Quantitative computed tomography-derived clusters: redefining airway remodeling in asthmatic patients.

BACKGROUND: Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)-assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms. OBJECTIVES: The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes. METHODS: Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes. RESULTS: Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm(3) [SD, 112.6 mm(3)], 259.0 mm(3) [SD, 53.3 mm(3)], 366.4 mm(3) [SD, 195.3 mm(3)], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects. CONCLUSIONS: Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies.

Single-step QuantiFERON screening of adult contacts: a prospective cohort study of tuberculosis risk.

BACKGROUND: The efffectiveness of tuberculosis (TB) contact screening programmes using interferon γ release assays remains uncertain as prospective contact TB risk is not well characterised. OBJECTIVES: To quantify 2-year TB risk and evaluate screening performance with single-step QuantiFERON TB Gold-In Tube (QFT) in adult contacts. To compare TB risk between QFT tested subgroups stratified by exposure type (smear positive pulmonary (SP) versus non-smear positive (NSP) TB) and age (younger (16-35 years) versus older (≥36 years)). METHODS: Screening involved QFT testing in older contacts of SP and all younger contacts, 8-12 weeks after index notification. Chemoprevention (3RH) was offered to QFT positive (+) younger adults. TB risk was determined in a prospective cohort study. RESULTS: 43 TB events occurred in 1769 adult contacts observed for median 717 days (2-year rate (95% CI)=2·5% (1.7 to 3.2)). Index-contact strain matching was demonstrable for 18 of 22 (82%) paired samples. No contacts (0/98) receiving 3RH developed TB. 215 of 817 appropriately tested adults (26.3%) were QFT+. 14 of 112 untreated QFT+ adults developed TB (2-year rate (95% CI)=13·4% (7.7 to 21.1)). The model required 35 contacts screened with QFT to identify one contact developing TB at 2 years. TB rates were comparable in QFT+ contacts of SP and NSP (rate ratio (RR)=0.98, p=0·962). For QFT+ older contacts, the disease rate was lower (8.9% (3.3 to 19.1)) and similar to the overall group rate (RR=1.4, p=0.503). CONCLUSIONS: QFT based single-step contact screening is effective in young adults.

Sputum mediator profiling and relationship to airway wall geometry imaging in severe asthma.

BACKGROUND: Severe asthma is a heterogeneous disease and the relationship between airway inflammation and airway remodelling is poorly understood. We sought to define sputum mediator profiles in severe asthmatics categorised by CT-determined airway geometry and sputum differential cell counts. METHODS: In a single centre cross-sectional observational study we recruited 59 subjects with severe asthma that underwent sputum induction and thoracic CT. Quantitative CT analysis of the apical segment of the right upper lobe (RB1) was performed. Forty-one mediators in sputum samples were measured of which 21 mediators that were assessable in >50% of samples were included in the analyses. RESULTS: Independent of airway geometry, sputum MMP9 and IL-1ß were elevated in those groups with a high sputum neutrophil count while sputum ICAM was elevated in those subjects with a low sputum neutrophil count. In contrast, sputum CCL11, IL-1α and fibrinogen were different in groups stratified by both sputum neutrophil count and airway geometry. Sputum CCL11 concentration was elevated in subjects with a low sputum neutrophil count and high luminal and total RB1 area, whereas sputum IL1α was increased in subjects with a high sputum neutrophil count and low total RB1 area. Sputum fibrinogen was elevated in those subjects with RB1 luminal narrowing and in those subjects with neutrophilic inflammation without luminal narrowing. CONCLUSIONS: We have demonstrated that sputum mediator profiling reveals a number of associations with airway geometry. Whether these findings reflect important biological phenotypes that might inform stratified medicine approaches requires further investigation.

Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study.

BACKGROUND: The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. METHODS: MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. FINDINGS: Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. INTERPRETATION: In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. FUNDING: Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust.

Quantitative analysis of high-resolution computed tomography scans in severe asthma subphenotypes.

