Flexible CO2 Laser in Therapeutic Bronchoscopy: Initial Experiences in a Tertiary Center.

BACKGROUND: CO2 Laser (CO2L) technology deployable through flexible endoscopes now allows for their use throughout the airway, although published data are limited. METHODS: Retrospective analysis of CO2L bronchoscopic procedures, excluding glottic and subglottic interventions. Procedural success was defined as >50% visual reduction in airway obstruction in the area treated or resolution of the procedural indication. RESULTS: Seventy-two procedures were performed on 36 patients. Nonmalignant indications comprised 66%: stent-associated granulation tissue (28%), granulomatosis with polyangiitis lesions (23%), and lung transplant-related granulation tissue (16%) were the most common. Bronchoscopic access was flexible only in 81% and primarily rigid (combined with flexible) in 18%. The site of intervention was the trachea at 19%, the mainstem at 56%, and lobar/segmental airways at 45%. Procedural success was 89%. CO2L was used exclusively in 19%; in 81%, additional techniques were required, most commonly balloon dilation (59%), cryo-debulking (23%), and rigid dilation (16%). Malignant indications had a nonsignificant trend toward requiring adjuvant techniques ( P =0.05). Seventy-six percent of the patients required more than 1 procedure. CO2L exclusive cases had no statistically different needs for subsequent therapeutic bronchoscopies ( P =0.10) or time to reintervention (109 vs. 41 days, P =0.07), and reintervention-free survival was similar ( P =0.10) and difficult to predict. The complication rate attributable to CO2L was 2.7%. CONCLUSION: CO2L is a safe and useful tool when precise cutting and vaporization are desired. Its use in multi-modality approaches has high levels of success in adequately selected lesions, adding an ablative potential to dilation techniques. Vasculitis-associated scars/webs and granulation tissue (including stent-associated) appear to be ideal targets.

Diagnostic Yield of 16S Ribosomal Ribonucleic Acid Gene-Based Targeted Metagenomic Sequencing for Evaluation of Pleural Space Infection: A Prospective Study.

Objective: To better understand the microbial profile of complicated parapneumonic effusions and empyema, and to evaluate whether antimicrobial selection would differ if guided by targeted metagenomic sequencing (tMGS) vs conventional cultures (CCs) alone. Patients and Methods: We analyzed the pleural fluid of a cohort of 47 patients undergoing thoracentesis from January 1, 2017 to August 31, 2019, to characterize their microbial profile. All samples underwent 16S ribosomal ribonucleic acid gene polymerase chain reaction, followed by tMGS. Results: Pleural space infection was deemed clinically present in 20 of the 47 (43%) participants. Of those, n=7 (35%) had positive pleural fluid cultures and n=14 (70%) had positive tMGS results. The organisms identified by tMGS were concordant with CCs; however, tMGS detected additional bacterial species over CCs alone. Streptococcus and Staphylococcus species were the most common organisms identified, with Streptococcus intermedius/constellatus identified in 5 patients. Polymicrobial infections were found in 6 of the 20 patients, with anaerobes being the most common organisms identified in these cases. Conclusion: Streptococci and staphylococci were the most common organisms identified in infected pleural fluid. Anaerobes were common in polymicrobial infections. When compared with CCs, tMGS had higher sensitivity than CCs. Targeted metagenomic sequencing identified additional organisms, not identified by CCs, with associated potential management implications.

Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination.

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19-vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2022.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Characterizing phenotypic abnormalities associated with high-risk individuals developing lung cancer using electronic health records from the All of Us researcher workbench.

OBJECTIVE: The study sought to test the feasibility of conducting a phenome-wide association study to characterize phenotypic abnormalities associated with individuals at high risk for lung cancer using electronic health records. MATERIALS AND METHODS: We used the beta release of the All of Us Researcher Workbench with clinical and survey data from a population of 225 000 subjects. We identified 3 cohorts of individuals at high risk to develop lung cancer based on (1) the 2013 U.S. Preventive Services Task Force criteria, (2) the long-term quitters of cigarette smoking criteria, and (3) the younger age of onset criteria. We applied the logistic regression analysis to identify the significant associations between individuals' phenotypes and their risk categories. We validated our findings against a lung cancer cohort from the same population and conducted an expert review to understand whether these associations are known or potentially novel. RESULTS: We found a total of 214 statistically significant associations (P < .05 with a Bonferroni correction and odds ratio > 1.5) enriched in the high-risk individuals from 3 cohorts, and 15 enriched in the low-risk individuals. Forty significant associations enriched in the high-risk individuals and 13 enriched in the low-risk individuals were validated in the cancer cohort. Expert review identified 15 potentially new associations enriched in the high-risk individuals. CONCLUSIONS: It is feasible to conduct a phenome-wide association study to characterize phenotypic abnormalities associated in high-risk individuals developing lung cancer using electronic health records. The All of Us Research Workbench is a promising resource for the research studies to evaluate and optimize lung cancer screening criteria.

