Airway Injury Caused by Aspiration of Iron Sulfate Pills: A Series of 11 Cases.

It is not widely recognized that iron (ferrous sulfate) pill aspiration causes airway damage. Clinical diagnosis is challenging because patients are often unaware that they have aspirated a pill. The literature on this entity consists mainly of case reports. The aim of this study is to describe the clinical and pathologic features of iron pill aspiration in a series of 11 patients. A retrospective review of our pathology archives was performed to identify cases of iron pill aspiration (2013-2023). All available histologic and cytologic material was rereviewed. Clinical information was collected from the electronic medical record, and imaging studies were rereviewed. Eighteen endobronchial biopsies were identified from 11 patients (7 women and 4 men; mean age, 70 years; range, 44-82 years). Eight patients had corresponding cytology (20 specimens). Medication history was available in 9 of 11 patients, all of whom were taking iron sulfate pills. Two patients reported possible aspiration episodes; 4 had risk factors for aspiration. The diagnosis of iron pill aspiration was suspected prior to biopsy in only 1 case. Histologically, iron pill particles were yellow, golden brown, or gray, were elongated and crystal or fiber like, and stained strongly with an iron stain. Common histologic findings included mucosal ulceration, acute and/or chronic inflammation, fibrosis, and squamous metaplasia. Iron pill particles were also identified in 11 cytology specimens from 6 patients. On Papanicolaou staining, iron pill particles were yellow to golden, fiber like, refractile, and crystalline. Reactive epithelial cells, squamous metaplasia, and acute inflammation were common. The combination of iron pill intake and discolored mucosa on bronchoscopy is a potential clue to the diagnosis of iron pill aspiration. Pathologists should familiarize themselves with the appearance of iron pill particles in endobronchial biopsies and cytology specimens from the respiratory tract as this diagnosis is seldom suspected on clinical grounds, and most patients lack a history of aspiration.

An institution-wide tracheostomy rounding team: Initial caregiver perceptions.

PURPOSE: To analyze and present the initial findings of provider perceptions regarding the impact of the implementation of a hospital-wide Tracheostomy Rounding Team (TRT) on the delivery of tracheostomy care at the Cleveland Clinic. MATERIALS AND METHODS: Based on prior literature, a novel multidisciplinary TRT was designed and implemented at the Cleveland Clinic in December of 2018. After the TRT began clinical care, a previously validated RedCap survey was administered anonymously to 358 caregivers to assess provider experience, comfort, and prior education regarding tracheostomy management. Survey results were collected, and descriptive statistics were applied. Answers were compared between providers who interacted with the TRT clinically and those who did not. RESULTS: 42.9% of providers who interacted with the TRT clinically reported that the TRT improved hands-on assistance with tracheostomy care, and 36.7% reported that the TRT improved the identification of safety concerns. Similarly, 34.7% reported that the TRT improved the overall quality of tracheostomy care at the Cleveland Clinic. Providers with active exposure to the TRT additionally reported statistically higher comfort with multiple topics surrounding tracheostomy care. CONCLUSIONS: The implementation of this team improved provider comfort in managing patients with tracheostomies both qualitatively and quantifiably. This intervention offered a perceived benefit to patient care at our institution. Further study of the impact of this team on quantitative patient outcomes is forthcoming.

Accuracy of a Robotic Endoscopic System in Cadaver Models with Simulated Tumor Targets: ACCESS Study.

BACKGROUND: Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear. OBJECTIVES: This study was performed to evaluate the performance of a robotic bronchoscopic system's ability to reach and access artificial tumor targets simulating peripheral nodules in human cadaveric lungs. METHODS: Artificial tumor targets sized 10-30 mm in axial diameter were implanted into 8 human cadavers. CT scans were performed prior to procedures and all cadavers were intubated and mechanically ventilated. Electromagnetic navigation, radial probe endobronchial ultrasound, and fluoroscopy were used for all procedures. Robotic-assisted bronchoscopy was performed on each cadaver by an individual bronchoscopist to localize and biopsy peripheral lesions. RESULTS: Sixty-seven nodules were evaluated in 8 cadavers. The mean nodule size was 20.4 mm. The overall diagnostic yield was 65/67 (97%) and there was no statistical difference in diagnostic yield for lesions <20 mm compared with lesions measuring 21-30 mm, the presence of a concentric or eccentric radial ultrasound image, or relative distance from the pleura. CONCLUSIONS: The robotic bronchoscopic system was successful at biopsying 97% of peripheral pulmonary lesions 10-30 mm in size in human cadavers. These findings support further exploration of this technology in prospective clinical trials in live human subjects.

Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis.

Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.

Pleural Disease in Women.

There are several pleural diseases that occur either predominantly or exclusively in females. Most of these entities are related to obstetric or gynecological conditions. In this article, we will provide an overview of Meigs' syndrome, ovarian hyperstimulation syndrome, endometriosis, catamenial pneumothorax, catamenial hemothorax, pleural effusions that occur in the peripartum period, lymphangioleiomyomatosis, and malignant pleural effusions related to breast cancer. As most of these diagnoses are rare, considerable expertise is required to identify, diagnose, and manage these patients. The aim of this article is to present an overview of the most common forms of pleural disease affecting women, and to provide an easy reference source on current best practice.

A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma.

New therapeutic strategies are needed for malignant pleural mesothelioma (MPM). We conducted a single-center, open-label, nonrandomized, pilot and feasibility trial using two intrapleural doses of an adenoviral vector encoding human IFN-α (Ad.IFN-α2b). Nine subjects were enrolled at two dose levels. The first three subjects had very high pleural and systemic IFN-α concentrations resulting in severe "flu-like" symptoms necessitating dose de-escalation. The next six patients had reduced (but still significant) pleural and serum IFN-α levels, but with tolerable symptoms. Repeated vector administration appeared to prolong IFN-α expression levels. Anti-tumor humoral immune responses against mesothelioma cell lines were seen in seven of the eight subjects evaluated. No clinical responses were seen in the four subjects with advanced disease. However, evidence of disease stability or tumor regression was seen in the remaining five patients, including one dramatic example of partial tumor regression at sites not in contiguity with vector infusion. These data show that Ad.IFN-α2b has potential therapeutic benefit in MPM and that it generates anti-tumor immune responses that may induce anatomic and/or metabolic reductions in distant tumor. Clinical trial registered with www.clinicaltrials.gov (NCT 01212367).

A phase I trial of repeated intrapleural adenoviral-mediated interferon-beta gene transfer for mesothelioma and metastatic pleural effusions.

We previously showed that a single intrapleural dose of an adenoviral vector expressing interferon-beta (Ad.IFN-beta) in patients with malignant pleural mesothelioma (MPM) or malignant pleural effusions (MPE) resulted in gene transfer, humoral antitumor immune responses, and anecdotal clinical responses manifested by modified Response Evaluation Criteria in Solid Tumors (RECIST) disease stability in 3 of 10 patients at 2 months and an additional patient with significant metabolic response on positron emission tomography (PET) imaging. This phase I trial was conducted to determine whether using two doses of Ad.IFN-beta vector would be superior. Ten patients with MPM and seven with MPE received two doses of Ad.IFN-beta through an indwelling pleural catheter. Repeated doses were generally well tolerated. High levels of IFN-beta were detected in pleural fluid after the first dose; however, only minimal levels were seen after the second dose of vector. Lack of expression correlated with the rapid induction of neutralizing Ad antibodies (Nabs). Antibody responses against tumor antigens were induced in most patients. At 2 months, modified RECIST responses were as follows: one partial response, two stable disease, nine progressive disease, and two nonmeasurable disease. One patient died after 1 month. By PET scanning, 2 patients had mixed responses and 11 had stable disease. There were seven patients with survival times longer than 18 months. This approach was safe, induced immune responses and disease stability. However, rapid development of Nabs prevented effective gene transfer after the second dose, even with a dose interval as short as 7 days.

