Molecular analysis of endobronchial ultrasound needle aspirates in patients with non-small cell lung cancer: Results from the SCOPE database.

OBJECTIVE: Molecular subtyping of non-small cell lung cancer (NSCLC) is critical in the diagnostic evaluation of patients with advanced disease. This study aimed to examine whether samples from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of intrathoracic lymph nodes and/or lung lesions are adequate for molecular analysis across various institutions. METHODS: We retrospectively reviewed all cases of linear EBUS-TBNA with a final bronchoscopic diagnosis of NSCLC entered in the Stather Canadian Outcomes registry for chest ProcEdures database. The primary outcome was specimen inadequacy rate for each molecular target, as defined by the local laboratory or pathologist. RESULTS: A total of 866 EBUS-TBNA procedures for NSCLC were identified. Specimen inadequacy rates were 3.8% for EGFR, 2.5% for ALK-1 and 3.5% for PD-L1. Largest target size was not different between adequate and inadequate specimens, and rapid onsite evaluation did not increase specimen adequacy rates. One centre using next-generation sequencing for EGFR had lower adequacy rates than 2 others using matrix-assisted laser desorption/ionization time-of-flight mass spectrophotometry. CONCLUSION: EBUS-TBNA specimens have a very low-specimen inadequacy rate for molecular subtyping of non-small cell lung cancer.

Diagnostic sensitivity of pleural fluid cytology in malignant pleural effusions: systematic review and meta-analysis.

BACKGROUND: Pleural fluid cytology is an important diagnostic test used for the investigation of pleural effusions. There is considerable variability in the reported sensitivity for the diagnosis of malignant pleural effusions (MPE) in the literature. OBJECTIVE: The purpose of this review is to determine the diagnostic sensitivity of pleural fluid cytology for MPE, both overall and by tumour type, to better inform the decision-making process when investigating pleural effusions. DATA SOURCES: A literature search of EMBASE and MEDLINE was performed by four reviewers. Articles satisfying inclusion criteria were evaluated for bias using the QUADAS-2 tool. DATA EXTRACTION: For quantitative analysis, we performed a metaanalysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on primary cancer site and meta-regression by year of publication. SYNTHESIS: Thirty-six studies with 6057 patients with MPE were included in the meta-analysis. The overall diagnostic sensitivity of pleural fluid cytology for MPE was 58.2% (95% CI 52.5% to 63.9%; range 20.5%-86.0%). There was substantial heterogeneity present among studies (I2 95.5%). For primary thoracic malignancies, sensitivity was highest in lung adenocarcinoma (83.6%; 95% CI 77.7% to 89.6%) and lowest in lung squamous cell carcinoma (24.2%; 95% CI 17.0% to 31.5%) and mesothelioma (28.9%; 95% CI 16.2% to 41.5%). For malignancies with extrathoracic origin, sensitivity was high for ovarian cancer (85.2%; 95% CI 74.2% to 96.1%) and modest for breast cancer (65.3%; 95% CI 49.8% to 80.8%). CONCLUSIONS: Pleural fluid cytology has an overall sensitivity of 58.2% for the diagnosis of MPE. Clinicians should be aware of the high variability in diagnostic sensitivity by primary tumour type as well as the potential reasons for false-negative cytology results.PROSPERO registration numberCRD42021231473.

Longitudinal follow-up of postacute COVID-19 syndrome: DLCO, quality-of-life and MRI pulmonary gas-exchange abnormalities.

129Xe MRI red blood cell to alveolar tissue plasma ratio (RBC:TP) abnormalities have been observed in ever-hospitalised and never-hospitalised people with postacute COVID-19 syndrome (PACS). But, it is not known if such abnormalities resolve when symptoms and quality-of-life scores improve. We evaluated 21 participants with PACS, 7±4 months (baseline) and 14±4 months (follow-up) postinfection. Significantly improved diffusing capacity of the lung for carbon monoxide (DLCO, Δ=14%pred ;95%CI 7 to 21, p<0.001), postexertional dyspnoea (Δ=-0.7; 95%CI=-0.2 to -1.2, p=0.019), St George's Respiratory Questionnaire-score (SGRQ Δ=-6; 95% CI=-1 to -11, p=0.044) but not RBC:TP (Δ=0.03; 95% CI=0.01 to 0.05, p=0.051) were observed at 14 months. DLCO correlated with RBC:TP (r=0.60, 95% CI=0.22 to 0.82, p=0.004) at 7 months. While DLCO and SGRQ measurements improved, these values did not normalise 14 months post-infection. ClinicalTrials.gov NCT04584671.