Utility of Transbronchial Biopsy in the Immunocompromised Host With New Pulmonary Radiographic Abnormalities.

OBJECTIVE: To assess how often transbronchial biopsy (TBBx) added unique positive findings apart from other synchronous bronchoscopic sampling techniques including the bronchoalveolar lavage-immunocompromised host (BAL-ICH) panel that justified changes in management in an array of immunocompromised patients with new pulmonary radiographic abnormalities. METHODS: We retrospectively reviewed all bronchoscopies performed at Mayo Clinic Rochester between January 2012 and December 2017; on the basis of the physician's selection of a BAL-ICH panel, we identified 192 immunocompromised patients who underwent bronchoscopy with both a BAL-ICH panel and TBBx. The results of the BAL-ICH panel and TBBx were compared and subsequent management decisions analyzed from clinical notes. We identified changes in immunosuppressive agents, antibiotics, chemotherapy, goals of care, and decisions on further evaluation and procedures. We assessed whether the TBBx findings added information not identified on the BAL-ICH panel and other bronchoscopic sampling methods performed during the same procedure that justified subsequent management changes. RESULTS: Of 192 bronchoscopic procedures performed on immunocompromised patients with acute and subacute pulmonary radiographic abnormalities, management changes justified by the unique positive results of the TBBx occurred 28% (51/192) of the time. Those immunocompromised by solid malignant neoplasms and receiving active immunosuppressive therapy had management changes justified 62.1% (18/29) of the time by the TBBx results. No additional fungal organisms were identified on TBBx that were accounted for on the BAL-ICH panel. CONCLUSION: Transbronchial biopsy may add information to other bronchoscopic findings in immunocompromised patients, especially those with solid malignant neoplasms receiving active immunosuppressive treatment. These potential benefits must be weighed against the risks inherent to the procedure.

Cigarette smoking enhances the metabolic activation of the polycyclic aromatic hydrocarbon phenanthrene in humans.

Although it is well established that human cytochrome P450 1 family enzymes are induced by cigarette smoking through activation of the Ah receptor, it is not known whether this leads to increased metabolic activation or detoxification of carcinogenic polycyclic aromatic hydrocarbons (PAH), which are present in cigarette smoke and the general environment. We gave oral doses of deuterated phenanthrene ([D10]Phe), a non-carcinogenic surrogate of carcinogenic PAH such as benzo[a]pyrene, to smokers (N = 170, 1 or 10 µg doses) and non-smokers (N = 57, 1 µg dose). Bioactivation products (dihydrodiol and tetraol) and detoxification products (phenols) of [D10]Phe were determined in 6-h urine to obtain a comprehensive metabolic profile. Cigarette smoking increased the bioactivation of [D10]Phe and decreased its detoxification resulting in significantly different metabolic patterns between smokers and non-smokers (P < 0.01), consistent with increased cancer risk in smokers. The Phe bioactivation ratios ([D10]PheT/total [D9]OHPhe) were significantly higher (2.3 (P < 0.01) to 4.8 (P < 0.001) fold) in smokers than non-smokers. With solid human in vivo evidence, our results for the first time demonstrate that cigarette smoking enhances the metabolic activation of Phe, structurally representative of carcinogenic PAH, in humans, strongly supporting their causal role in cancers caused by smoking. The results suggest potential new methods for identifying smokers who could be at particularly high risk for cancer.

Bronchoscopic Lung Volume Reduction: A New Hope for Patients With Severe Emphysema and Air Trapping.

