An enhanced IL17 and muted type I interferon nasal epithelial cell state characterizes severe COVID-19 with fungal coinfection.

Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our previous study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of Candida species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals. Using matched single-cell transcriptomic profiles of these individuals' respiratory mucosa, we identify epithelial immune signatures suggestive of IL17 stimulation and anti-fungal immunity. Further, we observe a significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggest that IL17 stimulation-in part driven by Candida colonization-and blunted interferon signaling represent a common feature of severe COVID-19 infection. IMPORTANCE: In this paper, we present an analysis suggesting that symptomatic and asymptomatic fungal coinfections can impact patient disease progression during COVID-19 hospitalization. By looking into the presence of other pathogens and their effect on the host immune response during COVID-19 hospitalizations, we aim to offer insight into an underestimated scenario, furthering our current knowledge of determinants of severity that could be considered for future diagnostic and intervention strategies.

Spray Cryotherapy for Benign Large Airway Stenosis: A Multicenter Retrospective Cohort Study of Safety and Practice Patterns.

BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS. METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record. RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality. CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.

Lung Cancer Screening Initiative in Slovakia: Guidelines of screening implementation.

Lung cancer (LC) represents a major healthcare issue worldwide. It is the leading cause of cancer-related mortality in Slovakia and European Union. Data from multiple randomized controlled trials have shown significant evidence of a mortality benefit in LC using screening with low-dose computed tomography of the chest (LDCT). Therefore, European healthcare authorities, relevant expert societies, and professional organizations recommend implementing national LC screening (LCS) programs in their member countries. This article outlines the basic methodology, guidelines, and practical aspects of LCS implementation strategies in Slovakia. We describe fundamental principles to identify asymptomatic high-risk patients reduce false positive and false negative results, decrease benign resection rates, and avoid unnecessary invasive procedures. The efficacious utilization of public resources to secure the highest possible quality standards of LDCT plays a crucial role in successfully implementing a nationwide LCS program (Tab. 1, Fig. 4, Ref. 31). Text in PDF www.elis.sk Keywords: lung cancer, screening, early detection, smoking cessation.

Therapeutic Bronchoscopy for Lung Nodules: Where Are We Now?

Lobar resection has been the established standard of care for peripheral early-stage non-small cell lung cancer (NSCLC). Over the last few years, surgical lung sparing approach (sublobar resection [SLR]) has been compared with lobar resection in T1N0 NSCLC. Three nonsurgical options are available in those patients who have a prohibitive surgical risk, and those who refuse surgery: stereotactic body radiotherapy (SBRT), percutaneous ablation, and bronchoscopic ablation. Local ablation involves placement of a probe into a tumor, and subsequent application of either heat or cold energy, pulsing electrical fields, or placement of radioactive source under an image guidance to create a zone of cell death that encompasses the targeted lesion and an ablation margin. Despite being in their infancy, the bronchoscopic ablative techniques are undergoing rapid research, as they extrapolate a significant knowledge-base from the percutaneous techniques that have been in the radiologist's armamentarium since 2000. Here, we discuss selected endoscopic and percutaneous thermal and non-thermal therapies with the focus on their efficacy and safety.

Microwave Ablation for Malignant Central Airway Obstruction: A Pilot Study.

BACKGROUND: Malignant central airway obstruction (CAO) is a debilitating complication of primary lung cancer and pulmonary metastases. Therapeutic bronchoscopy is used to palliate symptoms and/or bridge to further therapy. Microwave ablation (MWA) heats tissue by creating an electromagnetic field around an ablation device. We present a pilot study utilizing endobronchial MWA via flexible bronchoscopy as a novel modality for the management of malignant CAO. METHODS: Therapeutic bronchoscopy with a flexible MWA probe was performed in 8 cases. We reviewed tumor size, previous ablative techniques, number of applications, ablation time, amount of energy delivered, rate of successful recanalization, complications, and 30-day follow-up. RESULTS: Successful airway recanalization was achieved in all cases. No complications were noted. In 1 case, tumor in-growth within a silicone stent was ablated with no damage to the stent. DISCUSSION: Endobronchial MWA is a novel technique for tumor destruction while maintaining an airway axis. The oven effect and air gap around a tumor allow for safe and effective tissue devitalization and hemostasis without a thermal effect on structures surrounding the airway.

Bronchoscopy in Patients With Known or Suspected COVID-19: Results From the Global Pandemic SARS-CoV-2 Bronchoscopy Database (GPS-BD).

