Clinical characteristics of chronic bronchitic, emphysematous and ACOS phenotypes in COPD patients with frequent exacerbations.

PURPOSE: Chronic bronchitis (CB), emphysematous (EM) and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) phenotypes in COPD are well recognized. This study aimed to investigate distinguishing characteristics of these phenotypes in COPD patients with frequent exacerbations (FE). PATIENTS AND METHODS: A retrospective study was carried out. COPD patients with acute exacerbations were consecutively reviewed from November 2015 to October 2016. Patients were divided into FE and infrequent exacerbations (iFE) subgroups. RESULTS: A total of 142 eligible COPD subjects were reviewed. In the CB phenotype subgroup, age, body mass index, forced expiratory volume in 1 second (FEV1) % predicted, COPD assessment test (CAT), modified Medical Research Council breathlessness measurement (mMRC) dyspnea scale, emphysema scores and arterial carbon dioxide pressure (PaCO2) were significantly different in subjects with FE when compared to those in subjects with iFE of CB. In the EM phenotype subgroup, age, CAT, mMRC scores and history of COPD were different in subjects with FE when compared to those in CB subjects with iFE. Multivariate analysis indicated that FEV1% predicted (odds ratio [OR] =0.90, P=0.04) and PaCO2 (OR =1.22, P=0.02) were independent risk factors for FE in COPD with CB phenotype, and CAT (OR =2.601, P=0.001) was the independent risk factor for FE in COPD with EM phenotype. No significant differences in characteristics were observed in ACOS phenotype subgroups with FE or iFE. CONCLUSION: In CB or EM phenotypes, COPD patients with FE present several differential clinical characteristics compared to patients with iFE, while the characteristics of ACOS phenotype in patients with FE need more investigation.

Size variation and collapse of emphysema holes at inspiration and expiration CT scan: evaluation with modified length scale method and image co-registration.

A novel approach of size-based emphysema clustering has been developed, and the size variation and collapse of holes in emphysema clusters are evaluated at inspiratory and expiratory computed tomography (CT). Thirty patients were visually evaluated for the size-based emphysema clustering technique and a total of 72 patients were evaluated for analyzing collapse of the emphysema hole in this study. A new approach for the size differentiation of emphysema holes was developed using the length scale, Gaussian low-pass filtering, and iteration approach. Then, the volumetric CT results of the emphysema patients were analyzed using the new method, and deformable registration was carried out between inspiratory and expiratory CT. Blind visual evaluations of EI by two readers had significant correlations with the classification using the size-based emphysema clustering method (r-values of reader 1: 0.186, 0.890, 0.915, and 0.941; reader 2: 0.540, 0.667, 0.919, and 0.942). The results of collapse of emphysema holes using deformable registration were compared with the pulmonary function test (PFT) parameters using the Pearson's correlation test. The mean extents of low-attenuation area (LAA), E1 (<1.5 mm), E2 (<7 mm), E3 (<15 mm), and E4 (≥15 mm) were 25.9%, 3.0%, 11.4%, 7.6%, and 3.9%, respectively, at the inspiratory CT, and 15.3%, 1.4%, 6.9%, 4.3%, and 2.6%, respectively at the expiratory CT. The extents of LAA, E2, E3, and E4 were found to be significantly correlated with the PFT parameters (r=-0.53, -0.43, -0.48, and -0.25), with forced expiratory volume in 1 second (FEV1; -0.81, -0.62, -0.75, and -0.40), and with diffusing capacity of the lungs for carbon monoxide (cDLco), respectively. The fraction of emphysema that shifted to the smaller subgroup showed a significant correlation with FEV1, cDLco, forced expiratory flow at 25%-75% of forced vital capacity, and residual volume (RV)/total lung capacity (r=0.56, 0.73, 0.40, and -0.58). A detailed assessment of the size variation and collapse of emphysema holes may be useful for understanding the dynamic collapse of emphysema and its functional relation.

[Phenotype specific therapy of COPD]. / Phänotyp-spezifische Therapie der COPD.

COPD is not a homogenous disease but consists of at least four different phenotypes: Emphysema, COPD with chronic bronchitis, asthma-COPD overlap syndrome (ACOS), and COPD with recurrent exacerbations. With differentiation, treatment can be designed phenotype-specific. Some modern drugs are not indicated in all phenotypes.

La BPCO n'est pas une maladie homogène. Quatre différents phénotypes peuvent être différentiés: BPCO avec emphysème, BPCO avec bronchite chronique, l'asthme-BPCO overlap syndrome (ACOS) et la BPCO avec des exacerbations fréquentes. Avec la différentiation du type la thérapie devient phénotype-spécifique. Quelques médicaments modernes ne sont pas indiqués que dans certains phénotypes.