Chronic obstructive pulmonary disease (COPD) is common and has significant morbidity and mortality as the fourth leading cause of death in the United States. In many patients, particularly those with emphysema, COPD is characterized by markedly increased residual volume contributing to exertional dyspnea. Current therapies have limited efficacy. Surgical resection of diseased areas of the lung to reduce residual volume was effective in identified subgroups but also had significant mortality in and suboptimal cost effectiveness. Lung-volume reduction, using bronchoscopic techniques, has shown substantial benefits in a broader patient population with less morbidity and mortality. This review is meant to spread the awareness about bronchoscopic lung-volume reduction and to promote its consideration and early referral for patients with advanced COPD and emphysema frequently encountered by both primary care physicians and specialists. A search was conducted on PubMed (MEDLINE), EMbase, and Cochrane library for original studies, using the following keywords: "lung-volume reduction." "endobronchial valves," "intrabronchial valves," "bronchoscopic lung-volume reduction," and "endoscopic lung-volume reduction." We included reports from systematic reviews, narrative reviews, clinical trials, and observational studies. Two reviewers evaluated potential references. A total of 27 references were included in our review. Included studies report experience in the diagnosis and bronchoscopic treatment for emphysema; case reports and non-English or non-Spanish studies were excluded.

Bronchoscopic Cryobiopsy and Forceps Biopsy for the Diagnostic Evaluation of Diffuse Parenchymal Lung Disease in Clinical Practice.

OBJECTIVE: To assess the contribution and safety of bronchoscopic cryobiopsy vs traditional forceps biopsy used in clinical practice for diagnosing diffuse parenchymal lung disease (DPLD). PATIENTS AND METHODS: We identified 271 patients who underwent bronchoscopic biopsy for DPLD at Mayo Clinic, MN (June 1, 2013, through September 30, 2017). Medical records were reviewed including prebiopsy clinical and radiographic impressions. Diagnostic yield was assessed in terms of a specific histologic pattern resulting in a diagnosis when combined with the clinical-radiologic context. Clinical utility was defined as a biopsy result deemed useful in patient management. RESULTS: The cohort included 120 cryobiopsy and 151 forceps biopsy cases with mean age 61±14 years and 143 (53%) men. Diagnostic yield (55% vs 41%; odds ratio [OR], 1.73; 95% CI, 1.07 to 2.83; P=.026) and clinical utility (60% vs 40%; OR, 2.21; 95% CI, 1.36 to 3.63; P=.001) were higher for the cryobiopsy group, and the association remained after control for prebiopsy clinical impressions (OR, 2.21; 95% CI, 1.22 to 4.08; P=.010 and OR, 3.23; 95% CI, 1.76 to 6.10; P<.001, respectively). However, pneumothorax (5.4% vs 0.7%; P=.022) and serious bleeding (7.1% vs 0%; P=.001) rates were higher for the cryobiopsy group. Thirty-day mortality was 1.6% in the cryobiopsy group vs 0% for the forceps biopsy group (P=.20). CONCLUSION: Bronchoscopic cryobiopsy revealed higher diagnostic yield and clinical utility than did forceps biopsy. However, procedure-related complications were higher in the cryobiopsy group. The choice of bronchoscopic biopsy procedure for patients with DPLD depends on the clinicalradiologic context.

Diagnostic Yield and Bleeding Complications Associated With Bronchoscopic Biopsy of Endobronchial Carcinoid Tumors.

BACKGROUND: Bronchial carcinoid often appears hypervascular on bronchoscopic visualization and may be associated with hemoptysis. The diagnostic yield and bleeding complications associated with bronchoscopic biopsy of bronchial carcinoid tumors remain unclear. MATERIALS AND METHODS: Patients with bronchial carcinoid tumors that were bronchoscopically visualized and biopsied at our tertiary referral medical center, over an 8-year period from 2010 to 2017, were retrospectively identified and reviewed to assess diagnostic yield and bleeding complications. Correlations with patient characteristics and carcinoid tumor features were analyzed. RESULTS: Forty-nine patients were included (57% female). Tumors were predominantly (71%) located in proximal airways (mainstem and lobar bronchi). Bronchoscopic biopsy was diagnostic in 45 patients (92%). Thirteen patients (27%) experienced moderate (n=12, 25%) or severe (n=1, 2%) bleeding. Among these, 6 tumors (46%) had a vascular appearance and 4 patients (31%) had experienced recent hemoptysis. However, neither vascularity nor hemoptysis was associated with bleeding at biopsy (P=0.68 and 0.73, respectively). Carcinoid tumors were classified as typical in 79% and atypical in 21% with no difference in diagnostic yield or bleeding risk (P=0.28 and 0.92, respectively). Tumor size was also not associated with increased diagnostic yield or bleeding risk (P=0.54 and 0.39, respectively). CONCLUSION: Bronchoscopic biopsy of endobronchial carcinoid is associated with a high diagnostic yield and severe bleeding is rarely encountered. Diagnostic yield and bleeding seemed independent of vascular tumor appearance or history of recent hemoptysis.

