Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

The Use of Bronchoscopy During the Coronavirus Disease 2019 Pandemic: CHEST/AABIP Guideline and Expert Panel Report.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has swept the globe and is causing significant morbidity and mortality. Given that the virus is transmitted via droplets, open airway procedures such as bronchoscopy pose a significant risk to health-care workers (HCWs). The goal of this guideline was to examine the current evidence on the role of bronchoscopy during the COVID-19 pandemic and the optimal protection of patients and HCWs. STUDY DESIGN AND METHODS: A group of approved panelists developed key clinical questions by using the Population, Intervention, Comparator, and Outcome (PICO) format that addressed specific topics on bronchoscopy related to COVID-19 infection and transmission. MEDLINE (via PubMed) was systematically searched for relevant literature and references were screened for inclusion. Validated evaluation tools were used to assess the quality of studies and to grade the level of evidence to support each recommendation. When evidence did not exist, suggestions were developed based on consensus using the modified Delphi process. RESULTS: The systematic review and critical analysis of the literature based on six PICO questions resulted in six statements: one evidence-based graded recommendation and 5 ungraded consensus-based statements. INTERPRETATION: The evidence on the role of bronchoscopy during the COVID-19 pandemic is sparse. To maximize protection of patients and HCWs, bronchoscopy should be used sparingly in the evaluation and management of patients with suspected or confirmed COVID-19 infections. In an area where community transmission of COVID-19 infection is present, bronchoscopy should be deferred for nonurgent indications, and if necessary to perform, HCWs should wear personal protective equipment while performing the procedure even on asymptomatic patients.

Photodynamic therapy for the treatment of tracheobronchial papillomatosis: A multicenter experience.

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) causes mucosal wart-like growths of the upper aerodigestive tract, which can undergo malignant transformation. These tumors are difficult to treat, often requiring repeated debridement, which can be associated with high morbidity. Photodynamic therapy (PDT) uses a photosensitizing medication and a topically applied light source to treat early stage endobronchial lung cancer. Most data on the use of PDT in RRP pertain to laryngeal disease. Our objective was to evaluate the effectiveness of PDT in treating RRP involving the lower respiratory tract. METHODS: We performed a retrospective multicenter review of adult patients who had a diagnosis of RRP involving the lower airways. We documented details of their disease, treatments, and outcomes. RESULTS: Eight patients underwent PDT for ten RRP lesions. Lesions were located in the trachea and more distal airways. Pathology showed malignant conversion to squamous cell carcinoma in half of the cases. All patient underwent debulking and multimodal treatment concurrently with PDT. Treatment was successful in seven patients with improvement in luminal size. Duration of disease-free recurrence ranged from 4 to 33 months. Five of eight patients have sustained ongoing treatment effect, ranging from 10 to 33 months. Most patient had improved quality of life (83 %) and a reduction in interventions (87 %) after PDT. Complications were minimal. CONCLUSION: PDT can be a safe and effective tool when treating RRP of the lower respiratory tract, including lesions with malignant transformation. A multimodal treatment approach is associated with improved outcomes. Further prospective studies are needed to fully determine its effectiveness.

Interleukin-13 disrupts type 2 pneumocyte stem cell activity.

The T helper 2 (Th2) inflammatory cytokine interleukin-13 (IL-13) has been associated with both obstructive and fibrotic lung diseases; however, its specific effect on the epithelial stem cells in the gas exchange compartment of the lung (alveolar space) has not been explored. Here, we used in vivo lung models of homeostasis and repair, ex vivo organoid platforms, and potentially novel quantitative proteomic techniques to show that IL-13 disrupts the self-renewal and differentiation of both murine and human type 2 alveolar epithelial cells (AEC2s). Significantly, we find that IL-13 promotes ectopic expression of markers typically associated with bronchiolar airway cells and commonly seen in the alveolar region of lung tissue from patients with idiopathic pulmonary fibrosis. Furthermore, we identify a number of proteins that are differentially secreted by AEC2s in response to IL-13 and may provide biomarkers to identify subsets of patients with pulmonary disease driven by "Th2-high" biology.

Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Center Experience of Two Cases.

BACKGROUND Recurrent respiratory papillomatosis (RRP), caused by human papillomavirus (HPV), is the most common benign neoplasm of the larynx and central airways. RRP has a significant impact on quality life and high annual costs to healthcare. Currently, there is no cure for RRP, leading to repeated debulking operations for symptomatic palliation. Various local adjuvant therapies have also been studied with mixed efficacy. HPV oncogene products increase expression of vascular endothelial growth factor (VEGF) providing a potential target for treatment of RRP. Bevacizumab, a recombinant monoclonal antibody that inhibits VEGF, has shown efficacy in patients with localized disease. CASE REPORT We present two cases of extensive airway and parenchymal RRP successfully managed with systemically administered bevacizumab, a recombinant monoclonal antibody that inhibits VEGF. CONCLUSIONS Bevacizumab has shown efficacy in patients with localized disease, but here we illustrate the potential of bevacizumab for patients with extensive parenchymal burden as well as provide a brief review of the literature.

Safety of hyperbaric oxygen therapy for management of central airway stenosis after lung transplant.

BACKGROUND: Central airway stenosis (CAS) is common after lung transplantation and causes significant post-transplant morbidity. It is often preceded by extensive airway necrosis, related to airway ischemia. Hyperbaric oxygen therapy (HBOT) is useful for ischemic grafts and may reduce the development of CAS. METHODS: The purpose of this study was to determine whether HBOT could be safely administered to lung transplant patients with extensive necrotic airway plaques. Secondarily, we assessed any effects of HBOT on the incidence and severity of CAS. Patients with extensive necrotic airway plaques within 1-2 months after lung transplantation were treated with HBOT along with standard care. These patients were compared with a contemporaneous reference group with similar plaques who did not receive HBOT. RESULTS: Ten patients received HBOT for 18.5 (interquartile range, IQR 11-20) sessions, starting at 40.5 (IQR 34-54) days after transplantation. HBOT was well tolerated. Incidence of CAS was similar between HBOT-treated patients and reference patients (70% vs 87%, respectively; P=.34), but fewer stents were required in HBOT patients (10% vs 56%, respectively; P=.03). CONCLUSIONS: This pilot study is the first to demonstrate HBOT safety in patients who develop necrotic airway plaques after lung transplantation. HBOT may reduce the need for airway stent placement in patients with CAS.