Evaluating Tissue Heterogeneity in the Radiologically Normal-Appearing Tissue in IPF Compared to Healthy Controls.

RATIONALE AND OBJECTIVES: Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease characterised by heterogeneously distributed fibrotic lesions. The inter- and intra-patient heterogeneity of the disease has meant that useful biomarkers of severity and progression have been elusive. Previous quantitative computed tomography (CT) based studies have focussed on characterising the pathological tissue. However, we hypothesised that the remaining lung tissue, which appears radiologically normal, may show important differences from controls in tissue characteristics. MATERIALS AND METHODS: Quantitative metrics were derived from CT scans in IPF patients (N = 20) and healthy controls with a similar age (N = 59). An automated quantitative software (CALIPER, Computer-Aided Lung Informatics for Pathology Evaluation and Rating) was used to classify tissue as normal-appearing, fibrosis, or low attenuation area. Densitometry metrics were calculated for all lung tissue and for only the normal-appearing tissue. Heterogeneity of lung tissue density was quantified as coefficient of variation and by quadtree. Associations between measured lung function and quantitative metrics were assessed and compared between the two cohorts. RESULTS: All metrics were significantly different between controls and IPF (p < 0.05), including when only the normal tissue was evaluated (p < 0.04). Density in the normal tissue was 14% higher in the IPF participants than controls (p < 0.001). The normal-appearing tissue in IPF had heterogeneity metrics that exhibited significant positive relationships with the percent predicted diffusion capacity for carbon monoxide. CONCLUSION: We provide quantitative assessment of IPF lung tissue characteristics compared to a healthy control group of similar age. Tissue that appears visually normal in IPF exhibits subtle but quantifiable differences that are associated with lung function and gas exchange.

Quantitative Analysis of Lung Shape in Idiopathic Pulmonary Fibrosis: Insights Into Disease- and Age-Associated Patterns.

RATIONALE AND OBJECTIVES: Fibrotic scarring in idiopathic pulmonary fibrosis (IPF) typically develops first in the posterior-basal lung tissue before advancing to involve more of the lung. The complexity of lung shape in the costo-diaphragmatic region has been proposed as a potential factor in this regional development. Intrinsic and disease-related shape could therefore be important for understanding IPF risk and its staging. We hypothesized that lung and lobe shape in IPF would have important differences from controls. MATERIALS AND METHODS: A principal component (PC) analysis was used to derive a statistical shape model (SSM) of the lung for a control cohort aged > 50 years (N = 39), using segmented lung and fissure surface data from CT imaging. Individual patient shape models derived for baseline (N = 18) and follow-up (N = 16) CT scans in patients with IPF were projected to the SSM to describe shape as the sum of the SSM average and weighted PC modes. Associations between the first four PC shape modes, lung function, percentage of fibrosis (fibrosis%) and pulmonary vessel-related structures (PVRS%), and other tissue metrics were assessed and compared between the two cohorts. RESULTS: Shape was different between IPF and controls (P < 0.05 for all shape modes), with IPF shape forming a distinct shape cluster. Shape had a negative relationship with age in controls (P = 0.013), but a positive relationship with age in IPF (P = 0.026). Some features of shape changed on follow-up. Shape in IPF was associated with fibrosis% (P < 0.05) and PVRS% (P < 0.05). CONCLUSION: Quantitative comparison of lung and lobe shape in IPF with controls of a similar age reveals shape differences that are strongly associated with age and percent fibrosis. The clustering of IPF cohort shape suggests that it could be an important feature to describe disease.

Pulmonary vessel volume in idiopathic pulmonary fibrosis compared with healthy controls aged > 50 years.

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive fibrosing interstitial pneumonia with an associated irreversible decline in lung function and quality of life. IPF prevalence increases with age, appearing most frequently in patients aged > 50 years. Pulmonary vessel-like volume (PVV) has been found to be an independent predictor of mortality in IPF and other interstitial lung diseases, however its estimation can be impacted by artefacts associated with image segmentation methods and can be confounded by adjacent fibrosis. This study compares PVV in IPF patients (N = 21) with PVV from a healthy cohort aged > 50 years (N = 59). The analysis includes a connected graph-based approach that aims to minimise artefacts contributing to calculation of PVV. We show that despite a relatively low extent of fibrosis in the IPF cohort (20% of the lung volume), PVV is 2-3 times higher than in controls. This suggests that a standardised method to calculate PVV that accounts for tree connectivity could provide a promising tool to provide early diagnostic or prognostic information in IPF patients and other interstitial lung disease.

Lung and fissure shape is associated with age in healthy never-smoking adults aged 20-90 years.

Lung shape could hold prognostic information for age-related diseases that affect lung tissue mechanics. We sought to quantify mean lung shape, its modes of variation, and shape associations with lung size, age, sex, and Body Mass Index (BMI) in healthy subjects across a seven-decade age span. Volumetric computed tomography from 83 subjects (49 M/34 F, BMI [Formula: see text]) was used to derive two statistical shape models using a principal component analysis. One model included, and the other controlled for, lung volume. Volume made the strongest contribution to shape when it was included. Shape had a strong relationship with age but not sex when volume was controlled for, and BMI had only a small but significant association with shape. The first principal shape mode was associated with decrease in the antero-posterior dimension from base to apex. In older subjects this was rapid and obvious, whereas younger subjects had relatively more constant dimension. A shift of the fissures of both lungs in the basal direction was apparent for the older subjects, consistent with a change in tissue elasticity with age. This study suggests a quantifiable structure-function relationship for the healthy adult lung that can potentially be exploited as a normative description against which abnormal can be compared.

