Radiological-pathological correlation of negative CT biopsy results enables high negative predictive value for thoracic malignancy.

AIM: To evaluate multidisciplinary team (MDT) practice of radiological-pathological correlation of non-malignant biopsy results to examine the additive effect on the predictive values of computed tomography (CT) biopsy for malignancy and their subsequent management and outcomes. MATERIALS AND METHODS: A service evaluation of the MDT management of non-malignant lung biopsy results (May 2014- May 2017) was undertaken. RESULTS: Sixty patients had a non-malignant diagnosis on initial CT biopsy. Five patients were lost to follow-up leaving 55 in the final cohort. Forty-eight of the 55 patients had biopsy results classified as potentially non-specific, of which 26 were classified as concordant with radiology (e.g., organising pneumonia with compatible CT features), and 22 were classified as discordant (e.g., non-specific inflammation and yet sufficiently suspicious CT features). Patients with concordant negative pathology showed resolution (n=19) or stability (n=6) on imaging follow-up. One lesion demonstrated growth and was proven malignant on surgical resection. Discordant lesions were managed with repeat biopsy (n=8) or surgical resection (n=13), with 12 final benign diagnoses and nine malignancies. The negative predictive value of CT biopsy alone was 44/55 (80%), following repeat biopsy was 44/50 (88%), and following radiological-pathological assessment was 32/33 (97%). No patients underwent a shift in stage from time of biopsy to resection. CONCLUSION: Combining radiological-pathological interpretation of negative biopsy results offers superior negative predictive value for lung malignancy without delayed diagnosis of lung cancer.

The influence of inspiratory effort and emphysema on pulmonary nodule volumetry reproducibility.

AIM: To evaluate the impact of inspiratory effort and emphysema on reproducibility of pulmonary nodule volumetry. MATERIALS AND METHODS: Eighty-eight nodules in 24 patients with emphysema were studied retrospectively. All patients had undergone volumetric inspiratory and end-expiratory thoracic computed tomography (CT) for consideration of bronchoscopic lung volume reduction. Inspiratory and expiratory nodule volumes were measured using commercially available software. Local emphysema extent was established by analysing a segmentation area extended circumferentially around each nodule (quantified as percent of lung with density of -950 HU or less). Lung volumes were established using the same software. Differences in inspiratory and expiratory nodule volumes were illustrated using the Bland-Altman test. The influences of percentage reduction in lung volume at expiration, local emphysema extent, and nodule size on nodule volume variability were tested with multiple linear regression. RESULTS: The majority of nodules (59/88 [67%]) showed an increased volume at expiration. Mean difference in nodule volume between expiration and inspiration was +7.5% (95% confidence interval: -24.1, 39.1%). No relationships were demonstrated between nodule volume variability and emphysema extent, degree of expiration, or nodule size. CONCLUSION: Expiration causes a modest increase in volumetry-derived nodule volumes; however, the effect is unpredictable. Local emphysema extent had no significant effect on volume variability in the present cohort.

Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi trial): study design and rationale.

Although lung volume reduction surgery improves survival in selected patients with emphysema, there has been ongoing interest in developing and evaluating bronchoscopic approaches to try to reduce lung volumes with less morbidity and mortality. The placement of endobronchial valves is one such technique, and although some patients have had a significant improvement, responses have been inconsistent because collateral ventilation prevents lobar atelectasis. We describe the protocol of a trial (ISRCTN04761234) aimed to show that a responder phenotype, patients with heterogeneous emphysema and intact interlobar fissures on CT scanning, can be identified prospectively, leading to a consistent benefit in clinical practice.

Survival following lung volume reduction procedures: results from the UK Lung Volume Reduction (UKLVR) registry.

INTRODUCTION: Lung volume reduction surgery (LVRS) and endobronchial valve (EBV) placement can produce substantial benefits in appropriately selected people with emphysema. The UK Lung Volume Reduction (UKLVR) registry is a national multicentre observational study set up to support quality standards and assess outcomes from LVR procedures at specialist centres across the UK. METHODS: Data were analysed for all patients undergoing an LVR procedure (LVRS/EBV) who were recruited into the study at participating centres between January 2017 and June 2022, including; disease severity and risk assessment, compliance with guidelines for selection, procedural complications and survival to February 2023. RESULTS: Data on 541 patients from 14 participating centres were analysed. Baseline disease severity was similar in patients who had surgery n=244 (44.9%), or EBV placement n=219 (40.9%), for example, forced expiratory volume in 1 s (FEV1) 32.1 (12.1)% vs 31.2 (11.6)%. 89% of cases had discussion at a multidisciplinary meeting recorded. Median (IQR) length of stay postprocedure for LVRS and EBVs was 12 (13) vs 4 (4) days(p=0.01). Increasing age, male gender and lower FEV1%predicted were associated with mortality risk, but survival did not differ between the two procedures, with 50 (10.8%) deaths during follow-up in the LVRS group vs 45 (9.7%) following EBVs (adjusted HR 1.10 (95% CI 0.72 to 1.67) p=0.661) CONCLUSION: Based on data entered in the UKLVR registry, LVRS and EBV procedures for emphysema are being performed in people with similar disease severity and long-term survival is similar in both groups.

Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial.

BACKGROUND: Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. METHODS: We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of ≥0·65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0·965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. FINDINGS: All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0·749, below the Bayesian success threshold of 0·965). The 6-month composite primary safety endpoint was 14·4% (30 of 208) for airway bypass versus 11·2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1·00 [Bayesian success threshold >0·95]). INTERPRETATION: Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema. FUNDING: Broncus Technologies.

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial.

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

Position statement on endoscopic lung volume reduction in South Africa: 2022 update.

Chronic obstructive pulmonary disease (COPD) remains one of the most common causes of morbidity and mortality in South Africa. Endoscopic lung volume reduction (ELVR) was first proposed by the South African Thoracic Society (SATS) for the treatment of advanced emphysema in 2015. Since the original statement was published, there has been a growing body of evidence that a certain well-defined sub-group of patients with advanced emphysema may benefit from ELVR, to the point where the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines and the United Kingdom National Institute for Health and Care Excellence (NICE) advocate the use of endoscopic valves based on level A evidence. Patients aged 40 - 75 years with severe dyspnoea (COPD Assessment Test score ≥10) despite maximal medical therapy and pulmonary rehabilitation, with forced expiratory volume in one second (FEV1) 20 - 50%, hyperinflation with residual volume (RV) >175% or RV/total lung capacity (TLC) >55% and a six-minute walking distance (6MWD) of 100 - 450 m (post-rehabilitation) should be referred for evaluation for ELVR, provided no contraindications (e.g. severe pulmonary hypertension) are present. Further evaluation should focus on the extent of parenchymal tissue destruction on high-resolution computed tomography (HRCT) of the lungs and interlobar collateral ventilation (CV) to identify a potential target lobe. Commercially available radiology software packages and/or an endobronchial catheter system can aid in this assessment. The aim of this statement is to provide the South African medical practitioner and healthcare funders with an overview of the practical aspects and current evidence for the judicious use of the valves and other ELVR modalities which may become available in the country.

Summary of the British Thoracic Society guidelines for advanced diagnostic and therapeutic flexible bronchoscopy in adults.

This new guideline covers the rapidly advancing field of interventional bronchoscopy using flexible bronchoscopy. It includes the use of more complex diagnostic procedures such as endobronchial ultrasound, interventions for the relief of central airway obstruction due to malignancy and the recent development of endobronchial therapies for chronic obstructive pulmonary disease and asthma. The guideline aims to help all those who undertake flexible bronchoscopy to understand more about this important area. It also aims to inform respiratory physicians and other specialists dealing with lung cancer of the procedures possible in the management and palliation of central airway obstruction. The guideline covers transbronchial needle aspiration and endobronchial ultrasound-guided transbronchial needle aspiration, electrocautery/diathermy, argon plasma coagulation and thermal laser, cryotherapy, cryoextraction, photodynamic therapy, brachytherapy, tracheobronchial stenting, electromagnetic navigation bronchoscopy, endobronchial valves for emphysema and bronchial thermoplasty for asthma.

Atelectasis and survival after bronchoscopic lung volume reduction for COPD.

Bronchoscopic therapies to reduce lung volumes in chronic obstructive pulmonary disease are intended to avoid the risks associated with lung volume reduction surgery (LVRS) or to be used in patient groups in whom LVRS is not appropriate. Bronchoscopic lung volume reduction (BLVR) using endobronchial valves to target unilateral lobar occlusion can improve lung function and exercise capacity in patients with emphysema. The benefit is most pronounced in, though not confined to, patients where lobar atelectasis has occurred. Few data exist on their long-term outcome. 19 patients (16 males; mean±sd forced expiratory volume in 1 s 28.4±11.9% predicted) underwent BLVR between July 2002 and February 2004. Radiological atelectasis was observed in five patients. Survival data was available for all patients up to February 2010. None of the patients in whom atelectasis occurred died during follow-up, whereas eight out of 14 in the nonatelectasis group died (Chi-squared p=0.026). There was no significant difference between the groups at baseline in lung function, quality of life, exacerbation rate, exercise capacity (shuttle walk test or cycle ergometry) or computed tomography appearances, although body mass index was significantly higher in the atelectasis group (21.6±2.9 versus 28.4±2.9 kg·m(-2); p<0.001). The data in the present study suggest that atelectasis following BLVR is associated with a survival benefit that is not explained by baseline differences.

Learning curves for endobronchial ultrasound using cusum analysis.