Pilot randomized study comparing two techniques of airway anaesthesia during curvilinear probe endobronchial ultrasound bronchoscopy (CP-EBUS).

BACKGROUND AND OBJECTIVE: This study evaluates two different techniques for topically anaesthetizing the airway with lidocaine during curvilinear probe endobronchial ultrasound bronchoscopy (CP-EBUS): standard injection through the working channel and spray catheter application. METHODS: This was a randomized, non-blinded, single-centre pilot study. Patients with plans for CP-EBUS under moderate sedation were enrolled. All patients received nebulized lidocaine followed by posterior oropharyngeal lidocaine via atomizer and a cotton ball swab using McGill forceps. Patients were then randomly assigned to lidocaine administration using spray catheter instillation or direct application through the working channel. Lidocaine was administered in a uniform fashion by a single investigator throughout the study. The primary end-point was the number of significant coughing episodes in the first 30 min of bronchoscopy. Other end-points included lidocaine and intravenous sedation medication dosage; severe coughing session; and number of transbronchial needle aspirations. RESULTS: Forty patients were included in the study: 20 patients in each group. The median numbers of coughing episodes in the first 30 min were 1 (spray catheter group) and 2 (standard injection group) (P < 0.004). Six patients in the standard installation group experienced severe coughing sessions, while there was none in the spray catheter group (P = 0.02). There were no statistical differences between the groups in the dosage of lidocaine or intravenous sedation medications used. There were a greater number of transbronchial needle aspirations performed in the spray catheter group (P = 0.008). CONCLUSIONS: Lidocaine delivery via the spray catheter reduced the number of significant coughing episodes compared with standard working channel injection during CP-EBUS. Larger studies are needed to confirm these exploratory findings.

Epidemiology of Adult Pleural Disease in the United States.

BACKGROUND: Comprehensive US epidemiologic data for adult pleural disease are not available. RESEARCH QUESTION: What are the epidemiologic measures related to adult pleural disease in the United States? STUDY DESIGN AND METHODS: Retrospective cohort study using Healthcare Utilization Project databases (2007-2016). Adults (≥ 18 years of age) with malignant pleural mesothelioma, malignant pleural effusion, nonmalignant pleural effusion, empyema, primary and secondary spontaneous pneumothorax, iatrogenic pneumothorax, and pleural TB were studied. RESULTS: In 2016, ED treat-and-discharge (T&D) visits totaled 42,215, accounting for charges of $286.7 million. In 2016, a total of 361,270 hospitalizations occurred, resulting in national costs of $10.1 billion. A total of 64,174 readmissions contributed $1.16 billion in additional national costs. Nonmalignant pleural effusion constituted 85.5% of ED T&D visits, 63.5% of hospitalizations, and 66.3% of 30-day readmissions. Contemporary sex distribution (male to female ratio) in primary spontaneous pneumothorax (2.1:1) differs from older estimates (6.2:1). Decadal analyses of annual hospitalization rates/100,000 adult population (2007 vs 2016) showed a significant (P < .001) decrease for malignant pleural mesothelioma (1.3 vs 1.09, respectively), malignant pleural effusion (33.4 vs 31.9, respectively), iatrogenic pneumothorax (17.9 vs 13.9, respectively), and pleural TB (0.20 vs 0.09, respectively) and an increase for empyema (8.1 vs 11.1, respectively) and nonmalignant pleural effusion (78.1 vs 100.1, respectively). Empyema hospitalizations have high costs per case ($38,591) and length of stay (13.8 days). The mean proportion of readmissions attributed to a pleural cause varied widely: malignant pleural mesothelioma, 49%; malignant pleural effusion, 45%; nonmalignant pleural effusion, 31%; empyema, 27%; primary spontaneous pneumothorax, 27%; secondary spontaneous pneumothorax, 27%; and iatrogenic pneumothorax, 20%. Secondary spontaneous pneumothorax had the shortest time to readmission in 2016 (10.3 days, 95% CI, 8.8-11.8 days). INTERPRETATION: Significant epidemiologic trends and changes in various pleural diseases were observed. The analysis identifies multiple opportunities for improvement in management of pleural diseases.