5-year overall survival in patients with lung cancer eligible or ineligible for screening according to US Preventive Services Task Force criteria: a prospective, observational cohort study.

BACKGROUND: The US Preventive Services Task Force (USPSTF) recommends lung cancer screening among individuals aged 55-80 years with a 30 pack-year cigarette smoking history and, if they are former smokers, those who quit within the past 15 years. Our previous report found that two-thirds of newly diagnosed patients with lung cancer do not meet these criteria; they are reported to be either long-term quitters (≥15 years since quitting) or from a younger age group (age 50-54 years). We aimed to assess survival outcomes in these two subgroups. METHODS: For this prospective, observational cohort study we identified and followed up patients aged 50-80 years with lung cancer, with a smoking history of 30 pack-years or more, and included both current smokers and former smokers who quit within the past 30 years. We identified patients from two cohorts in the USA: a hospital cohort (Mayo Clinic, Rochester, MN) and a community cohort (Olmsted County, MN). Patients were divided into those meeting USPSTF criteria (USPSTF group) versus those not meeting USPSTF criteria (long-term quitters or the younger age group). The main outcome was overall survival at 5 years after diagnosis. 5-year overall survival was analysed with and without matching age and pack-years smoked for long-term quitters. The USPSTF group was subdivided into two age subgroups (55-69 years and 70-80 years) for multivariable regression analysis. FINDINGS: Between Jan 1, 1997, and Dec 31, 2017, 8739 patients with lung cancer were identified and followed up. Median follow-up was 6·5 (IQR 3·8-10·0) years, and median overall survival was 16·9 months (95% CI 16·2-17·5). 5-year overall survival was 27% (95% CI 25-30) in long-term quitters, 22% (19-25) in the younger age group, and 23% (22-24) in the USPSTF group. In both cohorts, 5-year overall survival did not differ significantly between long-term quitters and the USPSTF group (hospital cohort: hazard ratio [HR] 1·02 [95% CI 0·94-1·10]; p=0·72; community cohort: 0·97 [0·75-1·26]; p=0·82); matched analysis showed similar results in both cohorts. 5-year overall survival also did not differ significantly between the younger age group and the USPSTF group in both cohorts (hospital cohort: HR 1·16 [95% CI 0·98-1·38], p=0·08; community cohort: 1·16 [0·74-1·82]; p=0·52); multivariable regression analyses stratified by age group yielded similar findings. INTERPRETATION: Patients with lung cancer who quit 15 or more years before diagnosis and those who are up to 5 years younger than the age cutoff recommended for screening, but otherwise meet USPSTF criteria, have a similar risk of death to those individuals who meet all USPSTF criteria. Individuals in both subgroups could benefit from screening, as expansion of USPSTF screening criteria to include these subgroups could enable earlier detection of lung cancer and improved survival outcomes. FUNDING: National Institutes of Health and the Mayo Clinic Foundation.

Extracellular matrix fistula plug for repair of bronchopleural fistula.

INTRODUCTION: Bronchopleural fistula (BPF) is a feared complication of pulmonary resection. Fistula plugs (FP) have been described as an adequate treatment in anorectal disease. We describe our early experience placing an FP in the treatment of BPF. MATERIALS AND METHODS: We retrospectively reviewed 5 patients for whom a FP was placed for BPF at our institution. Demographic data, initial perioperative information, method and technique of FP placement, and success is reported. RESULTS: Five patients (4 male, 1 female) with a median age of 63 years (range, 57-76 years) underwent 6 FP placements for BPF. Two patients were post-pneumonectomy and 3 patients post-lobectomy. The median time to presentation following surgery was 118 days (range 22-218). Upon bronchoscopic or operative re-evaluation, 3 patients had successful cessation of their air leak at 0, 1 and 4 days. Two of three patients subsequently underwent a thoracic muscle flap placement to augment healing. One patient had a persistent air leak despite 2 separate FP placements. The air leak stopped with endobronchial valves (EBV) which were deployed proximal to the FP, 9 days after placement of the FP. Another patient had a successful muscle flap placed 80 days after FP placement. There were no complications associated with the FP. Three of five patients were deemed successfully treated with FP placement alone. CONCLUSION: In patients with a postoperative BPF and pleural window, placement of a FP had a modest success rate and can be considered as a treatment modality option for BPF.