Patient perspectives on the use of indwelling pleural catheters in malignant pleural effusions.

BACKGROUND: Indwelling pleural catheters are an effective treatment option for patients with malignant pleural effusions. Despite their popularity, there remains a paucity of data on the patient experience and key patient-centred outcomes. OBJECTIVE: To investigate the experience of patients receiving an indwelling pleural catheter to better inform and identify potential areas for improvement in care. METHODS: This was a multicentre survey study at three academic, tertiary-care centres in Canada. Patients with a diagnosis of malignant pleural effusion who had an indwelling pleural catheter inserted were included. An adapted questionnaire specific to indwelling pleural catheters was used with responses recorded on a 4-point Likert scale. Patients completed the questionnaire in-person or by phone at 2-week and 3-month follow-up appointments. RESULTS: A total of 105 patients were enrolled in the study with 84 patients included in the final analysis. At the 2-week follow-up, patient-reported improvements in dyspnoea and quality of life from indwelling pleural catheter were high at 93% and 87%, respectively. The predominant issues identified were discomfort at time of insertion (58%), itching (49%), difficulty with sleeping (39%), discomfort with home drainage (36%) and the pleural catheter reminding patients of their disease (63%). Avoiding hospitalisation for the management of dyspnoea was important to 95% of patients. Findings were similar at 3 months. CONCLUSIONS: Indwelling pleural catheters are an effective intervention to directly improve dyspnoea and quality of life but have important disadvantages for some; clinicians and patients should be aware of these when making an informed decision regarding treatment.

Postacute COVID-19 Syndrome: 129Xe MRI Ventilation Defects and Respiratory Outcomes 1 Year Later.

Background In individuals with postacute COVID-19 syndrome (PACS) and normal pulmonary function, xenon 129 (129Xe) MRI ventilation defects, abnormal quality-of-life scores, and exercise limitation were reported 3 months after infection; the longitudinal trajectory remains unclear. Purpose To measure and compare pulmonary function, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) in individuals with PACS evaluated 3 and 15 months after COVID-19 infection. Materials and Methods In this prospective study, participants with PACS aged 18-80 years were enrolled between July 2020 and August 2021 from two quaternary care centers. 129Xe MRI VDP, diffusing capacity of lung for carbon monoxide (Dlco), spirometry, oscillometry, 6-minute walk distance (6MWD), and St George Respiratory Questionnaire (SGRQ) scores were evaluated 3 months and 15 months after COVID-19 infection. Differences between time points were evaluated using the paired t test. Multivariable models were generated to explain exercise capacity and quality-of-life improvement. Odds ratios (ORs) were used to evaluate potential treatment influences. Results Overall, 53 participants (mean age, 55 years ± 18 [SD]; 27 women) attended both 3- and 15-month visits and were included in the analysis. The mean values for 129Xe MRI VDP (5.8% and 4.2%; P = .003), forced expiratory volume in the 1st second of expiration percent predicted (84% and 90%; P = .001), Dlco percent predicted (86% and 99%; P = .002), and SGRQ score (35 and 25; P < .001) improved between the 3- and 15-month visit. VDP measured 3 months after COVID-19 infection predicted the change in 6MWD (ß = -0.643, P = .006), while treatment with respiratory medication at 3 months predicted an improved quality-of-life score at 15 months (OR, 4.0; 95% CI: 1.2, 13.8; P = .03). Conclusion Pulmonary function, gas exchange, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) improved in participants with postacute COVID-19 syndrome at 15 months compared with 3 months after infection. VDP measured at 3 months after infection correlated with improved exercise capacity, while treatment with respiratory medication was associated with an improved quality-of-life score 15 months after infection. ClinicalTrials.gov registration no. NCT05014516 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Vogel-Claussen in this issue.

Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-acute COVID-19 Syndrome.

