Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for PD-L1 Testing in Non-small Cell Lung Cancer.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression on cancer cells is a clinically important biomarker to select patients with non-small cell lung cancer (NSCLC) for treatment with programmed death-1/PD-L1 inhibitors. Clinical trials of immunotherapy in patients with NSCLC have required histologic evidence for PD-L1 testing; in clinical practice, cytologic samples commonly are acquired in patients with advanced disease. RESEARCH QUESTION: This study aims to investigate whether endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples are adequate for PD-L1 testing in NSCLC. STUDY DESIGN AND METHODS: This study investigates the sampling adequacy of EBUS-TBNA for PD-L1 testing when compared with other methods. Furthermore, the relationship between clinicopathologic characteristics and PD-L1 expression in the study population have been examined. Five hundred seventy-seven NSCLC specimens were analyzed from consecutive patients with NSCLC across six centers in the United Kingdom and one center in the United States between January 2015 and December 2016. RESULTS: In the EBUS-TBNA group (189 specimens), the overall percentage of patients with successful PD-L1 testing was 94.7%. There was no significant difference in sampling adequacy with other methods of tissue acquisition. Older patients had higher failure rates of PD-L1 testing (OR, 1.06; P = .008). In multivariate analysis, advanced N-stage (P = .048) and presence of brain metastasis (P < .001) were associated with high PD-L1 expression. INTERPRETATION: This large multicenter study shows that EBUS-TBNA provides samples adequate for PD-L1 testing and that advanced N stage and the presence of brain metastasis are associated with high PD-L1 expression.

Once daily long-acting beta2-agonists and long-acting muscarinic antagonists in a combined inhaler versus placebo for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a respiratory condition causing accumulation of mucus in the airways, cough, and breathlessness; the disease is progressive and is the fourth most common cause of death worldwide. Current treatment strategies for COPD are multi-modal and aim to reduce morbidity and mortality and increase patients' quality of life by slowing disease progression and preventing exacerbations. Fixed-dose combinations (FDCs) of a long-acting beta2-agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) delivered via a single inhaler are approved by regulatory authorities in the USA, Europe, and Japan for the treatment of COPD. Several LABA/LAMA FDCs are available and recent meta-analyses have clarified their utility versus their mono-components in COPD. Evaluation of the efficacy and safety of once-daily LABA/LAMA FDCs versus placebo will facilitate the comparison of different FDCs in future network meta-analyses. OBJECTIVES: We assessed the evidence for once-daily LABA/LAMA combinations (delivered in a single inhaler) versus placebo on clinically meaningful outcomes in patients with stable COPD. SEARCH METHODS: We identified trials from Cochrane Airways' Specialised Register (CASR) and also conducted a search of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch). We searched CASR and trial registries from their inception to 3 December 2018; we imposed no restriction on language of publication. SELECTION CRITERIA: We included parallel-group and cross-over randomised controlled trials (RCTs) comparing once-daily LABA/LAMA FDC versus placebo. We included studies reported as full-text, those published as abstract only, and unpublished data. We excluded very short-term trials with a duration of less than 3 weeks. We included adults (≥ 40 years old) with a diagnosis of stable COPD. We included studies that allowed participants to continue using their ICS during the trial as long as the ICS was not part of the randomised treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results to determine included studies, extracted data on prespecified outcomes of interest, and assessed the risk of bias of included studies; we resolved disagreements by discussion with a third review author. Where possible, we used a random-effects model to meta-analyse extracted data. We rated all outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system and presented results in 'Summary of findings' tables. MAIN RESULTS: We identified and included 22 RCTs randomly assigning 8641 people with COPD to either once-daily LABA/LAMA FDC (6252 participants) or placebo (3819 participants); nine studies had a cross-over design. Studies had a duration of between three and 52 weeks (median 12 weeks). The mean age of participants across the included studies ranged from 59 to 65 years and in 21 of 22 studies, participants had GOLD stage II or III COPD. Concomitant inhaled corticosteroid (ICS) use was permitted in all of the included studies (where stated); across the included studies, between 28% to 58% of participants were using ICS at baseline. Six studies evaluated the once-daily combination of IND/GLY (110/50 µg), seven studies evaluated TIO/OLO (2.5/5 or 5/5 µg), eight studies evaluated UMEC/VI (62.5/5, 125/25 or 500/25 µg) and one study evaluated ACD/FOR (200/6, 200/12 or 200/18 µg); all LABA/LAMA combinations were compared with placebo.The risk of bias was generally considered to be low or unknown (insufficient detail provided), with only one study per domain considered to have a high risk of bias except for the domain 'other bias' which was determined to be at high risk of bias in four studies (in three studies, disease severity was greater at baseline in participants receiving LABA/LAMA compared with participants receiving placebo, which would be expected to shift the treatment effect in favour of placebo).Compared to the placebo, the pooled results for the primary outcomes for the once-daily LABA/LAMA arm were as follows: all-cause mortality, OR 1.88 (95% CI 0.81 to 4.36, low-certainty evidence); all-cause serious adverse events (SAEs), OR 1.06 (95% CI 0.88 to 1.28, high-certainty evidence); acute exacerbations of COPD (AECOPD), OR 0.53 (95% CI 0.36 to 0.78, moderate-certainty evidence); adjusted St George's Respiratory Questionnaire (SGRQ) score, MD -4.08 (95% CI -4.80 to -3.36, high-certainty evidence); proportion of SGRQ responders, OR 1.75 (95% CI 1.54 to 1.99). Compared with placebo, the pooled results for the secondary outcomes for the once-daily LABA/LAMA arm were as follows: adjusted trough forced expiratory volume in one second (FEV1), MD 0.20 L (95% CI 0.19 to 0.21, moderate-certainty evidence); adjusted peak FEV1, MD 0.31 L (95% CI 0.29 to 0.32, moderate-certainty evidence); and all-cause AEs, OR 0.95 (95% CI 0.86 to 1.04; high-certainty evidence). No studies reported data for the 6-minute walk test. The results were generally consistent across subgroups for different LABA/LAMA combinations and doses. AUTHORS' CONCLUSIONS: Compared with placebo, once-daily LABA/LAMA (either IND/GLY, UMEC/VI or TIO/OLO) via a combination inhaler is associated with a clinically significant improvement in lung function and health-related quality of life in patients with mild-to-moderate COPD; UMEC/VI appears to reduce the rate of exacerbations in this population. These conclusions are supported by moderate or high certainty evidence based on studies with an observation period of up to one year.