A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses.

PURPOSE: This phase 1 dose escalation study evaluated the safety and feasibility of single-dose intrapleural IFN-beta gene transfer using an adenoviral vector (Ad.IFN-beta) in patients with malignant pleural mesothelioma (MPM) and metastatic pleural effusions (MPE). EXPERIMENTAL DESIGN: Ad.IFN-beta was administered through an indwelling pleural catheter in doses ranging from 9 x 10(11) to 3 x 10(12) viral particles (vp) in two cohorts of patients with MPM (7 patients) and MPE (3 patients). Subjects were evaluated for (a) toxicity, (b) gene transfer, (c) humoral, cellular, and cytokine-mediated immune responses, and (d) tumor responses via 18-fluorodeoxyglucose-positron emission tomography scans and chest computed tomography scans. RESULTS: Intrapleural Ad.IFN-beta was generally well tolerated with transient lymphopenia as the most common side effect. The maximally tolerated dose achieved was 9 x 10(11) vp secondary to idiosyncratic dose-limiting toxicities (hypoxia and liver function abnormalities) in two patients treated at 3 x 10(12) vp. The presence of the vector did not elicit a marked cellular infiltrate in the pleural space. Intrapleural levels of cytokines were highly variable at baseline and after response to gene transfer. Gene transfer was documented in 7 of the 10 patients by demonstration of IFN-beta message or protein. Antitumor immune responses were elicited in 7 of the 10 patients and included the detection of cytotoxic T cells (1 patient), activation of circulating natural killer cells (2 patients), and humoral responses to known (Simian virus 40 large T antigen and mesothelin) and unknown tumor antigens (7 patients). Four of 10 patients showed meaningful clinical responses defined as disease stability and/or regression on 18-fluorodeoxyglucose-positron emission tomography and computed tomography scans at day 60 after vector infusion. CONCLUSIONS: Intrapleural instillation of Ad.IFN-beta is a potentially useful approach for the generation of antitumor immune responses in MPM and MPE patients and should be investigated further for overall clinical efficacy.

Robotic Endoscopic Airway Challenge: REACH Assessment.

PURPOSE: Bronchoscopy for peripheral pulmonary lesions continues to present challenges to clinicians. One potential limitation may be the inability to advance conventional bronchoscopes into close proximity of peripheral lesions before biopsy. This study was performed to assess the reach of a robotic endoscopic system within human cadaveric lungs compared with conventional thin bronchoscopes. DESCRIPTION: All segmental bronchi (RB1 to 10, LB1 to 10) were accessed in two human cadavers using a conventional thin bronchoscope and robotic endoscope of identical outer diameter. Bronchus generation count and insertion depth measured by electromagnetic navigation and external fluoroscopy were recorded. EVALUATION: The robotic endoscope was advanced beyond the conventional thin bronchoscope in all segments, particularly in bronchi with increased angulation such as RB1 (mean generation count 8 versus 3.5, respectively) and LB1+2 (mean generation count 8 versus 4.5). CONCLUSIONS: The robotic endoscopic system was advanced beyond a conventional thin bronchoscope with identical outer diameter into the periphery of human cadaveric lungs. Improved reach within the lung periphery may address some limitations with contemporary bronchoscopic approaches for peripheral lesion biopsy.

Bronchial effects of cryoballoon ablation for atrial fibrillation.

