INTRODUCTION:Current U.S. lung cancer screening guidelines use only age and smoking history; however, individual risk calculators may better stratify risk. METHODS:In a referred cohort design, we implemented a multisite lung cancer screening program across four states. We screened patients who qualified by either the USPSTF2013 criteria or a PLCOm2012 risk of greater than or equal to 1.34%. Invasive procedures were abstracted retrospectively. We compared the incidence and prevalence of lung cancer among patients who qualified by only USPSTF2013 or PLCOm2012 and along the continuum of prospective lung cancer risk using PLCOm2012. RESULTS:Of 2471 screened patients, 114 had lung cancer. Furthermore, 84% of all patients and 91% of patients who were diagnosed with having cancer qualified by both criteria. Prevalence of lung cancers were over 7 times higher in the 10% of the cohort with the highest prospective risk than the lowest risk 10%. Incidence of cancers were higher among patients who qualified only by PLCOm2012 (3.6 per 1000 person-years) compared with patients who qualified only by USPSTF2013 (0 per 1000 person-years). Of screen-detected NSCLC, 74% was stage I or II. Three (4.5%) surgical resections were performed for screen-identified nodules which proved to be benign. Overall, 106 patients (4.3%) underwent an invasive intervention due to screening. CONCLUSIONS:Most patients qualified for lung cancer screening by both UPSTSF2013 and PLCOm2012 criteria. Incidence cancers were higher among patients who qualified by PLCOm2012 but not USPSTF2013 criteria. Prevalence and incidence cancer identification increased with prospective risk. Invasive procedures and resections for benign disease were relatively low.

INTRODUCTION:Talc pleurodesis is a widely used intervention for recurrent pneumothorax and pleural effusion, particularly in nonsurgical candidates. However, some patients experience immediate failure or recurrence and require additional intervention. The safety and effectiveness of repeated talc administration remain unclear. This study investigated repeat-dose talc pleurodesis to determine its safety and efficacy in the management of initial failures and recurrence. METHODS:This retrospective study (January 2019-September 2024) analyzed hospitalized patients undergoing talc slurry pleurodesis. Data included demographics, comorbidities, indication, and number of talc doses for successful pleurodesis. The primary outcome was pleurodesis success after repeat dosing. Analyses used chi-square tests, Cox regression for recurrence risk, and Kaplan-Meier estimates for recurrence-free survival. RESULTS:Among 103 patients who underwent bedside talc slurry pleurodesis for pneumothorax (n = 70) or pleural effusion (n = 33), 80 (77.7%) achieved successful pleurodesis with a single 4 g dose (pneumothorax = 56; effusion = 24). Of the 23 patients with immediate pleurodesis failure, 16 (69.6%) achieved success following repeat-dose pleurodesis (pneumothorax = 7; effusion = 9), while 7 required alternative interventions. Recurrence after discharge occurred in 17 (21.3%) of the single-dose group (pneumothorax = 11; effusion = 6) compared with 1 (6.3%) in the repeat-dose group. Among 18 recurrence cases overall, 9 underwent repeat pleurodesis, with 8 (88.9%) achieving success. CONCLUSION:Repeat-dose talc pleurodesis may represent a reasonable management approach for patients experiencing immediate failure or recurrence after an initial successful pleurodesis with minimal complications. Further research is needed to optimize protocols and improve outcomes for patients undergoing pleurodesis.