BACKGROUND: In patients with post-acute COVID-19 syndrome (PACS), abnormal gas-transfer and pulmonary vascular density have been reported, but such findings have not been related to each other or to symptoms and exercise limitation. The pathophysiologic drivers of PACS in patients previously infected with COVID-19 who were admitted to in-patient treatment in hospital (or ever-hospitalized patients) and never-hospitalized patients are not well understood. PURPOSE: To determine the relationship of persistent symptoms and exercise limitation with xenon 129 (129Xe) MRI and CT pulmonary vascular measurements in individuals with PACS. MATERIALS AND METHODS: In this prospective study, patients with PACS aged 18-80 years with a positive polymerase chain reaction COVID-19 test were recruited from a quaternary-care COVID-19 clinic between April and October 2021. Participants with PACS underwent spirometry, diffusing capacity of the lung for carbon monoxide (DLco), 129Xe MRI, and chest CT. Healthy controls had no prior history of COVID-19 and underwent spirometry, DLco, and 129Xe MRI. The 129Xe MRI red blood cell (RBC) to alveolar-barrier signal ratio, RBC area under the receiver operating characteristic curve (AUC), CT volume of pulmonary vessels with cross-sectional area 5 mm2 or smaller (BV5), and total blood volume were quantified. St George's Respiratory Questionnaire, International Physical Activity Questionnaire, and modified Borg Dyspnea Scale measured quality of life, exercise limitation, and dyspnea. Differences between groups were compared with use of Welch t-tests or Welch analysis of variance. Relationships were evaluated with use of Pearson (r) and Spearman (ρ) correlations. RESULTS: Forty participants were evaluated, including six controls (mean age ± SD, 35 years ± 15, three women) and 34 participants with PACS (mean age, 53 years ± 13, 18 women), of whom 22 were never hospitalized. The 129Xe MRI RBC:barrier ratio was lower in ever-hospitalized participants (P = .04) compared to controls. BV5 correlated with RBC AUC (ρ = .44, P = .03). The 129Xe MRI RBC:barrier ratio was related to DLco (r = .57, P = .002) and forced expiratory volume in 1 second (ρ = .35, P = .03); RBC AUC was related to dyspnea (ρ = -.35, P = .04) and International Physical Activity Questionnaire score (ρ = .45, P = .02). CONCLUSION: Xenon 129 (129Xe) MRI measurements were lower in participants previously infected with COVID-19 who were admitted to in-patient treatment in hospital with post-acute COVID-19 syndrome, 34 weeks ± 25 after infection compared to controls. The 129Xe MRI measures were associated with CT pulmonary vascular density, diffusing capacity of the lung for carbon monoxide, exercise capacity, and dyspnea. Clinical trial registration no.: NCT04584671 © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Wild and Collier in this issue.

Endoscopic nodal staging in oligometastatic non-small cell lung cancer (NSCLC) being treated with stereotactic ablative radiotherapy (ENDO-SABR).

BACKGROUND: Research in treatment of non-small cell lung cancer (NSCLC) has shown promising results with stereotactic ablative radiotherapy (SABR) of oligometastatic disease, wherein distant disease may be limited to one or a few distant organs by host factors. Traditionally, PET/CT has been used in detecting metastatic disease and avoiding futile surgical intervention, however, sensitivity and specificity is limited to only 81 and 79%, respectively. Mediastinal staging still identifies occult nodal disease in up to 20% of NSCLC patients initially thought to be operative candidates. Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive tool for the staging and diagnosis of thoracic malignancy. When EBUS is combined with endoscopic ultrasound using the same bronchoscope (EUS-B), the diagnostic sensitivity and negative predictive value increase to 84 and 97%, respectively. Endoscopic staging in patients with advanced disease has never been studied, but may inform treatment if a curative SABR approach is being taken. METHODS: This is a multi-centre, prospective, cohort study with two-stage design. In the first stage, 10 patients with oligometastatic NSCLC (lung tumour ± hilar/mediastinal lymphadenopathy) with up to 5 synchronous metastases will be enrolled An additional 19 patients will be enrolled in the second stage if rate of treatment change is greater than 10% in the first stage. Patients will be subject to EBUS or combined modality EBUS/EUS-B to assess bilateral lymph node stations using a N3 to N2 to N1 progression. Primary endpoint is defined as the rate of change to treatment plan including change from SABR to conventional dose radiation, change in mediastinal radiation field, and change from curative to palliative intent treatment. DISCUSSION: If a curative approach with SABR for oligometastatic disease is being explored, invasive mediastinal staging may guide treatment and prognosis. This study will provide insight into the use of endoscopic mediastinal staging in determining changes in treatment plan of NSCLC. Results will inform the design of future phase II trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04852588. Date of registration: April 19, 2021. PROTOCOL VERSION: 1.1 on December 9, 2021.