BACKGROUND: Severe asthma is a heterogeneous condition. Airway remodelling is a feature of severe asthma and can be determined by the assessment of high-resolution computed tomography (HRCT) scans. The aim of this study was to assess whether airway remodelling is restricted to specific subphenotypes of severe asthma. METHODS: A retrospective analysis was performed of HRCT scans from subjects who had attended a single-centre severe asthma clinic between 2003 and 2008. The right upper lobe apical segmental bronchus (RB1) dimensions were measured and the clinical and sputum inflammatory characteristics associated with RB1 geometry were assessed by univariate and multivariate regression analyses. Longitudinal sputum data were available and were described as area under the time curve (AUC). Comparisons were made in RB1 geometry across subjects in four subphenotypes determined by cluster analysis, smokers and non-smokers, and subjects with and without persistent airflow obstruction. RESULTS: Ninety-nine subjects with severe asthma and 16 healthy controls were recruited. In the subjects with severe asthma the RB1 percentage wall area (%WA) was increased (p=0.009) and lumen area (LA)/body surface area (BSA) was decreased (p=0.008) compared with controls but was not different across the four subphenotypes. Airway geometry was not different between smokers and non-smokers and RB1 %WA was increased in those with persistent airflow obstruction. RB1 %WA in severe asthma was best associated with airflow limitation and persistent neutrophilic airway inflammation (model R(2)=0.27, p=0.001). CONCLUSIONS: Airway remodelling of proximal airways occurs in severe asthma and is associated with impaired lung function and neutrophilic airway inflammation.

Guidelines on the radical management of patients with lung cancer.

A joint initiative by the British Thoracic Society and the Society for Cardiothoracic Surgery in Great Britain and Ireland was undertaken to update the 2001 guidelines for the selection and assessment of patients with lung cancer who can potentially be managed by radical treatment.

Thoracic ultrasound prior to medical thoracoscopy improves pleural access and predicts fibrous septation.

BACKGROUND AND OBJECTIVE: Medical thoracoscopy (MT) is indicated for the investigation of unexplained pleural exudates. Not all MT units create artificial pneumothoraces because of time. Difficult pleural space access and thick fibrous adhesions may prevent MT and pleurodesis, respectively. The potential role of thoracic ultrasound (TUS) pre-MT has not been fully evaluated. We hypothesized TUS would reduce failure to access the pleural space and enable detection of thick fibrous adhesions. METHODS: Thirty patients underwent single port MT consecutively for investigation of pleural exudates without pre-MT TUS over a 6-month period. Over the following 6 months, 30 consecutive patients underwent TUS immediately prior to MT. Pleural access rate and thick fibrous adhesion detection at both MT and TUS were recorded. RESULTS: In the non-TUS cohort, pleural space access failure occurred in 16.7% (leading to five extra procedures), versus no failures in the TUS cohort (P = 0.0522). There were no differences in prevalence of MT fibrous adhesions between cohorts. TUS identified all cases of fibrous septation versus only 12.5% identified by CT in the non-TUS cohort (P = 0.001). All identified cases of thick fibrous septation on TUS did not receive pleurodesis at MT. TUS detected useful ancillary features in 43% of cases. CONCLUSIONS: A strong trend to reduction in single port MT pleural access failure was noted with pre-MT TUS thus reducing extra procedures and the need for artificial pneumothoraces. Pre-MT TUS also reliably detects thick fibrous adhesions at MT. TUS may also detect useful ancillary features. This study provides a rationale for ultrasound-guided single port MT if a pneumothorax is not created.

Current state and future directions of pleural mesothelioma imaging.

