Louis Irving

Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis

Improved diagnostic sensitivity of bronchsocopy for the investigation of peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial ultrasound (EBUS) has been reported, although diagnostic performance varies considerably. A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity. 16 studies with 1,420 patients fulfilled inclusion criteria. Significant inter-study variation in EBUS method was noted. EBUS had point specificity of 1.00 (95% CI 0.99–1.00) and point sensitivity of 0.73 (95% CI 0.70–0.76) for the detection of lung cancer, with a positive likelihood ratio of 26.84 (12.60–57.20) and a negative likelihood ratio of 0.28 (0.23–0.36). Significant inter-study heterogeneity for sensitivity was observed, with prevalence of malignancy, lesion size and reference standard used being possible sources. EBUS is a safe and relatively accurate tool in the investigation of PPLs. Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Further methodologically rigorous studies on well-defined patient populations are required to evaluate the generalisability of our results.

Pathways Activated during Human Asthma Exacerbation as Revealed by Gene Expression Patterns in Blood

Background Asthma exacerbations remain a major unmet clinical need. The difficulty in obtaining airway tissue and bronchoalveolar lavage samples during exacerbations has greatly hampered study of naturally occurring exacerbations. This study was conducted to determine if mRNA profiling of peripheral blood mononuclear cells (PBMCs) could provide information on the systemic molecular pathways involved during asthma exacerbations. Methodology/Principal Findings Over the course of one year, gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared using oligonucleotide arrays. For each of 118 subjects who experienced at least one asthma exacerbation, the gene expression patterns in a sample of peripheral blood mononuclear cells collected during an exacerbation episode were compared to patterns observed in multiple samples from the same subject collected during quiescent asthma. Analysis of covariance identified genes whose levels of expression changed during exacerbations and returned to quiescent levels by two weeks. Heterogeneity among visits in expression profiles was examined using K-means clustering. Three distinct exacerbation-associated gene expression signatures were identified. One signature indicated that, even among patients without symptoms of respiratory infection, genes of innate immunity were activated. Antigen-independent T cell activation mediated by IL15 was also indicated by this signature. A second signature revealed strong evidence of lymphocyte activation through antigen receptors and subsequent downstream events of adaptive immunity. The number of genes identified in the third signature was too few to draw conclusions on the mechanisms driving those exacerbations. Conclusions/Significance This study has shown that analysis of PBMCs reveals systemic changes accompanying asthma exacerbation and has laid the foundation for future comparative studies using PBMCs.

Serum amyloid A opposes lipoxin A4 to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) will soon be the third most common cause of death globally. Despite smoking cessation, neutrophilic mucosal inflammation persistently damages the airways and fails to protect from recurrent infections. This maladaptive and excess inflammation is also refractory to glucocorticosteroids (GC). Here, we identify serum amyloid A (SAA) as a candidate mediator of GC refractory inflammation in COPD. Extrahepatic SAA was detected locally in COPD bronchoalveolar lavage fluid, which correlated with IL-8 and neutrophil elastase, consistent with neutrophil recruitment and activation. Immunohistochemistry detected SAA was in close proximity to airway epithelium, and in vitro SAA triggered release of IL-8 and other proinflammatory mediators by airway epithelial cells in an ALX/FPR2 (formyl peptide receptor 2) receptor-dependent manner. Lipoxin A4 (LXA4) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA2 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA4. Human lung macrophages (CD68+) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC50 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA4 but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.