Assessment of precision irradiation in early non-small cell lung cancer and interstitial lung disease (ASPIRE-ILD): study protocol for a phase II trial.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD. METHODS: ASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1-2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy10 or 217 Gy3), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy10 or 133 Gy3) and 45 Gy in 15 fractions daily (58 Gy10 or 90 Gy3). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR. DISCUSSION: ASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03485378. Date of registration: April 2, 2018.

Life-threatening bronchiolitis related to electronic cigarette use in a Canadian youth.

BACKGROUND: Although electronic cigarettes (e-cigarettes) were initially marketed as a potential smoking-cessation aid and a safer alternative to smoking, the long-term health effect of e-cigarette use ("vaping") is unknown. Vaping e-liquids expose the user to several potentially harmful chemicals, including diacetyl, a flavouring compound known to cause bronchiolitis obliterans with inhalational exposure ("popcorn worker's lung"). CASE DESCRIPTION: We report the case of a 17-year-old male who presented with intractable cough, progressive dyspnea and malaise after vaping flavoured e-liquids and tetrahydrocannabinol intensively. Initial physical examination showed fever, tachycardia, hypoxemia, and bibasilar inspiratory crackles on lung auscultation. Computed tomography of the chest showed diffuse centrilobular "tree-inbud" nodularity, consistent with acute bronchiolitis. Multiple cultures, including from 2 bronchoalveolar lavage samples, and biopsy stains, were negative for infection. He required intubation, invasive mechanical ventilation and venovenous extracorporeal membrane oxygenation (ECMO) for refractory hypercapnia. The patient's condition improved with high-dose corticosteroids. He was weaned off ECMO and mechanical ventilation, and discharged home after 47 days in hospital. Several months after hospital discharge, his exercise tolerance remained limited and pulmonary function tests showed persistent, fixed airflow obstruction with gas trapping. The patient's clinical picture was suggestive of possible bronchiolitis obliterans, thought to be secondary to inhalation of flavouring agents in the e-liquids, although the exact mechanism of injury and causative agent are unknown. INTERPRETATION: This case of severe acute bronchiolitis, causing near-fatal hypercapnic respiratory failure and chronic airflow obstruction in a previously healthy Canadian youth, may represent vaping-associated bronchiolitis obliterans. This novel pattern of pulmonary disease associated with vaping appears distinct from the type of alveolar injury predominantly reported in the recent outbreak of cases of vaping-associated pulmonary illness in the United States, underscoring the need for further research into all potentially toxic components of e-liquids and tighter regulation of e-cigarettes.

129Xe MRI Ventilation Textures and Longitudinal Quality-of-Life Improvements in Long-COVID.

RATIONALE AND OBJECTIVES: It remains difficult to predict longitudinal outcomes in long-COVID, even with chest CT and functional MRI. 129Xe MRI reflects airway dysfunction, measured using ventilation defect percent (VDP) and in long-COVID patients, MRI VDP was abnormal, suggestive of airways disease. While MRI VDP and quality-of-life improved 15-month post-COVID infection, both remained abnormal. To better understand the relationship of airways disease and quality-of-life improvements in patients with long-COVID, we extracted 129Xe ventilation MRI textures and generated machine-learning models in an effort to predict improved quality-of-life, 15-month post-infection. MATERIALS AND METHODS: Long-COVID patients provided written-informed consent to 3-month and 15-month post-infection visits. Pyradiomics was used to extract 129Xe ventilation MRI texture features, which were ranked using a Random-Forest classifier. Top-ranking features were used in classification models to dichotomize patients based on St. George's Respiratory Questionnaire (SGRQ) score improvement greater than the minimal-clinically-important-difference (MCID). Classification performance was evaluated using the area under the receiver-operator-characteristic-curve (AUC), sensitivity, and specificity. RESULTS: 120 texture features were extracted from 129Xe ventilation MRI in 44 long-COVID participants (54 ± 14 years), including 30 (52 ± 12 years) with ΔSGRQ≥MCID and 14 (58 ± 18 years) with ΔSGRQ

Stereotactic Radiation Therapy in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease: A Nonrandomized Clinical Trial.