Interstitial pneumonitis associated with sirolimus: a dilemma for lung transplantation.

Rapamycin/sirolimus (SR), trade named Rapammune (Wyeth-Ayerst, Sydney, Australia), is a potent immunosuppressive drug associated with myelosuppression, hypertension, hyperlipidemia, and infection. Rapamycin/sirolimus-induced pneumonitis has been described previously in renal transplant recipients, and this report describes a stable heart-lung transplant recipient who developed a pulmonary infiltrate that reversed after ceasing SR therapy. We believe that immunosuppression-induced pneumonitis in a lung allograft is a serious dilemma for lung transplant physicians

The accuracy of multidetector computed tomography in the diagnosis of non-occlusive mesenteric ischaemia in patients after cardiovascular surgery.

OBJECTIVE: To determine the accuracy of multidetector computed tomography (MDCT) in the diagnosis of nonocclusive mesenteric ischaemia (NOMI) among patients after cardiovascular surgery. DESIGN, SETTING AND PARTICIPANTS: A retrospective review of 38 patients in a cardiothoracic intensive care unit who underwent MDCT examination before laparotomy for suspected NOMI between January 2001 and December 2012. INTERVENTION AND MAIN OUTCOME MEASURES: The MDCT studies were examined independently by three radiologists, who were asked to make a determination on the presence or absence of NOMI. The radiological diagnosis was compared against the surgical and/or histological outcome to determine the diagnostic accuracy of MDCT. RESULTS: The sensitivity and specificity of MDCT in the diagnosis of NOMI were 96% and 33%-60%, respectively. The positive and negative likelihood ratios and diagnostic odds ratio were 1.43-2.39, 0.072-0.13 and 11-33.2, respectively. The inter-rater agreement was 68%, with a Fleiss κ of 0.43. CONCLUSIONS: MDCT has high sensitivity but lacks specificity in the diagnosis of NOMI. Its main value is in selection of patients for non-operative management, at least in the short-to-medium term.

Ventilatory and cardiac responses to pulmonary embolism: consequences for gas exchange and blood pressure.

Acute thromboembolic pulmonary embolism (PE) is a life threatening condition that can lead to pulmonary hypertension and right ventricular dysfunction or failure. There is typically an increase in ventilation rate and cardiac output as a response to PE prior to cardiac failure, which is at least in part due to systemic hypoxemia. Here we assess the response of the lungs to changes in these parameters using anatomically-based computational models of pulmonary perfusion, ventilation and gas exchange. We show that increases in ventilation and cardiac output improve overall gas exchange in PE. However, this comes at the cost of an increased pulmonary blood pressure, which may contribute to pulmonary hypertension as a result of PE.

Neutrophilic asthma has different radiographic features to COPD and smokers.

BACKGROUND: Neutrophilic asthma and COPD are obstructive airway diseases common in older age and have a characteristic airway inflammation with neutrophilic bronchitis. The structural differences between neutrophilic asthma and COPD have not been investigated. The aim of this study was to examine the airway and parenchymal abnormalities using high resolution computed tomographic (HRCT) scanning in participants with neutrophilic asthma, COPD and smoking controls. METHODS: Participants (neutrophilic asthma (n=10), COPD (n=17) and smoking controls (n=8)) underwent clinical assessment and sputum induction. HRCT of the chest was performed and independently scored by a radiologist blinded to the subject group using a modified Bhalla scoring system. RESULTS: Participants were of a similar age and those with COPD had a similar degree of airflow obstruction to those with neutrophilic asthma. The pattern of radiographic abnormalities differed between groups. Abnormal bronchial wall thickening was significantly more common in neutrophilic asthma, compared to COPD or smoking controls. Emphysema was greatest in the COPD group, and not recorded as a feature of neutrophilic asthma. FEV(1)% predicted was negatively associated with bronchial wall thickening and consolidation while KCO% predicted was negatively associated with the total emphysema score. Bronchiectasis was minimal in all groups. CONCLUSION: The pattern of radiographic lung abnormality in neutrophilic asthma differs significantly from COPD, and resembles asthma. Neutrophilic asthma is a distinct inflammatory subtype of asthma with a different pathogenesis to COPD.

Exudative bronchiolitis after lung transplantation.

