Diagnostic value of bronchoscopy in Sars-Cov-2 infection: A systematic review.

OBJECTIVE: To investigate the diagnostic performance of bronchoscopy in patients with coronavirus disease 2019 infection. METHODS: The systematic review was conducted in April 2021 and comprised search of published articles and preprint servers for original articles assessing diagnostic performance of bronchoscopy in patients with suspected coronavirus disease 2019 infection. The primary outcome of interest was diagnostic sensitivity of bronchoalveolar lavage in the patients. The quality of each study was assessed using the Quality Assessment, Data Abstraction and Synthesis-2 tool. RESULTS: Of the 29 full-text articles assessed for eligibility, 4(13.8%) were included collectively comprising 209 patients who had undergone bronchoalveolar lavage. Mean sensitivity of bronchoalveolar lavage was 83.5% ± 10.63 (range: 68.2-940%). Overall, the 4 studies had an unclear or low risk of bias. CONCLUSIONS: Limited data suggested that bronchoscopy with bronchoalveolar lavage did not have reliably higher diagnostic sensitivity than that reported for either nasopharyngeal or oropharyngeal swabs.

Comparing modalities for risk assessment in patients with pulmonary lesions and nondiagnostic bronchoscopy for suspected lung cancer.

BACKGROUND: Bronchoscopy is commonly utilized for non-surgical sampling of indeterminant pulmonary lesions, but nondiagnostic procedures are common. Accurate assessment of the risk of malignancy is essential for decision making in these patients, yet we lack tools that perform well across this heterogeneous group of patients. We sought to evaluate the accuracy of three previously validated risk models and physician-assessed risk (PAR) in patients with a newly identified lung lesion undergoing bronchoscopy for suspected lung cancer where the result is nondiagnostic. METHODS: We performed an analysis of prospective data collected for the Percepta Bronchial Genomic Classifier Multicenter Registry. PAR and three previously validated risk models (Mayo Clinic, Veteran's Affairs, and Brock) were used to determine the probability of lung cancer (low, intermediate, or high) in 375 patients with pulmonary lesions who underwent bronchoscopy for possible lung cancer with nondiagnostic pathology. Results were compared to the actual adjudicated prevalence of malignancy in each pre-test risk group, determined with a minimum of 12 months follow up after bronchoscopy. RESULTS: PAR and the risk models performed poorly overall in the assessment of risk in this patient population. PAR most closely matched the observed prevalence of malignancy in patients at 12 months after bronchoscopy, but all modalities had a low area under the curve, and in all clinical models more than half of all the lesions labeled as high risk were truly or likely benign. The studied risk model calculators overestimate the risk of malignancy compared to PAR, particularly in the subset in older patients, irregularly bordered nodules, and masses > 3 cm. Overall, the risk models perform only slightly better when confined to lung nodules < 3 cm in this population. CONCLUSION: The currently available tools for the assessment of risk of malignancy perform suboptimally in patients with nondiagnostic findings following a bronchoscopic evaluation for lung cancer. More accurate and objective tools for risk assessment are needed. TRIAL REGISTRATION: not applicable.

Bilateral Bronchoscopic Lung Volume Reduction After Surgical Fissure Completion.

Although bilateral lung volume reduction surgery has been shown to be safe and effective in carefully selected patients with upper lobe-predominant emphysema and hyperinflation, bronchoscopic lung volume reduction via placement of endobronchial valves is conventionally performed only unilaterally. Furthermore, it is not offered to patients with interlobar collateral ventilation because of the lack of clinical efficacy. We describe two novel management approaches including (1) bilateral bronchoscopic lung volume reduction, and (2) a combined thoracic surgical and interventional pulmonary procedure involving surgical fissure completion followed by endobronchial valve placement, which culminated in safe and effective lung volume reduction of both lungs along with an excellent patient outcome.

Epidemiologic Trends in Pleural Infection. A Nationwide Analysis.