BACKGROUND: The assessment of medical trainees is becoming an increasingly prominent issue, with current methods having varying degrees of inherent subjectivity and bias. Cusum analysis is a technique used in quality control systems, and is starting to be employed in medical training. Endobronchial ultrasound (EBUS) is an established tool in the diagnosis and staging of lung cancer, although its use in the UK is currently restricted. As it becomes more widespread, there will be a need to assess trainees' competence accurately to ensure that those performing EBUS at new centres are appropriately skilled. METHODS: A retrospective review of clinical practice in tertiary referral centres in England, Scotland and Spain was carried out. The study group comprised 500 patients undergoing EBUS for the diagnosis and staging of lung cancer as part of a clinical service. Using cusum analysis, the first 100 cases from each of the five centres are presented. Each centre has one consultant physician as the primary EBUS operator, and all operators began using EBUS at their current centre (ie, no learning from prior experience). The data are presented as learning curves. RESULTS: It is evident that there is a wide range of time over which EBUS-guided transbronchial needle aspiration (TBNA) competence is attained. The pooled sensitivity was 67.4% (individual sensitivities 66.7, 70.7, 61.2, 80.3 and 59.7%). CONCLUSION: Cusum analysis is well suited to the assessment of procedures with a binary outcome, but accurate and appropriate standards of practice must be determined prior to assessment to ensure correct identification of underperformance. This report suggests that the learning curve for EBUS is greater than previously reported using different methods, and that even experienced bronchoscopists vary in their speed of learning.

Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis.

BACKGROUND: Endobronchial ultrasound (EBUS) with transbronchial needle aspiration (TBNA) is becoming widely used for mediastinal lymph node staging in patients with known or suspected lung cancer. While a substantial number of case series have evaluated test performance of this investigation, the small sample sizes limited the ability to accurately evaluate the precision of EBUS-TBNA as a staging modality. A systematic review was performed of published studies evaluating EBUS-TBNA for mediastinal lymph node staging to ascertain the pooled sensitivity and specificity of this investigation. METHODS: A literature search was constructed and performed by a professional medical librarian to identify the literature from 1960 to February 2008. Pooled specificity and sensitivity was estimated from the extracted data with an exact binomial rendition of the bivariate mixed-effects regression model. RESULTS: Of 365 publications, 25 were identified in which EBUS-TBNA was specifically focused on mediastinal node staging. Of these, only 10 had data suitable for extraction and analysis. The overall test performance was excellent with an area under the summary receiver operating characteristics curve of 0.99 (95% CI 0.96 to 1.00); similarly, EBUS-TBNA had excellent pooled specificity of 1.00 (95% CI 0.92 to 1.00) and good pooled sensitivity of 0.88 (95% CI 0.79 to 0.94). CONCLUSIONS: EBUS-TBNA has excellent overall test performance and specificity for mediastinal lymph node staging in patients with lung cancer. The results compare favourably with published results for computed tomography and positron emission tomography.

Multiplex immune serum biomarker profiling in sarcoidosis and systemic sclerosis.

Multiplex protein technology has the potential to identify biomarkers for the differentiation, classification and improved understanding of the pathogenesis of interstitial lung disease. The aim of this study was to determine whether a 30-inflammatory biomarker panel could discriminate between healthy controls, sarcoidosis and systemic sclerosis (SSc) patients independently of other clinical indicators. We also evaluated whether a panel of biomarkers could differentiate between the presence or absence of lung fibrosis in SSc patients. We measured 30 circulating biomarkers in 20 SSc patients, 21 sarcoidosis patients and 20 healthy controls using Luminex bead technology and used Fisher's discriminant function analysis to establish the groups of classification mediators. There were significant differences in median concentration measurements between study groups for 20 of the mediators but with considerable range overlap between the groups, limiting group differentiation by single analyte measurements. However, a 17-analyte biomarker model correctly classified 90% of study individuals to their respective group and another 14-biomarker panel correctly identified the presence of lung fibrosis in SSc patients. These findings, if they are corroborated by independent studies in other centres, have potential for clinical application and may generate novel insights into the modulation of immune profiles during disease evolution.

Risk of bleeding in patients undergoing pulmonary procedures on antiplatelet or anticoagulants: A systematic review.

As many as 25% of all patients undergoing invasive pulmonary procedures are receiving at least one antiplatelet or anticoagulant agent. For those undergoing elective procedures, the decision-making process is uncomplicated and the procedure may be postponed until the antiplatelet or anticoagulant agent may be safely held. However, many invasive pulmonary procedures are semi-elective or emergent in nature in which case a risk-benefit calculation and discussion occur between the provider and patient or surrogate decision-maker. Therefore, it is critical for providers to have an awareness of the risk of bleeding complications with different pulmonary procedures on various antiplatelet and anticoagulant agents. This systematic review summarizes the bleeding complications associated with different pulmonary procedures in patients on various antiplatelet or anticoagulant agents in the literature and reveals a paucity of high-quality evidence across a wide spectrum of pulmonary procedures and antiplatelet or anticoagulant agents. The results of this review can help inform providers of the bleeding risk in these patients to aid in the shared decision-making process and risk vs benefit discussion.