How should complete lung collapse secondary to primary spontaneous pneumothorax be managed? .

Management of primary spontaneous pneumothorax (PSP) depends on the symptoms and size of lung collapse. The British Thoracic Society recommends needle aspiration (NA) for all PSP requiring intervention, followed by intercostal drain (ICD) if NA fails. We compared the role of NA versus ICD as the first step in PSP with 'complete lung collapse'.This was a retrospective observational study of 877 consecutive pneumothorax episodes at University Hospitals of North Midlands, Stoke on Trent, UK. Chest X-ray (CXR) at presentation was reviewed to identify PSP with complete lung collapse. The primary outcome measure was successful lung re-inflation after initial intervention.Two-hundred and sixty-six PSP patients were identified; 69 had complete lung collapse on CXR of which 35 had NA and 34 had ICD. The ICD group had a significantly better immediate success compared with the NA group (62% versus 11%, odds ratio (OR) = 12.5, p<0.0001; after adjustment for potential confounders, OR increased to 26.4, p=0.0001) although long-term outcomes were comparable.There should be clear consensus on definition and management of complete lung collapse. PSP with complete lung collapse could be managed as a separate subgroup where ICD placement is considered to be the first intervention.

Unusual case of bilateral haemotympanum after endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA).

We present a case of bilateral haemotympanum (HT) during endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA). A 64 year-old-man underwent EBUS-TBNA for mediastinal lymph nodes (LN) staging. Medical history included emphysema and angina. Medication included aspirin until the day before procedure. Full blood count and clotting screen were normal. He received sedation (5 mg midazolam, 1000 mcg alfentanil) and topical anaesthesia (16 mL 1% lignocaine) but coughed excessively throughout the procedure. Left hilar LN was the only area sampled. Spontaneous bleeding ensued from both ears towards the end of the procedure. Patient remained haemodynamically stable. The procedure was aborted and otolaryngology consult sought. Otoscopy showed bilateral haematoma from anterior ear canal with normal tympanic membranes and no hearing loss. Nasendoscopy revealed erythematous ostium of both Eustachian tubes. Bleeding stopped spontaneously and patient required no further imaging or treatment. We report this case to increase awareness of this very rare complication resulting from excessive coughing during EBUS-TBNA.

Extracorporeal membrane oxygenation (ECMO) for near-fatal asthma refractory to conventional ventilation.

We describe a case of near-fatal asthma, treated successfully by initiation of extracorporeal membrane oxygenation (ECMO). A 29-year-old woman, known asthmatic on steroid inhalers, inhaled/nebulised bronchodilators, long-term oral prednisolone, theophylline and montelukast, presented with acute shortness of breath. She deteriorated following initial treatment with nebulised bronchodilators and magnesium sulfate requiring intubation and mechanical ventilation. Severe bronchospasm ensued following mechanical ventilation and peak airway pressures remained at 55 cm H2O with intrinsic positive end expiratory pressure(PEEP) of 14 cm H2O. Despite treatment with sedation, paralysis, intravenous salbutamol and inhaled sevoflurane, her condition deteriorated. She was commenced on mobile ECMO by the retrieval team. While on ECMO, her CO2 normalised within 48 hours. She was extubated within 72 hours of initiating ECMO and was discharged to the ward next day. We reiterate that ECMO should be considered sooner for status asthmatics not responding to maximal pharmacological therapy and ventilatory support to prevent ongoing lung injury and mortality.

An airway traffic jam: a plastic traffic cone masquerading as bronchial carcinoma.

Tracheobronchial foreign body (TFB) aspiration is a common occurrence in children compared with adults. Long-standing cases of TFB aspiration during childhood presenting in an adult have rarely been reported. We report the unique case of an endobronchial Playmobil traffic cone that went undetected for 40 years and presented as a suspected bronchogenic carcinoma. This was subsequently removed successfully with flexible bronchoscopy. To our knowledge this is the first case of a TFB that was overlooked this length of time.