Rationale: Recent trends in the care and outcomes of pleural infection are not well characterized.Objectives: To investigate trends in hospital-based healthcare use, outcomes, and management of pleural infection across the United States.Methods: We identified adult hospitalizations for pleural infection from 2005 through 2014 in the Healthcare Cost and Utilization Project-National Inpatient Sample using International Classification of Diseases, Ninth Edition Clinical Modification diagnosis codes. We calculated weighted estimates of national trends in hospitalization, hospital length of stay, hospital mortality, inflation-adjusted cost, and management practices. We tested trend significance using fitted regression models.Results: Over one decade, there was a significant decline in hospitalizations (54.4 per million to 41.2 per million U.S. adult population), length of stay (13.5 ± 0.2 to 11.2 ± 0.2 d), mortality (4.2-2.6%), and costs ($32,829 to $29,458) (all P < 0.001). Both tube thoracostomy and video-assisted thoracoscopic surgery saw an increase as the procedure of first choice, along with declining use of thoracotomy (all P < 0.001). Most patients who underwent video-assisted thoracoscopic surgery (94%) or tube thoracostomy (64.9%) as the initial procedure did not require a second invasive procedure.Conclusions: Over the 21st century's first decade and a half, inpatient costs, use, and mortality have improved among U.S. adults hospitalized with pleural infection. Simultaneously, there has been a shift toward less invasive interventions upfront.

Management of Malignant Pleural Effusions.

Malignant pleural effusion frequently complicates both solid and hematologic malignancies and is associated with high morbidity, mortality, and health care costs. Although no pleura-specific therapy is known to impact survival, both pleurodesis and indwelling pleural catheter (IPC) placement can significantly alleviate symptoms and improve quality of life. The optimal choice of therapy in terms of efficacy and particularly cost-effectiveness depends on patient preferences and individual characteristics, including lung expansion and life expectancy. Attempting chemical pleurodesis through an IPC in the outpatient setting appears to be a particularly promising approach in the absence of a nonexpandable lung.

Indwelling Pleural Catheter Drainage Strategy for Malignant Effusion: A Cost-Effectiveness Analysis.

Rationale: The likelihood of achieving pleurodesis after indwelling pleural catheter (IPC) placement for malignant pleural effusion varies with the specific drainage strategy used: symptom-guided drainage, daily drainage, or talc instillation through the IPC (IPC + talc). The relative cost-effectiveness of one strategy over the other is unknown.Objectives: We performed a decision tree model-based analysis to ascertain the cost-effectiveness of each IPC drainage strategy from a healthcare system perspective.Methods: We developed a decision tree model using theoretical event probability data derived from three randomized clinical trials and used 2019 Medicare reimbursement data for cost estimation. The primary outcome was incremental cost-effectiveness ratio (ICER) over an analytical horizon of 6 months with a willingness-to-pay threshold of $100,000/quality-adjusted life-year (QALY). Monte Carlo probabilistic sensitivity analysis and one-way sensitivity analyses were conducted to measure the uncertainty surrounding base case estimates.Results: IPC + talc was a cost-effective alternative to symptom-guided drainage, with an ICER of $59,729/QALY. Monte Carlo probabilistic sensitivity analysis revealed that this strategy was favored in 54% of simulations. However, symptom-guided drainage was cost effective for pleurodesis rates >20% and for life expectancy <4 months. Daily drainage was not cost effective in any scenario, including for patients with nonexpandable lung, in whom it had an ICER of $2,474,612/QALY over symptom-guided drainage.Conclusions: For patients with malignant pleural effusion and an expandable lung, IPC + talc may be cost effective relative to symptom-guided drainage, although considerable uncertainty exists around this estimation. Daily IPC drainage is not a cost-effective strategy under any circumstance.

Healthcare Costs and Utilization among Patients Hospitalized for Malignant Pleural Effusion.