Importance: Patients with interstitial lung disease (ILD) and early-stage non-small cell lung cancer (NSCLC) have been reported to be at high risk of toxic effects after stereotactic ablative radiotherapy (SABR), but for many patients, there are limited alternative treatment options. Objective: To prospectively assess the benefits and toxic effects of SABR in this patient population. Design, Setting, and Participants: This prospective cohort study was conducted at 6 academic radiation oncology institutions, 5 in Canada and 1 in Scotland, with accrual between March 7, 2019, and January 12, 2022. Patients aged 18 years or older with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgical resection were enrolled. Intervention: Patients were treated with SABR to a dose of 50 Gy in 5 fractions every other day. Main Outcomes and Measures: The study prespecified that SABR would be considered worthwhile if median overall survival-the primary end point-was longer than 1 year, with a grade 3 to 4 risk of toxic effects less than 35% and a grade 5 risk of toxic effects less than 15%. Secondary end points included toxic effects, progression-free survival (PFS), local control (LC), quality-of-life outcomes, and changes in pulmonary function. Intention-to-treat analysis was conducted. Results: Thirty-nine patients enrolled and received SABR. Median age was 78 (IQR, 67-83) years and 59% (n = 23) were male. At baseline, 70% (26 of 37) of patients reported dyspnea, median forced expiratory volume in first second of expiration was 80% (IQR, 66%-90%) predicted, median forced vital capacity was 84% (IQR, 69%-94%) predicted, and median diffusion capacity of the lung for carbon monoxide was 49% (IQR, 38%-61%) predicted. Median follow-up was 19 (IQR, 14-25) months. Overall survival at 1 year was 79% (95%, CI 62%-89%; P < .001 vs the unacceptable rate), and median overall survival was 25 months (95% CI, 14 months to not reached). Median PFS was 19 months (95% CI, 13-28 months), and 2-year LC was 92% (95% CI, 69%-98%). Adverse event rates (highest grade per patient) were grade 1 to 2: n = 12 (31%), grade 3: n = 4 (10%), grade 4: n = 0, and grade 5: n = 3 (7.7%, all due to respiratory deterioration). Conclusions and Relevance: In this trial, use of SABR in patients with fibrotic ILD met the prespecified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT03485378.

Risk of iatrogenic pneumothorax based on location of transbronchial biopsy: a retrospective cohort study.

OBJECTIVE: Transbronchial lung biopsy (TBB) is a commonly performed procedure to obtain parenchymal lung tissue during bronchoscopy. Pneumothorax is among the most common serious complications of TBB. The objective of this study was to assess whether location of TBB correlated with development of post-procedural pneumothorax. We also sought to identify additional risk factors associated with pneumothorax development. This was a single-centre, retrospective cohort study. All TBB performed between 2010 and 2020 underwent subsequent chart review. The primary outcome was radiologist reported pneumothorax on post-procedure chest x-ray. Multivariable logistic regression model was created with included variables chosen a priori based on clinical significance. RESULTS: There were a total of 222 TBB performed that met inclusion criteria. Radiographic evidence of pneumothorax was reported in 38 patients (15.4%). Ten patients (4.1%) required a chest tube. In the multivariable analysis, risk of pneumothorax was significantly higher for biopsies obtained from the left upper lobe (OR 3.3; 95% CI 1.3-9.1). There was an increased risk of pneumothorax following TBB when obtained from the left upper lobe. Clinicians should be aware of the increased risk and should consider alternative locations in patients with diffuse lung disease.

Investigation and outcomes in patients with nonspecific pleuritis: results from the International Collaborative Effusion database.

Introduction: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis. Methods: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis. Results: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09). Discussion: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP.

Synchronous metastatic lung adenocarcinoma and marginal B-cell lymphoma presenting as pleural nodules.

In this report, we present a 73 year old woman with synchronous metastatic lung adenocarcinoma and marginal B-cell lymphoma determined on histopathology of a parietal pleural biopsy. This case demonstrates radiological demonstration of pleural disease, procedural investigations and striking histopathology, along with a discussion around synchronous malignancy.

Effect of Needle Size on Diagnosis of Sarcoidosis with Endobronchial Ultrasound-guided Transbronchial Needle Aspiration: Systematic Review and Meta-Analysis.

