship of adiponectin to airway disease in smokers and have not evaluated the effect of other comorbid diseases on the relationship of adiponectin and lung disease. We postulated that adiponectin levels would associate with both airway disease and emphysema in smokers with and without COPD, and further postulated that body composition and the comorbid diseases of osteoporosis, cardiovascular disease and diabetes might influence adiponectin levels. Methods: Current and former smokers from the COPD Genetic Epidemiology study (COPDGene) (n= 424) were assigned to 4 groups based on CT lung characteristics and volumetric Bone Density (vBMD). Emphysema (% low attenuation area at -950) and airway disease (Wall area %) were used to assess smoking-related lung disease (SRLD). Group 1) Normal Lung with Normal vBMD; Group 2) Normal Lung and Osteoporosis; Group 3) SRLD with Normal vBMD; Group 4) SRLD with Osteoporosis. Cardiovascular disease (CVD), diabetes, C-reactive protein (CRP) and T-cadherin (soluble receptor for adiponectin) levels were defined for each group. Body composition was derived from chest CT. Multivariable regression assessed effects of emphysema, wall area %, bone density, comorbid diseases and other key factors on log adiponectin. Results: Group 4, SRLD with Osteoporosis, had significantly higher adiponectin levels compared to other groups and the effect persisted in adjusted models. Systemic inflammation (by CRP) was associated with SRLD in Groups 3 and 4 but not with osteoporosis alone. In regression models, lower bone density and worse emphysema were associated with higher adiponectin. Airway disease was associated with higher adiponectin levels when T-cadherin was added to the model. Male gender, greater muscle and fat were associated with lower adiponectin. Conclusions: Adiponectin is increased with both airway disease and emphysema in smokers. Bone density, and fat and muscle composition are all significant factors predicting adiponectin that should be considered when it is used as a biomarker of COPD. Increased adiponectin from chronic inflammation may play a role in the progression of bone loss in COPD and other lung diseases.

Performance of quantitative CT parameters in assessment of disease severity in COPD: A prospective study.

Background:Both emphysematous destruction of lung parenchyma and airway remodeling is thought to contribute to airflow limitation in cases of chronic obstructive pulmonary disease (COPD).Objective:To evaluate the value of quantitative computed tomography (QCT) parameters of emphysema and airway disease with disease severity in patients with COPD.Materials and Methods:We prospectively studied 50 patients with COPD, which included nonsmokers and patients with different degrees of cumulative smoking exposure. Three QCT parameters namely LAA% (low attenuation area percentage), WA% (Wall area percentage), and pi10 were calculated as per the standard technique. Forced expiratory volume in 1 s (FEV1), BODE score, and MMRC dyspnea scale were used as measures of disease severity.Results:FEV1 was inversely and significantly associated with all three QCT parameters. Receiver operated characteristic curves in prediction of GOLD class 3 COPD yielded cut-off values of 12.2, 61.45, and 3.5 for LAA%, WA%, and pi10, respectively, with high sensitivities and specificities. In multiple linear regression model, however, only LAA% proved to be significantly associated with FEV1, BODE, and dyspnea.Conclusion:QCT indices of both emphysema and airway disease influence FEV1, dyspnea, and BODE score in patients with COPD. Emphysema, however, appears to be more closely related to disease severity.

A CT Scan Harmonization Technique to Detect Emphysema and Small Airway Diseases.

Recent studies have suggested the central role of small airway destruction in the pathogenesis of COPD leading to further parenchymal destruction. This evidence has sparked the interest in in-vivo assessment of small airway disease overall at the early onset of the disease. The parametric response mapping (PRM) technique has been proposed to distinguish gas trapping due to small airway disease from low attenuation areas due to emphysema. Despite its success, the PRM technique shows some limitations that are precluding the interpretation of its results. The density value used to assess gas trapping highly depends on acquisition parameters, such as dose and reconstruction kernel, and changes in body size, that introduce inhomogeneous photon absorption patterns. In particular, many studies using PRM employ inspiratory and expiratory images that are obtained at different dose levels. Emphysema impact in early disease may be confounded with the gas trapping due to the noise introduced by differences in the acquisition during the PRM. In this work, we propose a CT harmonization technique to remove the nuisance factors to distinguish between small airway disease and emphysema. Our results show that the measurements based on CT harmonization provide an increase in the detection of both emphysema and airway disease, resulting in a statistically significant impact of both components and a better association with lung function measures.

Significance of Low-Attenuation Cluster Analysis on Quantitative CT in the Evaluation of Chronic Obstructive Pulmonary Disease.

ObjectiveTo assess clinical feasibility of low-attenuation cluster analysis in evaluation of chronic obstructive pulmonary disease (COPD).Materials and MethodsSubjects were 199 current and former cigarette smokers that underwent CT for quantification of COPD and had physiological measurements. Quantitative CT (QCT) measurements included low-attenuation area percent (LAA%) (voxels ≤ −950 Hounsfield unit [HU]), and two-dimensional (2D) and three-dimensional D values of cluster analysis at three different thresholds of CT value (−856, −910, and −950 HU). Correlation coefficients between QCT measurements and physiological indices were calculated. Multivariable analyses for percentage of predicted forced expiratory volume at one second (%FEV1) was performed including sex, age, body mass index, LAA%, and D value had the highest correlation coefficient with %FEV1 as independent variables. These analyses were conducted in subjects including those with mild COPD (global initiative of chronic obstructive lung disease stage = 0–II).ResultsLAA% had a higher correlation coefficient (-0.549, p < 0.001) with %FEV1 than D values in subjects while 2D D−910HU (−0.350, p < 0.001) revealed slightly higher correlation coefficient than LAA% (−0.343, p < 0.001) in subjects with mild COPD. Multivariable analyses revealed that LAA% and 2D D value−910HU were significant independent predictors of %FEV1 in subjects and that only 2D D value−910HU revealed a marginal p value (0.05) among independent variables in subjects with mild COPD.ConclusionLow-attenuation cluster analysis provides incremental information regarding physiologic severity of COPD, independent of LAA%, especially with mild COPD.