BACKGROUND: Malignant pleural effusion (MPE) poses a considerable healthcare burden, but little is known about trends in directly attributable hospital utilization. OBJECTIVE: We aimed to study national trends in healthcare utilization and outcomes among hospitalized MPE patients. METHODS: We analyzed adult hospitalizations attributable to MPE using the Healthcare Cost and Utilization Project - National Inpatient Sample (HCUP-NIS) databases from 2004, 2009, and 2014. Cases were included if MPE was coded as the principal admission diagnosis or if unspecified pleural effusion was coded as the principal admission diagnosis in the setting of metastatic cancer. Annual hospitalizations were estimated for the entire US hospital population using discharge weights. Length of stay (LOS), hospital charges, and hospital mortality were also estimated. RESULTS: We analyzed 92,034 hospital discharges spanning a decade (2004-2014). Yearly hospitalizations steadily decreased from 38,865 to 23,965 during this time frame, the mean LOS decreased from 7.7 to 6.3 days, and the adjusted hospital mortality decreased from 7.9 to 4.5% (p = 0.00 for all trend analyses). The number of pleurodesis procedures also decreased over time (p = 0.00). The mean inflation-adjusted charge per hospitalization rose from USD 41,252 to USD 56,951, but fewer hospitalizations drove the total annual charges down from USD 1.51 billion to USD 1.37 billion (p = 0.00 for both analyses). CONCLUSIONS: The burden of hospital-based resource utilization associated with MPE has decreased over time, with a reduction in attributable hospitalizations by one third in the span of 1 decade. Correspondingly, the number of inpatient pleurodesis procedures has decreased during this time frame.

Pleural Cryobiopsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Pleural biopsy using either video-assisted thoracoscopic surgery or medical pleuroscopy is the current diagnostic criterion standard for pleural pathology with a high, yet imperfect, diagnostic yield. Cryobiopsy may provide greater tissue, increase depth of sampled tissue, and/or reduce crush artifact. However, its impact on diagnostic yield remains uncertain, and there are potential concerns regarding its safety too. We performed a systematic review and meta-analysis to investigate the same. METHODS: We performed a systematic search of MEDLINE, Embase, and Google Scholar for studies evaluating the performance of pleural cryobiopsy, assessing the quality of each study using the Quality Assessment, Data Abstraction and Synthesis-2 tool. Using inverse variance weighting, we performed a meta-analysis of diagnostic yield estimations. We also reviewed specimen characteristics and complications related to the procedure. RESULTS: Seven observational studies involving 586 pleural biopsies (311 cryobiopsies and 275 flexible forceps biopsies) were evaluated. All but one study used a semi-rigid thoracoscope. Meta-analysis generated a diagnostic yield of 96.5% for cryobiopsy and 93.1% for forceps biopsy with an inverse variance-weighted OR of 1.61 (95% CI, 0.71-3.66) and an I2 of 16%. No instances of moderate to severe bleeding were reported with cryobiopsy. A funnel plot illustrated no major publication bias. CONCLUSIONS: Based on analysis of relatively homogenous observational data, pleural cryobiopsy is safe but does not increase diagnostic yield over flexible forceps biopsy. Adequately powered multicenter randomized trials are needed for further investigation.

The alveolar immune cell landscape is dysregulated in checkpoint inhibitor pneumonitis.

BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a highly morbid complication of immune checkpoint immunotherapy (ICI), one which precludes the continuation of ICI. Yet, the mechanistic underpinnings of CIP are unknown. METHODS: To better understand the mechanism of lung injury in CIP, we prospectively collected bronchoalveolar lavage (BAL) samples in ICI-treated patients with (n=12) and without CIP (n=6), prior to initiation of first-line therapy for CIP (high dose corticosteroids. We analyzed BAL immune cell populations using a combination of traditional multicolor flow cytometry gating, unsupervised clustering analysis and BAL supernatant cytokine measurements. RESULTS: We found increased BAL lymphocytosis, predominantly CD4+ T cells, in CIP. Specifically, we observed increased numbers of BAL central memory T-cells (Tcm), evidence of Type I polarization, and decreased expression of CTLA-4 and PD-1 in BAL Tregs, suggesting both activation of pro-inflammatory subsets and an attenuated suppressive phenotype. CIP BAL myeloid immune populations displayed enhanced expression of IL-1ß and decreased expression of counter-regulatory IL-1RA. We observed increased levels of T cell chemoattractants in the BAL supernatant, consistent with our pro-inflammatory, lymphocytic cellular landscape. CONCLUSION: We observe several immune cell subpopulations that are dysregulated in CIP, which may represent possible targets that could lead to therapeutics for this morbid immune related adverse event.

Recent Advances in Interventional Pulmonology.