Impact of emphysema heterogeneity on pulmonary function.

OBJECTIVES: To investigate the association between emphysema heterogeneity in spatial distribution, pulmonary function and disease severity. METHODS AND MATERIALS: We ascertained a dataset of anonymized Computed Tomography (CT) examinations acquired on 565 participants in a COPD study. Subjects with chronic bronchitis (CB) and/or bronchodilator response were excluded resulting in 190 cases without COPD and 160 cases with COPD. Low attenuations areas (LAAs) (≤ 950 Hounsfield Unit (HU)) were identified and quantified at the level of individual lobes. Emphysema heterogeneity was defined in a manner that ranged in value from -100% to 100%. The association between emphysema heterogeneity and pulmonary function measures (e.g., FEV1% predicted, RV/TLC, and DLco% predicted) adjusted for age, sex, and smoking history (pack-years) was assessed using multiple linear regression analysis. RESULTS: The majority (128/160) of the subjects with COPD had a heterogeneity greater than zero. After adjusting for age, gender, smoking history, and extent of emphysema, heterogeneity in depicted disease in upper lobe dominant cases was positively associated with pulmonary function measures, such as FEV1 Predicted (p<.001) and FEV1/FVC (p<.001), as well as disease severity (p<0.05). We found a negative association between HI% , RV/TLC (p<0.001), and DLco% (albeit not a statistically significant one, p = 0.06) in this group of patients. CONCLUSION: Subjects with more homogeneous distribution of emphysema and/or lower lung dominant emphysema tend to have worse pulmonary function.

Pulmonary interstitial emphysema in adults: a clinicopathologic study of 53 lung explants.

Pulmonary interstitial emphysema (PIE) is an unusual condition wherein air dissects through alveolar walls into the adjacent interstitial tissues where it forms cystic spaces with an associated inflammatory reaction. It is well described in premature infants with respiratory distress syndrome and is observed in adults, usually in association with ventilator use. The fibrotic and inflammatory appearance may mimic normal anatomic structures as well as pathologic changes such as granulomatous disease, organizing pneumonia, fibroblast foci of usual interstitial pneumonia, or lymphangiectasia. The presence of interstitial emphysema has not been well characterized in the adult population. We retrospectively reviewed 53 consecutive explanted lungs for the histologic presence of PIE, of which 19 (36%) cases were found to be positive. PIE was seen most commonly in patients with usual interstitial pneumonia. Review of the medical record for each patient revealed no correlation between the presence of PIE and duration of disease. A correlation was seen between prior ventilation and/or biopsy. These findings may indicate that PIE is a result of medical intervention; however, in the remainder of cases the disease process itself may have been a contributing factor.

Combined unclassifiable interstitial pneumonia and emphysema: a report of two cases.

We herein report two cases of combined pulmonary fibrosis and emphysema (CPFE), whose histological patterns of lung pathology could not be categorized into any subset of idiopathic interstitial pneumonias(IIPs). Case 1 was a 62-year-old man, who presented with dyspnea on exertion and cough. Case 2 was a 51-year-old man with a dry cough. The CT findings of both cases fit the definition of CPFE. Surgical lung biopsies of both patients revealed alveolar septal widening due to collagen deposition, with emphysema and respiratory bronchiolitis mainly in the subpleural parenchyma. These cases suggest that the fibrosis of CPFE includes smoking-related interstitial fibrosis other than the known histological patterns of IIPs.

Emphysema classification based on embedded probabilistic PCA.

In this article we investigate the suitability of a manifold learning technique to classify different types of emphysema based on embedded Probabilistic PCA (PPCA). Our approach finds the most discriminant linear space for each emphysema pattern against the remaining patterns where lung CT image patches can be embedded. In this embedded space, we train a PPCA model for each pattern. The main novelty of our technique is that it is possible to compute the class membership posterior probability for each emphysema pattern rather than a hard assignment as it is typically done by other approaches. We tested our algorithm with six emphysema patterns using a data set of 1337 CT training patches. Using a 10-fold cross validation experiment, an average recall rate of 69% is achieved when the posterior probability is greater than 75%. A quantitative comparison with a texture-based approach based on Local Binary Patterns and with an approach based on local intensity distributions shows that our method is competitive. The analysis of full lungs using our approach shows a good visual agreement with the underlying emphysema types and a smooth spatial relation.

Distinct quantitative computed tomography emphysema patterns are associated with physiology and function in smokers.