The diagnosis, staging, and response assessment of mesothelioma pose unique challenges to radiologic imaging. No single, conventional imaging approach captures the information necessary to direct all aspects of patient management. Instead, the complexities of this unique disease demand the integration of elements cleverly adapted from different modalities. Imaging-based studies presented at the 8th International Conference of the International Mesothelioma Interest Group (IMIG) in October 2006 sought to further define the current practice and future potential of radiology for the mesothelioma patient. The imaging studies selected through a peer-review process for presentation at the 2006 IMIG Conference were intended to frame this research in the context of the unique imaging challenges presented by mesothelioma while stimulating dialogue on the future resolution of these challenges. This communication conveys the pitfalls and potential of pleural mesothelioma imaging based on work presented at the Conference. From diagnosis to response, PET/CT to molecular bioprobes, volumetric analysis to computerized tumor assessment, imaging promises to provide valuable insight for patients with mesothelioma and the physicians who treat them.

The diagnostic role of ventilation/perfusion scans versus computed tomography pulmonary angiography in obstetric patients investigated for pulmonary embolism at Wellington Hospital from 2010 to 2012.

AIM: To develop best practice clinical guidelines for the use of ventilation/perfusion (V/Q) scanning and computed tomography perfusion angiography (CTPA) in pregnancy and the postpartum period. METHOD: Retrospective analysis of the clinical findings and radiologic investigation for pulmonary embolism (PE) in obstetric women at Wellington Hospital from 2010 to 2012. RESULTS: Fifty-four women were investigated for PE with a V/Q scan or CTPA, including 29 antenatal women and 25 postnatal women. Eleven (37.9%) antenatal women had V/Q scans and 18 (62%) had CTPAs. Five (20%) postnatal women had V/Q scans, 19 (76%) had CTPAs and one (4%) had a V/Q scan followed by a CTPA. Three of the 54 women (5.6%) had a positive radiologic finding of PE (two by V/Q scan and one by CTPA). Four (22.2%) antenatal women and 5 (25%) postnatal women had a diagnosis made on CTPA, which was not seen on chest x-ray. CONCLUSION: This audit found that clinicians varied in their investigation of cases suspected of PE. We have proposed a clinical pathway for the investigation of PE in pregnancy and the postpartum period.

The use of magnetic resonance imaging in malignant mesothelioma.

Magnetic resonance imaging (MRI) is not routinely used in investigations for patients with suspected malignant pleural mesothelioma but it can be a useful tool in some instances--particularly predicting malignancy in patients with asbestos exposure; differentiating between metastatic pleural disease and malignant pleural mesothelioma (MPM); assessing patients for radical surgery and post treatment evaluation of patients.

Pseudo tumors of the lung after lung volume reduction surgery.

We describe 2 patients who underwent lung volume reduction surgery, who postoperatively had computed tomographic scans that showed symptomatic mass lesions suggestive of malignancy and an inhaled foreign body. Investigations excluded these conditions with the remaining likely diagnosis of pseudotumor secondary to buttressing material. These potential sequelae of lung volume reduction surgery should be recognized in follow-up investigations.

Is there a role for pre-operative contrast-enhanced magnetic resonance imaging for radical surgery in malignant pleural mesothelioma?

OBJECTIVE: To assess the use of contrast-enhanced magnetic resonance imaging (CEMRI) in addition to computed tomography in the pre-operative assessment of patients for radical surgery in malignant pleural mesothelioma. METHODS: Over a 45-month period, 51 of 76 patients assessed (69 men and seven women), underwent extra-pleural pneumonectomy or radical pleurectomy/decortication. Post-operative pathological stage was correlated with radiological staging, with particular emphasis on tumour resectability. RESULTS: Seventeen (22%) patients were found on CEMRI to have unresectable, but histologically unconfirmed disease, not previously seen on CT. Fifty-one (67%) patients proceeded to radical surgery, but pathological nodal data were incomplete in three, so excluding these patients from further analyses. The median pre-operative interval after CEMRI was 17 days. Two patients were found to have unexpectedly extensive disease at thoracotomy, thus the sensitivity of CEMRI for prediction of resectability was 97%. Using the International Mesothelioma Interest Group system, tumour stage was correctly predicted by CEMRI in 48% of patients, but understaged in 50% of cases, largely due to the underestimation of pericardial involvement, but this did not affect resectability and had no significant effect on prognosis. Nodal stage was correctly identified in 60% of patients. CEMRI was successful in predicting pathological tumour stage T3 or less (sensitivity of 85%; specificity of 100%), but less so in identifying tumour stage T2 or less (sensitivity of 23%; specificity of 96%) or N2 nodal disease (sensitivity 66%; specificity 73%). CONCLUSIONS: CEMRI is most useful in the differentiation of T3 and T4 disease and may be unnecessary at earlier stages. Its multiplanar tumour localisation abilities are of value in the assessment of resectability. It is unlikely to contribute significantly to nodal staging, but it remains a valuable adjunct in the selection of patients for radical surgery.