The field of interventional pulmonology has grown rapidly since first being defined as a subspecialty of pulmonary and critical care medicine in 2001. The interventional pulmonologist has expertise in minimally invasive diagnostic and therapeutic procedures involving airways, lungs, and pleura. In this review, we describe recent advances in the field as well as up-and-coming developments, chiefly from the perspective of medical practice in the United States. Recent advances include standardization of formalized training, new tools for the diagnosis and potential treatment of peripheral lung nodules (including but not limited to robotic bronchoscopy), increasingly well-defined bronchoscopic approaches to management of obstructive lung diseases, and minimally invasive techniques for maximizing patient-centered outcomes for those with malignant pleural effusion.

Machine learning to predict lung nodule biopsy method using CT image features: A pilot study.

Computed tomography (CT)-based screening on lung cancer mortality is poised to make lung nodule management a growing public health problem. Biopsy and pathologic analysis of suspicious nodules is necessary to ensure accurate diagnosis and appropriate intervention. Biopsy techniques vary as do the specialists that perform them and the ways lung nodule patients are referred and triaged. The largest dichotomy is between minimally invasive biopsy (MIB) and surgical biopsy (SB). Cases of unsuccessful MIB preceding a SB can result in considerable delay in definitive care with potentially an adverse impact on prognosis besides potentially avoidable healthcare expenditures. An automated method that predicts the optimal biopsy method for a given lung nodule could save time and healthcare costs by facilitating referral and triage patterns. To our knowledge, no such method has been published. Here, we used CT image features and radiologist-annotated semantic features to predict successful MIB in a way that has not been described before. Using data from the Lung Image Database Consortium image collection (LIDC-IDRI), we trained a logistic regression model to determine whether a MIB or SB procedure was used to diagnose lung cancer in a patient presenting with lung nodules. We found that in successful MIB cases, the nodules were significantly larger and more spiculated. Our model illustrates that using robust machine learning tools on easily accessible semantic and image data can predict whether a patient's nodule is best biopsied by MIB or SB. Pending further validation and optimization, clinicians could use our publicly accessible model to aid clinical decision-making.

A radiogenomic dataset of non-small cell lung cancer.

Medical image biomarkers of cancer promise improvements in patient care through advances in precision medicine. Compared to genomic biomarkers, image biomarkers provide the advantages of being non-invasive, and characterizing a heterogeneous tumor in its entirety, as opposed to limited tissue available via biopsy. We developed a unique radiogenomic dataset from a Non-Small Cell Lung Cancer (NSCLC) cohort of 211 subjects. The dataset comprises Computed Tomography (CT), Positron Emission Tomography (PET)/CT images, semantic annotations of the tumors as observed on the medical images using a controlled vocabulary, and segmentation maps of tumors in the CT scans. Imaging data are also paired with results of gene mutation analyses, gene expression microarrays and RNA sequencing data from samples of surgically excised tumor tissue, and clinical data, including survival outcomes. This dataset was created to facilitate the discovery of the underlying relationship between tumor molecular and medical image features, as well as the development and evaluation of prognostic medical image biomarkers.

GFPT2-Expressing Cancer-Associated Fibroblasts Mediate Metabolic Reprogramming in Human Lung Adenocarcinoma.

Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-PET scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma and cell growth in squamous cell carcinoma (SCC). Next, we identified genes correlated to glucose uptake that were predominately overexpressed in a single cell-type comprising the tumor microenvironment. For SCC, most of these genes were expressed by malignant cells, whereas in adenocarcinoma, they were predominately expressed by stromal cells, particularly cancer-associated fibroblasts (CAF). Among these adenocarcinoma genes correlated to glucose uptake, we focused on glutamine-fructose-6-phosphate transaminase 2 (GFPT2), which codes for the glutamine-fructose-6-phosphate aminotransferase 2 (GFAT2), a rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which is responsible for glycosylation. GFPT2 was predictive of glucose uptake independent of GLUT1, the primary glucose transporter, and was prognostically significant at both gene and protein level. We confirmed that normal fibroblasts transformed to CAF-like cells, following TGFß treatment, upregulated HBP genes, including GFPT2, with less change in genes driving glycolysis, pentose phosphate pathway, and TCA cycle. Our work provides new evidence of histology-specific tumor stromal properties associated with glucose uptake in NSCLC and identifies GFPT2 as a critical regulator of tumor metabolic reprogramming in adenocarcinoma.Significance: These findings implicate the hexosamine biosynthesis pathway as a potential new therapeutic target in lung adenocarcinoma. Cancer Res; 78(13); 3445-57. ©2018 AACR.