RATIONALE: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. OBJECTIVES: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. METHODS: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. MEASUREMENTS AND MAIN RESULTS: Compared with percentage of low-attenuation area less than -950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). CONCLUSIONS: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.

BODE-index, modified BODE-index and ADO-score in chronic obstructive pulmonary disease: relationship with COPD phenotypes and CT lung density changes.

COPD is a heterogeneous disorder whose assessment is going to be increasingly multidimensional. Grading systems such as BODE (Body-Mass Index, Obstruction, Dyspnea, Exercise), mBODE (BODE modified in grading of walked distance), ADO (Age, Dyspnea, Obstruction) are proposed to assess COPD severity and outcome. Computed tomography (CT) is deemed to reflect COPD lung pathologic changes. We studied the relationship of multidimensional grading systems (MGS) with clinically determined COPD phenotypes and CT lung density. Seventy-two patients underwent clinical and chest x-ray evaluation, pulmonary function tests (PFT), 6-minute walking test (6MWT) to derive: predominant COPD clinical phenotype, BODE, mBODE, ADO. Inspiratory and expiratory CT was performed to calculate mean lung attenuation (MLA), relative area with density below-950 HU at inspiration (RAI(-950)), and below -910 HU at expiration (RAE(-910)). MGS, PFT, and CT data were compared between bronchial versus emphysematous COPD phenotype. MGS were correlated with CT data. The prediction of CT density by means of MGS was investigated by direct and stepwise multivariate regression. MGS did not differ in clinically determined COPD phenotypes. BODE was more closely related and better predicted CT findings than mBODE and ADO; the better predictive model was obtained for CT expiratory data; stepwise regression models of CT data did not include 6MWT distance; the dyspnea score MRC was included only to predict RA-950 and RA-910 which quantify emphysema extent. BODE reflect COPD severity better than other MGS, but not its clinical heterogeneity. 6MWT does not significantly increase BODE predictivity of CT lung density changes.

CT assessment of subtypes of pulmonary emphysema in females.

We performed a retrospective study examining the prevalence and subtypes of pulmonary emphysema (PE) identified by computed tomography (CT) in females. We reviewed the records of 1,687 female subjects who had undergone CT. They were divided into the following 2 age groups:group A (＜50 years) and group B (≥50 years). PE was diagnosed by the presence of low-attenuation areas using visual assessment (grades 0-3) on CT images. Two subtypes of PE were observed:centrilobular emphysema (CLE) and paraseptal emphysema (PSE). PE was divided into the following 3 categories:I (CLE or CLE-predominant);II (CLE and PSE of equal extent);and III (PSE or PSE-predominant). PE was found in 64 of 274 smokers (23.3%) and 54 of 1,413 non-smokers (3.8%). In smoking subjects, when grades 1 and 2 were grouped together as mild PE, the mean age for CT grade 3 (severe PE) was significantly higher than that for mild PE. In group A, category III predominated, whereas category I was more prevalent in group B, in both smoking and non-smoking subjects. A high incidence of PE was found in smoking subjects as compared with non-smoking subjects. PSE predominated in younger subjects, whereas CLE predominated in older subjects.

Malformaciones pulmonares: enfisema lobar congénito / Lung malformations: lobar congenital emphysema

Congenital lobar emphysema (CLE) is a rare congenital lung anomaly. Clinical presentation varies from acute neonatal respiratory failure to recurrent episodes of tachypnea or infections. Chest x-ray is often enough to make the diagnosis in newborn, but a normal chest x-ray does not exclude the diagnosis and a CT scan must be done when there is a lung malformation suspect. The better antenatal ultrasound diagnosis has led to detection CLE in asymptomatic and mildly symptomatic infants, and involution of CLE has been demonstrated in some cases. Lobectomy is the treatment of choice for very symptomatic children, but could be expectant in the less symptomatic ones.

El enfisema lobar congénito (ELC), es una malformación pulmonar poco frecuente. Su presentación clínica varía desde la falla respiratoria en el recién nacido (RN) hasta episodios recurrentes de taquipnea o infecciones. La radiografía de tórax, muchas veces es suficiente para realizar el diagnóstico en el RN, pero ante una radiografía normal se debe realizar TAC de tórax si se sospecha malformación pulmonar. El aumento del diagnóstico por ecografía prenatal ha llevado a la pesquisa del ELC en lactantes asintomáticos o levemente sintomáticos, algunos de los cuales se ha demostrado involución de la malformación. El tratamiento de elección en niños francamente sintomáticos es la lobectomía, pudiendo ser conservador en el resto de los pacientes.

Quantitative analysis of pulmonary emphysema using local binary patterns.

