Immune Checkpoint Inhibitor-Related Pulmonary Toxicity: A Comprehensive Review, Part II.

The development of immune checkpoint inhibitors (ICIs) has changed the treatment paradigm for cancer. The ICIs nivolumab, pembrolizumab, and cemiplimab target programmed cell death protein 1, and durvalumab, avelumab, and atezolizumab target programmed death ligand 1. Ipilimumab targets cytotoxic T lymphocyte-associated antigen-4. Used as monotherapy or in combination, they have shown remarkable efficacy in melanoma, lung cancer, and many other solid tumors, and indications continue to evolve. These checkpoint inhibitors are typically well tolerated; however, they may cause immune-mediated adverse effects, resulting in inflammation of any organ system. Pulmonary toxicity is vital to recognize, and it can be more challenging to diagnose in patients with lung cancer, given the nature of the disease course and treatment.

A Comprehensive Systemic Literature Review of Pericardial Decompression Syndrome: Often Unrecognized and Potentially Fatal Syndrome.

BACKGROUND: Pericardial Decompression Syndrome (PDS) is defined as paradoxical hemodynamic deterioration and/or pulmonary edema, commonly associated with ventricular dysfunction. This phenomenon was first described by Vandyke in 1983. PDS is a rare but formidable complication of pericardiocentesis, which, if not managed appropriately, is fatal. PDS, as an entity, has discrete literature; this review is to understand its epidemiology, presentation, and management. METHODOLOGY: Medline, Science Direct and Google Scholar databases were utilized to do a systemic literature search. PRISMA protocol was employed. Abstracts, case reports, case series and clinical studies were identified from 1983 to 2019. A total of 6508 articles were reviewed, out of which, 210 were short-listed, and after removal of duplicates, 49 manuscripts were included in this review. For statistical analysis, patient data was tabulated in SPSS version 20. Cases were divided into two categories surgical and percutaneous groups. t-test was conducted for continuous variable and chi-square test was conducted for categorical data used for analysis. RESULTS: A total of 42 full-length case reports, 2 poster abstracts, 3 case series of 2 patients, 1 case series of 4 patients and 1 case series of 5 patients were included in the study. A total of 59 cases were included in this manuscript. Our data had 45.8% (n=27) males and 54.2% (n=32) females. The mean age of patients was 48.04 ± 17 years. Pericardiocentesis was performed in 52.5% (n=31) cases, and pericardiostomy was performed in 45.8% (n=27). The most common identifiable cause of pericardial effusion was found to be malignancy in 35.6% (n=21). Twenty-three 23 cases reported pre-procedural ejection fraction, which ranged from 20%-75% with a mean of 55.8 ± 14.6%, while 26 cases reported post-procedural ejection fraction which ranged from 10%-65% with a mean of 30% ± 15.1%. Data was further divided into two categories, namely, pericardiocentesis and pericardiostomy. The outcome as death was significant in the pericardiostomy arm with a p-value of < 0.00. The use of inotropic agents for the treatment of PDS was more common in needle pericardiocentesis with a p-value of 0.04. Lastly, the computed recovery time did not yield any significance with a p-value of 0.275. CONCLUSION: Pericardial decompression syndrome is a rare condition with high mortality. Operators performing pericardial drainage should be aware of this complication following drainage of cardiac tamponade, since early recognition and expeditious supportive care are the only therapeutic modalities available for adequate management of this complication.

Immune Checkpoint Inhibitor-Related Pulmonary Toxicity: Focus on Nivolumab.

The development of checkpoint inhibitors has changed the treatment paradigm for cancer. Checkpoint inhibitors nivolumab, pembrolizumab, and cemiplimab target programmed death-1 (PD-1), whereas durvalumab, avelumab, and atezolizumab target PD-ligand 1. Ipilimumab targets cytotoxic T lymphocyte-associated antigen 4. Used as monotherapy or in combination, these inhibitors have shown remarkable efficacy in melanoma, lung cancer, urothelial cancer, and many other solid tumors, and indications are continuing to evolve. Checkpoint inhibitors are well tolerated when compared with traditional chemotherapy. The major adverse effect profiles are idiosyncratic immune-mediated toxicities resulting from the abnormal activation of autoreactive T cells, which can lead to inflammation in any organ system. The most commonly affected organs are bowel, lung, skin, and endocrine. Pulmonary toxicity is important to recognize, and it can be more challenging to diagnose in lung cancer patients, given the nature of the disease course and treatment. This review article focuses on all of the pulmonary adverse effects of a single PD-1 inhibitor (nivolumab) that have been described in the literature. These complications include dyspnea, pneumonitis, pleural effusion, pulmonary sarcoidosis, pulmonary tuberculosis, acute fibrinous organizing pneumonia, organizing pneumonia, eosinophilic pneumonia, adult respiratory distress syndrome, and lung cavitation. Clinicians must be aware of these toxicities and mindful when prescribing these medications in patients with known lung dysfunction due to chronic lung diseases or lung cancer.

Paecilomyces in an immune competent host.

Paecilomyces species was first recognized to cause human disease in 1963. It is a rare cause of invasive fungal infection, with cases sporadically reported in immunocompromised patients. Here we report the first case of pulmonary Paecilomyces in an immunocompetent patient that was successfully treated with amphotericin B and posaconazole.