Rational: Talc pleurodesis is an effective intervention for preventing recurrent pleural effusions and pneumothoraces, particularly in non-surgical candidates. Due to its efficacy and safety, it is recommended as the most effective sclerosant for pleurodesis. However, in some cases, the initial pleurodesis fails, necessitating a repeat procedure. The efficacy of repeat talc pleurodesis after an initial failure is an area that requires further exploration. This study explores the safety and efficacy of repeat talc pleurodesis among patients who did not respond to the initial intervention. Methods: This retrospective study analyzed hospitalized patients who underwent 4g talc slurry pleurodesis from 2019 to 2024, focusing on demographics, comorbidities, initial pleurodesis failure, and recurrence rates. Pleurodesis failure was identified by lung sliding, recurrent effusion, or pneumothorax during the same hospitalization. The primary outcome was recurrence post-discharge, assessed by pleural effusion or pneumothorax within 180 days post-repeat pleurodesis. Results: This study included 94 patients (52.1% male, 47.9% female) with a mean age of 67.6. Among them, 79 (84%) received a single 4g dose of talc, while 15 (16%) received multiple 4g talc doses for initial pleurodesis. Recurrence occurred in 20 (25.3%) of the single-dose group and 1 (6.7%) of the multiple-dose group within 180 days, though the difference was not statistically significant (p=0.112). Recurrence-free rates were 93.6% at 30 days, 85.1% at 90 days, and 77.7% at 180 days. Of the 20 patients with recurrence after a single 4g dose of talc, 8 (40%) underwent repeat pleurodesis, with only one recurrence requiring surgical intervention. Additionally, there was no recurrence after repeat talc pleurodesis in the one patient with recurrence after receiving multiple 4g talc doses for initial pleurodesis. No associations were found between recurrence rates and factors like gender (p=0.213) or comorbidities (emphysema, COPD, lung malignancy). Chest pain was a common complaint, but no cases of respiratory distress were reported post-pleurodesis. Conclusion: The efficacy of initial talc pleurodesis (77.7%-93.6%) in this cohort aligns with existing literature. Multiple-dose talc pleurodesis effectively prevented recurrence in 93.3% of patients, with no reported respiratory distress. Additionally, repeat talc pleurodesis was successful in 87.5% of those with recurrence after an initial single 4g dose. These findings support multiple-dose talc pleurodesis and repeat talc pleurodesis as safe and effective options for preventing recurrence post-initial failure and post-repeat talc pleurodesis, respectively. Although no significant recurrence predictors were identified, future research could focus on patient-specific factors to enhance treatment selection and optimize outcomes.

Rationale: Airway-stenosing disease is a significant clinical problem in multiple populations. While the immediate endoscopic and clinical response to bronchoscopic interventions are high, rates of clinically significant recurrence are elevated, and often require multiple and frequent reinterventions. Newer strategies to prevent recurrence of central and proximal airway stenosis are needed. Methods: Retrospective review of bronchoscopic balloon bronchoplasties performed at the Mayo Clinic utilizing paclitaxel coated balloons (PCB) in 2023-2024 for recurrent airway stenosis. IN.PACT Admiral and AV balloons (sizes 5-12 mm, 3.5 mcg/mm2 paclitaxel dose) were used with an inflation time of 2-3 minutes. Procedural success was defined as <50% airway stenosis or resolution of the procedural indication. Reintervention was considered only if a therapeutic bronchoscopy was subsequently required to address the same lesion treated with PCB. Only patients with follow-ups >90 days were included in the reintervention inter-procedural time analysis. Results: Thirty-three procedures were performed in 18 patients. Seventeen (51%) for lung transplantation-associated stenosis (29% anastomotic/perianastomotic, 76% lobar and segmental stenoses), 8 (24%) for granulomatous polyangiitis-associated stenosis, 3 for postintubation tracheal stenosis and 2 for chemical/pill injury. Eighteen cases (54%) utilized an additional dilation modality (12 non-coated balloon dilation, 4 rigid dilation), 5 spray cryotherapy, 6 other ablative therapies (4 CO2-laser, 2 electrocautery cuts), and 6 received an airway stent during the same procedure. 57% percent of interventions occurred in the lobar, 27% mainstem/bronchus intermedius, 9% tracheal, 7% segmental airways. Thirty-one (93%) cases had a satisfactory initial endoscopic result. The median number of bronchoscopic therapeutic interventions required before the use pf PCB was 5 (IQR 2.5-11.5), which significantly decreased to 0.1 (IQR 0-1, range 0-9) after PCB (p <0.001). The reintervention-free survival significantly increased after PCB dilation from a median 35 days (IQR 28.7-80.5) to 132 days (IQR 64-197; p=0.004). Twenty-one cases required subsequent bronchoscopies, sixteen (76%) of which demonstrated improvement in lesion severity when compared to the results of prior interventions. Only 16 (48%) required therapeutically addressing the same lesion. Only 2 minor complications occurred (6%, self-limited bleeding and unplanned admission), none related to paclitaxel use. Six-month mortality was 3% from an unrelated cause. Conclusions: The locoregional antiproliferative effects of paclitaxel show promise in preventing recurrence, minimizing the need for repeat procedures, and extending intervals between interventions in patients with recurrent, predominantly benign airway stenosis. Its use is feasible, safe, and future research is warranted, particularly comparing PCB with the currently available strategies.

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.

BACKGROUND:Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS:We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS:78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS:Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.