Paclitaxel-coated balloon dilation for central airway obstruction.

INTRODUCTION: Central airway obstruction (CAO) often requires repeated interventional procedures which offer variable efficacy, a time-limited effect, and have inherent limitations. Paclitaxel has been used to prevent restenosis in blood vessels. The literature describing the use of paclitaxel to prevent recurrent airway stenosis is limited. We sought to describe our experience using a paclitaxel-coated balloon (PCB) for CAO. MATERIAL AND METHODS: We performed a retrospective review of all patients who underwent PCB airway dilation. We collected: basic demographics, details of the CAO, details of the bronchoscopes used, PCB size, PCB dilation pressure, duration of PCB inflation, concurrent non-PCB interventions, estimated pre- and post-PCB CAO luminal diameter, follow up bronchoscopy date and luminal diameter, and spirometry results. RESULTS: PCB dilation was performed in 10 cases on 5 patients. Eight PCB dilations were performed for CAO related to distal airway stent stenosis. Concurrent non-PCB interventions were performed with 6 PCB dilations. Nine cases documented improvements and 1 was unchanged immediately post-PCB dilation. Median luminal diameter pre-PCB dilation was 2 mm. Immediately post-PCB dilation, the median change in luminal diameter was 2 mm. Follow up bronchoscopy information was available for 9 cases. For these 9 cases, luminal diameter was unchanged in 5 and worse in 4 when compared to immediate post-PCB dilation. CONCLUSION: PCB dilation in benign CAO produced a modest effect in this cohort of challenging airways. Larger prospective studies are needed to assess how a PCB would perform when compared to a non-drug coated balloon.

Creation of a Balloon-Expandable Bifurcated Covered Stent to Treat a Complex Left Anastomotic Stricture in a Lung Transplant Recipient.

Airway complications after lung transplant occur in approximately 10-15% of the recipients and often occur at the anastomosis, largely due to ischemia. To decrease anastomotic ischemia, surgeons minimize the length of the donor bronchus. However, a shortened donor bronchus creates technical challenges if a stent is required to treat an airway complication. We present a case of a lung transplant recipient with the combination of left main stem bronchial malacia and a triad of severe strictures at the left anastomosis, entrance to the left upper lobe, and left lower lobe. After failing several attempts using other modalities, success was achieved with in situ creation of a bifurcated fully covered balloon-expandable metallic stent. We describe a novel technique of punching a side branch hole through the wall of the stent to allow a left upper lobe stent to be placed through a stent directed into the left lower lobe in a Y configuration with a good clinical outcome.

Comparison of Programmed Death Ligand-1 Immunohistochemical Staining Between Endobronchial Ultrasound Transbronchial Needle Aspiration and Resected Lung Cancer Specimens.

BACKGROUND: In advanced non-small cell lung cancer (NSCLC), small biopsy specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are often the only available material from cancer tissue for the analysis of programmed death ligand-1 (PD-L1) expression. We aim to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression at ≥ 1% and ≥ 50% on EBUS-TBNA samples compared with their corresponding surgically resected tumor. METHODS: We retrospectively reviewed all patients who underwent EBUS-TBNA followed by surgical resection of NSCLC between July 2006 and September 2016. Demographic information and periprocedural/surgical data were collected. The archived specimens were retrieved and assessed for PD-L1. A positive PD-L1 stain was defined using two separate cutoff points: ≥ 1% and ≥ 50% of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, PPV, and NPV. RESULTS: Sixty-one patients were included. For PD-L1 ≥ 1%, the sensitivity, specificity, PPV, and NPV were 72%, 100%, 100%, and 80%, respectively. For PD-L1 ≥ 50%, the sensitivity, specificity, PPV, and NPV were 47%, 93%, 70%, and 84%, respectively. The concordance rates for PD-L1 ≥ 1% and ≥ 50% were 87% and 82%, respectively. CONCLUSIONS: A PD-L1 cutoff of ≥ 1% on EBUS-TBNA has a strong correlation with resected tumor specimen. For PD-L1 ≥ 50%, there is a significant decrease in the sensitivity and PPV of EBUS-TBNA specimen when compared with resected tumor. When analyzing for PD-L1 expression using a cutoff of ≥ 50%, EBUS-TBNA specimens may misclassify the status of PD-L1.