Reproducibility of optical coherence tomography airway imaging

Optical coherence tomography (OCT) is a promising imaging technique to evaluate small airway remodeling. However, the short-term insertion-reinsertion reproducibility of OCT for evaluating the same bronchial pathway has yet to be established. We evaluated 74 OCT data sets from 38 current or former smokers twice within a single imaging session. Although the overall insertion-reinsertion airway wall thickness (WT) measurement coefficient of variation (CV) was moderate at 12%, much of the variability between repeat imaging was attributed to the observer; CV for repeated measurements of the same airway (intra-observer CV) was 9%. Therefore, reproducibility may be improved by introduction of automated analysis approaches suggesting that OCT has potential to be an in-vivo method for evaluating airway remodeling in future longitudinal and intervention studies. (C) 2015 Optical Society of Americ

A prospective safety and feasibility study of metered cryospray for patients with chronic bronchitis in COPD

BACKGROUND: No currently approved intervention counteracts airway metaplasia and mucus hypersecretion of Chronic Bronchitis (CB) in COPD. Metered Cryospray (MCS) delivering liquid nitrogen (LN2) to the tracheobronchial airways ablates abnormal epithelium and facilitates healthy mucosal regeneration. The objective of this study was to evaluate the feasibility, efficacy and safety of MCS in CB. METHODS: Patients with a FEV1, 30-80% of expected, taking optimal medication were recruited. Primary outcomes: feasibility - completion of treatments; efficacy - 3-month change in St George's Respiratory Questionnaire (SGRQ); safety - incidence of adverse events (AEs). SECONDARY OUTCOMES: lung function, exercise capacity, additional patient-reported outcomes (PROs). RESULTS: 35 patients, 19 male/16 female, aged 47-76 years, GOLD grade I (3), II (10) and III (22), underwent staggered LN2 treatments to the tracheobronchial tree.34 patients completed three treatments, each lasting 34·3±12·1 min, separated by 4-6 weeks: one withdrew after the first treatment. Approximately 1800 doses of MCS were delivered.Clinically meaningful improvements in PROs were observed at 3-months; ΔSGRQ -6·4 [95% CI -11.4, -1.3; p=0·01], COPD Assessment Test (CAT) -3·8 [95% CI -6.4, -1.3; p<0·01] and Leicester Cough Questionnaire (LCQ) 21·6 [95% CI 7.3, 35.9; p<0·01]. CAT changes were durable to 6-months (-3·4 [95% CI -5.9, -0.9; p=0·01]), SGRQ and LCQ to 9-months (-6·9 [95% CI -13.0, -0.9; p=0·03] and 13·4 [95% 2.1, 24.6; p=0·02], respectively).At 12-months, 14 serious AEs were recorded in 11 (31·4%) subjects, 6 moderate (43%) and 8 severe (57%). 9 were respiratory-related: 6 exacerbations of COPD, 2 pneumonias, and 1, increased coughing, recovered without sequelae. None were serious device or procedure-related AEs. CONCLUSION: MCS is safe, feasible and associated with clinically meaningful improvements in multidimensional PROs

Current Practice in the Management of Pulmonary Nodules Detected on Computed Tomography Chest Scans

Lung cancer is associated with high mortality. It can present as one or more pulmonary nodules identified on computed tomography (CT) chest scans. The National Lung Screening Trial has shown that the use of low-dose CT chest screening can reduce deaths due to lung cancer. High adherence to appropriate follow-up of positive results, including imaging or interventional approaches, is an important aspect of pulmonary nodule management. Our study is one of the first to evaluate the current practice in managing pulmonary nodules and to explore potential causes for nonadherence to follow-up. This is a retrospective analysis at St. Paul’s Hospital, a tertiary healthcare center in Vancouver, British Columbia, Canada. We first identified CT chest scans between January 1 to June 30, 2014, that demonstrated one or more pulmonary nodules equal to or greater than 6 mm in diameter. We then looked for evidence of interventional (surgical resection or biopsy, or bronchoscopy for transbronchial biopsy and cytology) and radiological follow-up of the pulmonary nodule by searching on the province-wide CareConnect eHealth Viewer patient database. A total of 1614 CT reports were analyzed and 139 (8.6%) had a positive finding. Out of the 97 patients who received follow-up, 54.6% (N = 53) was referred for a repeat CT chest scan and 36.1% (N = 35) and 9.3% (N = 9) were referred for interventional biopsy and surgical resection, respectively. In our study, 30.2% (N = 42) of the patients with pulmonary nodules were nonadherent to follow-up. Despite the radiologist’s recommendation for follow-up within a certain time interval, only 36% had repeat imaging in a timely manner. Our findings reflect the current practice in the management of pulmonary nodules and suggest that there is a need for improvement at our academic center. Adherence to follow-up is important for the potentially near-future implementation of lung cancer screening