BACKGROUND: After lung transplantation patients frequently develop small airways disease. Exudative bronchiolitis (EB) has not been described previously in this population. We describe a case series of patients who have developed EB after lung transplantation. METHODS: We reviewed the clinical records and radiologic data of 99 patients who underwent single and bilateral lung transplantation. Data relating to ethnicity, transplant indication, human leukocyte antigen (HLA) status, complications and survival were recorded. The EB cohort, defined by high-resolution computed tomographic (HRCT) evidence of the disease, was compared with a group of patients who had not developed EB. RESULTS: The majority of patients had chronic obstructive pulmonary disease (COPD; n = 51), followed by cystic fibrosis (CF; n = 22), pulmonary fibrosis (n = 8), pulmonary hypertension (n = 7), bronchiectasis (n = 5), lymphangioleiomyomatosis (n = 3) and Eisenmenger's syndrome (n = 3). Thirteen patients were found to have developed EB. EB was more commonly seen in Maori and Pacific Island patients (p < 0.05). EB was significantly associated with early infection post-transplant (p < 0.05) and a history of Aspergillus infection (p < 0.005) or diabetes (p < 0.05). The patients with EB were also significantly more likely to develop bronchiolitis obliterans syndrome (p < 0.0005), bronchiectasis (p < 0.0005) or small airways disease (p < 0.05). Patients with EB had a varied response to treatment, with the majority showing improvement. CONCLUSIONS: EB was noted to occur after lung transplantation in a significant proportion of patients, but will not be detected unless HRCT is used routinely. It has been associated with patients' ethnicity, donor haplotype, infection and the development of airways disease. EB may be a prominent indicator of the likelihood of developing BOS.

Interstitial lung disease: effects of thin-section CT on clinical decision making.

PURPOSE: To retrospectively quantify the change in the diagnosis and management of suspected interstitial lung disease when thin-section computed tomography (CT) is added to pretest probabilities. MATERIALS AND METHODS: The institutional review board does not require approval or patient informed consent for retrospective study of case records and CT studies. Six pulmonologists reviewed data sheets containing clinical information and results of pulmonary function tests and chest radiographs of 168 consecutive patients (86 women and 82 men; mean age, 59.8 years; age range, 22-86 years) suspected of having interstitial lung disease. Differential diagnoses and responses to specific questions regarding patient care were recorded before and after assimilation of thin-section CT findings. Both unweighted and weighted kappa analyses were used to determine agreement between pulmonologists before and after CT. RESULTS: First-choice diagnosis changed in 520 (51%) of 1008 cases, and agreement on first-choice diagnosis increased from 0.47 to 0.72 after thin-section CT. In addition, confidence in the first-choice diagnosis increased, and there was a reduction in the number of differential diagnoses offered by all pulmonologists (P < .005 and P < .001, respectively). Agreement on diagnostic probabilities for individual disorders increased substantially, particularly for diagnoses of idiopathic pulmonary fibrosis (weighted kappa = 0.58-0.89). With CT findings, pulmonologists changed their pre-CT responses regarding the use of bronchoalveolar lavage, transbronchial biopsy, and thoracoscopic biopsy in 242 (24.0%), 282 (28.0%), and 292 (29.0%) of 1008 cases, respectively. However, agreement for the use of these investigations was low both before and after CT. The request rate for thoracoscopic biopsy in patients in whom idiopathic fibrosis was diagnosed decreased from 48 of 179 (26.8%) to 26 of 233 (11.2%) after CT. CONCLUSION: Thin-section CT resulted in a change in first-choice diagnosis in half the cases. Diagnostic confidence improved, and CT findings increased agreement between pulmonologists on diagnostic probabilities across a range of interstitial lung diseases.

Thin-section CT in obstructive pulmonary disease: discriminatory value.

PURPOSE: To use thin-section computed tomography (CT) to distinguish between causes of obstructive pulmonary disease, to determine which distinctions give rise to diagnostic imprecision, and to identify the most useful CT features. MATERIALS AND METHODS: Thin-section CT scans of 105 patients with obstructive pulmonary disease (asthma, n = 35; centrilobular emphysema, n = 30; panlobular emphysema, n = 21; and obliterative bronchiolitis, n = 19) and 33 healthy subjects were assessed independently by two observers. The most likely diagnosis and a confidence rating were assigned. Individual thin-section CT features were recorded. Accuracy, sensitivity, specificity, negative predictive value, and positive predictive value for first-choice diagnoses were calculated. The prevalence of CT features between pairs of conditions was compared with the chi(2) or Fisher exact test as appropriate. RESULTS: A correct first-choice diagnosis was made in 199 of 276 (72%) observations. A correct first-choice diagnosis was made in 35 of 38 (92%) observations in patients with obliterative bronchiolitis, in 53 of 60 (88%) observations in patients with centrilobular emphysema, in 53 of 66 (80%) observations in healthy subjects, in 37 of 70 (53%) observations in patients with asthma, and in 20 of 42 (48%) observations in patients with panlobular emphysema. The major sources of diagnostic inaccuracy were differentiation between panlobular and centrilobular emphysema, asthma and normality, and asthma and obliterative bronchiolitis. There were significant increases in prevalence of (a) bronchial wall thickening and vascular attenuation in patients with asthma when compared with healthy subjects and (b) vascular attenuation and decreased attenuation in patients with obliterative bronchiolitis when compared with patients with asthma (P <.001). CONCLUSION: CT helps to distinguish diseases that cause airflow obstruction. Thin-section CT is particularly accurate in the identification of obliterative bronchiolitis.