Dornase alfa.

Cystic fibrosis is characterised by chronic bronchopulmonary sepsis. Various therapeutic modalities attempt to enhance the clearance of airway secretions. Dornase alfa (recombinant human deoxyribonuclease) reduces the viscoelasticity of sputum from patients with cystic fibrosis by depolymerising extracellular DNA. The drug is administered as an aerosol using a jet nebuliser at a dosage of 2.5mg once daily. It improves pulmonary function and reduces the risk of respiratory exacerbations requiring parenteral antibacterials. Various clinical trials have demonstrated a heterogeneous response to dornase alfa and have been unable to predict which groups of patients benefit from treatment. Patient selection is further complicated because some individuals do not exhibit improvements in lung function, but benefit in terms of a decrease in infective exacerbations. All patients with cystic fibrosis who produce purulent sputum are potential candidates for dornase alfa therapy. We suggest that compliant patients be considered for treatment with dornase alfa, irrespective of disease severity, but should be closely monitored and be assessed at regular intervals to monitor treatment response.

Two years experience with recombinant human DNase I in the treatment of pulmonary disease in cystic fibrosis.

Recombinant human DNase I (rhDNase) has been shown to improve pulmonary function in patients treated for up to 6 months. A cohort of 52 cystic fibrosis patients with a FVC > 40% predicted were enrolled into an open label study in order to evaluate longer-term effects of rhDNase. They received 2.5 mg rhDNase twice daily for 6 months followed by a 2-week wash-out period, and for the subsequent 18 months were treated with rhDNase once daily. Twenty-six male and 26 female patients with a mean FVC of 2.941 and FEV1 of 1.471 were recruited. Thirteen patients did not complete the study; there were seven deaths, three patients withdrew consent and three patients were lost to follow-up. Improvement in pulmonary function was seen following treatment and changes were evaluated as mean percent change from baseline. The maximum improvement occurred in the first month followed by a plateau at a lower level of improvement. The mean improvement in FEV1 over the first month was 13.3% (range 12-14.1%), followed by a plateau at around 7.1% (range 4.6-11.0%) for the subsequent 23 months. Mean FVC was improved by 12.03% (range 9.0-14.3%) over the first month and subsequently 4.2% (range - 2.2-10.2%). The effects on pulmonary function were similar for both treatment doses of rhDNase. There was also a steady improvement in weight from a mean of 54.2 kg to 55.7 kg at the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Current developments in the treatment of pulmonary disease in patients with cystic fibrosis.

Cystic fibrosis is a genetic disease that affects one in 2500 live births. A basic defect in chloride transport leads to impaired clearance of airway secretions and a susceptibility to bacterial infection. Once infection is established there is a vicious cycle that leads to progressive inflammation and infection. Although cystic fibrosis is a multisystem disorder, pulmonary disease is the main cause of morbidity and respiratory failure remains the main cause of death. This review discusses the strategies for treating pulmonary disease in patients with cystic fibrosis and focuses on some of the therapeutic developments.

New treatment strategies in cystic fibrosis: rhDNase.

Cystic fibrosis (CF) is the commonest inherited disease of the Caucasian population, with a high morbidity and mortality from pulmonary disease. The high viscoelasticity of CF sputum is due, in part, to the high deoxyribonucleic acid (DNA) content. Recombinant human deoxyribonuclease I (rhDNase) has been developed and in vitro studies have shown that it reduces the viscoelasticity of CF sputum. This article reviews the in vivo clinical studies conducted to determine the safety and efficacy of rhDNase in the treatment of pulmonary disease in CF. Initial Phase I studies showed preliminary safety and some evidence of clinical benefit. Subsequently, two Phase II studies were conducted in the US and UK during which patients received rhDNase for 10 days. A Phase III study of 24 weeks duration involving 968 patients in 51 centres in North America is also reported in detail. Longer term open-label studies, the results of intermittent administration, administration to severely ill patients and the use of different delivery systems are reviewed. The Phase II study reported improvements in pulmonary function and had a good safety profile. The Phase III study showed improvement in forced expiratory volume in one second (FEV1) of 5.8 and 5.6% in patients treated once and twice daily, respectively. The risk of developing an exacerbation was reduced by 28% with once daily treatment and 37% with twice daily treatment compared to placebo. The drug was safe and there was some improvement in quality of life data. Recombinant human deoxyribonuclease is a new therapy for pulmonary disease in cystic fibrosis which has been shown to benefit patients when used in conjunction with conventional therapy.