Background: Sarcoidosis is a multisystem disease characterized by noncaseating granulomatous inflammation that most commonly involves the lungs. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an invaluable tool in the assessment of patients with mediastinal and/or hilar lymphadenopathy. Objective: It has been hypothesized that use of the larger 19-gauge (G) needle with EBUS-TBNA improves diagnostic sensitivity in sarcoidosis. However, it is unclear whether the existing literature supports this supposition. Data Sources: A literature search of Embase and Medline was performed by two reviewers. Included articles were evaluated for bias using the QUADAS-2 tool. Data Extraction: For quantitative analysis, we performed a meta-analysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on needle size, use of rapid on-site evaluation (ROSE), study design, and prevalence of sarcoidosis in study group. Synthesis: Sixty-five studies with a total of 4,242 patients were included in the meta-analysis. Overall pooled sensitivity for diagnosis of sarcoidosis was 83.99% (95% confidence interval [CI], 81.22-86.53) among all studies. The 19G subgroup had a significantly higher sensitivity (93.73%; 95% CI, 89.72-97.74%; I2 = 0.00%; P < 0.01) compared with the 21G subgroup (84.61%; 95% CI, 78.80-90.42%; I2 = 69.83%), 22G subgroup (84.07%; 95% CI, 80.90-87.24%; I2 = 85.21%) or unspecified 21G/22G subgroup (78.85%; 95% CI, 70.81-86.90%; I2 = 84.47%). There were no significant differences with use of ROSE or prevalence of sarcoidosis or by study design. Conclusions: The use of 19G needles during EBUS-TBNA had the highest diagnostic sensitivity based on available studies. Further randomized controlled trials using 19G needles should be considered in patients with suspected sarcoidosis.

Rapid On-site Evaluation (ROSE) in Capillary Pull Versus Suction Biopsy Technique With Endobronchial Ultrasound-transbronchial Needle Aspiration (EBUS-TBNA).

BACKGROUND: Suction and capillary pull are 2 biopsy techniques used in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Although these techniques have been shown to perform comparably in terms of overall diagnostic yield, we hypothesized that the capillary pull technique would be associated with improved rapid on-site evaluation (ROSE) adequacy rates thus allowing for a shorter procedure time. METHODS: One hundred eighteen patients undergoing EBUS-TBNA for any indication were randomized to suction or capillary pull techniques for the first biopsy pass; the technique used for all subsequent passes was based on operator preference and was not recorded. The first pass was subjected to ROSE and an adequacy assessment was given. ROSE slides were also scored for cellularity of diagnostic/lesional cells and blood contamination. The overall procedure time was also recorded. RESULTS: There were no significant differences between suction and capillary pull techniques in terms of ROSE adequacy rates. Cellularity of diagnostic/lesional cells and blood contamination scores were also comparable. There was no significant difference in procedure time for the 2 techniques. CONCLUSION: This study suggests no differences in ROSE outcomes between suction and capillary pull techniques in EBUS-TBNA. The technique used should therefore be left to the discretion of the operator.

Endobronchial Ultrasound Transbronchial Needle Aspiration With a 19-Gauge Needle vs 21- and 22-Gauge Needles for Mediastinal Lymphadenopathy.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used to evaluate mediastinal lymphadenopathy. Studies focusing on malignant lymphadenopathy have compared 21- and 22-gauge (21G and 22G, respectively) needles and have not identified an advantage of one needle size over the other in terms of diagnostic yield. RESEARCH QUESTION: Does the 19-gauge (19G) EBUS needle offer greater diagnostic yield and sensitivity vs the 21G and 22G EBUS needles for a diagnosis of sarcoidosis, lymphoma, or mediastinal lymphadenopathy not yet diagnosed? STUDY DESIGN AND METHODS: This study retrospectively examined records of 730 patients from the Stather Canadian Outcomes Registry for Chest Procedures (SCOPE) database who underwent EBUS-TBNA for a diagnosis of suspected sarcoidosis, lymphoma, or mediastinal lymphadenopathy not yet diagnosed. A propensity score analysis of two groups was performed. One group comprised patients undergoing EBUS-TBNA with a 19G needle, the other with a 21G or 22G needle. Cases for analysis were selected with a 1:2 ratio of 19G vs 21/22G using logistic regression and random matching with all eligible 19G cases included. RESULTS: There were 137 patients (312 targets) in the 19G group and 274 patients (631 targets) in the 21/22G group in the propensity score analysis. The diagnostic yield was 107 of 137 (78.1%) in the 19G group vs 194 of 274 (70.8%) in the 21/22G group (difference, 7.3%; 95% CI, -1.9 to 15.6; P = .116). The sensitivity of EBUS-TBNA for sarcoidosis was 80 of 83 (96.4%) in the 19G group vs 150 of 156 (96.2%) in the 21/22G group (difference, 0.24%; 95% CI, -6.6 to 85.1; P = .93). In patients with a final diagnosis of lymphoma, EBUS was diagnostic in 10 of 13 (76.9%) in the 19G group vs 12 of 12 (100%) in the 21/22G group (difference, 23.1%; 95% CI, -5.4 to 50.3; P = .08). INTERPRETATION: The study did not identify an advantage of the 19G EBUS needle over the 21/22G EBUS needles for diagnostic yield nor sensitivity for sarcoidosis or lymphoma.