We present a noteworthy case of allergic bronchopulmonary aspergillosis (ABPA) in a patient with chronic obstructive pulmonary disease (COPD) without a history of asthma or cystic fibrosis. The radiological findings on CT scans revealed the classic "finger-in-glove" sign of ABPA. This case report emphasizes the importance of finding ABPA as a possible cause for mucoid impaction in COPD even in the absence of typical risk factors, as well as precise differential diagnosis to guide appropriate care for patients and treatment.

FOR RELATED ARTICLE, SEE PAGE 128Bronchoscopy is a fundamental tool in the armamentarium of the intensivist.1Olopade C.O. Prakash U.B. Bronchoscopy in the critical-care unit.Mayo Clin Proc. 1989; 64: 1255-1263Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar Single-use and reusable flexible bronchoscopes are readily available in the United States, and the learning curve is steep for most of the common procedures encountered in the ICU.2Ho E. Wagh A. Hogarth K. Murgu S. Single-use and reusable flexible bronchoscopes in pulmonary and critical care medicine.Diagnostics (Basel). 2022; 12: 174Crossref PubMed Scopus (7) Google Scholar,3Voduc N. Adamson R. Kashgari A. et al.Development of learning curves for bronchoscopy: results of a multicenter study of pulmonary trainees.Chest. 2020; 158: 2485-2492Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Bronchoscopy is useful in the diagnosis and management of acute respiratory failure. It can be rapidly implemented at any time, at the bedside, and requires minimal assistance to perform. Bronchoscopy in the ICU does not replace more complex procedures (eg, tissue biopsy or interventional bronchoscopy) that are best performed by highly specialized proceduralists and usually in a dedicated suite.4Raoof S. Mehrishi S. Prakash U.B. Role of bronchoscopy in modern medical intensive care unit.Clin Chest Med. 2001; 22 (vii): 241-261Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar The indications for bronchoscopy in the ICU are many. The procedure can facilitate the location and potentially treatment of a source of bleeding when faced with hemoptysis, and recognition and removal of an endobronchial obstruction such as mucus plugging. BAL assists with the diagnosis of infectious and noninfectious causes of acute hypoxemic respiratory failure (AHRF). Bronchoscopy can facilitate the correct placement of a percutaneous tracheostomy tube, can be used to intubate a patient with a difficult airway, and can allow the placement of an endobronchial blocker in the setting of massive hemoptysis. Bronchoscopy is easily performed in a patient who is intubated on invasive mechanical ventilation (IMV) but also can be carefully performed in patients undergoing noninvasive mechanical ventilation, CPAP, or high-flow nasal cannula and can be particularly helpful when the goal is not to intubate a fragile patient.5Patolia S. Farhat R. Subramaniyam R. Bronchoscopy in intubated and non-intubated intensive care unit patients with respiratory failure.J Thorac Dis. 2021; 13: 5125-5134Crossref PubMed Scopus (3) Google Scholar The intensivist also may use bronchoscopy judiciously outside the ICU to prevent unnecessary transfer to the ICU.6Menditto V.G. Mei F. Fabrizzi B. Bonifazi M. Role of bronchoscopy in critically ill patients managed in intermediate care units: indications and complications—a narrative review.World J Crit Care Med. 2021; 10: 334-344Crossref PubMed Google Scholar The performance of the procedure does not come without risk: Bronchoscopy may be associated with hypoxemia or hypotension, which may be life-threatening.7Ergan B. Nava S. The use of bronchoscopy in critically ill patients: considerations and complications.Exp Rev Respir Med. 2018; 12: 651-663Crossref PubMed Scopus (30) Google Scholar Bronchoscopy also may be associated with pneumomediastinum or pneumothorax. FOR RELATED ARTICLE, SEE PAGE 128 The benefit of bronchoscopy, defined by both its diagnostic yield and its therapeutic yield, needs to be weighed against the potential harm of complications. The diagnostic yield can be a positive or negative finding that will alter the pretest probability and modify management such as a positive sampling by coronavirus disease 2019 polymerase chain reaction in an otherwise negative patient, or the absence of a progressively bloody return and lack of hemosiderin-laden macrophage when alveolar hemorrhage was suspected.8Yasuda H. Tsukune Y. Watanabe N. et al.Persistent COVID-19 pneumonia and failure to develop anti-SARS-CoV-2 antibodies during rituximab maintenance therapy for follicular lymphoma.Clin Lymphoma Myeloma Leuk. 2020; 20: 774-776Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar Bronchoscopy can confirm a diagnosis of Pneumocystis pneumonia in a patient unable to produce sputum, and it has proved effective and safe in immunosuppressed patients when noninvasive testing has failed to achieve a diagnosis.9Al-Qadi M.O. Cartin-Ceba R. Kashyap R. Kaur S. Peters S.G. The diagnostic yield, safety, and impact of flexible bronchoscopy in non-HIV immunocompromised critically ill patients in the intensive care unit.Lung. 2018; 196: 729-736Crossref PubMed Scopus (7) Google Scholar The therapeutic yield includes improvement in ventilation with clearance of the airways and, overall, a change in management. Despite the apparent necessity of the bronchoscope to the intensivist, the data supporting improved outcomes in respiratory failure could be more robust. In this issue of CHEST, Wayne et al10Wayne M.T. Valley T.S. Arenberg D.A. De Cardenas J. Prescott H.C. Temporal trends and variation in bronchoscopy use for acute respiratory failure in the United States.Chest. 