Pulmonary arteriovenous malformation: a rare anterior mediastinal mass.

Pulmonary arteriovenous malformations are rare pulmonary vascular lesions which are associated with Osler Weber Rendu syndrome (hereditary haemorrhagic telangectasia). They act as right-to-left shunts and have cardiovascular and embolic complications. We present a patient with an apparent anterior mediastinal mass secondary to a pulmonary arteriovenous malformations which was successfully treated percutaneously.

Out of hours multidetector computed tomography pulmonary angiography: are specialist resident reports reliable?

RATIONALE AND OBJECTIVES: The purposes of this study were to assess the accuracy of trainee radiologists' reports for computed tomographic pulmonary angiographic (CTPA) imaging and to determine agreement or discrepancy with final verified consultant reports. MATERIALS AND METHODS: A total of 100 consecutive out-of-hours CTPA examinations were prospectively analyzed. Fifty-one male and 49 female subjects were included in the study. The mean age of patients scanned was 63.7 years (range, 17-98 years). RESULTS: Eighteen of the 100 subjects (18%) had findings positive for pulmonary embolism. The interobserver agreement for pulmonary embolism between on-call radiology residents and consultant radiologists was almost perfect (κ = 0.932; 95% confidence interval, 0.84-1.0; P < .0001). There was one false-negative CTPA report. Eighty-two CTPA scans (82%) were reported as negative for pulmonary embolism by consultant radiologists. In this group, there was a single false-positive interpretation by the on-call specialist resident. The interobserver agreement for all findings between resident and consultant reports was almost perfect (weighted κ = 0.87; 95% confidence interval, 0.79-0.96; P < .0001). The overall discrepancy rate, including both false-positive and false-negative findings, between the on-call radiology resident and consultant radiologist was 8% (eight of 100). CONCLUSIONS: CTPA reports by radiology residents can be relied and acted upon without any major discrepancies. There is a relatively much higher proportion of patients with alternative diagnoses, mainly infective consolidation and heart failure presenting with similar symptoms and signs as pulmonary emboli. It is imperative for trainees to be systematic and review all images if observational omissions are to be reduced.

Is There a Role of Double Reporting and CT Pelvis for Lung Cancer Staging?

BACKGROUND: Lung cancer is the most common cancer in the world. Staging of lung cancer involves CT of chest and abdomen. Subsequently these are discussed in MDT and if required PET imaging is arranged. We have performed a study to assess double reporting of the initial staging CT would identify in field metastasis and hence decrease the use of PET. METHODS: A refined search from the lung cancer database over 2 years of 980 patients was performed. Metastasis identified on PET (SUV > 2.5) was nominated as the gold standard, 219 patients had both PET and staging CT (chest and abdomen) with 38 patients having metastasis on both PET and CT. CT images were reviewed by two independent radiologist who were blinded to the report. Identified metastases were graded if identified. These were grade as 1- definite, 2- equivocal, 3- normal. Subsequently through a process of arbitration a combined decision about the in field metastasis was achieved. RESULTS: There were 21 metastasis which were within the field of chest and abdomen (in field metastasis). Only a half of these were identified by blinded observers. Following an arbitration there was no significant improvement in the pick up rate. There were 19 out of field metastasis in 15 patients out of this cohort. Majority of these (72%) were in the bony pelvis which would have been reported if a CT pelvis was performed as a part of staging. We estimate that one would have to perform 10 CT pelvises to save one PET-CT. CONCLUSION: Double reading of staging scan would not identify all infield metastasis. The increased contrast in PET images makes it easy to spot metastases. Hence there is no role for double reporting of staging CT in lung cancer management. Inclusion of pelvis in staging of lung cancer may be effective and would improve the detection of out of field metastases hence decreasing the use of PET.