129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised people with post-acute COVID-19 syndrome.

BACKGROUND: Patients often report persistent symptoms beyond the acute infectious phase of COVID-19. Hyperpolarised 129Xe MRI provides a way to directly measure airway functional abnormalities; the clinical relevance of 129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised patients who had COVID-19 has not been ascertained. It remains unclear if persistent symptoms beyond the infectious phase are related to small airways disease and ventilation heterogeneity. Hence, we measured 129Xe MRI ventilation defects, pulmonary function and symptoms in ever-hospitalised and never-hospitalised patients who had COVID-19 with persistent symptoms consistent with post-acute COVID-19 syndrome (PACS). METHODS: Consenting participants with a confirmed diagnosis of PACS completed 129Xe MRI, CT, spirometry, multi-breath inert-gas washout, 6-minute walk test, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnoea scale, modified Borg scale and International Physical Activity Questionnaire. Consenting ever-COVID volunteers completed 129Xe MRI and pulmonary function tests only. RESULTS: Seventy-six post-COVID and nine never-COVID participants were evaluated. Ventilation defect per cent (VDP) was abnormal and significantly greater in ever-COVID as compared with never-COVID participants (p<0.001) and significantly greater in ever-hospitalised compared with never-hospitalised participants who had COVID-19 (p=0.048), in whom diffusing capacity of the lung for carbon-monoxide (p=0.009) and 6-minute walk distance (6MWD) (p=0.005) were also significantly different. 129Xe MRI VDP was also related to the 6MWD (p=0.02) and post-exertional SpO2 (p=0.002). Participants with abnormal VDP (≥4.3%) had significantly worse 6MWD (p=0.003) and post-exertional SpO2 (p=0.03). CONCLUSION: 129Xe MRI VDP was significantly worse in ever-hospitalised as compared with never-hospitalised participants and was related to 6MWD and exertional SpO2 but not SGRQ or mMRC scores. TRIAL REGISTRATION NUMBER: NCT05014516.

The Tricky Trachea: Tracheitis and Mediastinitis Treated With Infliximab and Steroids in a Patient With Ulcerative Colitis.

Pulmonary extra-intestinal manifestations of inflammatory bowel disease are rare, comprising 0.21% to 0.4% of the inflammatory bowel disease population. Common symptoms include cough, chest pain, and dyspnea. Abnormal pulmonary function tests are common in these patients, with restrictive, obstructive, and diffusion capacity defects. CT scanning remains the most sensitive imaging technique to detect abnormalities. Pulmonary manifestations are diverse and include airway, parenchymal, and pleural disease. Large airway disease predominates, particularly bronchiectasis. Upper airway disease is rare but concerning for the development of acute airway compromise. To our knowledge, there are no reports of concurrent mediastinitis with tracheitis in the setting of inflammatory bowel disease. We present a case of a patient with ulcerative proctitis who experienced the development of inflammatory tracheitis and mediastinitis. Her disease responded to systemic steroids and biologic therapy. In addition to our case, we reviewed the literature and provide an approach to pulmonary complications as extra-intestinal manifestation of inflammatory bowel disease.

Avoid the Trap: Nonexpanding Lung.

Nonexpanding lung is a mechanical complication in which part of the lung is unable to expand to the chest wall, preventing apposition of the visceral and parietal pleura. This can result from various visceral pleural disease processes, including malignant pleural effusion and empyema. Nonexpanding lung can be referred to as trapped lung or lung entrapment, both with distinct clinical features and management strategies. Early evaluation of pleural effusions is important to address underlying causes of pleural inflammation and to prevent the progression from lung entrapment to trapped lung. Some patients with trapped lung will not experience symptomatic relief with pleural fluid removal. Therefore, misrecognition of trapped lung can result in patients undergoing unnecessary procedures with significant cost and morbidity. We reviewed the current understanding of nonexpanding lung, which included causes, common presentations, preventative strategies, and recommendations for clinical care.