We aim at improving quantitative measures of emphysema in computed tomography (CT) images of the lungs. Current standard measures, such as the relative area of emphysema (RA), rely on a single intensity threshold on individual pixels, thus ignoring any interrelations between pixels. Texture analysis allows for a much richer representation that also takes the local structure around pixels into account. This paper presents a texture classification-based system for emphysema quantification in CT images. Measures of emphysema severity are obtained by fusing pixel posterior probabilities output by a classifier. Local binary patterns (LBP) are used as texture features, and joint LBP and intensity histograms are used for characterizing regions of interest (ROIs). Classification is then performed using a k nearest neighbor classifier with a histogram dissimilarity measure as distance. A 95.2% classification accuracy was achieved on a set of 168 manually annotated ROIs, comprising the three classes: normal tissue, centrilobular emphysema, and paraseptal emphysema. The measured emphysema severity was in good agreement with a pulmonary function test (PFT) achieving correlation coefficients of up to |r| = 0.79 in 39 subjects. The results were compared to RA and to a Gaussian filter bank, and the texture-based measures correlated significantly better with PFT than did RA.

Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disorder in which a number of different pathological processes lead to recognition of patient subgroups that may have individual characteristics and distinct responses to treatment. OBJECTIVES: We tested the hypothesis that responses of lung function to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid might differ among patients with various COPD subtypes. METHODS: We classified 165 COPD patients into four subtypes according to the severity of emphysema and airflow obstruction: emphysema-dominant, obstruction-dominant, mild-mixed, and severe-mixed. The emphysema-dominant subtype was defined by an emphysema index on computed tomography of more than 20% and FEV(1) more than 45% of the predicted value. The obstruction-dominant subtype had an emphysema index < or = 20% and FEV(1) < or = 45%, the mild-mixed subtype had an emphysema index < or = 20% and FEV(1) > 45%, and the severe-mixed subtype had an emphysema index > 20% and FEV(1) < or = 45%. Patients were recruited prospectively and treated with 3 months of combined inhalation of long-acting beta-agonist and corticosteroid. RESULTS: After 3 months of combined inhalation of long-acting beta-agonist and corticosteroid, obstruction-dominant subtype patients showed a greater FEV(1) increase and more marked dyspnea improvement than did the emphysema-dominant subgroup. The mixed-subtype patients (both subgroups) also showed significant improvement in FEV(1) compared with the emphysema-dominant subgroup. Emphysema-dominant subtype patients showed no improvement in FEV(1) or dyspnea after the 3-month treatment period. CONCLUSION: The responses to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid differed according to COPD subtype.

Distinct clinical phenotypes of airways disease defined by cluster analysis.

Airways disease is currently classified using diagnostic labels such as asthma, chronic bronchitis and emphysema. The current definitions of these classifications may not reflect the phenotypes of airways disease in the community, which may have differing disease processes, clinical features or responses to treatment. The aim of the present study was to use cluster analysis to explore clinical phenotypes in a community population with airways disease. A random population sample of 25-75-yr-old adults underwent detailed investigation, including a clinical questionnaire, pulmonary function tests, nitric oxide measurements, blood tests and chest computed tomography. Cluster analysis was performed on the subgroup with current respiratory symptoms or obstructive spirometric results. Subjects with a complete dataset (n = 175) were included in the cluster analysis. Five clusters were identified with the following characteristics: cluster 1: severe and markedly variable airflow obstruction with features of atopic asthma, chronic bronchitis and emphysema; cluster 2: features of emphysema alone; cluster 3: atopic asthma with eosinophilic airways inflammation; cluster 4: mild airflow obstruction without other dominant phenotypic features; and cluster 5: chronic bronchitis in nonsmokers. Five distinct clinical phenotypes of airflow obstruction were identified. If confirmed in other populations, these findings may form the basis of a modified taxonomy for the disorders of airways obstruction.

Development of an automatic classification system for differentiation of obstructive lung disease using HRCT.

The motivation is to introduce new shape features and optimize the classifier to improve performance of differentiating obstructive lung diseases, based on high-resolution computerized tomography (HRCT) images. Two hundred sixty-five HRCT images from 82 subjects were selected. On each image, two experienced radiologists selected regions of interest (ROIs) representing area of severe centrilobular emphysema, mild centrilobular emphysema, bronchiolitis obliterans, or normal lung. Besides 13 textural features, additional 11 shape features were employed to evaluate the contribution of shape features. To optimize the system, various ROI size (16 x 16, 32 x 32, and 64 x 64 pixels) and other classifier parameters were tested. For automated classification, the Bayesian classifier and support vector machine (SVM) were implemented. To assess cross-validation of the system, a five-folding method was used. In the comparison of methods employing only the textural features, adding shape features yielded the significant improvement of overall sensitivity (7.3%, 6.1%, and 4.1% in the Bayesian and 9.1%, 7.5%, and 6.4% in the SVM, in the ROI size 16 x 16, 32 x 32, 64 x 64 pixels, respectively; t test, P < 0.01). After feature selection, most of cluster shape features were survived ,and the feature selected set shows better performance of the overall sensitivity (93.5 +/- 1.0% in the SVM in the ROI size 64 x 64 pixels; t test, P < 0.01). Adding shape features to conventional texture features is much useful to improve classification performance of obstructive lung diseases in both Bayesian and SVM classifiers. In addition, the shape features contribute more to overall sensitivity in smaller ROI.

