Role of computed tomography in quantitative assessment of emphysema

Pulmonary emphysema, together with chronic bronchitis is a part of chronic obstructive pulmonary disease (COPD), which is one of the leading causes of death in the United States and worldwide. There are many methods to diagnose emphysema. Unfortunately many of them, for example pulmonary function tests (PFTs), clinical signs and conventional radiology are able to detect emphysema usually in its late stages when a great portion of lung parenchyma has been already destroyed by the disease. Computed tomography (CT) allows for early detection of emphysema. CT also makes it possible to quantify the total amount of emphysema in the lungs which is important in order to precisely estimate the severity of the disease. Those abilities of CT are important in monitoring the course of the disease and in attempts to prevent its further progression. In this review we discuss currently available methods for imaging emphysema with emphasis on the quantitative assessment of emphysema. To date, quantitative methods have not been widely used clinically, however, the initial results of several research studies regarding this subject are very encouraging

Comorbid Conditions in Idiopathic Pulmonary Fibrosis: Recognition and Management.

Idiopathic pulmonary fibrosis (IPF), a fibrosing interstitial pneumonia of unknown etiology, primarily affects older adults and leads to a progressive decline in lung function and quality of life. With a median survival of 3-5 years, IPF is the most common and deadly of the idiopathic interstitial pneumonias. Despite the poor survivorship, there exists substantial variation in disease progression, making accurate prognostication difficult. Lung transplantation remains the sole curative intervention in IPF, but two anti-fibrotic therapies were recently shown to slow pulmonary function decline and are now approved for the treatment of IPF in many countries around the world. While the approval of these therapies represents an important first step in combatting of this devastating disease, a comprehensive approach to diagnosing and treating patients with IPF remains critically important. Included in this comprehensive assessment is the recognition and appropriate management of comorbid conditions. Though IPF is characterized by single organ involvement, many comorbid conditions occur within other organ systems. Common cardiovascular processes include coronary artery disease and pulmonary hypertension (PH), while gastroesophageal reflux and hiatal hernia are the most commonly encountered gastrointestinal disorders. Hematologic abnormalities appear to place patients with IPF at increased risk of venous thromboembolism, while diabetes mellitus (DM) and hypothyroidism are prevalent metabolic disorders. Several pulmonary comorbidities have also been linked to IPF, and include emphysema, lung cancer, and obstructive sleep apnea. While the treatment of some comorbid conditions, such as CAD, DM, and hypothyroidism is recommended irrespective of IPF, the benefit of treating others, such as gastroesophageal reflux and PH, remains unclear. In this review, we highlight common comorbid conditions encountered in IPF, discuss disease-specific diagnostic modalities, and review the current state of treatment data for several key comorbidities

Current concepts on the role of inflammation in COPD and lung cancer

Chronic obstructive pulmonary disease (COPD) and lung cancer are leading cause of death, and both are associated with cigarette smoke exposure. It has been shown that 50–70% of patients diagnosed with lung cancer suffer from COPD, and reduced lung function is an important event in lung cancer suggesting an association between COPD and lung cancer. However, a causal relationship between COPD and lung tumorigenesis is not yet fully understood. Recent studies have suggested a central role of chronic inflammation in pathogenesis of both the diseases. For example, immune dysfunction, abnormal activation of NF-κB, epithelial-to-mesenchymal transition, altered adhesion signaling pathways, and extracellular matrix degradation/altered signaling are the key underlying mechanisms in both COPD and lung cancer. These parameters along with other processes, such as chromatin modifications/epigenetic changes, angiogenesis, and autophagy/apoptosis are altered by cigarette smoke, are crucial in the development of COPD and lung cancer. Understanding the cellular and molecular mechanisms underlying these processes will provide novel avenues for halting the chronic inflammation in COPD and devising therapeutic strategies against lung cancer

Diagnosing and mapping pulmonary emphysema on X-ray projection images

To assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution. Lungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology. Transmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology. In a murine model, the complementary information provided by X-ray transmission and dark-field images adds incremental diagnostic value in detecting pulmonary emphysema and visualizing its regional distribution as compared to conventional X-ray projections

Allosteric modulation of beta1 integrin function induces lung repair in animal model of emphysema.