2023; 163: 128-138Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar report trends and variations in the use of bronchoscopy in patients on IMV for AHRF in the United States from 2012 to 2018.10Wayne M.T. Valley T.S. Arenberg D.A. De Cardenas J. Prescott H.C. Temporal trends and variation in bronchoscopy use for acute respiratory failure in the United States.Chest. 2023; 163: 128-138Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar They used data from the National Inpatient Sample, which is highly representative of hospitalizations in the United States.11Healthcare Cost & Utilization ProjectUser Support. Overview of the National (Nationwide) Inpatient Sample (NIS).https://www.hcup-us.ahrq.gov/nisoverview.jspDate accessed: August 19, 2022Google Scholar They excluded those hospitalized for major thoracic surgery and ear, nose, & throat surgery, where bronchoscopy is part of routine postoperative care. The authors found that 10% of patients who were on IMV underwent bronchoscopy; among them, 24% were immunocompromised. The proportion of those receiving bronchoscopy increased over the study period from 2012 to 2018 by 1.3%. In those who were on IMV and immunocompromised, use increased by 1.4%. The rate of bronchoscopy for hemoptysis remained stable, with only a 0.6% increase over time and fewer than half of the patient with hemoptysis had bronchoscopy. The proportion of bronchoscopy among those on IMV varied dramatically across hospitals, from 0% to 57.1%. The intrahospital variation was 16% and persisted over time, particularly among those who were immunosuppressed. Among those hospitalized with AHRF, 7.4% received bronchoscopy, and the rate of bronchoscopy decreased over time by 1.3%, even though the number of patients hospitalized with AHRF increased while the proportion of those intubated decreased by 15%. Regional variations were also identified. Mortality among those intubated increased by 1% and among those hospitalized by 2% during the study period. Overall, more patients were hospitalized with AHRF over time, fewer who were intubated, but more who received bronchoscopy, particularly among those immunocompromised but with a large intra- and inter-hospital variation. These findings are not surprising given that increasing severity of illness correlates with more testing performed.12Bauer P.R. Chevret S. Yadav H. et al.Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.Eur Respir J. 2019; 541802442Crossref Scopus (31) Google Scholar The 1.3% increase in the use of bronchoscopy over time in patients receiving IMV was statistically significant, but the trend is small and may be attributable to factors such as the adoption of disposable scopes and variance in procedure captures with electronic medical records, rather than a true change. The variability in bronchoscopy use among hospitals is stark (0%-57%), but perhaps should not be, given the lack of outcomes data in this setting. Practice patterns vary among centers; in fact, this variability may be healthy if it leads us to discover why and when it is beneficial, and when it is to be avoided. A higher rate of bronchoscopy in urban teaching hospitals and the rise over time may simply reflect more transfers to a higher level of care for challenging and more severely ill patients, as is suggested by the higher frequency of multi-organ dysfunction among them. The higher likelihood of bronchoscopy among those who have private insurance may reflect the role of social determinants of health in intensity if not quality of care. The limitations of a retrospective, national database study are many and include the lack of any detail of the indications for bronchoscopy for hemoptysis and for the immunocompromised. Neither does it provide any outcomes data. We applaud the authors for shining a bright light on dramatic practice variability in the use of bronchoscopy in those on IMV. May we use that light to direct us to discover beneficial outcomes from the use of bronchoscopy, cost efficacy, and those indications for which the risks of bronchoscopy (or the absence of outcome change) outweigh the benefits and are to be avoided. Financial/nonfinancial disclosures: None declared. Temporal Trends and Variation in Bronchoscopy Use for Acute Respiratory Failure in the United StatesCHESTVol. 163Issue 1PreviewBronchoscopy use among hospitalizations treated with IMV has increased over time. The large variation in use of bronchoscopy across hospitals suggests potentially unwarranted practice variation and need for further studies to clarify which patients benefit from bronchoscopy. Full-Text PDF

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.