Imaging of pulmonary emphysema: a pictorial review.

The term 'emphysema' is generally used in a morphological sense, and therefore imaging modalities have an important role in diagnosing this disease. In particular, high resolution computed tomography (HRCT) is a reliable tool for demonstrating the pathology of emphysema, even in subtle changes within secondary pulmonary lobules. Generally, pulmonary emphysema is classified into three types related to the lobular anatomy: centrilobular emphysema, panlobular emphysema, and paraseptal emphysema. In this pictorial review, we discuss the radiological--pathological correlation in each type of pulmonary emphysema. HRCT of early centrilobular emphysema shows an evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders. With enlargement of the dilated airspace, the surrounding lung parenchyma is compressed, which enables observation of a clear border between the emphysematous area and the normal lung. Because the disease progresses from the centrilobular portion, normal lung parenchyma in the perilobular portion tends to be preserved, even in a case of far-advanced pulmonary emphysema. In panlobular emphysema, HRCT shows either panlobular low attenuation or ill-defined diffuse low attenuation of the lung. Paraseptal emphysema is characterized by subpleural well-defined cystic spaces. Recent topics related to imaging of pulmonary emphysema will also be discussed, including morphometry of the airway in cases of chronic obstructive pulmonary disease, combined pulmonary fibrosis and pulmonary emphysema, and bronchogenic carcinoma associated with bullous lung disease.

New simple classification for operated bullous emphysema.

OBJECTIVES: Optimal results in bullectomy depend on both the size of the resected bulla volume and the reexpansion of the adjacent collapsed healthy pulmonary parenchyma. We hypothesized that the bigger the bulla is compared with residual volume, the greater are the possible benefits. We suggested a new prognostic classification according to bulla volume and its relationship with residual volume. METHODS: We retrospectively reviewed 121 patients with emphysematous bulla (>200 mL) who, from 1996 to 2006, underwent unilateral single (n = 64), unilateral multiple (n = 16), bilateral 1-stage (n = 9), and bilateral 2-stage (n = 32) bullectomies. Bulla volume and residual volume were measured by computed tomography and body plethysmography, respectively. Six-month postoperative decrement of residual volume values and their persistence below the baseline for 5 years were considered primary outcomes. Logistic regression was used to select significant variables. The receiver operating characteristic curve was used to identify the cutoff point for a possible classification system. RESULTS: There was no postoperative mortality. Significant postoperative improvements in respiratory function were found and correlated with bulla size. Residual volume improved in 75 patients (62%) and persisted in 20 patients (35% of the patients followed for > 5 years). Logistic regression selected bulla/residual volume ratio as the most predictive variable for both outcomes (P < .0001). The best cutoff individuated by the receiver operating characteristic curve analysis was 20% to achieve a high probability of residual volume improvement and 30% to minimize residual volume recurrence. CONCLUSIONS: Bullectomy provides good results, but more significant and long-lasting improvements are achievable with a greater ratio bulla/residual volume: scant for less than 20%, good but temporaneous for 20% to 30%, and good and long-lasting results for more than 30%.

[Imaging of emphysema]. / Bildgebung des Lungenemphysems.

Emphysema is defined as a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole accompanied by destruction of the alveolar walls and without obvious fibrosis. It is a very common disease with high morbidity and mortality. Histopathologically, there are two types of emphysema: panlobular emphysema, typically occurring in alpha1-antitrypsin deficiency, and centrilobular emphysema, which is strongly associated with cigarette smoking. Computed tomography (CT) allows detection of emphysema with higher sensitivity than conventional chest radiography and pulmonary function tests. CT also allows quantification of emphysema and depicts associated changes and complications. The differential diagnosis of emphysema, which is characterized by the absence of clearly definable walls on CT, includes cystic lung disease, bullae, lung laceration, Langerhans cell histiocytosis, and lymphangioleiomyomatosis -which are all characterized by visible walls on CT.