Emphysema is a progressive lung disease characterised by loss of lung parenchyma with associated functional changes including decreased tissue elastance. Here we report beta1 integrin is a novel target for tissue repair and regeneration in emphysema. We show a single dose of a monoclonal antibody against beta1 integrin induced both functional and structural reversal of elastase-induced lung injury in vivo, and we found that similar matrix remodelling changes occurred in human lung tissue. We also identified a potential mechanism of action as this allosteric modulation of beta1 integrin inhibited elastase-induced caspase activation, F-actin aggregate formation and changes in cellular ATP levels. This was accompanied by maintenance of beta1?integrin levels and inhibition of caveolin-1 phosphorylation. We propose that allosteric modulation of beta1 integrin-mediated mechanosensing prevents cell death associated with lung injury and progressive emphysema, thus allowing cells to survive and for repair and regeneration to ensue

Automatic Emphysema Detection using Weakly Labeled HRCT Lung Images

A method for automatically quantifying emphysema regions using High-Resolution Computed Tomography (HRCT) scans of patients with chronic obstructive pulmonary disease (COPD) that does not require manually annotated scans for training is presented. HRCT scans of controls and of COPD patients with diverse disease severity are acquired at two different centers. Textural features from co-occurrence matrices and Gaussian filter banks are used to characterize the lung parenchyma in the scans. Two robust versions of multiple instance learning (MIL) classifiers, miSVM and MILES, are investigated. The classifiers are trained with the weak labels extracted from the forced expiratory volume in one minute (FEV$_1$) and diffusing capacity of the lungs for carbon monoxide (DLCO). At test time, the classifiers output a patient label indicating overall COPD diagnosis and local labels indicating the presence of emphysema. The classifier performance is compared with manual annotations by two radiologists, a classical density based method, and pulmonary function tests (PFTs). The miSVM classifier performed better than MILES on both patient and emphysema classification. The classifier has a stronger correlation with PFT than the density based method, the percentage of emphysema in the intersection of annotations from both radiologists, and the percentage of emphysema annotated by one of the radiologists. The correlation between the classifier and the PFT is only outperformed by the second radiologist. The method is therefore promising for facilitating assessment of emphysema and reducing inter-observer variability.Comment: Accepted at PLoS ON

Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a global health problem, and current therapy for COPD is poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. Imbalance of oxidant/antioxidant balance caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g. NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervening COPD

Influencing factors of pneumothorax and parenchymal haemorrhage after CT-guided transthoracic needle biopsy : single-institution experience

Purpose: To evaluate the incidences and influencing factors of pneumothorax and parenchymal haemorrhage after computed tomography (CT)-guided transthoracic needle biopsy (TTNB). Material and methods: A retrospective analysis of 216 patients who underwent CT-guided TTNB was performed. The frequencies and risk factors of pneumothorax and parenchymal haemorrhage were determined. P values less than 0.05 were considered statistically significant. Results: The incidences of pneumothorax and parenchymal haemorrhage were 23.1% and 45.4%, respectively. Twenty-two per cent of patients with pneumothorax needed percutaneous drainage, but all patients with parenchymal haemorrhage had clinical improvement after conservative treatment. No procedure-related mortality was detected. Univariate analysis showed that underlying pulmonary infection, lesion size of less than 1 cm, and lesion depth of more than 2 cm were significant influencing factors of pneumothorax. A significant relationship between the underlying chronic obstructive pulmonary disease (COPD) and the need for drainage catheter insertion was found. Pulmonary haemorrhage was more likely to occur in patients with underlying malignancy, solid pulmonary nodule, lesion size of 3 cm or less, and lesion depth of more than 3 cm. Consolidation was the protective factor for pulmonary haemorrhage. Sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV), and accuracy of CT-guided core needle biopsy (CNB) for the diagnosis of malignancy were 95.7%, 100%, 100%, 93.3%, and 97.3%, respectively. The rate of diagnostic failure was 10.2%. Conclusions: Pulmonary hemorrhage is the most common complication after CT-guided TTNB. Influencing factors for pneumothorax are underlying pulmonary infection, lesion size 2 cm. Underlying malignancy, solid pulmonary nodule, lesion size ≤ 3 cm, and lesion depth > 3 cm are associated with pulmonary haemorrhage