BACKGROUND: Damage to extracardiac structures, including the esophagus and phrenic nerve, is a known complication of cryoballoon ablation (CBA) during pulmonary vein (PV) isolation for atrial fibrillation (AF). Other adjacent structures, including the pulmonary bronchi and lung parenchyma, may be affected during CBA at the PV ostia. OBJECTIVE: The purpose of this study was to prospectively study the bronchial effects of CBA in humans undergoing CBA for PV isolation. METHODS: Ten patients undergoing CBA for AF under general anesthesia were enrolled in an institutional review board-approved prospective observational study. Real-time bronchoscopy was performed during cryoablation of PVs adjacent to pulmonary bronchi to monitor for thermal injury. Patients were followed for the development of respiratory complaints postprocedure. RESULTS: In 7 of 10 patients (70%) and in 13 of 22 freezes (59%), ice formation was visualized in the left mainstem bronchus during CBA in the left upper PV. Ice formation was not seen in the right mainstem bronchus during right upper PV CBA. The average time to ice formation was 89 seconds. There was no significant difference (P = -.45) in average minimum balloon temperature during freezes with ice formation (-48.5°C) and freezes without ice formation (-46.3°C). No patients went on to develop respiratory complications. CONCLUSION: Unrecognized ice formation occurs frequently in the left mainstem bronchus during CBA for AF. This information helps explain the source of cough and hemoptysis in some patients who undergo CBA. The long-term consequences of this novel finding and the implications for procedural safety are unknown.

Interferon beta adenoviral gene therapy in a patient with ovarian cancer.

Background A 47-year-old woman with a history of ovarian cancer and a 6-year disease-free remission presented with dyspnea and increased abdominal girth. The patient was found to have ascites and a large left pleural effusion, both of which contained malignant cells consistent with recurrent ovarian cancer. Her disease progressed despite treatment with chemotherapeutic and hormonal agents. She was then enrolled in a phase I clinical trial of adenoviral-mediated interferon beta gene therapy. Investigations Abdominal and chest CT scans, 2-[(18)F]fluoro-2-deoxyglucose PET scan, viral cultures, interferon cytokine analysis, immunophenotyping, and tumor cytotoxicity analyses. Diagnosis Stage IV ovarian cancer with malignant ascites and pleural effusion. Management Tunneled pleural catheter and intrapleural adenoviral-mediated interferon beta gene therapy.

Rare Middle Mediastinal Paraganglioma Mimicking Metastatic Neuroendocrine Tumor.

Mediastinal paragangliomas are rare neural crest derived tumors that may produce symptoms of excess catecholamine production or mass effect. Paragangliomas can histologically mimic neuroendocrine tumors. Further, both can arise in similar locations. We report a patient who presented with a right upper lobe as well as middle mediastinal lesion. Preoperative biopsy as well as intraoperative frozen section of these lesions failed to distinguish between paraganlioma or neuroendocrine tumor, necessitating a right upper lobectomy and complete mediastinal lymphadenectomy. Final pathology revealed carcinoid tumorlets in the right upper lobe and a middle mediastinal paraganglioma.

Secondary carina Y-stent placement for post-lung-transplant bronchial stenosis.

BACKGROUND: Post-lung-transplant bronchial stenosis (TBS) may cause significant morbidity and mortality. Although often transiently relieved by balloon bronchoplasty, stents may be required for long-term airway patency. We report a series of lung transplant patients in whom a silicone Y-stent was placed at the secondary carina for long-standing relief of post-transplant-airway stenosis. METHODS: Six lung transplant patients received 10 silicone Y-stents in the secondary carina over the past 18 months for post-transplant-bronchial stenosis. All patients failed other interventional therapeutic procedures including balloon bronchoplasty and/or conventional stenting before secondary carina Y-stent placement. Patient data include 12 months' follow-up after Y-stent insertion. The number of procedures and the interval between procedures was examined before and after secondary carina silicone Y-stent placement. RESULTS: There was a significantly prolonged therapeutic effect accomplished in these patients after secondary carina Y-stent placement with the exception of 1 patient. When stents were tolerated by the patient, the mean number of procedures before secondary carina Y-stent insertion was 15.6, but only 4.8 after Y-stent insertion. The number of days between procedures was 24.5 days before the Y-stent insertion and 85.8 days after the Y-stent insertion. There were no complications in any patient during secondary carina Y-stent insertion. CONCLUSIONS: Secondary carina silicone Y-stent placement in TBS decreased the number of therapeutic procedures and provided longer-lasting results in most posttransplant patients who required multiple prior procedures for TBS.