Diagnostic bronchoscopy-current and future perspectives

Lung cancer is the leading cause of cancer-related mortality worldwide. Standard bronchoscopy has limited ability to accurately localise and biopsy pulmonary lesions that cannot be directly visualised. The field of advanced diagnostic bronchoscopy is rapidly evolving due to advances in electronics and miniaturisation. Bronchoscopes with smaller outer working diameters, coupled with miniature radial and convex ultrasound probes, allow accurate central and peripheral pulmonary lesion localisation and biopsy while at the same time avoiding vascular structures. Increases in computational processing power allow three-dimensional reconstruction of computed tomographic raw data to enable virtual bronchoscopy (VB), providing the bronchoscopist with a preview of the bronchoscopy prior to the procedure. Navigational bronchoscopy enables targeting of peripheral pulmonary lesions (PPLs) via a "roadmap", similar to in-car global positioning systems. Analysis of lesions on a cellular level is now possible with techniques such as optical coherence tomography (OCT) and confocal microscopy (CM). All these tools will hopefully allow earlier and safer lung cancer diagnosis and in turn better patient outcomes. This article describes these new bronchoscopic techniques and reviews the relevant literature

Coinfection with Cryptococcus gattii and Mycobacterium tuberculosis in an otherwise healthy 18-year-old woman

Although tuberculosis is a major health problem globally, concomitant cryptococcosis has rarely been reported, especially in immunocompetent individuals. This report describes a case involving an otherwise healthy young woman who was diagnosed with a concomitant infection and emphasizes the importance of considering more than one infection occurring simultaneously in patients with significant comorbidities or immunodeficiency

Tracheal Epstein-Barr Virus-Associated Smooth Muscle Tumour in an Hiv-Positive Patient

Epstein-Barr virus-related smooth muscle tumours (EBV-SMTs) are a rare but well recognized non-AIDS-defining malignancy that can also be found in several other immunosuppressed states. Pulmonary involvement of EBVSMTs is not uncommon, but it can present with multifocal lesions in any anatomical site. The present article describes an HIV-positive woman with dyspnea who was found to have a large tracheal EBV-SMT. The authors discuss their approach to diagnosis and management, and present unique follow-up bronchoscopic imaging

Reproducibility of optical coherence tomography airway imaging

Optical coherence tomography (OCT) is a promising imaging technique to evaluate small airway remodeling. However, the short-term insertion-reinsertion reproducibility of OCT for evaluating the same bronchial pathway has yet to be established. We evaluated 74 OCT data sets from 38 current or former smokers twice within a single imaging session. Although the overall insertion-reinsertion airway wall thickness (WT) measurement coefficient of variation (CV) was moderate at 12%, much of the variability between repeat imaging was attributed to the observer; CV for repeated measurements of the same airway (intra-observer CV) was 9%. Therefore, reproducibility may be improved by introduction of automated analysis approaches suggesting that OCT has potential to be an in-vivo method for evaluating airway remodeling in future longitudinal and intervention studies. (C) 2015 Optical Society of Americ

Decreased telomere length in the small airway epithelium suggests accelerated aging in the lungs of persons living with human immunodeficiency virus (HIV)

Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic obstructive pulmonary disease (COPD) independent of cigarette smoke exposure. Previous studies have demonstrated that decreased peripheral leukocyte telomere length is associated with HIV, suggesting an accelerated aging phenomenon. We demonstrate that this process of telomere shortening also occurs in the lungs, with significant decreases in telomere length observed in small airway epithelial cells collected during bronchoscopy. Molecular evidence of accelerated aging in the small airway epithelium of persons living with HIV may be one clue into the predisposition for chronic lung disease observed in this population.Medicine, Faculty ofOther UBCNon UBCMedicine, Department ofRespiratory Medicine, Division ofReviewedFacult

HIV proviral genetic diversity, compartmentalization and inferred dynamics in lung and blood during long-term suppressive antiretroviral therapy.

The lung is an understudied site of HIV persistence. We isolated 898 subgenomic proviral sequences (nef) by single-genome approaches from blood and lung from nine individuals on long-term suppressive antiretroviral therapy (ART), and characterized genetic diversity and compartmentalization using formal tests. Consistent with clonal expansion as a driver of HIV persistence, identical sequences comprised between 8% to 86% of within-host datasets, though their location (blood vs. lung) followed no consistent pattern. The majority (77%) of participants harboured at least one sequence shared across blood and lung, supporting the migration of clonally-expanded cells between sites. The extent of blood proviral diversity on ART was also a strong indicator of diversity in lung (Spearman's ρ = 0.98, p<0.0001). For three participants, insufficient lung sequences were recovered to reliably investigate genetic compartmentalization. Of the remainder, only two participants showed statistically significant support for compartmentalization when analysis was restricted to distinct proviruses per site, and the extent of compartmentalization was modest in both cases. When all within-host sequences (including duplicates) were considered, the number of compartmentalized datasets increased to four. Thus, while a subset of individuals harbour somewhat distinctive proviral populations in blood and lung, this can simply be due to unequal distributions of clonally-expanded sequences. For two participants, on-ART proviruses were also phylogenetically analyzed in context of plasma HIV RNA populations sampled up to 18 years prior, including pre-ART and during previous treatment interruptions. In both participants, on-ART proviruses represented the most ancestral sequences sampled within-host, confirming that HIV sequences can persist in the body for decades. This analysis also revealed evidence of re-seeding of the reservoir during treatment interruptions. Results highlight the genetic complexity of proviruses persisting in lung and blood during ART, and the uniqueness of each individual's proviral composition. Personalized HIV remission and cure strategies may be needed to overcome these challenges