Screening for lung cancer: a systematic review and meta-analysis of controlled trials

Background: Lung cancer is a substantial public health problem in western countries. Previous studies have examined different screening strategies for lung cancer but there have been no published systematic reviews. Methods: A systematic review of controlled trials was conducted to determine whether screening for lung cancer using regular sputum examinations or chest radiography or computed tomography (CT) reduces lung cancer mortality. The primary outcome was lung cancer mortality; secondary outcomes were lung cancer survival and all cause mortality. Results: One non-randomised controlled trial and six randomised controlled trials with a total of 245 610 subjects were included in the review. In all studies the control group received some type of screening. More frequent screening with chest radiography was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, 95% CI 1.00 to 1.23). A non-statistically significant trend to reduced mortality from lung cancer was observed when screening with chest radiography and sputum cytological examination was compared with chest radiography alone (RR 0.88, 95% CI 0.74 to 1.03). Several of the included studies had potential methodological weaknesses. Controlled studies of spiral CT scanning have not been reported. Conclusions: The current evidence does not support screening for lung cancer with chest radiography or sputum cytological examination. Frequent chest radiography might be harmful. Further methodologically rigorous trials are required before any new screening methods are introduced into clinical practice.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for the Evaluation of Suspected Lymphoma

Background: Evidence regarding the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the assessment of isolated mediastinal lymphadenopathy (IMLN) is evolving. Its diagnostic accuracy in the evaluation of suspected lymphoma remains uncertain. Methods: We reviewed a prospectively recorded database of consecutive patients with suspected lymphoma who underwent EBUS-TBNA to evaluate IMLN. Patients in whom EBUS-TBNA was nondiagnostic subsequently underwent surgical biopsy or a minimum of 6 months radiologic surveillance. Results: Ninety-eight patients underwent EBUS-TBNA for evaluation of IMLN. Clinicoradiologic features suggested sarcoidosis as the likely diagnosis in 43 patients. In the remaining 55 patients, EBUS-TBNA achieved definitive diagnosis in 42 patients (76%; 95% confidence interval [CI] 55–90). Lymphoma was ultimately diagnosed in 21 of 55 patients (38%). EBUS-TBNA demonstrated lymphoma in 16 (76%) patients; however, four patients required further surgical biopsy to completely characterize lymphoma subtypes. Surgical biopsy was required to diagnose specific lymphoma subtypes not readily amenable to diagnosis with low volume specimens. Sensitivity and specificity for definitive diagnosis of lymphoma were 57% (95% CI 37–76) and 100% (95% CI 91–100), respectively. Conclusions: Although the diagnostic accuracy of EBUS-TBNA for lymphoma is lower than that for the lung cancer staging, the procedure is an appropriate investigative technique for the patients with IMLN because of the low incidence of lymphoma in this population, and the significant proportion of such patients (76%) in whom surgical biopsy is obviated.

Bronchoscopic evaluation of the mediastinum using endobronchial ultrasound: A description of the first 216 cases carried out at an Australian tertiary hospital

Background: Performance of linear probe endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) for staging non‐small‐cell lung cancer has been extensively studied. Alternate indications for its use are less well characterised, and performance in other clinical settings may differ.

Influenza vaccine effectiveness against hospitalisation with confirmed influenza in the 2010-11 seasons: a test-negative observational study.

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons.

Cost-benefit of minimally invasive staging of non-small cell lung cancer: a decision tree sensitivity analysis.

Background: Accurate staging of non-small cell lung cancer (NSCLC) is critical for optimal management. Minimally invasive pathologic assessment of mediastinal lymphadenopathy is increasingly being performed. The cost-benefit (minimization of health care costs) of such approaches, in comparison with traditional surgical methods, is yet to be established. Methods: Decision-tree analysis was applied to compare downstream costs of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), conventional TBNA, and surgical mediastinoscopy. Calculations were based on real costs derived from actual patient data at a major teaching hospital in Melbourne, Australia. One- and two-way sensitivity analyses were undertaken to account for potential variation in input parameter values. Results: For the base-case analysis, initial evaluation with EBUS-TBNA (with negative results being surgically confirmed) was the most cost-beneficial approach (AU

Incidence of bacteraemia following endobronchial ultrasound-guided transbronchial needle aspiration

2961) in comparison with EBUS-TBNA (negative results not surgically confirmed) (

Comparative effectiveness of radial probe endobronchial ultrasound versus CT-guided needle biopsy for evaluation of peripheral pulmonary lesions: A randomized pragmatic trial

3344), conventional TBNA (