PURPOSE:Pain is a common complication of complicated parapneumonic effusions that require a thoracostomy tube.Pain may be secondary to the infectious or inflammatory process, irritation from the tube itself, or caused by other interventions, such as intrapleural lytic therapy.A local anesthetic, such as intrapleural lidocaine, offers an alternative to systemic and dermal analgesics, but there is little evidence regarding efficacy and safety in this population.We present a case series of patients with empyema and complicated parapneumonic effusions treated with intrapleural lidocaine, evaluating its efficacy and complications. METHODS:We conducted a single-center retrospective observational study between 1/1/2018 and 12/30/2022.We recorded patient characteristics, the reason for pigtail placement, pleural fluid characteristics, pre and post-intrapleural lidocaine pain scores in an 11-point numeric point rating scale (NRS), and complications from intrapleural lidocaine.Patients were divided into two groups depending on the response to intrapleural lidocaine: Patients with a change in the NRS of 1.3 or more were labeled as responders, and those with a change of less than 1.3 were labeled as nonresponders.Chi-square and t-test analyses were performed to evaluate the statistical differences among experimental groups.Results with P < 0.05 were considered statistically significant. RESULTS:We identified 58 patients with empyema or complicated parapneumonic effusions treated with intrapleural lidocaine.Forty-two percent were female, and the average age was 62.4.As for the pleural fluid characteristics, the average pH was 7.08, LDH 2372 U/L, and protein 3.74 g/dL.Gram stain was positive in 19% of cases.Cultures were positive for bacteria in 36% of cases, and one patient had a positive mycobacterial culture.Most patients had 14-Fr indwelling locking pigtails.Intrapleural lytics were administered in 83% of cases, and systemic analgesics were given to 57 patients (98%).Fifty-eight percent of patients were classified as responders.Responders had a median improvement of 3 points in NRS, whereas non-responders had a median change of 0 points (p<0.001).There were no statistically significant differences in patient or pleural fluid characteristics between the two groups.Although the pH values of nonresponders were lower for the non-responders (7.02 vs 7.12), this did not meet statistical significance.No complications of intrapleural lidocaine were documented.CONCLUSIONS: More than half of the patients with indwelling thoracostomy tubes secondary to complicated parapneumonic effusions/empyema had decreased pain scores following the administration of intrapleural lidocaine, independent of fluid characteristics.No complications of this treatment were reported.CLINICAL IMPLICATIONS: The use of intrapleural lidocaine through an indwelling thoracostomy tube appears safe and effective in patients with empyema and complicated parapneumonic effusions.Prospective, placebo-controlled studies are necessary to demonstrate efficacy.

Vaccination is the key for controlling COVID-19 pandemic. SARS-CoV-2 mRNA vaccines have been demonstrated to induce robust and persistent humoral and cellular immunity in the circulation, but the vaccine-induced immune responses in the respiratory tract remain largely elusive. Here, we examined SARS-CoV-2 S-specific antibody, B and T cell immune responses in the bronchoalveolar lavage (BAL) fluid and blood from unvaccinated, COVID-19 vaccinees or COVID-19 convalescents that recovered from prior moderate to severe SARS-CoV-2 infection. We found that mRNA vaccination induced significant SARS-CoV-2 S-specific CD4+ and CD8+ T cell responses in the blood but not in the BAL. Similarly, mRNA vaccination failed to provoke detectable SARS-CoV-2 S RBD-specific B cell responses in the BAL despite marked RBD-specific B cells were observed in the blood of COVID-19 vaccinees. In contrast, robust SARS-CoV-2 S-specific B and T cell responses were present in the BAL of COVID-19 convalescents. Furthermore, significant neutralizing antibody responses were only observed in the BAL from convalescents but not vaccinees, while both COVID-19 vaccinee and convalescent groups mounted marked neutralizing antibody responses in the blood. Thus, despite their induction of robust circulating humoral and cellular immunity, the current COVID-19 vaccines provoke relatively weak cellular and neutralizing antibody responses in the lower respiratory tract. Our results indicate that a mucosal booster vaccine may be needed to establish robust immunity in the respiratory mucosa, which could provide a strong first line of defense against SARS-CoV-2 re-infection.

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.

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.

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.

ObjectiveTo 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.MethodsWe 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.ResultsOf 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.ConclusionTransbronchial 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.

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.

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.

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.