The concept of navigation bronchoscopy is not new, but has evolved over past few decades. Clinicians performing bronchoscopy have utilized various forms of navigation technology ranging from fluoroscopy or computed tomography (CT)-aided guidance in earlier years, now to virtual bronchoscopy and real-time tracking using electromagnetic navigation (EMN) platforms. EMN bronchoscopy relies on a pre-procedural CT of the chest to create a three-dimensional (3D) virtual airway map. This approach is utilized for diagnostic sampling of lung and mediastinal lesions, placement of fiducial markers, or dye marking of the overlying pleura. The diagnostic yield, using this technology, is superior to conventional bronchoscopy techniques and is discussed. The respiratory motion of the airways, lung, and nodule hysteresis creates unique challenges for targeting the lesion. Use of fluoroscopy and radial-probe ultrasound provide meaningful information and additional confirmation with difficult lesions. We continue to evolve in our understanding of how best to utilize the technology, modify diagnostic tools, and improve next-generation platforms. Even so, EMN bronchoscopy has changed the landscape of tissue acquisition for peripheral lung lesions. This review provides important principles and practical aspects of pre-procedure preparation, assessment of airway-lesion relationships, procedural workflow and performance, and points for consideration when contemplating acquisition of an EMN system. The future is in development of intuitive platforms that will allow consistent targeting with higher accuracy so ablation techniques could be performed safely via the endobronchial approach.

African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.

Multiple myeloma is a plasma cell dyscrasia accounting for 10% of haematologic malignancies. Lenalidomide is an immunomodulatory drug analogous to thalidomide that is approved for use in patients with myelodysplastic syndrome, and in combination with dexamethasone for refractory or relapsed multiple myeloma. Lenalidomide is preferred to thalidomide because of reduced toxicity, and pulmonary side effects are considered rare. We present, to our knowledge, an unusual and first reported case of a patient with relapsed multiple myeloma who received lenalidomide after autologous stem cell transplant, then developed eosinophilic pneumonia presenting as dyspnoea, peripheral eosinophilia, and bilateral pulmonary opacities. Bronchoscopy with bronchoalveolar lavage was negative for infection, and transbronchial lung biopsies showed eosinophilic pneumonia. After discontinuation of lenalidomide and initiation of prednisone therapy, his dyspnoea improved and eosinophilia resolved; however, symptoms recurred when the drug was restarted at a lower dose, confirming its causative role. In the absence of infection, clinicians should always bear in mind drug toxicity in the differential diagnosis of patients receiving lenalidomide and related agents.

To the Editor: Intrapleural fibrinolytic and mucolytic therapy has been shown to improve fluid drainage, reduce frequency of thoracic surgical referral, and decrease the duration of hospitalization in patients with pleural space infection. Although relatively uncommon, one of the anticipated complications of this therapy is bleeding. Among 52 patients who received combination therapy, 2 patients suffered intrapleural hemorrhage and 1 patient encountered hemoptysis.1 We report the first known case of diffuse alveolar hemorrhage (DAH) caused by tissue plasminogen activator (tPA) and dornase alpha (DNase) administration through chest tube catheter (CTC) placement for complicated parapneumonic pleural effusion. A 78-year-old man with history of ischemic cardiomyopathy and chronic kidney disease presented with altered mental status secondary to Streptococcal pneumoniae pneumonia. A left apical complex pleural effusion was noted on ultrasound and a small bore CTC was placed. Intrapleural tPA and DNase were instilled per standard protocol of 10 mg tPA and 5 mg DNase twice daily for 3 days with 1 hour dwell time. The CTC was accidentally dislodged during the course of intrapleural therapy and replaced under ultrasound guidance without difficulty. The CTC was removed a few hours after the last intrapleural treatment due to lack of pleural fluid output, radiographic improvement of pleural space and patient’s expressed discomfort at the CTC entry site. Twelve hours after CTC removal, the patient reported increasing chest pain and developed sudden onset hemoptysis resulting in respiratory failure. Chest computed tomography obtained 15 hours after the last administration of tPA and DNase therapy and removal of the CTC demonstrated new onset left-sided alveolar opacities (Fig. 1). Bronchoscopy was performed demonstrating DAH pattern on bronchoalveolar lavage. Patient’s international normalized ratio was within normal limits at 1.2 and platelet dysfunction secondary to chronic kidney disease was suspected without thrombocytopenia. Because of the concern for a loculated hemothorax, videoscopic assisted thoracic surgery with decortication was performed. Intraoperatively, left lung alveolitis and hemothorax was demonstrated without visceral pleural tears. The patient was successfully discharged to rehabilitation following recovery from surgery. Intrapleural t-PA/DNase therapy in pleural infection has been shown to reduce the frequency of surgical referral and duration of hospital stay. The incidence of intrapleural hemorrhage has been reported to be low, ranging from 1.8% to 7%.1 The risk and incidence of bleeding complications is increased with use of higher doses of tPA and the presence of underlying coagulopathy. To our knowledge, DAH secondary to intrapleural fibrinolytic therapy has not previously been reported. Systemic absorption of tPA is minimal with quick systemic clearance, which makes bleeding from intrapleural fibrinolytic unlikely.2,3 Further, the laterality of the hemorrhage to the side of chest tube placement is less likely to be explained by accidental systemic administration of tPA. There are a number of possible mechanisms for bleeding in this patient. CTC migration before receiving the last dose of tPA could have resulted in extrapleural or systemic administration of thrombolytic therapy resulting in a higher risk of pleural and parenchymal hemorrhage. Migration of the CTC to an intraparenchymal location before the last dose of tPA may be a possibility explaining the left-sided predominant alveolar hemorrhage; however, lack of manipulation and absence of visceral pleural injury on thoracoscopic surgery argues against this mechanism. Another possible mechanism of introducing tPA into the alveolar space includes possible bronchopleural fistula as a complication of empyema.4 TPA administration in the presence of a known bronchopleural fistula is considered a relative contraindication, though this risk is generally considered theoretical.