The role and safety of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis and management of infected bronchogenic mediastinal cysts in adults.

Bronchogenic and other duplication cysts are congenital abnormalities that can present at any age including adulthood years. They are usually asymptomatic and discovered incidentally on radiological imaging of the chest. They are commonly treated by surgical resection. Recently, endobronchial ultrasound has been used to assist in diagnosis when radiologic imaging is not definitive. Endobronchial ultrasound has been used rarely to drain infected cysts, a rare complication of the bronchogenic cyst. We present a unique case of an infected large bronchogenic cyst treated with endobronchial ultrasound drainage combined with conservative medical therapy. We also review the scarce available literature describing such an approach and its potential complications and add recommendations based on our experience in managing these anomalies.

Congestive Adenopathy: A Mediastinal Sequela of Volume Overload.

BACKGROUND: Endosonography has improved our ability to reach thoracic lymph nodes and to diagnose pathologic conditions with nodal involvement and has lowered the threshold for biopsy. The purpose of this study was to avoid unnecessary procedures, it is important to recognize benign adenopathy. Congestive heart failure (CHF) is both common and a common cause of adenopathy. The purpose of this study was to study the association between CHF and adenopathy and to describe the typical presentation of congestive adenopathy. METHODS: We performed a retrospective correlation of computed tomographic (CT) and laboratory findings for patients admitted to hospital with a diagnosis of CHF. RESULTS: Of 500 patients admitted with a diagnosis of CHF, 215 appeared to have CT scans of the chest, and not to have a potentially confounding etiology of adenopathy. The incidence of adenopathy in this study group was 68%. Pulmonary edema on CT and pleural effusion were both significantly associated with adenopathy (P<0.01 for both). The pattern of congestive adenopathy was one of enlargement of several mediastinal nodes and less likely to involve hilar nodes and single stations in isolation. CONCLUSION: Congestive adenopathy is common in patients with evidence for acute volume overload. The pattern of presentation should allow clinicians to recognize congestive adenopathy and to separate it from other adenopathy for which biopsy might be appropriate.

The intubated patient with mediastinal disease--a role for esophageal access using the endobronchial ultrasound bronchoscope.

Ultrasound-guided transbronchial needle aspiration using the bronchoscope with a dedicated curvilinear probe has emerged as a primary tool for the investigation of mediastinal pathology. Recently, the utility of this scope has been expanded to include access via the esophagus. In this case series, we describe a role for esophageal ultrasound using the endobronchial ultrasound bronchoscope in the diagnostic evaluation of critically ill/intubated patients with mediastinal disease. Esophageal access with the ultrasound bronchoscope allows the pulmonologist to diagnose mediastinal disease in the intubated patient with minimal risk.

Is chest tube insertion with ultrasound guidance safe in patients using clopidogrel?

BACKGROUND AND OBJECTIVE: Drainage of the pleural space is a common procedure. The safety of chest tube insertion in patients using clopidogrel has not been investigated. METHODS: Ultrasound-guided chest tube insertions performed on 24 patients who were being actively treated with clopidogrel were retrospectively reviewed. RESULTS: No excessive bleeding occurred in any of these patients. CONCLUSIONS: Given the known effects of clopidogrel on platelet function, these results were interpreted as indicating that clopidogrel therapy is a relative but not an absolute contraindication to chest tube insertion, if an experienced operator places a small-bore tube under ultrasound guidance.

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in a Geographical Region With Endemic Histoplasmosis Infection.

BACKGROUND AND OBJECTIVE: In a geographical area with high prevalence of calcific granulomatous inflammation, calcified lymph nodes may affect the diagnostic adequacy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to describe the diagnostic performance of EBUS-TBNA in a region endemic of histoplasmosis related granulomatous inflammation. METHODOLOGY: A retrospective review was done for all patients referred for EBUS-TBNA over a 7-month period at 2 institutions. Computed tomographic (CT) chest studies were reviewed in a blinded manner by 2 radiologists. In parallel, CT images from 100 unselected sequential control patients were reviewed. Cytologic analysis of EBUS-TBNA aspirates was compared with a reference standard of definitive pathologic tissue diagnosis or a composite of ≥6-month clinical follow-up. RESULTS: The prevalence of calcified lymph nodes in the 100 control patients was 56%. All 61 patients undergoing EBUS-TBNA were included. In total, 97 lymph nodes (mean size=13.8 mm) and 7 masses were biopsied. Definitive lymph node sampling was achieved in 51 of 61 patients (83%). The sensitivity, specificity, and positive and negative predictive values of EBUS-TBNA for malignancy (primary lung cancer staging, restaging, and reevaluation after cancer therapy, small cell lung cancer, lymphoma, and metastatic cancer) were 81%, 100%, 100%, and 84% respectively. On pre-EBUS CT chest scan, 60.6% had nodal calcification. The prevalence of cancer was not different in those with and without nodal calcification (49%). There was no difference in frequency of definitive lymph node sampling in those patients with or without nodal calcification. CONCLUSION: In a geographical area with endemic histoplasmosis-related nodal calcification, there was no evidence of nodal calcification affecting the frequency of EBUS-TBNA definitive lymph node sampling.