BACKGROUND: Amid the Coronavirus Disease 2019 (COVID-19) pandemic, the benefits and risks of bronchoscopy remain uncertain. This study was designed to characterize bronchoscopy-related practice patterns, diagnostic yields, and adverse events involving patients with known or suspected COVID-19. METHODS: An online survey tool retrospectively queried bronchoscopists about their experiences with patients with known or suspected COVID-19 between March 20 and August 20, 2020. Collected data comprised the Global Pandemic SARS-CoV-2 Bronchoscopy Database (GPS-BD). All bronchoscopists and patients were anonymous with no direct investigator-to-respondent contact. RESULTS: Bronchoscopy procedures involving 289 patients from 26 countries were analyzed. One-half of patients had known COVID-19. Most (82%) had at least 1 pre-existing comorbidity, 80% had at least 1 organ failure, 51% were critically ill, and 37% were intubated at the time of the procedure. Bronchoscopy was performed with diagnostic intent in 166 (57%) patients, yielding a diagnosis in 86 (52%). and management changes in 80 (48%). Bronchoscopy was performed with therapeutic intent in 71 (25%) patients, mostly for secretion clearance (87%). Complications attributed to bronchoscopy or significant clinical decline within 12 hours of the procedure occurred in 24 (8%) cases, with 1 death. CONCLUSION: Results from this international database provide a widely generalizable characterization of the benefits and risks of bronchoscopy in patients with known or suspected COVID-19. Bronchoscopy in this setting has reasonable clinical benefit, with diagnosis and/or management change resulting from about half of the diagnostic cases. However, it is not without risk, especially in patients with limited physiological reserve.

Feasibility of Using the O-Arm Imaging System During ENB-rEBUS-guided Peripheral Lung Biopsy: A Dual-center Experience.

BACKGROUND: There is a paucity of real-time imaging modalities available for the bronchoscopic biopsy of peripheral lung nodules. We aim to demonstrate the feasibility of the O-arm imaging system to guide real-time biopsies of peripheral lung nodules during electromagnetic navigation bronchoscopy. METHODS: A retrospective review was performed at 2 academic medical centers utilizing O-arm guidance. RESULTS: The average nodule size was 2.1×2.0 cm and were mostly solid (66%) with a positive bronchus sign (83%). O-arm imaging confirmed tool-in-lesion in all cases. The diagnostic yield was 33%. Four cases were nondiagnostic of the 6 cases performed. In these cases, necrotic tissue was the most common (75%) and showed resolution following subsequent imaging. The average 3-dimensional (3D) spin time was 23.5 seconds. The average number of 3D spins performed per case was 4.33. The average effective dose per 3D spin was 3.73 mSv. CONCLUSION: We have demonstrated the O-arm's feasibility with electromagnetic navigation bronchoscopy for peripheral lung nodules. The O-arm was able to confirm tool-in-lesion in all cases which added confidence to the biopsy. Four high-resolution 3D spins per case may limit the total computed tomography effective dose. We also noted that both metal and radiation scatter were minimal when appropriate radiation safety standards were met. Although additional experience and data will be required to verify the O-arm approach for routine use, our initial experience is promising.

Increased ACE2 Levels and Mortality Risk of Patients With COVID-19 on Proton Pump Inhibitor Therapy.

INTRODUCTION: Proton pump inhibitor (PPI) use was recently reported to be associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and worse clinical outcomes. The underlying mechanism(s) for this association are unclear. METHODS: We performed a prospective study of hospitalized coronavirus disease 2019 (COVID-19) patients and COVID-negative controls to understand how PPI use may affect angiotensin-converting enzyme 2 (ACE2) expression and stool SARS-CoV-2 RNA. Analysis of a retrospective cohort of hospitalized patients with COVID-19 from March 15, 2020 to August 15, 2020 in 6 hospitals was performed to evaluate the association of PPI use and mortality. Covariates with clinical relevance to COVID-19 outcomes were included to determine predictors of in-hospital mortality. RESULTS: Control PPI users had higher salivary ACE2 mRNA levels than nonusers, 2.39 ± 1.15 vs 1.22 ± 0.92 (P = 0.02), respectively. Salivary ACE2 levels and stool SARS-CoV-2 RNA detection rates were comparable between users and nonusers of PPI. In 694 hospitalized patients with COVID-19 (age = 58 years, 46% men, and 65% black), mortality rate in PPI users and nonusers was 30% (68/227) vs 12.1% (53/439), respectively. Predictors of mortality by logistic regression were PPI use (adjusted odds ratio [aOR] = 2.72, P < 0.001), age (aOR = 1.66 per decade, P < 0.001), race (aOR = 3.03, P = 0.002), cancer (aOR = 2.22, P = 0.008), and diabetes (aOR = 1.95, P = 0.003). The PPI-associated mortality risk was higher in black patients (aOR = 4.16, 95% confidence interval: 2.28-7.59) than others (aOR = 1.62, 95% confidence interval: 0.82-3.19, P = 0.04 for interaction). DISCUSSION: COVID-negative PPI users had higher salivary ACE2 expression. PPI use was associated with increased mortality risk in patients with COVID-19, particularly African Americans.