The Role of Multi Detector Computed Tomographic Imaging Prior to Clinic Consultation in Patients Suspected to Have Lung Cancer.

BACKGROUND: Scanning patients early in their diagnostic journey helps in differentiating benign from malignant aetiology. There is increasing pressure on diagnostic practices for rapid diagnoses and thereby early commencement of treatment in patients suspected to have lung cancer (LC). In our practice, multi detector computed tomography (MDCT) imaging is performed in selected patients referred to the LC service prior to them seeing a chest physician in the LC clinic. This study evaluates the role of such practice and reviews its potential impact on LC services. METHODS: Prospective review of our practice from January 2007 to Apr 2007 was performed. Consecutive patients referred to the service with suspected LC were included. Chest radiograph (CXR) report and clinical information from general practitioners were reviewed and graded as high, medium or low risk for presence of LC. Patients with sufficient clinical and/or radiological concern underwent MDCT imaging prior to their clinic. Combined risk scores and modified risk scores were formulated and assessed against MDCT findings. RESULTS: A total of 139 patients were referred to the service, 124 of these had pre-clinic MDCT. Fifty-three patients (43%) had malignancy, 39 (31%) had non-malignant significant abnormalities, 17 (14%) had other incidental findings and 15 (12%) were normal. Modified combined risk score was the best predictor of presence of cancer. CONCLUSION: Pre-clinic MDCT scanning in patients with suspected LC is feasible and has a promising role in the modern care of LC patients. It also empowers physicians with additional information at the primary consultation.

Implications of new (seventh) TNM classification of lung cancer on general radiologists--a pictorial review.

The new TNM (seventh) classification of lung cancer, published by Union Internationale Centre le Cancer, has been in use since January 2010. It is vital for general radiologists to be well versed with this system and be aware of the impact of these changes on patient management and prognosis. It is also important that radiologists appreciate the implications of the new system on reporting different imaging modalities and its limitations. This pictorial essay outlines the proposed changes, its limitations, and implications for radiologists.

The role of CT scanning in multidimensional phenotyping of COPD.

BACKGROUND: COPD is a heterogeneous disease characterized by airflow obstruction and diagnosed by lung function. CT imaging is emerging as an important, noninvasive tool in phenotyping COPD. However, the use of CT imaging in defining the disease heterogeneity above lung function is not fully known. METHODS: Seventy-five patients with COPD (58 men, 17 women) were studied with CT imaging and with measures of airway inflammation. Airway physiology and health status were also determined. RESULTS: The presence of emphysema (EM), bronchiectasis (BE), and bronchial wall thickening (BWT) was found in 67%, 27%, and 27% of subjects, respectively. The presence of EM was associated with lower lung function (mean difference % FEV(1), -20%; 95% CI, -28 to -11; P < .001). There was no difference in airway inflammation, exacerbation frequency, or bacterial load in patients with EM alone or with BE and/or BWT ± EM. The diffusing capacity of the lung for carbon monoxide/alveolar volume ratio was the most sensitive and specific parameter in identifying EM (area under the receiver operator characteristic curve, 0.87; 95% CI, 0.79-0.96). Physiologic cluster analysis identified three clusters, two of which were EM predominant and the third characterized by a heterogeneous combination of EM and BE. CONCLUSIONS: The application of CT imaging can be useful as a tool in the multidimensional approach to phenotyping patients with COPD.